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Neuroprotection in traumatic br
ain injury: a complex struggle
against the biology of natureJoost W. Schouten
Purpose of review
Translating the efficacy of neuroprotective agents in
experimental traumatic brain injury to clinical benefit has
proven an extremely complex and, to date, unsuccessful
undertaking. The focus of this review is on neuroprotective
agents that have recently been evaluated in clinical trials
and are currently under clinical evaluation, as well as on
those that appear promising and are likely to undergo
clinical evaluation in the near future.
Recent findings
Excitatory neurotransmitter blockage and magnesium have
recently been evaluated in phase III clinical trials, but
showed no neuroprotective efficacy. Cyclosporin A,
erythropoietin, progesterone and bradykinin antagonists are
currently under clinical investigation, and appear promising.
Summary
Traumatic brain injury is a complex disease, and
development of clinically effective neuroprotective agents is
a difficult task. Experimental traumatic brain injury has
provided numerous promising compounds, but to date
these have not been translated into successful clinical trials.
Continued research efforts are required to identify and test
new neuroprotective agents, to develop a better
understanding of the sequential activity of pathophysiologic
mechanisms, and to improve the design and analysis of
clinical trials, thereby optimizing chances for showing
benefit in future clinical trials.
Keywords
clinical trial, head injury, neuroprotection, neurotrauma,
traumatic brain injury
Curr Opin Crit Care 13:134–142. � 2007 Lippincott Williams & Wilkins.
Department of Neurosurgery, Erasmus Medical Center, Rotterdam, TheNetherlands
Correspondence to Joost W. Schouten, MD, Department of Neurosurgery, ErasmusMedical Center, Postbus 2040, 3000 CA, Rotterdam, The NetherlandsE-mail: [email protected]
Current Opinion in Critical Care 2007, 13:134–142
Abbreviations
CSF c
opyrigopyrig
134
erebrospinal fluid
iNOS in ducible nitric oxide synthase NMDA N -methyl-D-aspartic acid NOS n itric oxide synthase TBI tr aumatic brain injury
Table 1 Neuroprotective strategies evaluated in experimental traum
Pharmacological target Remarks
Excitatory amino acids Numerous compounds have been evadifferent pharmacological profiles (e
Calcium channels Extensively studied, also in clinical TBinjury seems to limit further clinical
Scavenging oxygen radicals Tirilazad Mesylate, PEG-SOD and Lubcompounds are at least promising i
Inflammation A double-edged sword in TBI, both dis a high potential target for neuropand nitroxides.
Caspases Caspases are important enzymes in amatter of debate whether apoptosis
Calpains Calcium-dependent proteases involveTBI reduce damage to fiber tracts,
Hormonal treatment Progesterone is currently being evaluapast. Experimental compounds attrathyrotropin-releasing hormone and t
Neurotransmission Widespread changes in neurotransmiserotonin, histamine, g-aminobutyricpotential interest following TBI. Cogwhich might benefit from this appro
Neurotrophic factors These growth/survival factors effectiveTBI. Many questions about dosage,
Coagulation Recombinant human factor VII has befollowing TBI, relate to outcome, antreatment of microvascular thrombo
Anticonvulsants Seizures occur frequently following TBacute administration can be neurop
Immunophilin ligands Cyclosporin A is currently being evaluinvestigation.
Minocycline Minocycline is a broad-spectrum antibOthers In experimental research additional ho
improvement of axonal outgrowth aclinical trial in pediatric TBI has bee
TBI, traumatic brain injury. Neuroprotective strategies are discussed more e
clinical trials join a growing list of neuroprotective agents
without proven clinical benefit (Table 2 [14–24]). The
focus of this review is on neuroprotective agents that
have recently been evaluated in clinical trials and are
currently under clinical evaluation, as well as on those
that appear promising and are likely to undergo clinical
evaluation in the near future.
Excitatory neurotransmitter antagonismDisturbances in neurotransmitter concentration occur
frequently following TBI. Excitotoxicity refers to an
excessive release of excitatory neurotransmitters
(primarily glutamate) initiating various pathophysiologic
processes including excessive calcium influx in neurons,
resulting in neuronal cell death [10]. High concentrations
of extracellular glutamate have been demonstrated in
both experimental models and clinical patients with TBI.
Experimental research has elucidated many aspects of
excitotoxicity and identified a number of glutamate
antagonists acting either pre- or postsynaptically on
5-methyl-4-isoxazolyl-propionic acid (AMPA)/kainate or
metabotropic receptors, in a competitive, noncompetitive
or modulating way. However, glutamate receptors are of
utmost importance to normal functioning, so antagonism
of excessive excitotoxic activity must be achieved
orized reproduction of this article is prohibited.
atic brain injury
luated and reviewed elsewhere [8��,10]. New compounds with.g. memantine) require further experimental evaluation.I (Nimodipine and SNX-111); the short time frame followinguse.eluzole have been clinically evaluated; many new
n experimental TBI.etrimental and beneficial. The massive inflammatory responserotection, with special attention for NO inhibitors, nitrones
poptotic cell death known to occur following TBI. It is however still ais a good or bad thing compared to necrosis following TBI.
d in cytoskeletal remodeling. Calpain inhibitors in experimentaland therefore are of major interest in axonal injury.ted in a clinical trial. Steroids have been extensively studied in thecting a lot of attention are dehydroepiandrosterone,heir analogs.tters occur following TBI. All compounds interfering in cathecholamine,
acid (GABA) and acetylcholine metabolism are therefore ofnitive problems and depression frequently present following TBI,ach, although a rationale for more acute administration exists.ly reduce apoptosis and improve functional outcome in experimentaltime-window and route of administration remain to be answered.
en evaluated in a clinical trial. Coagulation disorders are commond will be a hot topic for future research. Controversies regardingsis and progressive hemorrhagic contusions require attention [11].I, and anticonvulsants may reduce early seizures. In addition,
rotective [12,13].ated in a clinical trial, other compounds are under experimental
iotic, shown to be neuroprotective in experimental studies.t topics far from translation into clinical trials are neurogenesis,nd stem-cell transplantation, although for the latter a smalln initiated.
tective agent in the injured brain should be required,
ensuring adequate tissue penetration once the agent is
studied in efficacy trials. A more sensitive analysis of
outcome in new types of clinical trials is advocated,
with an important role for surrogate outcome measures
as well as new types of outcome analysis. Further
standardization in treatment is likely to benefit from
further development of evidence-based treatment
guidelines. Implementation of these suggestions, even
though a complex challenge, is likely to improve the
chance that experimentally effective agents will show
positive results in future clinical trials.
References and recommended readingPapers of particular interest, published within the annual period of review, havebeen highlighted as:� of special interest�� of outstanding interest
Additional references related to this topic can also be found in the CurrentWorld Literature section in this issue (pp. 226–227).
1
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This paper summarizes the current knowledge on the epidemiology of TBI inEurope and serves to highlight the lack of standardized data.
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3 Maas AI, Marmarou A, Murray GD, et al. Prognosis and clinical trial design intraumatic brain injury: the IMPACT� study. J Neurotrauma (in press).
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Neuroprotection in traumatic brain injury Schouten 141
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25 Chen HS, Lipton SA. The chemical biology of clinically tolerated NMDAreceptor antagonists. J Neurochem 2006; 97:1611–1626.
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27
�Maas AI, Murray G, Henney H 3rd, et al. Efficacy and safety of dexanabinol insevere traumatic brain injury: results of a phase III randomised, placebo-controlled, clinical trial. Lancet Neurol 2006; 5:38–45.
This paper reports the results of one of the most recent phase III trials in TBI; this isthe first trial in TBI to use the sliding-dichotomy approach to improve outcomeanalysis.
28 Willis C, Lybrand S, Bellamy N. Excitatory amino acid inhibitors for traumaticbrain injury. Cochrane Database Syst Rev 2004; 1:CD003986.
31 van den Heuvel C, Vink R. The role of magnesium in traumatic brain injury. ClinCalcium 2004; 14:9–14.
32
�Temkin NR, Anderson GD, Winn HR, et al. Magnesium sulfate for neuropro-tection after traumatic brain injury: a randomized controlled trial. Lancet Neurol2007; 6:29–38.
This paper reports results of a single-center phase III trial of magnesium in TBI. Incontrast to general belief the results show that magnesium is not effective and mayeven have harmful effects.
33 Muir KW, Lees KR, Ford I, et al. Magnesium for acute stroke (IntravenousMagnesium Efficacy in Stroke trial): randomised controlled trial. Lancet 2004;363:439–445.
34 McKee JA, Brewer RP, Macy GE, et al. Analysis of the brain bioavailability ofperipherally administered magnesium sulfate: a study in humans with acutebrain injury undergoing prolonged induced hypermagnesemia. Crit Care Med2005; 33:661–666.
35 McKee JA, Brewer RP, Macy GE, et al. Magnesium neuroprotection is limitedin humans with acute brain injury. Neurocrit Care 2005; 2:342–351.
36 Sakamoto T, Takasu A, Saitoh D, et al. Ionized magnesium in the cerebrospinalfluid of patients with head injuries. J Trauma 2005; 58:1103–1109.
37 Sullivan PG, Rabchevsky AG, Waldmeier PC, Springer JE. Mitochondrialpermeability transition in CNS trauma: cause or effect of neuronal cell death?J Neurosci Res 2005; 79:231–239.
38
�Merenda A, Bullock R. Clinical treatments for mitochondrial dysfunctions afterbrain injury. Curr Opin Crit Care 2006; 12:90–96.
Recent review on the central role of mitochondria in the pathophysiology of TBI.
39 Mazzeo AT, Kunene NK, Gilman CB, et al. Severe human traumatic braininjury, but not cyclosporin A treatment, depresses activated T lymphocytesearly after injury. J Neurotrauma 2006; 23:962–975.
40 Empey PE, McNamara PJ, Young B, et al. Cyclosporin A disposition followingacute traumatic brain injury. J Neurotrauma 2006; 23:109–116.
41 Lee LL, Galo E, Lyeth BG, et al. Neuroprotection in the rat lateral fluidpercussion model of traumatic brain injury by SNX-185, an N-type voltage-gated calcium channel blocker. Exp Neurol 2004; 190:70–78.
42 Hasselblatt M, Ehrenreich H, Siren AL. The brain erythropoietin system and itspotential therapeutic exploitation in brain disease. J Neurosurg Anesth 2006;18:132–138.
43 Yatsiv I, Grigoriadis N, Simeonidou C, et al. Erythropoietin is neuroprotective,improves functional recovery, and reduces neuronal apoptosis and inflamma-tion in a rodent model of experimental closed head injury. FASEB J 2005;19:1701–1703.
44 Ehrenreich H, Hasselblatt M, Dembowski C, et al. Erythropoietin therapy foracute stroke is both safe and beneficial. Mol Med 2002; 8:495–505.
45 Xenocostas A, Cheung WK, Farrell F, et al. The pharmacokinetics oferythropoietin in the cerebrospinal fluid after intravenous administration ofrecombinant human erythropoietin. Eur J Clin Pharmacol 2005; 61:189–195.
46 Mushkudiani N, Engel DC, Steyerberg EW, et al. The prognostic valueof demographic characteristics in traumatic brain injury: results from theIMPACT� study. J Neurotrauma (in press).
47 Stein DG, Hoffman SW. Estrogen and progesterone as neuroprotectiveagents in the treatment of acute brain injuries. Pediatr Rehabil 2003;6:13–22.
49 Robertson CL, Puskar A, Hoffman GE, et al. Physiologic progesteronereduces mitochondrial dysfunction and hippocampal cell loss after traumaticbrain injury in female rats. Exp Neurol 2006; 197:235–243.
50 He J, Hoffman SW, Stein DG. Allopregnanolone, a progesterone metabolite,enhances behavioral recovery and decreases neuronal loss after traumaticbrain injury. Restor Neurol Neurosci 2004; 22:19–31.
51 Djebaili M, Guo Q, Pettus EH, et al. The neurosteroids progesterone andallopregnanolone reduce cell death, gliosis, and functional deficits aftertraumatic brain injury in rats. J Neurotrauma 2005; 22:106–118.
52 Wright DW, Ritchie JC, Mullins RE, et al. Steady-state serum concentrationsof progesterone following continuous intravenous infusion in patients withacute moderate to severe traumatic brain injury. J Clin Pharmacol 2005;45:640–648.
53 Wright DW, Kellermann AL, Hertzberg VS, et al. ProTECT: A randomizedclinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med2006 [epub ahead of print].
54 Marmarou A, Guy M, Murphey L, et al. A single dose, three-arm, placebo-controlled, phase I study of the bradykinin B2 receptor antagonist Anatibant(LF16-0687Ms) in patients with severe traumatic brain injury. J Neurotrauma2005; 22:1444–1455.
55 Wada K, Chatzipanteli K, Busto R, Dietrich WD. Role of nitric oxide intraumatic brain injury in the rat. J Neurosurg 1998; 89:807–818.
57 Guix FX, Uribesalgo I, Coma M, Munoz FJ. The physiology and pathophysiol-ogy of nitric oxide in the brain. Prog Neurobiol 2005; 76:126–152.
58 Clark RSB, Kochanek PM, Obrist WD, et al. Cerebrospinal fluid and plasmanitrite and nitrate concentrations after head injury in humans. Crit Care Med1996; 24:1243–1251.
59 Pou S, Pou WS, Bredt DS, et al. Generation of superoxide by purified brainnitric oxide synthase. J Biol Chem 1992; 267:24173–24176.
60 Stuehr D, Pou S, Rosen GM. Oxygen reduction by nitric-oxide synthases.J Biol Chem 2001; 276:14533–14536.
61 Gahm C, Holmin S, Wiklund PN, et al. Neuroprotection by selective inhibitionof inducible nitric oxide synthase after experimental brain contusion. J Neuro-trauma 2006; 23:1343–1354.
62 Werner ER, Schmidt HH. Nitric oxide synthase inhibitors: pterin antagonistsand antipterins. In Handbook of experimental pharmacology. Berlin: SpringerVerlag; 2000: pp.137–157.
63 Morales DM, Marklund M, Lebold D, et al. Experimental models of traumaticbrain injury: do we really need to build a better mousetrap? Neuroscience2005; 136:971–989.
64 Doppenberg EM, Choi SC, Bullock R. Clinical trials in traumatic brain injury:lessons for the future. J Neurosurg Anesthesiol 2004; 16:87–94.
65 Hillered L, Persson L, Nilsson P, et al. Continuous monitoring of cerebralmetabolism in traumatic brain injury: a focus on cerebral microdialysis. CurrOpin Crit Care 2006; 12:112–118.
orized reproduction of this article is prohibited.
This is a brief review with the same topic as the current review. There is someoverlap in the drugs discussed, some points of view are different.
67 Murray GD, Barer D, Choi S, et al. Design and analysis of phase III trials withordered outcome scales: the concept of the sliding dichotomy. J Neurotrauma2005; 22:511–517.
68 Clifton GL, Miller ER, Choi SC, et al. Lack of effect of induction of hypothermiaafter acute brain injury. N Engl J Med 2001; 344:556–563.
69 Hukkelhoven CW, Steyerberg EW, Farace E, et al. Regional differences inpatient characteristics, case management, and outcomes in traumaticbrain injury: experience from the tirilazad trials. J Neurosurg 2002; 97:549–557.
Airway Management in Adults after Cervical Spine TraumaEdward T. Crosby, M.D., F.R.C.P.C.*
This article has been selected for the AnesthesiologyCME Program. After reading the article, go to http://www.asahq.org/journal-cme to take the test and apply forCategory 1 credit. Complete instructions may be found inthe CME section at the back of this issue.
Cervical spinal injury occurs in 2% of victims of blunt trau-ma; the incidence is increased if the Glasgow Coma Scale scoreis less than 8 or if there is a focal neurologic deficit. Immobili-zation of the spine after trauma is advocated as a standard ofcare. A three-view x-ray series supplemented with computedtomography imaging is an effective imaging strategy to rule outcervical spinal injury. Secondary neurologic injury occurs in2–10% of patients after cervical spinal injury; it seems to be aninevitable consequence of the primary injury in a subpopula-tion of patients. All airway interventions cause spinal move-ment; immobilization may have a modest effect in limitingspinal movement during airway maneuvers. Many anesthesiol-ogists state a preference for the fiberoptic bronchoscope tofacilitate airway management, although there is considerable,favorable experience with the direct laryngoscope in cervicalspinal injury patients. There are no outcome data that wouldsupport a recommendation for a particular practice option forairway management; a number of options seem appropriateand acceptable.
THE provision of acute medical care to patients withcervical spinal injuries (CSIs) is a complex, challenging,and rewarding task. It is also an anxiety-provoking en-deavor because care is provided in a milieu where thereis constant concern about medical interventions result-ing in the conversion of a spinal injury without neuro-logic sequelae to one in which the two are now concur-rent. It is also a topic of continuous debate because careproviders struggle in an environment of limited data andincomplete answers to try to craft clinical care para-digms designed to optimize preservation and return ofneurologic function, while minimizing the risk of creat-ing additional injury and neurologic compromise. Manyquestions regarding the initial care of these patients,particularly as they relate to airway management, remain
unresolved, but there has been great effort, energy, andenthusiasm expended during the past two decadessearching for these answers. This article reviews theliterature that has been generated on the topic of airwaymanagement after CSI, particularly that published in thepast 10 yr, identifying new areas of knowledge andevolving practice patterns. It also attempts to addressand resolve controversy surrounding areas of care thathave proven more contentious, most particularly the useof the direct laryngoscope to facilitate direct trachealintubation in these patients.
The Adult Cervical Spine: Stability, Injury,and Instability
Movement and Stability of the Upper Cervical SpineFlexion–extension occurs in the upper cervical spine
at both the atlanto-occipital and atlantoaxial articula-tions, and a combined 24° of motion may be achieved.1
Flexion is limited by contact between the odontoid pro-cess and the anterior border of the foramen magnum atthe atlanto-occipital articulation and by the tectorialmembrane and posterior elements at the Cl–C2 level.Extension is limited by the contact of the posterior archof the atlas with the occiput superiorly and with the archof the axis inferiorly. The distance from the posteriorarch of the atlas to the occiput is termed the atlanto-occipital gap, and a narrow atlanto-occipital gap hasbeen cited as being a cause of difficult intubation.2 Ni-chol and Zuck2 suggested that attempts to extend thehead in patients with a narrow atlanto-occipital gapresults in anterior bowing of the cervical spine, forwarddisplacement of the larynx, and a poor view duringlaryngoscopy. This concept, although offering an elegantanatomical explanation for the clinical experience ofdifficult laryngoscopy, has yet to be validated, and thetruth may be simpler. Calder et al.3 have reported thatlimited separation of the occiput from the atlas and theatlas from the axis yields an immobile upper spine andreduces both cervical spine extension and mouth open-ing, resulting in difficult direct laryngoscopy.
The ligaments contributing to the stability of the uppercomplex are the transverse, apical, and alar ligamentsas well as the superior terminations of the anterior andposterior longitudinal ligaments (fig. 1). In adults, thetransverse ligament normally allows no more than 3mm of anteroposterior translation between the dens and
* Professor.
Received from the Department of Anesthesiology, University of Ottawa, Ot-tawa, Ontario, Canada. Submitted for publication March 10, 2005. Accepted forpublication October 24, 2005. Support was provided solely from institutionaland/or departmental sources.
Address correspondence to Dr. Crosby: Department of Anesthesiology, TheOttawa Hospital–General Campus, Room 2600, 501 Smyth Road, Ottawa, On-tario, Canada, K1H 8L6. [email protected]. Individual article reprints may bepurchased through the Journal Web site, www.anesthesiology.org.
Anesthesiology, V 104, No 6, Jun 2006 1293
the anterior arch of the atlas. This may be measured onlateral radiographs of the neck and is termed the atlas–dens interval. If the transverse ligament alone is dis-rupted and the alar and apical ligaments remain intact,up to 5 mm of movement may be seen. If all the liga-ments have been disrupted, 10 mm or more of displace-ment may be seen. Destruction of these ligaments is acommon consequence of severe and long-standing rheu-matoid arthritis.4
Significant posterior displacement of the dens reducesthe space available for the spinal cord (SAC) in thevertebral column. The SAC is defined as the diameter ofthe spinal canal measured in the anteroposterior plane,at the Cl level, that is not occupied by the odontoidprocess. The SAC represents the area composed of bothcord and space. The area of the spinal canal at Cl may bedivided into one third odontoid, one third cord, and onethird “space.” The one third space allows for some en-croachment of the spinal lumen without cord compro-mise. However, when this margin of safety has beenexhausted, compression of neural elements will occur;persistent compression will eventually lead to myelopa-thy and neurologic deficit. The cord occupies a greaterproportion of the available SAC in the subaxial spine; atthe C6 level, approximately 75% of the SAC is occupiedby the cord.5
Movement and Stability of the Lower CervicalSpineA further 66° of flexion–extension may be achieved in
the lower cervical spine, with the C5–C7 segments con-tributing the largest component. There is an inverserelation between age and range of motion, i.e., as ageincreases, mobility decreases. However, most of the de-crease occurs at the C5–C7 motion segments, and thisusually does not have a significant impact on the ease ofdirect laryngoscopy. With the head in the standard sniff-ing position, the cervical spine below C5 is relativelystraight; there is increasing flexion from C4 to C2, andthe occipitoatlantoaxial complex is at or near full exten-sion.
In the lower cervical spine, the structures contributing
to stability include, from anterior to posterior, the ante-rior longitudinal ligament, the intervertebral discs, theposterior longitudinal ligament, the facet joints withtheir capsular ligaments and the intertransverse liga-ments, the interspinous ligament, and the supraspi-nous ligaments (fig. 2). The posterior longitudinal lig-ament and the structures anterior to it are grouped asthe anterior elements or anterior column (fig. 3). Theposterior elements or posterior column are thosegrouped behind the posterior ligament. Motion seg-ments are defined as two adjacent vertebrae and theintervening soft tissue elements.
Fig. 1. Ligaments of the atlantoaxial joint. View is from above,with the skull removed.
Fig. 2. The ligaments of the lower cervical spine, sagittal section.
Fig. 3. Schematic representation of the two column concept ofthe spine. From White AA III, Panjabi MM: Clinical biomechan-ics of the spine. Philadelphia, JB Lippincott, 1978; used withpermission.
1294 EDWARD T. CROSBY
Anesthesiology, V 104, No 6, Jun 2006
Cervical Spinal Instability after Injury: Mechanismsand ConsequencesWhite et al.6 have defined stability as “the ability of the
spine to limit its pattern of displacement under physio-logic loads so as not to allow damage or irritation of thespinal cord or nerve roots.” Instability occurs whenphysiologic loading causes patterns of vertebral displace-ment that jeopardize the spinal cord or nerve roots.7
Instability may result from congenital anomalies, ac-quired conditions related to chronic disease, and acutelyafter trauma. The following discussion will primarilyrelate to traumatic instability.
One element in the injured column must be preservedto achieve spinal stability. Clinically, to ensure a marginof safety, preservation of elements in the injured columncannot be assumed, and the spine must be considered tobe potentially unstable until proven otherwise. The an-terior column contributes more to the stability of thespine in extension, and the posterior column exerts itsmajor forces in flexion. Therefore, the anterior elementstend to be disrupted in hyperextension injuries, and theposterior elements tend to be disrupted in hyperflexioninjuries. With extreme flexion or extension or if either acompressive or rotational force is added, both columnsmay be disrupted.
Flexion injuries usually cause compression of the an-terior column and distraction of the posterior column(fig. 4).5 Pure flexion trauma may result in wedge frac-ture of the vertebral body without ligamentous injuries.These injuries are stable and are rarely associated withneurologic injuries. With more extreme trauma, ele-ments of the posterior column are disrupted as well, andfacet joint dislocation may result. These injuries are un-stable and are associated with a high incidence of corddamage. Flexion–rotation injuries also commonly dis-rupt the posterior ligamentous complex and may alsoproduce facet joint dislocation. They tend to be stableand are not usually associated with spinal cord injury,although cervical root injury is common. Hyperexten-sion injuries cause compression of the posterior column
and distraction of the anterior column (fig. 4). Hyperex-tension combined with compressive forces (e.g., divinginjury) may result in injury to the lateral vertebralmasses, pedicles, and laminae. Because both anterior andposterior columns are disrupted, this injury is unstableand is associated with a high incidence of cord injury.Violent hyperextension, with fracture of the pedicles ofC2 and forward movement of C2 on C3, produces atraumatic spondylolisthesis of the axis, or hangman’sfracture. The fracture is unstable, but the degree ofneurologic compromise is highly variable, because thebilateral pedicular fractures serve to decompress thespinal cord at the site of injury.
Burst fractures are caused by compressive loading ofthe vertex of the skull in the neutral position and are notas common as flexion–extension injuries. Compressionforces in the lower cervical spine result in the explosionof intervertebral disc material into the vertebral body.Depending on the magnitude of the compression load-ing and associated angulating forces, the resulting injuryranges from loss of vertebral body height with relativelyintact margins, to complete disruption of the vertebralbody. Posterior displacement (retropulsion) of commi-nuted fragments may result, producing cord injury; thespine is usually stable. Pure distraction injuries areuncommon but, if severe, may result in ligamentousdisruption causing both cord trauma and an unstablespine.
Determining Stability of the Cervical Spine afterInjuryBecause spinal instability usually results in vertebral
displacement, it may be detected in many instances byradiography. White and Panjabi8 identified the upperlimit of vertebral displacement and that which is beyondthe physiologic range. They concluded that a normaladult spine would not permit horizontal motion greaterthan 2.7 mm between vertebrae. Therefore, if horizontaldisplacement exceeding 3.5 mm (corrected for x-raymagnification) or 20% of the vertebral body width was
Fig. 4. Injuring force mechanisms and re-sulting lesions. In A, a compression hy-perextension force has resulted in dis-traction of the elements of the anteriorcolumn and compression of posteriorcolumn elements; an avulsion fracturefrom the anterior-inferior margin of thevertebral body (small arrow 2) and afracture of the articular process (smallarrow 1) have resulted. In B, a flexion(large arrow 2), compression (large ar-row 1) force has produced a wedge frac-ture of the vertebral body (small arrow2) and an incomplete disruption of theinterspinous and supraspinous liga-ments (small arrow 1).
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found on lateral radiographs of the neck (or with flex-ion–extension views or dynamic fluoroscopy), this mo-tion was deemed abnormal and the spine was consid-ered unstable. With respect to angular displacement, theupper limit of physiologic angular displacement of avertebral body compared with adjacent vertebrae was11°. If there is greater angulation of the vertebra inquestion demonstrated on imaging studies, the spine isdeemed unstable at the site of the excessively rotatedvertebra.
The ligamentous structures, intervertebral discs, andosseous articulations have been extensively studied, andtheir major role in determining clinical stability has beendemonstrated.7 Although the muscles in the neck exertsome stabilizing forces, the contribution that they maketoward clinical stability has not been studied. The re-peated observation that secondary neurologic injuriesoccur frequently in spine-injured patients who are notimmobilized suggests that muscle splinting is not highlyprotective after injury.9,10
Not all cervical spine injuries result in clinical instabil-ity. Generally, fractures are considered to be clinicallyinsignificant if failing to identify them would be unlikelyto result in harm to the patient or, alternatively, recog-nizing the injury would prompt no specific treatment.Two groups have categorized, by expert consensus, anumber of injuries as not clinically important.11,12 TheNational Emergency X-Radiography Utilization Study(NEXUS) group identified the following injuries as notclinically significant: spinous process fractures, wedgecompression fractures with loss of 25% or less of bodyheight, isolated avulsion fractures without ligament in-jury, type 1 odontoid fractures, end-plate fractures, iso-lated osteophyte fractures, trabecular fractures, and iso-lated transverse process fractures.11 Similarly, theCanadian CT Head and Cervical Spine Study group iden-tified the following injuries as not significant: simpleosteophyte fractures, transverse process fractures, spi-nous process fractures, and compression fractures withloss of less than 25% of body height.12
Mechanisms of Spinal Cord InjuryThere are a number of mechanisms implicated in pri-
mary spinal cord injuries. Immediate neural damage mayresult from shear, compressive, ballistic, or distractingforces, which primarily avulse and devitalize tissues.Persistent cord compression from fracture–dislocationmay lead to ischemia. The cord may be injured by bonefragment or missile injury with resultant laceration, con-tusion or concussion.13 Secondary and progressive in-jury may also result from local perfusion deficits due tovascular compression by deranged anatomy (e.g., tissuedamage or edema) or from global perfusion compromisecaused by systemic hypotension. In addition, tissue hy-poxemia leading to secondary injury may also occur as aresult of hypoventilation caused by head or cord injury
or by primary lung trauma. Finally, there are multiplemechanisms at the cellular and subcellular level that mayresult in exacerbation of the injury resulting in an exten-sion of the clinical deficit.14
The impact of persistent cord compression and thebenefits of urgent decompression of injured cord havebeen assessed by a number of authors. Carlson et al.15
determined the relation between the duration of sus-tained spinal cord compression and the extent of spinalcord injury and the capacity for functional recovery afterimmediate decompression. Sixteen dogs underwent spi-nal cord compression for 30 or 180 min. Sustained cordcompression was associated with a gradual decline inthe amplitude of evoked potentials. Within 1 h of de-compression, dogs that had experienced 30 min of com-pression had recovery of the evoked potentials, but noanimal that had been subjected to 180 min of compres-sion had similar recovery. Motor tests demonstratedrapid recovery of hind-limb function in the 30-mingroup, but there was considerable impairment in the180-min group, and this impairment was persistent. In asimilar model, Delamarter et al.16 demonstrated thatneurologic recovery after 1 h of cord compression oc-curred after immediate decompression but not whencord compression persisted for 6 h or more.
Despite the basic science support for early decompres-sion after spinal cord injury, two recent reviews haveconcluded that the evidence supports decompression asa practice option only.17,18 The authors of these reviewsconcluded that the data assessing the impact of earlydecompression on neurologic outcomes was limited,consisted of primarily class III (case series, retrospectivereviews, and opinion) and limited class II (prospectivecohort studies or controlled studies with comparisoncohorts) evidence, and demonstrated a possible benefitto patients with incomplete injury only. Both early de-compression and conservative management were asso-ciated with neurologic improvement in some patientsand deterioration in others. Both groups of authors ac-knowledged the need for randomized, controlled trialsto better delineate the role of surgery in the managementof acute spinal cord injury.17,18
Biomechanics of the Spinal Cord and CanalFor proper functioning of the spinal cord, a minimum
canal lumen is required, both at rest and during move-ment. Cord compromise will result if the canal space isless than that required for cord function; neurologicinjury will occur if this reduction in canal space is per-sistent. The neurologic injury results from sustained me-chanical pressure on the cord leading to both anatomicaldeformation and ischemia. A reduction in canal size isoften seen with age-related changes in spinal anatomysuch as disc degeneration, osteophyte formation, hyper-trophy of the ligaments of the spinal column, and thevertebral subluxations common in the chronic arthriti-
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des. Canal size may also be reduced acutely with trau-matic injury to the spinal column. Although neurologicdeficits do not directly correlate with the degree ofposttraumatic reduction of the spinal canal, canal im-pingement is more commonly observed in patients withboth spinal injury and neurologic deficit than in patientswho do not have a deficit after spinal injury.19
The functional size of the spinal canal may be furtherreduced with movement. The spinal canal is a column ofrelatively fixed volume.20 As it lengthens, its cross-sec-tional area will be reduced, and as it is shortened, its areawill be increased; this behavior is termed the Poissoneffect. With flexion, the canal length is increased and itsarea is reduced; the cord is stretched. This occurs be-cause the axis of rotation of the spine is centered in thevertebral body.21 As the spine flexes, the rotation pointswill transcribe an arc; posterior spinal elements, includ-ing the canal, will also transcribe an arc, but that of alarger circle and will axially lengthen (fig. 5).22 ThePoisson effect dictates that both the lumen of the canaland the spinal cord will narrow as they lengthen. Thecord will tolerate a degree of elastic deformation whilemaintaining normal neurologic function.20 It may befurther stretched and deformed if there is a local anom-aly such as an osteophyte, prolapsed disc, or subluxedvertebral body projecting into the canal. These deforma-tions may, over time, result in the application of strainand shear forces to the cord and ultimately result inaxonal injury and myelopathy.23
With extension, the canal length is decreased and itsarea is increased; the cord is shortened. Again, this is aneffect of the axis of rotation being centered in the ver-tebral bodies and the posterior spinal elements includingthe canal now transcribing the arc of a smaller circle; thePoisson effect will dictate canal widening. However, theshortening and folding of the cord when the spine is inextension may result in a relative increase in the ratio ofcord size to canal lumen, despite the potential increasein the lumen. As well, there is posterior protrusion of thedisc annulus and buckling of the ligamentum flavum inextension, which may further reduce canal dimensionsand the space available for the cord at any given verte-
bral level. A number of age-related pathologic processes,including osteophyte formation and ossification of theposterior longitudinal ligament, may lead to further im-pingement on the canal lumen; these typically manifesta greater impact during spinal extension.
Ching et al.24 measured the impact of different posi-tioning on canal occlusion in a cervical spine burstfracture model. Extension increased the canal occlusionto levels normally associated with the onset of neuro-logic injury. Flexion did not result in a significant in-crease in canal occlusion. These observations run coun-terintuitive to what might be expected on the basis ofthe Poisson effect and are likely manifestations of boththe soft tissue buckling and bone fragment retropulsionwhich occur during extension. Prone positioning is alsooften associated with modest degrees of extension, andthere is evidence that canal stenosis is increased withpatients with cervical myelopathy who are positionedprone compared with supine positioning.25 Again, this islikely a manifestation of the soft tissue encroachment onthe spinal canal with extension and aggravated by thepreexistent canal compromise. The clinical relevance ofthese findings is that a persistent malposition of an ab-normal neck may result in a degree of cord compression.If the abnormality is modest, it is likely that the malpo-sition will need to be of greater magnitude and moreprolonged to cause harm; as the anatomical derange-ment is increased, the duration of positional stress re-quired to cause harm is shortened.15,26 Prone position-ing is also associated with increases in vena cavalpressures that may further reduce cord blood flow al-ready compromised by cord compression.27
Dominguez et al.28 reported the occurrence of irre-versible tetraplegia in a 21-yr-old woman without cervi-cal pathology whose neck was maintained in extremeflexion after tracheal reconstruction; a magnetic reso-nance imaging (MRI) study was consistent with cordinfarction. Deem et al.29 reported the occurrence ofquadriparesis in a 60-yr-old man with severe cervicalstenosis after thoracolumbar surgery in the prone posi-tion. The patient’s trachea was intubated, and he waspositioned prone while still awake; anesthesia was in-
Fig. 5. The Poisson effect: schematic rep-resentation. The axis of rotation is indi-cated by the small squares superimposedon the vertebral bodies. In the neutralposition (A), the gentle arc of the normallordotic curve is transcribed. In exten-sion (B), the elements posterior to thebodies, including the canal, transcribethe arc of a smaller circle than that of thevertebral bodies, indicated by the smallcircles. In flexion (C), the opposite effectis seen, and the arc of a larger circle istranscribed by the posterior elements.The Poisson effect dictates that as thelength increases (the arc is of a largercircle), the cross-sectional area (lumen)of the column will decrease.
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duced after his cervical spinal positioning was ascer-tained to be near neutral, and neurologic examinationresults were deemed normal. When he awoke from an-esthesia after 6 h of surgery, there was evidence of acentral cord syndrome. The authors acknowledge thepossibility that, even though extreme degrees of flexionand extension were avoided, more subtle degrees ofmalpositioning may have been present. Unfortunately,cord injury may occur when positions detrimental tocanal architecture are persistent; the greater the degreeof underlying spinal pathology is, the lesser the magni-tude of malpositioning required to cause harm is. Theprone position may be especially threatening in theseinstances for the reasons already outlined.
Patients with severe cervical spondylosis may manifestsuch severe positional intolerance that they developsymptoms of cord compromise with degrees of malpo-sition that may be imperceptible to the caregivers. Milleret al.30 described exacerbation of neurologic symptomsin a 74-yr-old women with an osseous bar at C3–C4 whopresented with signs of cord compression and wasbooked for cervical laminectomy. On the first surgicaloccasion, after awake tracheal intubation accomplishedwith sedation, she was considerably weaker than beforeintubation. Surgery was cancelled, and her trachea wasextubated; her neurologic condition returned to baselinewithin 2 h. Four days later, she presented for surgery inhalo traction, and after sedation with intravenous diaze-pam, her neurologic condition deteriorated. A joint de-cision was made to induce anesthesia and proceed withtracheal intubation and surgical laminectomy at theC3–C5 spinal levels. Although she awoke with signs ofneurologic deterioration, she recovered to her baselinecondition by the fourth hour. The authors of this reportpostulated that the increased neurologic symptoms werean effect of the medications administered to facilitateawake intubation. Whether the drugs actually causeddeterioration in the patient’s neurologic status or madethe neurologic assessment less reliable is not certain.Equally unknown is whether, in general, patients mightbe more likely to overlook or underreport neurologicchanges that occur if they were sedated during awakeintubation. The reliability of a neurologic assessment ina sedated patient might be questioned, especially if oneis seeking evidence of subtle changes.
Bejjani et al.31 reported the case of a 54-yr-old womanwith cervical spondylosis and canal stenosis from C4 toC7 who developed signs of cord compression while herhead was restrained in a plastic head-holder for thepurpose of cerebral angiography. Approximately 45 minafter the procedure had begun, she reported neck painand upper extremity weakness; her symptoms were at-tributed to anxiety, and she was sedated. At the termi-nation of the procedure, she was hemiparetic on the leftside; an MRI study revealed a high-signal lesion consis-tent with edema. She recovered completely over the
next 6 weeks. The potential for general anesthesia topermit positioning for MRI in postures not tolerated byawake patients with resultant neurologic injury has alsobeen reported.32
Magnaes33 measured cerebral spinal fluid pressurewith the neck in the extended position for trachealintubation, in eight patients with a compromised spinalcanal due to cervical spondylosis. Pressures up to ap-proximately 140 cm H2O were recorded. Longitudinalskeletal traction with the tong placed frontally signifi-cantly reduced the pressure on the spinal cord in allpatients. This finding would suggest that there is likely abenefit, in terms of decreased intracanal pressures, inmaintaining the compromised cervical spine in as closeto the neutral position as possible at all times after injury.As has already been noted, it may be very difficult todetermine neutral position in some patients.
Persistent severe malpositioning at the extremes of thespinal range of motion has the potential to cause harmeven in the normal spine–cord complex. In patientswith disease processes that result in spinal canal com-promise, minor degrees of malpositioning may also re-sult in severe stress to the cord. If these positions areenforced, especially for prolonged periods, neurologicinjury may result. As well, the use of sedation or anes-thesia to allow patients to be maintained in positions thatare neurologically intolerable to them while awake mayalso result in neurologic injury.
The Incidence of Cervical Spinal Injury after BluntTraumaThe incidence of CSI in victims of blunt trauma is
estimated to be 0.9–3%, with a weighted average of1.8%.34 Many of these previously published studies eval-uating CSI after blunt trauma involved data from individ-ual institutions or limited populations of trauma victims;there have been few data available regarding injury pat-terns at a national level. A substudy of NEXUS wasdesigned to provide such data regarding the prevalence,spectrum, and distribution of CSI after blunt trauma.35 Atotal of 34,069 patients with blunt trauma undergoingcervical spine radiography at 21 US institutions wereenrolled. Consistent with past reports, 818 (2.4%) oftrauma victims had a total of 1,496 distinct CSIs. Thesecond cervical vertebra (C2) was the most commonlevel of injury (24.0% of all fractures), and 39.3% offractures occurred in the two lowest cervical vertebrae(C6, C7). The vertebral body was the most frequentanatomical site of fracture; nearly one third of all injuries(29.3%) were considered clinically insignificant.
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Cervical Spine Injury and AssociatedCraniocerebral TraumaAlthough it has been reported that patients with
craniocerebral trauma had an incidence of CSI similar tothat of the general trauma population, review of thelarge databases evolving at major trauma centers nowdispute this finding. Holly et al. 36 reviewed 447 consec-utive, moderately to severely head-injured patients pre-senting to two level l trauma centers. Twenty-four pa-tients (5.4%) had a CSI; patients with an initial GlasgowComa Scale (GCS) score less than 8 were more likely tosustain both a CSI and a cord injury than those withhigher scores. Demetriades et al.37 conducted a similarreview of all CSI patients admitted over a 5-yr period ata major trauma center. During the study period, therewere 14,755 admissions and 292 patients with CSI, foran overall incidence of 2.0%. Again, the incidence of CSIvaried with the GCS score, being 1.4% if the GCS scorewas 13–15, 6.8% when it was 9–12, and 10.2% when itwas less than 8. Hackl et al.38 used a large computerizeddatabase to assess the association between CSI and facialinjuries in 3,083 patients with facial injuries. Two hun-dred six (6.7%) of these patients had experienced aconcomitant CSI, an incidence substantially higher thanwould be expected after blunt trauma. Blackmore etal.39 reviewed their institutional experience with 472patients with trauma (168 with cervical fractures, 302without fractures) to delineate the clinical characteris-tics of trauma patients with cervical fracture. The clinicalpredictors of cervical spine injury included severe headinjury (odds ratio, 8.5; 95% confidence interval [CI],4–17) and focal neurologic deficit (odds ratio, 58; 95%CI, 12–283). In patients with head injury, those whowere persistently unconscious had an even higher like-lihood of spinal injury (odds ratio, 14; 95% CI, 6–35)than those with head injury who were not unconscious.Therefore, new evidence has emerged that consistentlysuggests a higher incidence of cervical injury in patientswho have experienced craniocerebral trauma, especiallyamong those with increasing severity of craniocerebralinjury as determined by low GCS score and unconscious-ness. The finding of a focal neurologic deficit has beenidentified as a highly important clinical finding predict-ing spinal injury.39
Systemic Injuries Associated with Cervical SpineInjuryThe majority of patients with CSI also have other
injuries; in only 20% of instances are traumatic injuriesrestricted to the cervical spine.40 Although 2–10% ofpatients with craniocerebral trauma have CSI, 25–50% ofpatients with CSI have an associated head injury. Patientswith additional injuries are more likely to experiencehypoxia and hypotension, both of which may not onlyprompt urgent airway intervention, but may also predis-pose to secondary neurologic injury. There is data to
suggest reduced neurologic recovery and increased mor-tality in cord-injured patients who have concurrent in-jury. It is not clear whether these patients experiencedmore severe primary injury or whether they are morelikely to experience secondary injury leading to thepoorer outcome.
Defining the Low-risk Trauma PatientThe National Emergency X-Radiography Utiliza-
tion Study. The majority of patients who have experi-enced a blunt traumatic injury do not have a CSI. Enor-mous resources are currently expended to clear thespine (determine the absence of injury when injury doesnot exist) in these patients. The NEXUS project at-tempted to derive a set of clinical criteria to identifyblunt trauma victims at low risk for CSI.41 The decisioninstrument required patients to meet five criteria to beclassified as having a low probability of injury: (1) nomidline cervical tenderness; (2) no focal neurologic def-icit; (3) normal alertness; (4) no intoxication; and (5) nopainful, distracting injury. Distracting injuries were de-fined as including long bone fractures; visceral injuriesrequiring surgical consultation; large lacerations; burns;degloving or crush injuries; or any injury that mightimpair the patient’s ability to participate in a generalphysical, mental, or neurologic examination. The deci-sion instrument was applied to 34,069 patients and iden-tified as high risk all but 8 of the 818 patients who hada CSI (sensitivity, 99%; 95% CI, 98–99.6%). The negativepredictive value was 99.8% (95% CI, 99.6 –100%),the specificity was 12.9%, and the positive predictivevalue was 2.7%. Only two of the eight patients missedby the screening protocol had a clinically significantinjury. In the NEXUS study, plain radiographs alonerevealed 932 injuries in 498 patients but missed 564injuries in 320 patients.42 The majority of missed in-juries (436 injuries in 237 patients) occurred in casesin which plain radiographs were interpreted as abnor-mal (but not diagnostic of injury) or inadequate. How-ever, 23 patients had 35 injuries (including three po-tentially unstable injuries) that were not visualized onadequate plain film imaging. In the absence of all fiveclinical risk factors identified by the NEXUS study aspredicting an increased risk of CSI, the likelihood of asignificant injury is low. The practice of withholdingimaging for patients who meet these exclusionarycriteria has been endorsed by recent neurosurgicalguidelines.43
The Canadian C-Spine Rule for Radiography afterTrauma. The Canadian CT Head and Cervical SpineStudy Group attempted to derive an optimally sensitiveclinical decision rule to allow for selectivity in the use ofradiography in alert and stable trauma patients.12 A pro-spective cohort study was conducted in 10 large Cana-dian hospitals and included 8,924 consecutive adult pa-tients presenting to emergency departments after
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sustaining acute blunt trauma to the head or neck. Pa-tients were eligible for enrollment if they were alert(GCS of 15), if they had stable vitals signs, and if they hadeither neck pain after injury or had no neck pain butvisible injury above the clavicles after a dangerous mech-anism of injury. The patients were assessed using 20standardized clinical findings from the history, generalphysical examination, and an assessment of neurologicstatus. Patients then underwent diagnostic imaging atthe discretion of the treating physician; this imagingconsisted of a minimum of three views of the cervicalspine.
Among the study sample, 151 patients (1.7%) had animportant cervical injury. The resultant rule that wasderived comprises three questions: (1) Is there any high-risk factor present that mandates radiography? (2) Arethere low-risk factors that would allow a safe assessmentof a range of motion? and (3) Is the patient able toactively rotate the neck 45° to the left and to the right?When applied to the study population, the derived rulehad 100% sensitivity and 42.5% specificity for identifyingpatients with clinically important injuries. The rule alsoidentified 27 of 28 patients with clinically unimportantcervical injuries (primarily avulsion fractures), defined asthose not requiring stabilization or follow-up.
The NEXUS Low-Risk Criteria were compared prospec-tively with the Canadian C-Spine Rule in 8,283 patientspresenting to Canadian hospital emergency departmentsafter trauma.44 Two percent of patients had clinicallyimportant cervical injuries, and the C-Spine Rule wasboth more sensitive than the NEXUS criteria (99.4% vs.90.7%) and more specific (45.1% vs. 36.8%) for injury.The C-Spine Rule would have missed one patient, andthe NEXUS criteria would have missed 16 patients withimportant injuries.
Strategies to define a low-risk clinical population con-tinue to evolve. It must be emphasized that the primaryfocus and utility of these strategies is to allow for selec-tive use of diagnostic imaging in patients who have alow-risk of injury, thus reducing imaging use and patientexposure, conserving resources, and allowing for expe-dited and simplified care for this patient group. A criti-cism leveled at the NEXUS protocol is that applicationwould have a limited impact in reducing imaging be-cause only 12.9% of patients presenting after traumawould be deferred; most would not meet at least onedeferral criteria.45 Application of the C-Spine Rule wouldallow for the exclusion of 42.5% of trauma patients fromradiographic imaging. The original rationale for the der-ivation of the protocols, to provide more efficient careand conserve imaging resources, is satisfied to a verylimited degree by the NEXUS protocol but to a greaterdegree by the C-Spine Rule. Application of either proto-col will still demand imaging in a large portion of thetrauma patient population at low risk for CSI.
There will be a small population of patients presenting
for urgent surgical intervention after minor injury whoare fully evaluable using either the NEXUS criteria(12.9%) or the C-Spine Rule (42.5%); it is likely notnecessary to delay surgery to clear the cervical spine ofthese patients with detailed imaging. Unfortunately,many patients presenting for urgent operative interven-tions after trauma will manifest more severe injuries; itwill not be possible to clinically rule out injury in thispatient cohort, and they will still require diagnostic im-aging. As well, application of these protocols is compli-cated by the fact that there is a lack of agreement on thedefinitions of both distracting injury and intoxication.Failure to appreciate the degree of both distraction andintoxication may reduce the clinical index of suspicionfor injury, resulting in missed diagnosis.
Patterns of Practice in Evaluating and Clearing theCervical Spine after TraumaTwo authors have recently reported descriptions of
patterns of practice in the United States and the UnitedKingdom obtained through postal surveys regardingevaluation and clearance of the cervical spine after trau-ma.46,47 Grossmann et al.46 surveyed 165 US traumacenters and reported that between 26 and 73% hadwritten protocols for cervical spine clearance aftertrauma. It was more common for level I and academiccenters to have protocols. In most instances where aprotocol existed, it also described the radiographic ap-proach to clearance; most centers did not consider thateither computerized tomography (CT) or MRI was thestandard of care in this setting. The use of a five-viewseries was moderately prevalent in response to specificscenarios, and the problem of visualizing the cervicotho-racic junction was dealt with in most centers (68%) usingan axillary/swimmer’s radiographic view. For patientswith a head injury who are comatose or who havealtered mental status and who have normal plain films,21% of level II and 10% of level I centers advocatedremoval of the cervical collar without further testingbeyond a five-view series.
Jones et al.47 surveyed 27 United Kingdom neurosur-gical and spine injury units to determine the methods ofcervical spine clearance used in unconscious, adulttrauma patients and the point at which immobilizationwas discontinued. Most centers did not have either awritten protocol to perform clearance or one regardingdiscontinuing cervical immobilization (78%). All unitsrelied to some degree on plain radiography for clear-ance; 10 units (37%) performed only a single lateral viewas the initial evaluation, and the remainder performedtwo more views. Five units routinely used CT imaging,and 17 units (63%) made no use of CT to screen forcervical injury. If the initial investigations were normal,12 units (44%) would discontinue immobilization, and10 units continued it until the patient could be evaluated
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clinically irregardless as to the results of the screeningimaging.
The Eastern Association for the Surgery of Traumarecently reported the results of a survey of 31 largeAmerican and Canadian trauma centers.† Centers wereasked to identify their routine practice for determiningcervical spinal stability in obtunded or comatose patients.Twenty-four centers (77%) reported using three views ofthe cervical spine (lateral, odontoid, and antero-posteriorviews) supplemented by CT through suspicious or poorlyvisualized areas. Three centers (9.7%) relied on three viewsonly, and three centers (9.7%) added a swimmer’s view tovisualize the lower cervical spine and the cervicothoracicjunction.
There is considerable variation in the approach thatdifferent centers take in the performance of radiographicevaluation of at-risk patients, making the determinationthat the spine has been cleared, and reaching the deci-sion that immobilizing devices can be safely removed.The most common pattern of practice in North Ameri-can centers is to rely on multiple (at least three views)plain radiographs; the use of supplementary CT is alsocommon.
Radiographic Assessment after Blunt Trauma:Evolving a Best PracticeAn evaluative approach that would provide timely and
accurate assessment of cervical stability in patients whomay not be reliably examined clinically so that immobi-lizing devices can be safely removed is desirable. Thiswould minimize the potential for sequelae related toprolonged immobilization. The reader is referred tothree excellent reviews on the topic of evaluating andclearing the cervical spine in high-risk patients; thesereviews form the basis of the subsequent discus-sion.45,48,49
The cross-table lateral radiograph, of acceptable qual-ity and interpreted by an expert, will disclose the major-ity of injuries. However, the sensitivity of the cross-tableview is such that up to 20% of patients with cervicalinjury will have a normal study. Half of cross-table viewsare deemed inadequate to properly assess the entirecervical anatomy; injuries at both the craniocervical andthe cervicothoracic junctions are often not well visual-ized in the cross-table view. Too many injuries aremissed when only a cross-table view is used for it to beconsidered an acceptable study to rule out injury in ahigh-risk patient. The sensitivity of three views (cervicalseries) approximates 90%; the cervical series was longregarded as an acceptable radiologic evaluation in pa-tients deemed at risk for CSI. Similar technical concerns
apply to the cervical series as to the cross-table lateralview with respect to both anatomical limitations at thecervical junctions and inadequate studies being issues. Itis estimated that 1% of clinically important injuries willbe missed even with a technically adequate cervicalseries.
A three-view cervical series supplemented by CTthrough areas that are either difficult to visualize orsuspicious on plain radiography will detect most spinalinjuries. The negative predictive value of this combina-tion of studies is reported to be 99–100% in several classII and III evidence studies.45,48,49 In the obtunded pa-tient with a normal cervical series and appropriate sup-plemental CT of the cervical spine, the incidence ofsignificant spine injury is less than 1%. High-resolutionCT scanning with sagittal reconstruction of the entirecervical spine rather than directed scanning of only at-risk areas may be even more effective in capturing vir-tually all injuries.
The use of MRI in addition to plain radiography andsupplemental CT has been advocated to perform spinalclearance; the significance of a positive MRI study in thesetting of negative CT imaging is currently unclear be-cause many false-positive findings are reported withMRI. As well, MRI is less sensitive than CT for injuries inthe upper and posterior cervical spine. Shuster et al.50
studied the role of MRI in assessing the spines of patientswith persistent cervical pain and no motor deficits aftertrauma when the CT imaging was negative for injury.Ninety-three patients (3.4%) had a normal admissionmotor examination, a CT result negative for trauma, andpersistent cervical spine pain; they underwent MRI ex-amination. All MRI examinations were negative for clin-ically significant injury, and no patient subsequently ex-perienced a neurologic deterioration. Hogan51 assessedthe role of magnetic resonance imaging in 366 obtundedor unreliable patients who had normal CT imaging aftertrauma. Magnetic resonance images were negative foracute injury in 354 of 366 patients; the most commoninjury seen was a cervical cord contusion, identified in 7patients. Magnetic resonance images were also negativefor spinal ligament injuries in 362 of 366 patients; 4patients had ligament injuries, but in all cases, the injurywas limited to the ligaments of a single column. CT hadnegative predictive values of 98.9% for ligament injuryand 100% predictive value for unstable cervical injury;MRI identified a small number of patients with ligamentinjuries not diagnosed with CT, but none of these weredeemed to be unstable injuries.
In summary, in a patient at high risk for cervical injury,who cannot be evaluated clinically, a three-view cervicalseries supplemented by high-resolution CT scanningwith sagittal reconstruction will reduce the likelihood ofan occult fracture to less than 1%. After a technicallyadequate imaging series has been reviewed and clearedby a radiologist, it is prudent to remove cervical immo-
† Eastern Association for the Surgery of Trauma: Determination of cervicalspine stability in trauma patients. Winston-Salem, North Carolina, EAST, 2000.Available at: www.east.org/tpg/chap3u.pdf. Accessed October 27, 2005.
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bilization. If there is evidence of a neurologic deficitreferable to the cervical spine despite the finding ofnormal cervical radiography and CT imaging, MRI shouldbe considered.
Spinal Ligament Injuries and Spinal Cord Injurywithout Radiographic AbnormalitySpinal ligament injuries are of particular concern be-
cause of the high incidence of resultant spinal instability,the potential for cord injury, and the hemodynamicinstability common at presentation in this subpopula-tion. In Demetriades’37 review of CSI patients admittedduring 5 yr to a major trauma center, 31 patients (10.6%)had a ligament injury (subluxation without fracture), and11 patients (3.8%) had an isolated spinal cord injurywithout fracture or subluxation (spinal cord injury with-out radiographic abnormality [SCIWORA]). Of the 31patients with ligament injury, one third required trachealintubation before clinical evaluation of the spine wascompleted. Of the 11 patients with spinal cord injurywithout radiographic abnormality, 27.3% required intu-bation before spinal evaluation occurred. The diagnosisof cord injury was made on admission in only 5 patients(45.5%) with spinal cord injury without radiographicabnormality. In 3 patients, the neurologic examinationon admission was normal, and neurologic deficits ap-peared a few hours later. In the remaining 3 patients (2intubated, 1 intoxicated), the diagnosis was missed ini-tially. Patients who required urgent airway interventionwere less likely to have had a complete neurologic eval-uation and were more likely to have neurologic injurythan those who did not require urgent interventions.Chiu et al.52 also investigated the incidence of cervicalspinal ligament injury in 14,577 blunt trauma victims. Sixhundred fourteen patients (4.2%) had CSI, and 87 (14%of CSI) had dislocation without evidence of fracture.There were 2,605 (18%) patients who could not beassessed for symptoms, and 143 (5.5%) of these unreli-able patients had a CSI; 129 (90%) had a fracture, and 14had no fracture.
Trauma patients with greater severity of injury aremore likely to have had a CSI; clinical evaluation is moredifficult in these patients, typically because of depressedconsciousness. Patients with ligament injury of the cer-vical spine without fractures frequently require urgentintubation, and not uncommonly, clinical evaluation iseither not possible or not complete at the time thatintervention is required; delay in the diagnosis of injuryis common in these patients.
Failure to Diagnose Cervical Spine Injury at InitialAssessment: Factors and ConsequencesPatients with decreased mental status from trauma,
alcohol, or drugs and patients with other painful ordistracting injuries have an unreliable history andphysical examination for CSI; patients with these char-
acteristics have spinal injuries that are also more likelyto be missed on initial presentation. The commonestreasons for missed diagnosis are failure to obtainradiographs, poor quality of the imaging study, ormisinterpretation of the radiographs.9,10 Inadequateradiographic studies are more likely in patients withhemodynamic compromise on admission or in thosepatients urgently requiring intervention for operativetreatment of associated injuries. Unfortunately, missedinjuries are often unstable, and secondary neurologiclesions occur in 10 –29% of patients whose injuries arenot diagnosed at initial evaluation.9,10 Failure to im-mobilize the spine in patients whose injuries aremissed at the initial assessment is considered to be aleading cause of secondary injury.
Poonnoose et al.53 conducted a detailed review of theexperience of a specialty spinal cord injury unit to de-termine both the incidence of missed injury and theclinical mismanagement that occurred in the setting ofmissed injury. The medical records of 569 patients withneurologic deficits secondary to traumatic spinal cordinjury were reviewed. In 52 instances (9.1%), the diag-nosis was initially missed, and 26 of these patients (50%)had evidence of neurologic deterioration after admissionto care. The median time to recognition of the injury was4 days. Therapeutic interventions were performed in 34patients that were deemed inappropriate to their condi-tion before the diagnosis was made. In 19 patients, therewere significant neurologic findings present on initialassessment, and in 7, the initial neurologic deficit wasminimal. Nine patients eventually developed paralysis,and 6 died with the deaths attributed to the delay indiagnosis. Again, the major cause for delayed diagnosiswas related to radiographic assessments: In 18 cases, theinitial images were of poor quality; in 11 patients, thearea of concern was not adequately visualized; in 10cases, an obvious fracture was missed; in 11 cases, facetjoint malalignment was not recognized; and in 10 cases,prevertebral hematoma went undetected. It was com-mon for the clinicians to consider the spine clearedwhen the radiographs “failed” to reveal injury and toattribute neurologic findings to either preexistent con-ditions (e.g., ankylosing spondylitis) or peripheral trau-matic injuries. As well, 7 patients with evidence of neu-rologic deficits were initially labeled as “hysterical” andnot managed as at-risk.
It is unfortunately the case that patients with CSI arefrequently not correctly diagnosed at the time of initialpresentation.9,10,53,54 This may occur in a small percent-age of CSI patients because the injury is a ligamentousone and the screening imaging seems on initial review tobe negative.37,54 However, it more commonly occursbecause there is a low index of suspicion for injurydespite high-risk mechanisms, inadequate radiographicstudies are deemed acceptable, and neurologic signs orsymptoms are either attributed to other causes or ig-
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nored entirely. Delayed diagnosis is associated with avery high incidence of secondary injury, and the magni-tude of that injury is often considerable.9,10,53,54
Secondary Neurologic Injury after Cervical SpineInjurySecondary injury may be precipitated in CSI victims
when management is suboptimal, and in particular whenthe injured spine is not immobilized. However, there isalso evidence that neurologic deterioration occurs afteracute injury despite appropriate management para-digms; the reported incidence of neurologic deteriora-tion in this setting ranges from 2 to 10%.55 Frankel56
reported the occurrence of an ascending myelopathy2–18 days after spinal cord injury despite appropriateclinical management. Only patients with ascension ofinjury level of at least four levels were included in thisanalysis; despite the high threshold for inclusion, thismagnitude of secondary injury occurred in 1% of 808patients admitted to the center. Frankel attributed thedeterioration to either vascular catastrophes (arterial in-sufficiency or venous thrombosis) or inflammation; thisreport predated MRI, so no imaging is available in thesepatients to support the clinical conjecture. Marshall etal.55 reported a prospective study assessing neurologicdeterioration in cord-injured patients conducted in fiveUS trauma centers. Deterioration occurred in 4.9% ofpatients and was consistent across the five centers. Al-though the deterioration was often associated with aspecific intervention (surgery in 4 patients, traction ap-plication in 3, halo vest application in 2, Stryker framerotation in 2, and rotobed rotation in 1), there was noevidence that these procedures were performed poorlyor that they could have been performed in an alteredfashion to prevent the deterioration. There were 375such interventions recorded among the 283 patients.The authors concluded that deterioration is an inevitableconsequence of providing care to cord-injured patientsand will occur in some patients despite acceptable carepractices.
Farmer et al.57 reported the experience of a US re-gional spinal cord center regarding neurologic deterio-ration after cervical cord injury. Deterioration was evi-dent in 1.84% of 1,031 patients assessed. The averagetime from injury to deterioration was 3.95 days, anddeteriorations were associated with early surgery (� 5days after injury), sepsis, ankylosing spondylitis, andtracheal intubation. Tracheal intubation was associatedwith two minor and two major deteriorations, but nofurther details were offered regarding this cohort; it ispossible that the intubation was necessitated by theneurologic deterioration and not the cause of it. In thepatients who experienced deterioration and survived,92% of patients eventually had improvement in theirneurologic status. Harrop et al.58 analyzed the cases of
12 of 186 patients (6%) with acute traumatic cord inju-ries who demonstrated neurologic ascension within 30days after injury. Three subgroups were defined: an earlydeterioration group who worsened within 24 h, a de-layed deterioration group (1–7 days), and a late (beyond7 days) deterioration group. Two patients in the lategroup had vertebral artery injury; vertebral artery injuryis common after midcervical injury, and its clinical sig-nificance is uncertain.59,60
Yablon et al.61 described 14 cases of ascending my-elopathy (involving 1–4 levels) that occurred in the first4 weeks after injury. These cases were attributed tospinal cord edema; MRI studies demonstrated evidenceof this as well as diffuse intrathecal hemorrhage. Be-langer et al.62 identified a similar occurrence of ascend-ing myelopathy, which they labeled as subacute post-traumatic ascending myelopathy, occurring within thefirst 2 weeks after injury. This syndrome occurred inthree patients who experienced neurologic deteriora-tion with a secondary injury ascending six or more levels(6, 9, and 17 levels) from the initial level after an un-eventful early course. No etiologic factors could be iden-tified. In all three patients, T2 weighted MRI studiesrevealed a high signal intensity located centrally withinthe cord and extending rostrally from the site of injury.T2-weighted images are sensitive to the presence ofedema and effectively distinguish pathologic from nor-mal tissue; the high signal intensity identified indicatesinjury and edema.
The above reports suggest that there is a progressivepostinjury course in some patients leading to a second-ary neurologic injury and ascension of injury level, some-times to a striking degree. In some instances, this dete-rioration has been associated with clinical interventions,including immobilization, traction, surgery, intubation,and sepsis. In other instances, no clear factors are asso-ciated, and in particular, both extrinsic cord compres-sion and vascular interruptions have been excluded. Thissyndrome, when witnessed early in the course afterinjury, has usually been attributed to vascular perturba-tions or cord edema and inflammation; MRI studies havebeen consistent with this attribution. More recent workhas also suggested a role for apoptosis in the causationand progression of ascending myelopathy.63 A diagnosisof ascending myelopathy must be considered when asecondary injury has occurred; there is natural tempta-tion to attribute the deterioration to temporally relatedclinical interventions but, in fact, these interventions arerarely associated with neurologic sequelae. Progressiveneurologic injury after CSI may be inevitable in somepatients because of pathophysiologic processes initiatedat the time of the application of the injuring forces andmay occur despite the provision of appropriate manage-ment paradigms and interventions.
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Clinical Care of the Spine-injured Patient
Spinal Immobilization in Trauma Patients: TheOverviewDuring the past 30 yr, the neurologic status of spinal
cord–injured patients arriving in emergency depart-ments has dramatically improved, and the odds of dyingduring the first year after injury have been significantlyreduced.64,65 The improvement in the neurologic statusof patients has been attributed to improved initial careand retrieval systems, recognition of the importance ofinstituting prehospital spinal immobilization, maintain-ing immobilization until clearance is obtained or defini-tive therapy is applied, and hospital practices designedto prevent secondary injury. The routine use of spineimmobilization for all trauma patients, particularly thosewith a low likelihood of spinal injury, has been chal-lenged on the basis that it is unlikely that all patientsrescued from the scene of an accident or site of trau-matic injury require spine immobilization.66 A Cochranesystematic review also concluded that the impact ofimmobilization on mortality, neurologic injury, and spi-nal stability was uncertain and that direct evidence link-ing immobilization to improved outcomes was lacking.67
The Cochrane review further concluded that the poten-tial for immobilization to actually increase morbidity ormortality could not be excluded based on a review of theliterature. However, the current consensus among ex-perts remains that all patients with the potential for a CSIafter trauma should be treated with spinal column im-mobilization until injury has been excluded or definitivemanagement for CSI has been initiated.64
The benefits, consequences, and sequelae of spinalimmobilization in at-risk patients have been recentlyanalyzed, and the reader is referred to these reviews formore detailed discussions.64,68,69 The chief concern dur-ing the initial management of patients with potential CSIis that neurologic function may be further compromisedby pathologic motion of the injured vertebrae. Manage-ment of the potentially traumatized spine emphasizesthree principles: (1) restoration and maintenance of spi-nal alignment, (2) protection of the cord with preserva-tion of intact pathways, and (3) establishment of spinalstability. To achieve these principles, immobilization ofthe cervical spine before radiographic assessment andclearance is the accepted standard of care. The rationalebehind early immobilization is the prevention of neuro-logic injury in the patient with an unstable spine. Insti-tution of a clinical care paradigm that features immobi-lization as a core element has resulted in improvedneurologic outcomes in spine-injured patients during thepast three decades.64,65 Failure to immobilize in thecontext of missed or delayed diagnosis is also associatedwith an increased incidence of neurologic injury.9,10,53
Lack of immobilization has been cited as a cause ofneurologic deterioration among acutely injured trauma
patients being transported to medical facilities for defin-itive care.70
A number of complications to prolonged immobiliza-tion have been identified.64,68,69 Cutaneous ulcerations(pressure sores) are common, and the incidence in-creases when immobilization is prolonged beyond48–72 h. Airway management, central venous accessand line care, provision of oral care, enteral nutrition,and physiotherapy regimes are all made more difficultwhen immobilization must be maintained. The need formultiple staff to allow for safe positioning and transfer ofimmobilized patients makes barrier nursing more diffi-cult and may result in higher rates of cross-contamina-tion and infection in high-dependency units.
The application of cervical collars has also been asso-ciated with increased intracranial pressure (ICP) in bothinjured patients and healthy volunteers. Davies71 pro-spectively analyzed ICP in a series of injured patientstreated with a rigid collar. The ICP increased a mean of4.5 mmHg when the collar was firmly in place. Kolb72
also examined changes in ICP after the application of arigid Philadelphia collar in 20 adult patients. ICP aver-aged 17.68 cm H2O initially and increased to an averageof 20.15 cm H2O after collar placement. Although thedifference in ICP of 2.47 mm H2O was statistically sig-nificant, it remains uncertain that it has clinical rele-vance. Nonetheless, this modest increase in pressuremay be magnified in patients who already have increasedICP and poor intracranial compliance. The potential forcomplications should not discourage the use of immobi-lization where indicated. Rather, because many of thecomplications are time dependent, they should encour-age attempts to promptly assess the patient for cervicalinjury to expedite the discontinuance of immobilizationin those patients whose spines can be cleared.
Techniques and Devices for Preadmission SpinalImmobilizationThe position in which the injured spine should be
placed and held immobile, the “neutral position,” ispoorly defined. De Lorenzo et al.,73 in an MRI study of 19adults, found that 2 cm of occiput elevation produced afavorable increase in spinal canal/spinal cord ratio at theC5 and C6 levels, a region of frequent unstable cervicalspine injuries. Podolsky et al.74 evaluated the efficacy ofcervical spine immobilization techniques. Hard foam andhard plastic collars were better at limiting cervical spinemotion than soft foam collars, although the use of collarsalone did not effectively restrict spinal motion. The useof sandbag-tape immobilization was more effective atreducing spinal movement than any of the other individ-ual methods tested. Adding a Philadelphia collar to thesandbag–tape construct reduced neck extension but hadno effect on any other motion of the cervical spine.These authors found that sandbags and tape combinedwith a rigid cervical collar was the most effective con-
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struct of those evaluated to limit cervical spine motion,restricting movement to approximately 5% of the normalrange. The sandbag–tape–backboard–collar and varia-tions thereof have become the most commonly usedextrication and transport assembly in prehospital traumacare to provide spinal immobilization.
Bednar75 assessed the efficacy of soft, semirigid, andhard collars to immobilize the neck in a destabilizedelderly cadaver model. Bednar’s experiment involvedcreation of unstable motion segments at the C3–C4,C4–C5, or C5–C6 levels; isolated posterior column, com-bined column, and then anterior column injuries weresequentially assessed. Soft, semirigid, and rigid collarswere used in an attempt to restrict neck movements, andthen the spines were subjected to unrestrained gravita-tional forces with flexion, lateral side-bending, and ex-tension. The collars were not effective in reducing spinalmovement; in fact, there was evidence for increasedspinal movement. Bednar hypothesized that the in-creased movement resulted from the levering of themobile head and proximal cadaver neck over the collaredge. The model described allowed for the applicationof forces that would rarely be applied or permitted inclinical settings but did emphasize the very limited rolethat collars would play in limiting spinal movement if thespine were subjected to very hostile forces.
Goutcher and Lochhead76 measured maximal mouthopening (interincisor distance) in 52 volunteers, beforeand after the application of a semirigid cervical collar.Three collars were assessed: the Stifneck (Laerdal Medi-cal Corp., Wappinger’s Falls, NY), the Miami J (JeromeMedical, Moorestown, NJ) and the Philadelphia (Phila-delphia Cervical Collar Co., Thorofare, NJ). Applicationof a collar significantly reduced interincisor distancefrom a mean of 41 � 7 mm in the control state to 26 �8 mm with the Stifneck, 29 � 9 mm with the Miami J,and 29 � 9 mm with the Philadelphia. There was a widevariation between subjects, and a significant proportionhad an interincisor distance reduced to less than 20 mmafter application of the collar (Stifneck, 25%; Miami J,21%; Philadelphia, 21%). Goutcher and Lochhead con-cluded that the presence of a semirigid collar signifi-cantly reduced mouth opening and would likely ofteninterfere with airway management; removal of the ante-rior portion of the collar before attempts at trachealintubation was encouraged by these authors.
Manual In-line ImmobilizationThe goal of manual in-line immobilization (MILI) is to
apply sufficient forces to the head and neck to limit themovement which might result during medical interven-tions, most notably, airway management. MILI is typi-cally provided by an assistant positioned either at thehead of the bed or, alternatively, at the side of thestretcher facing the head of the bed. The patient ispositioned supine with the head and the neck in neutral
position. Assistants either grasp the mastoid processedwith their fingertips and cradle the occiput in the palmsof their hands (head-of-bed assistant) or cradle the mas-toids and grasp the occiput (side-of-bed assistant). WhenMILI is in place, the anterior portion of the cervical collarcan be removed to allow for greater mouth opening,facilitating airway interventions. During laryngoscopy,the assistant ideally applies forces that are equal in forceand opposite in direction to those being generated bythe laryngoscopist to keep the head and neck in theneutral position.
Avoiding traction forces during the application of MILImay be particularly important when there is a seriousligamentous injury resulting in gross spinal instability.Lennarson et al.77 noted excess distraction at the site ofa complete ligamentous injury when traction forceswere applied for the purposes of spinal stabilizationduring direct laryngoscopy. Similarly, Kaufmann et al.78
demonstrated that in-line traction applied for the pur-poses of radiographic evaluation resulted in spinal col-umn lengthening and distraction at the site of injury infour patients with ligamentous disruptions. Bivins etal.79 reported that traction applied during orotrachealintubation in four victims of blunt traumatic arrest withunstable spinal injuries resulted in both distraction andposterior subluxation at the fracture site. It is possiblethat the fracture site distraction that was observed re-sulted from application of traction forces not appropri-ately axially aligned.
Majernick et al.80 demonstrated that MILI reduced totalspinal movement during the process of laryngoscopyand tracheal intubation; movement was not reduced to asimilar degree by collars. Similarly, Watts et al.81 mea-sured a reduction of spinal movement with the applica-tion of MILI during tracheal intubation in patients withnormal spines during general anesthesia. However, Len-narson et al.82 were unable to demonstrate that applica-tion of MILI resulted in any significant reduction inmovement during intubation in a cadaver model with aposterior column injury. In a cadaver model with com-plete ligamentous instability, Lennarson et al.77 reportedthat application of MILI minimized distraction and angu-lation at the injured level but had no effect on subluxa-tion at the site of injury.
Manual in-line immobilization may be effective in re-ducing overall spinal movements recorded during airwaymaneuvers but may have lesser restraining effects at theactual point of injury. This may be because spinal move-ment is restricted by the weight of the torso at the caudalend and the MILI forces at the cephalad end but isunrestricted by any force at its cervical midpoint. It ispossible that application of traction forces during MILIwould also reduce midcervical movement in some pa-tients, but traction forces may also result in distraction atthe site of injury; the use of such forces during applica-
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tion of in-line immobilization continues to be discour-aged.
Impact of MILI on the View Obtained atLaryngoscopyThe application of MILI during airway maneuvers may
result in decreases in overall spinal movement, but theevidence also suggests modest, if any, effect at individualmotion segments.77,82 However, the use of MILI mayhave lesser impact on the view obtained during directlaryngoscopy than relying on other immobilization tech-niques, such as axial traction or a cervical collar, tape,and sandbags. Heath83 examined the effect on laryngos-copy of two different immobilization techniques in 50patients. A grade 3 or 4 laryngoscopic view (partial or noview of the glottic structures) was obtained in 64% ofpatients immobilized with a collar, tape, and sandbagscompared with 22% of patients stabilized with MILI. Thelaryngeal view improved by one grade in 56% of patientsand by two grades in 10% when MILI was substituted forthe collar, tape, and sandbags. The main factor contrib-uting to the increased difficulty of laryngoscopy whenpatients were wearing cervical collars was reducedmouth opening. Gerling et al.84 reported the findings ofan analogous study using a cadaver model with a C5–C6destabilization and arrived at similar findings. MILI al-lowed less spinal movement than did cervical collarimmobilization during laryngoscopy and intubation andwas associated with improved laryngeal visualization.
Hastings and Wood85 measured the degree of headextension required to expose the arytenoid cartilagesand glottis and determined the impact of applied MILI.The subjects were 31 anesthetized patients (24 study, 7control) with normal cervical spines and Mallampati 1views on preoperative airway assessment. Two methodsof immobilization were assessed. Either axial tractionwas applied, wherein the assistant pulled the head in acaudal to cephalad direction as strongly as he or shethought was necessary to immobilize the neck, or forcewas applied to the head in a downward direction to holdthe head onto the table. Without stabilization, the bestview of the glottis was achieved with 10°–15° of headextension. Head immobilization reduced extension an-gles of 4°–5° compared with no stabilization, and it wasmore effective than axial traction immobilization in lim-iting extension. In 4 of the 24 study patients (17%), 2 ineach immobilization group, the laryngoscopic view de-teriorated from grade I or II to grade III with the appli-cation of immobilizing forces. Therefore, the use of MILIreduced the amount of head extension that was neces-sary for laryngoscopy but resulted in a poorer view in aportion of the patients studied.
Although MILI seems to have the least impact of allimmobilization techniques on airway management, itmay make direct laryngoscopy more difficult in somepatients than if no immobilizing forces are being applied.
Nolan and Wilson86 assessed the impact of MILI withcricoid pressure on the view obtained at laryngoscopy in157 normal patients and compared it with the viewobtained in the same patients while in the sniffing posi-tion. With application of MILI and cricoid pressure, theview remained the same in 86 patients (54.8%), wasworse by one grade in 56 (35.6%), and was worse by twogrades in 15 (9.5%). A grade 3 view (partial glottic view)was obtained in 34 restrained patients (21.6%) comparedwith 2 (1.3%) in the sniffing position. Wood et al.87 alsostudied the effect of cervical stabilization maneuvers onthe view obtained at laryngoscopy in 78 uninjured, elec-tive surgical patients and concluded that cervical immo-bilization commonly worsened laryngoscopic view. Theeffects of MILI on laryngeal view were in a similar direc-tion to those reported by Hastings but occurred morecommonly in Wood’s study. Anterior laryngeal or cricoidpressure often improved the view of the larynx whenthe neck was immobilized. Concern has been expressedin the past regarding the use of anterior cervical pressurein patients at risk for CSI, but Donaldson et al.88 reportedthat application of cricoid pressure did not result inmovement in an injured upper cervical spine in a ca-daver model.
Manual in-line immobilization may have lesser impacton airway interventions than do other forms of immobi-lization. The experience supports routinely removing atleast the anterior portion of collars to facilitate airwayinterventions provided that cervical spinal immobiliza-tion is maintained by MILI. Removal of the anteriorportion of the collar improves mouth opening and facil-itates airway management; reapplication of the mechan-ical immobilization should occur promptly when airwayinterventions are complete. MILI may increase laryngo-scopic grade in some patients; this may be counteredwith anterior laryngeal or cricoid pressure.
Spinal Movement during Airway InterventionsThe early biomechanical analyses of spinal motion typ-
ically used static radiography to determine the relationsbetween the vertebral elements of the cervical spine andto quantify spinal movements. Unfortunately, no stan-dardized technique of measurement has been used in theworks since published, which have evaluated spinalmovement during airway interventions. Both static radi-ography and dynamic fluoroscopy have been used; studyfindings have been reported movement as absolute dis-tances, relative distances (typically a percentage of ver-tebral body width), and degrees of motion and havefurther been categorized relative to individual motionsegments or upper and lower cervical spinal divisions orsummated across the entire cervical spine. There is alsolittle guidance available as to the clinical importance ofthe movements recorded, especially as they relate to theinjured spine. Those spinal movements that fall withinphysiologic ranges have usually been considered to be
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nonthreatening to the cord; whether they are in fact andremain so in a spine with a canal lumen already compro-mised by an acute, a chronic, or an acute superimposedon chronic anatomical derangement is by no meanscertain. Unfortunately, as we analyze the publishedworks, we typically find ourselves in the position ofcomparing the recorded results with physiologic normsand then drawing an empiric conclusion as to the po-tential risk of such movements.
The Effects of Basic Airway Maneuvers on theInjured Neck. Aprahamian89 studied the effect of bothairway maneuvers on a human cadaver, unstable spinemodel. The anterior and most of the posterior columnwere surgically disrupted; the interspinous and supraspi-nous ligaments were spared. Lateral cervical spine radio-graphs were taken during both basic and advanced air-way maneuvers. Basic maneuvers included chin lift, jawthrust, head tilt, and placement of both oral and esoph-ageal airways. Advanced maneuvers included placementof the following: an esophageal obturator airway; anorotracheal tube placed with both a straight and acurved laryngoscopic blade; and a nasotracheal tube,blindly placed. Chin lift and jaw thrust resulted in ex-pansion of the disc space more than 5 mm at the site ofinjury. When blind nasotracheal intubation was facili-tated by anterior pressure to stabilize the airway, 5 mmof posterior subluxation occurred at the site of injury.The other advanced airway maneuvers produced 3–4mm of disc space enlargement. The study was repeatedafter the application of both soft and semirigid cervicalcollars; collars did not effectively immobilize the neckfor either basic or advanced airway maneuvers.
Hauswald90 also determined the impact of basic airwaymaneuvers on cervical spine movement. Eight humantraumatic arrest victims were studied within 40 min ofdeath. All subjects were ventilated by mask, and theirtracheas were intubated orally with a direct laryngo-scope, over a lighted oral stylet and using a flexiblelaryngoscope, and nasally. Cinefluoroscopic measure-ment of maximum cervical displacement during eachprocedure was made with the subjects supine and im-mobilized by a hard collar, backboard, and tape. Themean maximum cervical spine displacement was foundto be 2.93 mm for mask ventilation, 1.51 mm for oralintubation, 1.85 mm for guided oral intubation, and 1.20mm for nasal intubation. Ventilation by mask causedmore cervical spine displacement than the other proce-dures studied. It was concluded that mask ventilationmoves the cervical spine more than any of the com-monly used methods of tracheal intubation.
Airway maneuvers will result in some degree of neckmovement, both in general and specifically at the sites ofinjury. The amounts of movement are small, typicallywell within physiologic ranges, and their impact onsecondary neurologic injury has not been defined. How-ever, as will be subsequently discussed, airway interven-
tions are frequently performed on at-risk trauma pa-tients, and there seems to be a very low incidence ofsecondary injury in these patients associated with airwayclinical interventions.
Cervical Spinal Movement during Direct Laryn-goscopy in Normal Patients. Sawin et al.91 deter-mined the nature, extent, and distribution of segmentalcervical motion produced by direct laryngoscopy andorotracheal intubation in normal human subjects. Tenpatients underwent laryngoscopy while paralyzed andduring general anesthesia. Minimal displacement of theskull base and cervical vertebral bodies was observedduring laryngoscope blade insertion; elevation of thelaryngoscope blade to achieve laryngeal visualizationcaused superior rotation of the occiput and Cl and mildinferior rotation of C3–C5. The largest magnitude mo-tions were at the atlanto-occipital and atlantoaxial joints,but there was extension at each motion segment as-sessed. Tracheal intubation created slight additional su-perior rotation at the craniocervical junction but causedlittle alteration in the postures of C3–C5. Horton et al.92
conducted a similar experiment in volunteers duringtopical anesthesia only. Subjects in a supine, sniffingposition underwent direct laryngoscopy, and at full glot-tic exposure, a lateral radiograph of the head and neckwas performed. The radiographs indicated that exten-sion at the craniocervical junction was near maximal andthat there was progressively increasing extension fromC4 to the base of the skull, but that the position of thelower cervical spine remained static during laryngos-copy. Both Sawin et al. and Horton et al. agreed that,during laryngoscopy, in both awake and unconscioussubjects, most cervical motion occurs at the craniocer-vical junction; the subaxial cervical segments subjacentto and including C4 are minimally displaced (fig. 6).91,92
Spinal Movement during Laryngoscopy in In-jured Spine Models. Donaldson et al.88 studied themotion that occurred during intubation in a cadavermodel with an unstable C1–C2 segment. The followingwere measured in the intact specimen and then againafter creation of the unstable segment: angulation, dis-traction, and the space available for the cord (SAC). Withmaximum flexion and extension, the SAC was narrowed
Fig. 6. Impact of direct laryngoscopy and tracheal intubation oncervical spine movement.91,92
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1.49 mm in the intact cervical spine but 6.06 mm in theunstable spine. Chin lift and jaw thrust reduced the SACby 1 mm and 2.5 mm, respectively; oral intubation andnasal intubation created a similar (1.6 mm) reduction ofSAC. Distraction at the unstable injured level was similarfor chin lift, jaw thrust, and crash intubation (1–2 mm);distraction during gentle oral intubation and nasal intu-bation was less than 1 mm. Chin lift and jaw thrustcreated similar angulations (4°–5°) to those of the oralintubation techniques, but nasal intubation caused less(2.5°). Cricoid pressure resulted in no significant move-ments when it was applied in either the stable or unsta-ble model. Donaldson et al. concluded that (1) the SACwas narrowed to a greater degree by preintubation ma-neuvers than it was by intubation techniques, (2) nasaland oral intubation techniques resulted in similaramounts of SAC narrowing, and (3) application of cri-coid pressure produced no significant movement at thecraniocervical junction.
Stabilization during Airway Interventions in Ca-daver Models of an Injured Spine. Lennarson et al.82
evaluated the impact of commonly used immobilizationtechniques in limiting spinal motion in an injured-spinemodel; the model involved the creation of a posteriorligamentous injury at the C5 level and compared theeffects of MILI and Gardner-Wells traction. The predom-inant motion measured at all spinal levels during laryn-goscopy and intubation in the intact spine was exten-sion; this was consistent with the findings of Donaldsonet al.,88 Sawin et al.,91 and Horton et al.92 Subluxation inthe anterior–posterior dimension remained less than 1mm in both the intact and the partially destabilizedspine; rotatory or angular movements were the onlysignificant movement recorded. Application of Gardner-Wells traction limited rotatory motion at the craniocer-vical junction after destabilization; MILI did not have asimilar effect.
Lennarson et al.77 conducted a similar experimentassessing the efficacy of immobilization maneuvers in amodel of complete C4–C5 segmental instability. Move-ment was measured at the injured level during the ap-plication of traction, during MILI, and without stabiliza-tion. Traction resulted in distraction at the site of injurywhen instability was complete; the magnitude of thesemovements was not reduced by MILI, although theyremained within physiologic limits. Gerling et al.84 alsoevaluated the effect of both MILI and cervical collarimmobilization on spinal movement during direct laryn-goscopy in an unstable C5–C6 cadaver model. Althoughthere was less displacement (2 mm) measured withapplication of MILI compared with collars, the magni-tude of movement was small overall and within physio-logic ranges.
Brimacombe et al.93 assessed spinal movement in acadaver model with a posterior injury at C3, with MILIapplied as various airway interventions (facemask venti-
lation, direct laryngoscopy and tracheal intubation, fiber-optic nasal intubation, laryngeal mask insertion, intubat-ing laryngeal mask airway insertion followed byfiberoptic intubation, and insertion of a Combitube)were performed. Posterior displacement was less whenintubation was performed nasally with a flexible scope(0.1 � 0.7 mm) than for any other maneuver; mostmaneuvers caused 2–3 mm of displacement.
Influence of Laryngoscope Blade Type on SpinalMovement during Direct Laryngoscopy. Three au-thors have assessed the influence of the type of laryngo-scope blade on the spinal movements generated duringdirect laryngoscopy. MacIntyre et al.94 compared theMacintosh and McCoy blades in patients with normalspines during general anesthesia with cervical collarsapplied. There were no significant differences betweenthe two blades with respect to the amount of spinalmovement generated during intubation. Hastings et al.95
compared head movement occurring during laryngos-copy in patients with normal spines using Macintosh andMiller laryngoscopes, and again, there were no differ-ences in the amount of movement measured. Finally,Gerling et al.84 compared spine movement in a cadavermodel with a C5–C6 transection injury while performinglaryngoscopy with Miller, Macintosh, and McCoy-typeblades. There was no difference in the movements re-corded with the different blades with regard to eitheranteroposterior displacement or angular rotation. Lessaxial distraction was measured with the Miller bladecompared with the other two blade types; in absoluteterms, the differences was 1.7 mm. Overall, there seemsto be little difference in the spinal movement resultingfrom direct laryngoscopy relative to the type of bladeused during laryngoscopy.
Cervical Spinal Movement with Indirect Rigid Fi-beroptic Laryngoscopes. Watts et al.81 compared cer-vical spine extension and time to intubation with theBullard (ACMI Corp., Southborough, MA) and Macintoshlaryngoscopes during a simulated emergency with cervi-cal spine precautions taken. Twenty-nine patients wereplaced on a rigid board, and anesthesia was induced.Laryngoscopy was performed on four occasions, twiceeach with the Bullard and Macintosh laryngoscopes,both with and without MILI applied (MILI was appliedwith cricoid pressure). Cervical spine extension (fromthe occiput to C5) was greatest with the Macintosh andwas reduced both when the Macintosh was used withMILI and when the Bullard was used with or withoutstabilization. Times to intubation were similar for theMacintosh with MILI and for the Bullard without MILI.MILI applied during laryngoscopy with the Bullard re-sulted in further reduction in cervical spine extensionbut a prolonged the time to intubation, although it stillwas achieved in less than a minute. In a study designsimilar to that of Watts et al., Hastings et al.95 found thatcervical spine extension from the occiput to C4 was
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decreased when comparing the Bullard with both theMacintosh and the Miller laryngoscope blades.
The times to achieve intubation using the Bullard la-ryngoscope, in the study of Watts et al.,81 are similar toothers reported in the literature. Twenty-two of 29 pa-tients (76%) were intubated in less than 30s when usingthe Bullard under standard conditions.81 In a study usingthe dedicated intubating stylet, Cooper et al.96 found70% of patients were intubated in less than 30 s. Therewas also better exposure of the larynx during laryngos-copy with the Bullard than with the direct laryngoscope.Application of MILI resulted in deterioration in the gradeview of the larynx when using the Macintosh in 19 of 29patients (65%). In contrast, only 2 patients (7%) pre-sented an inferior view of the larynx after application ofMILI and cricoid pressure when using the Bullard laryn-goscope.
Rudolph et al.97 compared movement in the uppercervical spine in 20 patients scheduled to undergo elec-tive surgery, when laryngoscopy was performed withthe Bonfils intubation fiberscope (Karl Storz EndoscopyLtd., Tuttlingen, Germany) and the Macintosh laryngo-scope. With the patient’s head in neutral position on thetable and no pillow used, a baseline lateral radiographwas taken. The head was extended, laryngoscopy wasperformed using the Macintosh, a second radiographwas taken, and the head was returned to the neutralposition. Laryngoscopy was then performed with theBonfils fiberscope, and the trachea was intubated. Withthe Macintosh, views at laryngoscopy were class I in 8patients, II in 5, and III in 7; all views obtained with theBonfils fiberscope were class I. The time between inser-tion of the instrument and achievement of optimumview was similar for both instruments. Laryngoscopywith the Macintosh resulted in spinal movement thatwas greater in magnitude than that measured duringBonfils fiberscopy.
The Glidescope (Saturn Biomedical Systems, Burnaby,British Columbia, Canada) is a new video laryngoscopethat incorporates a high resolution digital camera in theblade tip; the image is transmitted to a liquid crystaldisplay monitor via a dedicated video cable. Agro et al.98
compared the laryngeal view obtained initially with aMacintosh and then with the Glidescope in 15 normalpatients presenting for general anesthesia who werewearing cervical collars. The laryngeal view was reducedby one Cormack grade in 14 of the 15 patients (93%)studied when the Glidescope was used compared withthe Macintosh; the average time to intubation with theGlidescope was 38 s. Turkstra et al.99 compared cervicalspine movement, measured fluoroscopically, during in-tubation with a Macintosh, a light wand, and the Glide-scope. In-line immobilization was achieved by taping thepatients’ heads into a Mayfield-type headrest; movementwas measured at the Oc–C1, C1–C2, C2–C5, and C5–Thlevels. The largest amount of motion measured was at
the Oc–C1 complex with all devices. Cervical spinalmovement was reduced 57% overall (all segments com-bined) comparing the light wand with the Macintosh;reduced movement was apparent at each level. Spinalmovement was reduced only at the C2–C5 segmentwhen the Glidescope was compared with the Macin-tosh; 6.9° � 5.2° of flexion was measured during Macin-tosh laryngoscopy, and this was reduced by 50% usingthe Glidescope. Motion was not significantly altered atthe three other segments studied. The time to intubationwas longest with the Glidescope (27 � 12 s) but similarwith the light wand (14 � 9 s) and the Macintosh (16 �7 s).
Cervical spine movements are generally less whenrigid indirect laryngoscopes are used compared with theML direct laryngoscope. Visualization of the glottis is alsoimproved with the use of the rigid laryngoscopes, butthe time to achieve the best view is somewhat longer;these times tend to be short, and the difference com-pared with the direct laryngoscope is likely to be of littleclinical relevance.
Cervical Spinal Movement and Laryngeal MaskAirways. Kihara et al.100 measured cervical movementproduced by the intubating laryngeal mask airway dur-ing MILI in 20 anesthetized patients with cervical pathol-ogy undergoing cervical spine surgery. During the inser-tion of the intubating laryngeal mask airway, C5 andsuperior segmental levels were flexed by less than 2°.During intubation, C4 and superior segmental levelswere flexed by 3° or less, and C3 and levels above wereflexed by an average of 1° during removal. There wassome posterior displacement at the C2–C5 levels duringinsertion and intubation but not during removal.
Keller et al.101 implanted microchip sensors into thepharyngeal surfaces of C2 and C3 in 20 cadavers todetermine the pressures exerted against the cervicalvertebrae by both the standard laryngeal mask airwayand the intubating laryngeal mask airway during inser-tion and manipulation. The impact of these pressures oncervical spine movement was also determined. Keller etal. concluded that laryngeal mask devices exert highpressures against the upper cervical vertebrae duringinsertion, during inflation, and while in situ; these pres-sures could produce posterior displacement of the up-per cervical C-spine. The clinical relevance of thesefindings as they relate to CSI has yet to be clarified.
Cervical Spinal Movement during Surgical Crico-thyrotomy. Surgical cricothyrotomy was initially advo-cated as a preferred airway intervention in patients atrisk for CSI compared with orotracheal intubation andnow is deemed to be an appropriate alternative if oral ornasal routes cannot be used or are unsuccessful. Al-though long considered safe in the presence of a CSI, itsapplication in this scenario has not been well studiedwith respect to either spinal movements or neurologicoutcomes. Gerling et al.102 used a cadaver model to
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quantify movement during cricothyrotomy. Standardopen cricothyrotomy was performed in 13 cadavers withcomplete C5–C6 transection injuries, and cervical spineimages were recorded fluoroscopically during the pro-cedure. Peak axial distraction was measured at 4.5% ofthe C5 width, amounting to 1–2 mm of axial compres-sion; peak antero-posterior displacement was measuredat 6.3% of the C5 width, equivalent to 1–2 mm of dis-placement. Although these values were statistically sig-nificant, there clinical relevance has yet to be deter-mined.
The Clinical Practice of Airway Management inPatients with Cervical Spine InjurySurveys of Patterns of Clinical Practice Regarding
Airway Management after Cervical Spine Injury.Four authors have surveyed North American anesthesi-ologists as to their preferred methods of airway manage-ment in patients with cervical spine trauma or disease.Lord et al.103 compared practice preferences amongsurgical members of the Eastern Association for the Sur-gery of Trauma with anesthesiologists in US anesthesiol-ogy training programs. In the elective situation (CSI butbreathing spontaneously with stable vital signs), anesthe-siologists stated that they were less likely to use nasotra-cheal intubation (53% vs. 69%), equally likely to useorotracheal intubation, and more likely to use the fiber-optic bronchoscope than were trauma surgeons. In theurgent scenario (patient with unstable vital signs), anes-thesiologists tended to use both nasotracheal and orotra-cheal intubation in a manner similar to that of the sur-geons but more frequently (16%) preferred thebronchoscope. In an emergency situation (apneic pa-tient with unstable vital signs), both anesthesiologistsand surgeons relied extensively on the direct laryngo-scope (78% and 81%); anesthesiologists were more likelyto use the bronchoscope (15%) than were surgeons butused a surgical airway less frequently than did the sur-geons (7% vs. 19%).
Rosenblatt et al.104 received 472 responses from 1,000active members of the American Society of Anesthesiol-ogists who were surveyed as to their preferences formanagement methods for the difficult airway in cooper-ative adult patients. With respect to patients with CSI,78% of respondents expressed a preference for an awakeintubation and the use of bronchoscope; the bulk of theremainder induced general anesthesia and used a directlaryngoscope. Rosenblatt et al. did not request informa-tion regarding the levels of experience attained with thedevices preferred but did ascertain that they were avail-able to the practitioners who stated that they would usethem. Jenkins et al.105 collected 833 responses from1,702 members of the Canadian Anesthesiologists’ Soci-ety surveyed regarding their management choices forthe difficult airway in Canada. When faced with a patientwith a cervical cord compression and neurologic deficit
presenting for discectomy, 67% expressed a preferencefor awake intubation, and most (63%) stated that theywould use a bronchoscope. Thirty-one percent wouldinduce general anesthesia before airway intervention,and slightly more would use a direct laryngoscope thanpreferred a lighted stylet in this setting. Jenkins et al. didnot solicit information regarding the level of experiencewith the methods identified as being preferred by thesurvey respondents.
Ezri et al.106 surveyed 452 American-trained AmericanSociety of Anesthesiologists members attending the 1999Annual Meeting. When faced with a cooperative adultpatient with cervical spine disease (rheumatoid arthritisor ankylosing spondylitis) presenting for elective sur-gery, awake fiberoptic intubation was preferred by most.Although 75% stated that they would use it in some ofthe scenarios outlined, only 59% or respondents re-ported skill in the use of the bronchoscope.
The surveys are consistent in revealing that manyNorth American anesthesiologists express a preferencefor the use of a fiberoptic bronchoscope during airwaymanagement in patients with cervical spine disease orinjury including in apneic trauma scenarios. This prefer-ence persists despite the fact that some who state thispreference also acknowledge that they are not confidentregarding their skill levels with the bronchoscope. De-pending on the setting and the perceived urgency of thesituation, direct laryngoscopy is still commonly used,and use of the lightwand is preferred by a significantminority of anesthesiologists, at least in Canada.
Airway Management of Cervical Spine–injuredPatients: The Experience and Outcomes Reported.Meschino et al.107 reviewed their experience with 454patients with critical cervical cord or spine injuries orboth. One hundred sixty-five patients underwent awaketracheal intubation within 2 months of injury; 289 didnot require intubation during the same period. The di-rect laryngoscope was used in 36 patients (22%), thefiberoptic bronchoscope was used in 76 (46%), and 51patients (32%) underwent blind nasal intubation. Pa-tients undergoing intubation were more severely im-paired than those who did not require intubation. De-spite this, there was no difference in the incidence ofneurologic deterioration over time between the twogroups, and tracheal intubation was not associated withneurologic deterioration in any patient. Holley and Jor-dan108 conducted a retrospective analysis of traumatic,unstable cervical spine fractures requiring operativemanagement to determine both the airway managementtechniques used and the incidence of neurologic com-plications. One hundred thirty-three patients with 140fractures were reviewed. Ninety-four patients under-went nasal intubation in the operating room, and 29were intubated with direct laryngoscopy and in-line sta-bilization. No neurologic complications were recognizedin any patient.
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Rhee et al.109 analyzed their experience with 21 pa-tients with cervical cord or spine injury who underwenttracheal intubation in the emergency room. Orotrachealintubation was used in 81% of CSI patients; neuromus-cular blockers were used in 82% of these intubations.The authors concluded that no injury was recognized tobe caused or exacerbated by airway maneuvers. How-ever, one patient with a C7–T1 dislocation and a C7 cordtransection was noted to have absent sensation belowthe nipples before intubation (T4 level) and motor andsensory examination results consistent with a C7 cordtransection after intubation. Whether this disparity re-flect an ascension in the level of injury from T4 to C7 orthe difference in findings between an emergency roomscreening neurologic exam and a more precise examina-tion performed later is not certain; the authors’ conclu-sions seem to prefer the latter explanation. Scanell etal.110 reviewed their experience with 81 patients withCSI, including 58 with unstable fractures, who receivedemergency orotracheal intubations performed by expe-rienced anesthesiologists. Neurologic assessment wasdocumented before and after intubation, and in no in-stance was there a recognized deterioration of neuro-logic functions after tracheal intubation. Shatney et al.111
reviewed their experience with 81 patients with 98fractures who were neurologically intact on initial pre-sentations. Orotracheal intubation was performed in 48patients, and no neurologic deteriorations were recog-nized. In-line immobilization was used during the airwaymaneuvers, and agitated or combative patients weresedated, paralyzed, or both. Talucci et al.112 reviewedtheir experience with 335 patients requiring urgent in-tubations. Seven patients with unstable CSI underwentorotracheal intubation after induction of anesthesia andparalysis; none experienced neurologic compromise as aresult of airway management.
Suderman et al.113 reviewed the experience of 150patients with traumatic CSI and well-preserved neuro-logic function presenting for operative stabilization.General anesthesia before intubation was induced in 83patients, of whom 65 had their tracheas intubated withthe direct laryngoscope; 22 patients were intubatedwhile awake using the direct laryngoscope. The remain-der had tracheal intubation performed with a variety ofalternatives to the direct laryngoscope, most commonlythe bronchoscope; the majority of those latter intuba-tions were performed with the patient awake. Two pa-tients experienced new neurologic deficits; one had awire passed through the cervical cord accidentally dur-ing operative stabilization and was rendered quadriple-gic, the second recovered from a new single level radic-ulopathy attributed to the operative decompression.Both of these patients had their tracheas intubated witha direct laryngoscope while anesthetized. McCrory114
performed a similar retrospective analysis of the recordsof 45 patients who presented for operative stabilization
of cervical injuries resulting from trauma. Tracheal intu-bation was performed after induction of general anesthe-sia with neuromuscular block in 40% of cases; in theremainder, intubation was performed with a broncho-scope while the patient was awake. One awake trachealintubation was abandoned as a result of patient noncom-pliance; this patient’s trachea was intubated after induc-tion of general anesthesia. Weighted traction was used inall cases to immobilize the spine. No patient developedeither a new neurologic finding or worsening of a pre-existent deficit.
Wright et al.115 reviewed the records of 987 blunttrauma patients; 60 of the patients had a cervical frac-ture, and 53 of these were deemed to be unstable.Twenty-six patients’ tracheas were intubated orally, 25were intubated nasally, and two were intubated by cri-cothyrotomy. One patient who underwent nasotrachealintubation experienced a neurologic deterioration. Lordet al.103 reviewed the case records of 102 patients whohad a CSI and were admitted to their center after trauma.Sixty-two patients required airway management. Themost common method used was orotracheal intubationfacilitated by direct laryngoscopy (43%), followed bybronchoscope-assisted intubation (27%), nasotracheal in-tubation (22%), and tracheostomy (2%); in 4%, themethod could not be determined. No patient was recog-nized to have experienced a neurologic deteriorationassociated with airway management. Other authors havereported similar findings in smaller series of trauma pa-tients with CSI.112,116
These studies are limited by both their small samplesize and their retrospective nature. However, they doreveal that neurologic deterioration in CSI patients isuncommon after airway management, even in high-riskpatients undergoing urgent tracheal intubation. They arenot sufficient to rule out the potential that airway man-agement provided in isolation or as part of a more com-plex clinical intervention, even provided with the ut-most care, may rarely result in neurologic injury. To doso would require a study of enormous proportions. Asnoted previously, progressive neurologic deteriorationoccurs in a minority of CSI patients. If this incidence wasset at 2% and a study was designed to prove that anairway intervention did not double this baseline inci-dence, approximately 1,800 patients would need to bestudied. No method of airway intervention has beenevaluated with such a study, or anything close to it, andtherefore, statements comparing the relative safety ofdifferent methods have tenuous evidentiary support.
The Use of the Direct Laryngoscope after CervicalSpine Injury: The Debate. As part of the early effortsaimed at reducing secondary injuries in spine-injuredpatients, a hypothesis was generated that the tracheas ofpatients with unstable cervical spines could not be safelymanaged by direct laryngoscopy and oral intubation.117
Oral intubation was deemed dangerous because it alleg-
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edly caused excessive spinal movement, and this move-ment could lead to secondary injury. Such secondaryinjury could theoretically be avoided by the careful per-formance of nasotracheal intubation or cricothyrotomy.These techniques were advocated as the emergencyairway maneuvers of choice in patients at risk for spinalinjury. There were no data at that time to support thisthesis, and the data collected since seem to suggest thatsecondary neurologic injury associated with any form ofairway management is exceedingly rare. The early Ad-vanced Trauma Life Support protocols for airway man-agement were consistent in their support for the nasalintubation/cricothyrotomy strategy, implying a lack ofsupport for the use of direct laryngoscopy in this clinicalsetting. Not all practitioners agreed that the use of directlaryngoscopy was contraindicated in patients at risk forcervical injury. There was evidence made available soonafter publication of these protocols that some experi-enced trauma centers (including our own) were ignoringthe Advanced Trauma Life Support recommendationsand performing direct laryngoscopy in at-risk popula-tions.107,113,118
McLeod and Calder119 examined the association be-tween the use of the direct laryngoscope in patients andsubsequent spinal injury or pathology. They suggestedthat the following five case features would add credenceto the diagnosis of a laryngoscopy-induced cord injury:(1) a short period of unconsciousness, (2) myelopathypresent on recovery, (3) autonomic disturbances afterlaryngoscopy, (4) difficult laryngoscopy, and (5) cranio-cervical disease or gross instability below C3. Thesecriteria were then used to evaluate the likelihood thatlaryngoscopy was the causative factor for neurologicdeterioration in the reports. Although they do makeintuitive sense, whether these criteria discriminate wellin assigning cause to injury recognized after intubation isnot established. Six reports dealing with 10 patients inwhich it was alleged that direct laryngoscopy contrib-uted to a neurologic injury were reviewed.57,120–124
With the possible exception of one case, they concludedafter review and analysis of the case reports, that thereports did not provide sufficient data to allow them tomake the determination that the use of the direct laryn-goscope was the cause of the neurologic injuries re-ported.
The first report analyzed was that of Farmer et al.,57
who reviewed their institutional experience with cord-injured patients. They reported that four patients hadneurologic deteriorations associated with tracheal intu-bation. Two deteriorations were classified as minor andtwo were classified as major, but no further details wereprovided regarding the cases or the intubations. Thesecond report was that of Muckart et al.,120 who re-ported two cases of neurologic deterioration after clini-cal interventions. The first patient was a 45-yr-old maninvolved in a motor vehicle accident who sustained
bilateral femoral fractures and a closed head injury. De-spite the mechanism of injury, a period of unconscious-ness, and the presence of neck pain, no imaging wasperformed, and his spine was not immobilized. He un-derwent anesthesia for operative repair of the femoralfractures and was quadriplegic on awakening; a C2 frac-ture–dislocation was subsequently diagnosed, and herecovered completely. The second patient was a 22-yr-old man with multiple gunshot wounds to the neck; hearrived in the hospital neurologically intact. Imaging ofthe neck revealed no apparent injury to the cervicalspine to a level of C5; the radiograph showed only theupper five vertebrae. He underwent emergency surgeryduring general anesthesia without neck immobilizationand was quadriplegic after. A CT scan demonstrated aburst fracture of C6 with a retropulsed fragment imping-ing on the canal. He was placed in traction, had opera-tive fixation, and recovered completely. Although directlaryngoscopy and tracheal intubation were componentparts of the care of both patients, they were not the soleinterventions; the lack of immobilization and the poten-tial for malpositioning cannot be excluded as significantrisk factors in both cases. The complete recovery in bothpatients suggests that malpositioning may have been anetiologic factor inducing a transient, compressive neura-praxia-like injury.
The third report analyzed was that of Redl,121 whodescribed the case of an 18-yr-old man with undiagnosedspondyloepiphyseal dysplasia congenita resulting in un-recognized craniocervical instability. He underwent gen-eral anesthesia and direct laryngoscopy with trachealintubation for removal of retained knee hardware. Theintraoperative and early postoperative course was un-eventful, but he developed a spastic quadriparesis theday after surgery. A CT scan demonstrated a congenitallyabnormal craniocervical junction with an os odontoi-deum (congenitally nonfused odontoid process) in theforamen magnum compressing the spinal cord. Al-though he made a full recovery, he awoke quadriplegicafter a subsequent craniocervical stabilization procedurefor which his trachea was intubated using a fiberopticbronchoscope. The precise role of the laryngoscopy inthe development of transient neurologic symptoms in apatient with a congenitally abnormal and unstable spineis uncertain; the development of symptoms on the dayafter laryngoscopy reduces the strength of a causativeassociation. The fourth report reviewed is that of Yanand Diggan,122 who described the occurrence of a cen-tral cord syndrome in a 42-yr-old woman with acquiredimmune deficiency syndrome who underwent urgentlaryngoscopy and intubation for respiratory failure. Be-fore her admission, she was using a walker and wheel-chair to ambulate. Following the recognition of upperextremity weakness after intubation and resuscitation,she underwent imaging and evaluation of her central andperipheral nervous system. There was no evidence of
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spinal anomaly or instability; there was imaging evidenceof marked and generalized cerebral atrophy and a spinalcord contusion and electrodiagnostic evidence of bothcentral and peripheral neuropathy. The etiology of injurywas attributed to hyperextension, but there was alsoevidence of advanced neurologic disease likely related toinfection with human immunodeficiency virus. The fifthreport was that by Yaszemski et al.,123 who reported thecase of a 59-yr-old woman with advanced rheumatoidarthritis. She underwent a right wrist fusion during gen-eral anesthesia, and her trachea was intubated with abronchoscope while she was awake. Her trachea wasextubated at the end of the procedure, and the earlypostoperative course was uneventful. She had a cardiacarrest 10 h postoperatively and was intubated with di-rect laryngoscopy, but could not be resuscitated. Atautopsy, she was confirmed to have atlantoaxial instabil-ity (recognized preoperatively), and there was micro-scopic evidence of focal areas of ischemia and infarctionin the upper cord and lower medulla oblongata. Theauthors attributed the damage and the cause of death tothe resuscitation intubation, although she was alreadydead at the time of that intubation. Further, the patho-logic finding of infarction suggests that the injury likelytook place remotely from the time of death, perhapsduring the surgery, and may well have been a position-ing injury that was progressive.
The case that MacLeod and Calder cited as being mostlikely (four of five features present) a laryngoscopy-in-duced cord injury was that reported by Hastings andKelley.124 They reported of the case of a 65-yr-old manadmitted to hospital after a motor vehicle accident. De-spite reporting neck pain and exhibiting left arm weak-ness, CSI was not ruled out, nor was spinal immobiliza-tion enforced. His condition deteriorated some hourssubsequently, and after repeated, failed attempts at di-rect laryngoscopy without spinal immobilization, he un-derwent cricothyrotomy; 3 h later, he was found to beparaplegic. A review of the original cervical spine radio-graph demonstrated a widened disc space at C6–C7suggesting disruption of the anterior longitudinal liga-ment. CT scans confirmed that finding as well as notingcongenital spinal stenosis from C3 to C7, osteophytefragments in the spinal canal at C6, a fracture of theC6–C7 facet joint, a C7 laminar fracture, and a C6 spi-nous fracture. The constellation of symptoms could notbe attributed to a single cord lesion, and he was diag-nosed as having both an anterior cord syndrome affect-ing the T11 and subjacent levels and a central cordsyndrome at the cervical level. No MRI study was per-formed to detail the nature of the cord injuries, and it ispossible that his neurologic deterioration was inevitableand perhaps the cause of his respiratory insufficiency.However, at no time from admission until the occur-rence of his neurologic deterioration was his spine im-mobilized.
Two additional cases of intubation-associated neuro-logic injury not reviewed by MacLeod and Calder havebeen reported.125,126 Liang et al.125 reported a case sim-ilar to that of Hastings and Kelley of a man involved in amotor vehicle accident with a suspected CSI who wasleft quadriplegic after airway management. Despite theevidence of a CSI (nature of injury not reported) and aneurologic deficit (limited movement in both upper ex-tremities), repeated and failed attempts were made atboth nasal (five attempts) and then oral intubation witha direct laryngoscopy (five attempts). The last threeattempts at oral intubation were made after removal ofthe cervical collar, but MILI was not used. The tracheawas eventually intubated via a surgical airway. There isno discussion of the care afforded after intubation withrespect to the spine injury or any description of subse-quent imaging studies performed. The next day, it wasrecognized that he was quadriplegic. Powell andHeath126 reported the case of 59-yr-old man found col-lapsed and unconscious. Paramedics found him to beapneic, cyanosed, and unresponsive and attempted butfailed to intubate his trachea. Tracheal intubation wasperformed in the emergency room, and then the spinewas immobilized. A lateral cervical radiograph revealedan odontoid peg fracture, and the patient’s conditionwas consistent with a complete cord injury at the C2level. Although it was inferred that the cord injury mayhave been caused or aggravated by the airway manage-ment, it was acknowledged by the authors that the injurywas probably sustained at the time of the accident.
A number of reports detailing a relation between air-way management and the occurrence of secondary neu-rologic injury in CSI patients have been reviewed. Thesereports consist typically of observations made in a singlepatient or in a small series of patients admitted to a singleinstitution. Although the deterioration has often beenassociated temporally with airway management, in mostcases, it is impossible to determine with certainty thecause of the deterioration because confounding factorsare typically present and acknowledged by the reportingauthors. As well, it is possible in some instances that theassociation between airway management and a worsen-ing neurologic state arises not because of cause andeffect but because the airway intervention was madenecessary by a progressively deteriorating clinical condi-tion such as an ascending myelopathy. It may well bethat the magnitude of the deterioration does not be-comes apparent until after clinical interventions, atwhich time they, themselves, become suspect culprits.As unsatisfactory as it might be, determining the truenature of the association (causal or otherwise) betweenairway management and adverse neurologic outcomes inCSI patients is not possible at this time, given the currentstate of our knowledge.
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The Use of the Flexible Fiberoptic Bronchoscopein Cervical Spine Injury. There is considerable enthu-siasm, particularly among anesthesiologists, for the useof the fiberoptic bronchoscope in patients at risk forcervical spine disease. The advantages are its potentialfor use in awake patients, the minimal cervical move-ment required to achieve tracheal intubation, and theability to perform postintubation neurologic assessmentsin cooperative and cognitively intact patients. However,there have been have been relatively few reports recog-nized in the literature regarding the use of the broncho-scope in the emergency management of the airway aftertrauma.127 The overall success rate for intubation usingthe bronchoscope in the trauma setting has been cited at83.3% (95% CI, 72–94.6%).127 There is a report detailingthe successful use of the bronchoscope to facilitateawake intubation in 327 consecutive patients presentingfor elective cervical spine surgery; the bulk of the pro-cedures were surgeries for cervical disc prolapse, andthere were no patients with traumatic injuries includedin the review.128 Although the procedure was well tol-erated by the majority of the patients, 38 (12%) devel-oped low oxygen saturations; in this group, the meanoxygen saturation measured by pulse oximetry was 84 �4% (range, 72–89%). The potential for desaturation dur-ing bronchoscope-facilitated intubation seems to be asgreat or greater in CSI patients compromised by trau-matic injury as in these elective surgical patients; theincidence and magnitude of hypoxemia in a series ofCSI-trauma patients undergoing such management hasnot been reported.
There are no published data in the English literaturethat would indicate that the cited advantages of thefiberoptic bronchoscope translate into improved out-comes among CSI patients compared with other intuba-tion techniques. As well, Ezri et al.106 reported, after asurvey of American anesthesiologists, that more than40% of respondents acknowledged that they were notcomfortable using a bronchoscope for airway manage-ment. McGuire and El-Beheiry129 reported two cases ofcomplete airway obstruction during elective awakebronchoscope-assisted intubation in patients with unsta-ble cervical spine fractures; both patients were salvagedwith emergency surgical airways. In patients with braininjury, a common concurrent injury to CSI, the use of thebronchoscope is associated with significant increases inICP that are not prevented by the administration ofmorphine, midazolam, and nebulized lidocaine.130
Comparing Rigid and Flexible Fiberoptic Endo-scopes in At-risk Populations. Cohn and Zornow131
compared the fiberoptic bronchoscope and the Bullardlaryngoscope with respect to rapidity of glottic visualiza-tion and intubation in patients requiring cervical immo-bility during tracheal intubation. Seventeen adult pa-tients scheduled to undergo neurosurgical correction ofa cervical spine problem were studied. Each patient was
considered at risk for neurologic injury during trachealintubation based on a request for awake fiberoptic tra-cheal intubation by the neurosurgical team, or radicularsymptoms initiated or exacerbated by neck extension.Most showed evidence of spinal canal impingement on apreoperative MRI. Patients were allocated randomly toone of two study groups for tracheal intubation with theBullard (n � 8) or the fiberoptic bronchoscope (n � 9);before intubation, glottic visualization was performedusing the alternative technique. All intubations wereperformed with the neck in a comfortable position forthe patient and with any preexisting immobilization de-vice (e.g., collar, traction) in place. Glottic visualizationwas uniformly successful on the first attempt in bothgroups. Tracheal intubation was also uniformly success-ful, although one intubation in the bronchoscope grouptook 183 s because of difficulty passing the endotrachealtube through the glottis after an easy laryngoscopy. Nonew neurologic deficits were observed after trachealintubation in either group.
Practice Options for Airway Management afterCervical Spine Injury. There is discordant opinionexpressed in the literature regarding the optimal meansof securing the airway in patients with CSI. Enthusiasmis expressed by some neuroanesthesia experts for theexclusive use of the fiberoptic bronchoscope to facilitatetracheal intubation in spine-injured patients.132 Thereare a number of theoretical factors that would supportsuch a choice. The head and neck may be left in a neutralposition, and little spinal movement is required toachieve laryngeal visualization and tracheal intubation.The patient’s protective reflexes are largely left intact,and the potential for deleterious movements and posi-tioning is perhaps reduced. A neurologic assessment canbe made after intubation to ensure that there has beenno change in the patient’s status, although the accuracyof this evaluation may be diminished by sedation. Finally,the patient could be positioned awake to increase thelikelihood that potentially injurious position could beavoided. These considerations support the use of thetracheal intubation facilitated by a fiberoptic broncho-scope and performed by an experienced care provider asa practice option in the management of the airway inspine-injured patients. Survey evidence also supports theconclusion that many anesthesiologists are of the opin-ion that it is the preferred option, especially in electivescenarios. This preference persists even among physi-cians who acknowledge limited skills with the device.However, there are no data to suggest that better neu-rologic outcomes are achieved with its use. In fact, theapplication of a technique by practitioners not expert inits use may carry risk. Failed awake intubation has beenidentified as a cause of morbidity and mortality in thelatest analysis of difficult airway claims by the AmericanSociety of Anesthesiologists’ Closed Claims Project.133
The use of a direct laryngoscope after induction of
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anesthesia is also deemed an acceptable practice optionby the American College of Surgeons as outlined in thestudent manual of the Advanced Trauma Life SupportProgram for Doctors; by experts in trauma, anesthesiol-ogy, and neurosurgery; and by the Eastern Associationfor the Surgery of Trauma.3,107,109,119,127,134–143 Theprinciple advantages of the direct laryngoscope are thatanesthesiologists are very experienced in its use and thatit is a highly effective tool; many anesthesiologists do notconsider themselves similarly skilled with other practiceoptions.106 Direct laryngoscopy can also be performedmore quickly than some, but not all, alternative tech-niques, and it does not require time to obtain and set upspecialized equipment. However, it has the potential tocause greater spinal movement than indirect techniques.In addition, if laryngoscopy is performed after the induc-tion of general anesthesia, the potential for difficult ven-tilation, a failed intubation, and a cannot-intubate, can-not-ventilate scenario cannot be excluded. Finally, ifthere is underlying severe, chronic cervical spinal pa-thology, difficult laryngoscopy should be anticipated be-cause it is more likely to occur.3 This is particularly trueif the upper cervical spine is severely impacted by thedisease process.
The use of the direct laryngoscope is a practice optionaccepted by expert practitioners; its use is commonlyencouraged in urgent or emergent situations. Otherpractice options, such as light wands, rigid fiberopticlaryngoscopes, and laryngeal mask airways, are alsodeemed appropriate. There is no published evidencethat would indicate that one intubation option is supe-rior to others with respect to outcomes in general and, inparticular, with respect to neurologic outcomes. Anycomparative study that could or would support a singlepractice option would have to be very large to be per-suasive.
Summary of the Literature
There is an incidence of CSI approximating 2% amongvictims of blunt trauma, and this incidence is trebled ifthe patient presents unconscious or with a GCS scorereduced to 8 or below. A finding of a focal neurologicdeficit also significantly increases the likelihood of acervical injury. The need to evaluate all at-risk patientswith a complete and technically adequate imaging seriesseems to be accepted as the standard of care, althoughthere is debate as to what constitutes the at-risk popula-tion and an acceptable imaging series. A three-viewspine series (lateral, antero-posterior, and odontoidviews) supplemented by computerized tomographic im-aging through areas that are difficult to visualize or sus-picious is effective in ruling out injury in both coopera-tive and noncooperative patients. MRI studies may beuseful in patients with neurologic symptoms but nega-
tive radiography and CT imaging; they seem to add littleto the evaluation of patients with persistent pain but anormal neurologic examination and negative imaging. Aswell, although MRI may identify CSI not captured by CT,these injuries are not usually unstable. Failure to diag-nose the injury at time of presentation is associated witha worse neurologic outcome; it occurs most commonlyas a result of either failure to appropriately image thespine or misinterpretation of appropriate imaging.
Immobilization of the spine in at-risk patients at thetime of first system contact and maintenance of theimmobilization until the spine is cleared is accepted byexpert consensus as the standard of care. However,there is some debate about the need for immobilizationin patients at low risk. Prolonged spinal immobilizationis costly in terms of system resources and not withoutrisk to the patient. Strategies that permit efficient andprudent spine clearance are available and their use isencouraged so as to reduce costs, conserve resources,and, most importantly, to prevent harm.
Secondary neurologic injury occurs after CSI and maybe associated with clinical care interventions. There isnow recognized a syndrome of progressive, ascendingmyelopathy that occurs in some patients and that ischaracterized by a widely distributed cord injury. It mayoccur after a period of relative clinical stability and in theabsence of both mechanical instability and canal com-promise at the spinal levels to which the injury hasascended. The use of MRI (especially T2-weighted stud-ies) has been instrumental in documenting both theoccurrence and the nature of this injury. It may alsopresent at a time when clinical interventions are ongoingto treat the original traumatic injuries. Although therehas been a past tendency to attribute many secondaryinjuries to clinical interventions, especially in a medical–legal context, critical examination of these cases, sup-plemented with MRI evaluations, may reveal that some,and perhaps most, are an inevitable consequence of theprimary injury.
The routine use of some form of immobilization duringairway maneuvers in at-risk patients is accepted as thestandard of care. All airway maneuvers will result insome degree of neck movement, both in general andspecifically at the sites of injury. The amounts of move-ment are small and may be restrained by in-line immo-bilization, but they are not eliminated. The available dataand the accumulated clinical experience support a con-clusion at the current time that these movements areunlikely to result in neurologic injury provided that rea-sonable care is taken during airway interventions. How-ever, a study of sufficient size to validate this statementhas not been performed.
The most appropriate technique for performing tra-cheal intubation in patients with cervical spine injurycontinues to be debated. There are no clinical outcomedata that suggest better neurologic outcomes with any
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particular technique, and it is acknowledged that a verylarge study would be required to furnish such data.Surveys indicate that the majority of American anesthe-siologists would prefer to use a fiberoptic bronchoscopeto intubate the trachea of at-risk patients and to do sowith the patient awake. A significant proportion of thosesharing this preference acknowledge limited skills withthe bronchoscope. As well, failed awake intubation hasbeen associated with morbidity and mortality in recentanalyses of closed claims. Surprisingly, there are no re-ports of series of CSI patients treated in this fashion, andso it is not possible to comment on the outcomes of thisstrategy.
There are a large number of reports that confirm thatrapid sequence induction of general anesthesia followedby direct laryngoscopy and tracheal intubation is widelyperformed in patients at risk for and with confirmed CSI;the resulting neurologic outcomes compare favorably tosimilar patient populations undergoing awake trachealintubation and to patients who do not require airwayintervention after traumatic injury. This technique doesnot seem to be associated with a higher incidence ofsecondary injury when compared with any other tech-nique of intubation. Unfortunately, these reports arelimited by small sample size and their retrospective na-ture. The current evidence and opinion expressed in theliterature support the use of a range of practice optionsin the management of the airway in CSI patients.
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124. Hastings RH, Kelley SD: Neurologic deterioration associated with airwaymanagement in a cervical spine–injured patient. ANESTHESIOLOGY 1993; 78:580–3
125. Liang BA, Cheng MA, Tempelhoff R: Efforts at intubation: Cervical injuryin an emergency circumstance? J Clin Anesth 1999; 11:349–52
126. Powell RM, Heath KJ: Quadriplegia in a patient with an undiagnosedodontoid peg fracture: The importance of cervical spine immobilization inpatients with head injuries. J Roy Army Med Corps 1996; 142:79–81
127. Dunham CM, Barraco RD, Clark DE, Daley BJ, Davis FE III, Gibbs MA,Knuth T, Letarte PB, Luchetter FA, Omert L, Weirter LJ, Wiles CE III , EASTPractice Management Guidelines Work Group: Guidelines for emergency tra-cheal intubation immediately after traumatic injury. J Trauma 2003; 55:162–79
128. Fuchs G, Schwarz G, Baumgartner A, Kaltenbock F, Voit-Augustin H,Planinz W: Fiberoptic intubation in 327 patients with lesions of the cervicalspine. J Neurosurg Anesth 1999; 11:11–6
130. Kerwin AJ, Croce MA, Timmons SD, Maxwell RA, Malhotra AK, FabianTC: Effects of fiberoptic bronchoscopy on intracranial pressure in patients withbrain injury: A prospective clinical study. J Trauma 2000; 48:878–83
131. Cohn AI, Zornow MH: Awake endotracheal intubation in patients withcervical spine disease: A comparison of the Bullard laryngoscope and the fiber-optic bronchoscope. Anesth Analg 1995; 81:1283–6
132. Chestnut RM: Management of brain and spine injuries. Crit Care Clin2004; 20:25–55
133. Peterson GN, Domino KB, Caplan RA, Posner KL, Lee LA, Cheney FW:Management of the difficult airway: A closed claims analysis. ANESTHESIOLOGY 2005;103:33–9
134. Urdanetta F, Layon AJL: Respiratory complications in patients with trau-matic cervical spine injuries: Case report and review of the literature. J ClinAnesth 2003; 15:398–405
135. Richards CF, Mayberry JC: Initial management of the trauma patient. CritCare Clin 2004; 20:1–11
136. Advanced Trauma Life Support for Physicians Student Manual, 6th edi-tion. Chicago, American College of Surgeons, 1997
137. Ball PA: Critical care of spinal cord injury. Spine 2001; 26 (suppl):S27–S30
138. Ford P, Nolan J: Cervical spine injury and airway management. Curr OpinAnaesth 2000; 15:193–201
139. Ivy ME, Cohn SM: Addressing the myths of cervical spine injury manage-ment. Am J Emerg Med 1997; 15:591–5
140. Abrams KJ, Grande CM: Airway management of the trauma patient withcervical spine injury. Curr Opin Anaesth 1994; 7:184–90
cooperation among the different disciplines involved.
References and recommended readingPapers of particular interest, published within the annual period of review, havebeen highlighted as:� of special interest�� of outstanding interest
1 Kotob F, Twersky RS. Anesthesia outside the operating room: general over-view and monitoring standards. Int Anesthesiol Clin 2003; 41:1–15.
2 Alspach D, Falleroni M. Monitoring patients during procedures conductedoutside the operating room. Int Anesthesiol Clin 2004; 42:95–111.
3 Castagnini HE, van Eijs F, Salevsky FC, Nathanson MH. Sevoflurane forinterventional neuroradiology procedures is associated with more rapid earlyrecovery than propofol. Can J Anaesth 2004; 51:486–491.
�Holmstrom A, Akeson J. Desflurane increases intracranial pressure more andsevoflurane less than isoflurane in pigs subjected to intracranial hypertension.J Neurosurg Anesthesiol 2004; 16:136–143.
One of the many papers describing the effect of volatile agents on cerebralhemodynamics in the year reviewed.
6 Sponheim S, Skraastad Ø, Helseth E, et al. Effects of 0.5 and 1.0 MACisoflurane, sevoflurane and desflurane on intracranial and cerebral perfusionpressures in children. Acta Anaesthesiol Scand 2003; 47:932–938.
7 Hall JE, Uhrich TD, Barney JA, et al. Sedative, amnestic, and analgesicproperties of small-dose dexmedetomidine infusions. Anesth Analg 2000;90:699–705.
8 Bekker AY, Kaufman B, Samir H, Doyle W. The use of dexmedetomidineinfusion for awake craniotomy. Anesth Analg 2001; 92:1251–1253.
9 Ard J, Doyle W, Bekker A. Awake craniotomy with dexmedetomidine inpediatric patients. J Neurosurg Anesthesiol 2003; 15:263–266.
10 Bustillo MA, Lazar RM, Finck AD, et al.Dexmedetomidine may impair cognitivetesting during endovascular embolization of cerebral arteriovenous malforma-tions: a retrospective case report series. J Neurosurg Anesthesiol 2002;14:209–212.
11 Soeda A, Sakai N, Sakai H, et al. Thromboembolic events associated withGuglielmi detachable coil embolization of asymptomatic cerebral aneurysms:evaluation of 66 consecutive cases with use of diffusion-weighted MRimaging. Am J Neuroradiol 2003; 24:127–132.
12 Fiorella D, Albuquerque FC, Han P, McDougall CG. Strategies for themanagement of intraprocedural thromboembolic complications with abcix-imab (ReoPro). Neurosurgery 2004; 54:1089–1097.
13 Kubalek R, Berlis A, Schwab M, et al. Activated clotting time or activatedpartial thromboplastin time as the method of choice for patients undergoingneuroradiological intervention. Neuroradiology 2003; 45:325–327.
14 Cetta F, Graham LC, Wrona LL, et al. Argatroban use during pediatricinterventional cardiac catheterization. Catheter Cardiovasc Intervent 2004;61:147–149.
15 Doerfler A, Wanke I, Egelhof T, et al. Aneurysmal rupture during embolizationwith Guglielmi detachable coils: causes, management, and outcome. Am JNeuroradiol 2001; 22:1825–1832.
16 Hahnel S, Schellinger PD, Gutschalk A, et al. Local intra-arterial fibrinolysis ofthromboemboli occurring during neuroendovascular procedures with recom-binant tissue plasminogen activator. Stroke 2003; 34:1723–1728.
17 Scheufler KM, Zentner J. Total intravenous anesthesia for intraoperativemonitoring of the motor pathways: an integral view combining clinical andexperimental data. J Neurosurg 2002; 96:571–579.
18 Niimi Y, Sala F, Deletis V, et al. Neurophysiologic monitoring and pharma-cologic provocative testing for embolization of spinal cord arteriovenousmalformations. Am J Neuroradiol 2004; 25:1131–1138.
19 Liu AY, Lopez JR, Do HM, et al. Neurophysiological monitoring in theendovascular therapy of aneurysms. Am J Neuroradiol 2003; 24:1520–1527.
20 Molyneux A, Kerr R, Stratton I, et al., the International Subarachnoid AneurysmTrial (ISAT) Collaborative Group. International Subarachnoid Aneurysm Trial(ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patientswith ruptured intracranial aneurysms: a randomised trial. Lancet 2002;360:1267–1274.
21 Kwon BJ, Han MH, Oh CW, et al. Procedure-related haemorrhage in embo-lisation of intracranial aneurysms with Guglielmi detachable coils. Neurora-diology 2003; 45:562–569.
22 Hoh BL, Topcuoglu MA, Singhal AB, et al. Effect of clipping, craniotomy, orintravascular coiling on cerebral vasospasm and patient outcome after aneur-ysmal subarachnoid hemorrhage. Neurosurgery 2004; 55:779–786.
23 Biondi A, Ricciardi GK, Puybasset L, et al. Intra-arterial nimodipine for thetreatment of symptomatic cerebral vasospasm after aneurysmal subarachnoidhemorrhage: preliminary results. Am J Neuroradiol 2004; 25:1067–1076.
24 Badjatia N, Topcuoglu MA, Pryor JC, et al. Preliminary experience with intra-arterial nicardipine as a treatment for cerebral vasospasm. Am J Neuroradiol2004; 25:819–826.
26 Soderman M, Andersson T, Karlsson B, et al. Management of patients withbrain arteriovenous malformations. Eur J Radiol 2003; 46:195–205.
27 Taylor CL, Dutton K, Rappard G, et al.Complications of preoperative emboliza-tionofcerebralarteriovenousmalformations. JNeurosurg2004;100:810–812.
28 Hartmann A, Pile-Spellman J, Stapf C, et al. Risk of endovascular treatment ofbrain arteriovenous malformations. Stroke 2002; 33:1816–1820.
29
��Pelz D, Andersson T, Lylyk P, et al. Stroke review. Advances in interventionalneuroradiology 2004. Stroke 2005; 36:211–214.
This is an excellent review of the recent advances in the field of interventionalneuroradiology.
30 Yadav JS,WholeyMH, Kuntz RE, et al. Protected carotid-artery stenting versusendarterectomy in high-risk patients. N Engl J Med 2004; 351:1493–1501.
31 MlekuschW, Schillinger M, Sabeti S, et al.Hypotension and bradycardia afterelective carotid stenting: frequency and risk factors. J Endovasc Ther 2003;10:851–859.
32 Howell M, Krajcer Z, Dougherty K, et al. Correlation of periprocedural systolicblood pressure changes with neurological events in high-risk carotid stentpatients. J Endovasc Ther 2002; 9:810–816.
33
�Keles GE. Intracranial neuronavigation with intraoperative magnetic reso-nance imaging. Curr Opin Neurol 2004; 17:497–500.
This is a comprehensive review of fast changing trends in intraoperative MRI.
34 Schmitz B, Nimsky C, Wendel G, et al. Anesthesia during high-field intrao-perative magnetic resonance imaging experience with 80 consecutive cases.J Neurosurg Anesthesiol 2003; 15:255–262.
35 Gooden CK, Dilos B. Anesthesia for magnetic resonance imaging. IntAnesthesiol Clin 2003; 41:29–37.
36 Birkholz T, Schmid M, Nimsky C, et al. ECG artifacts during intra-operative high-field MRI scanning. J Neurosurg Anesthesiol 2004; 16:271–276.
Anesthesia for neuroradiology See and Manninen 441
Spinal cord injury is a devastating event, often
resulting in long-term disability. The injury may
occur in isolation or in conjunction with other
injuries. A thorough understanding of the patho-
physiological processes involved aids manage-
ment. This article aims to provide advice on
understanding and managing some of the prob-
lems encountered by the anaesthetist.
Aetiology and incidenceThere are approximately 1000 new cases of
spinal cord injury per year in the UK, predomi-
nantly young males. Over 50% of spinal cord
injuries occur as a result of road traffic accidents,
the other major causes are sports injuries, assaults
and industrial accidents.
ClassificationLevel
Spinal cord injury may occur at any level (Table
1) but certain areas, particularly the lower cervi-
cal spine and the thoracolumbar junction, are
structurally more vulnerable. The level of the
injury determines the extent of the neurological
deficit with higher cervical lesions having the
most serious consequences.
Stability
Anatomically, the vertebral column is described
as being composed of anterior, middle and poste-
rior columns. These columns include bony and
ligamentous structures which are both important
for maintaining stability. An isolated anterior or
posterior column injury will be stable but injuries
involving more than one column are not.
In the cervical spine, C1–C2 and C5–C7 cervi-
cal vertebrae are the most vulnerable to injury.
These injuries are often unstable requiring immo-
bilisation to prevent further damage. Although
injuries of the cervical vertebral column are more
common, the spinal canal is relatively spacious at
this level and cord injury is not inevitable.
However, the mid-thoracic region is much less
mobile and the small circular vertebral canal
leaves little space around the spinal cord making
cord compression more likely. The same princi-
ple of immobilisation should be adhered to for
thoracic and lumbar spine injuries, although, in
general, these injuries are more stable.
Instability allows actual or potential abnormal
movement of one vertebral segment upon anoth-
er, thereby compromising neural structures.
Defining the stability of a vertebral column injury
is important, as it may influence the anaesthetic
and surgical management. All spinal injuries
should be treated as potentially unstable until
proven otherwise.
Neurological deficit
In general, a spinal cord injury can be described
as being complete or incomplete. An incomplete
spinal cord injury is defined by partial preserva-
tion of neurological function more than one level
below the level of spinal cord injury. Sacral spar-
ing and preserved sensory or motor function are
examples of incomplete lesions. There are sever-
al recognised patterns of incomplete lesions (e.g.
anterior cord syndrome, Brown-Sequard syn-
drome, cauda equina syndrome). If a lesion is
complete there is absence of motor and sensory
function below the level of the lesion. Complete
transection occurs in approximately 50% of
spinal cord injuries.
Anaesthesia and acute spinal cordinjury
Philippa Veale BSc MBBS FRCAJoanne Lamb MBBS FRCA
139British Journal of Anaesthesia | CEPD Reviews | Volume 2 Number 5 2002
Lu J,Ashwell KWS,Waite P.Advances in secondary spinal cord injury: role ofapoptosis. Spine 2000; 25: 1859–66
Mcleod A, Calder I. Spinal cord injury and direct laryngoscopy – the legendlives on. Br J Anaesth 2000; 84: 705–9
Short DJ, El Masry WS, Jones PW. High dose methylprednisolone in the man-agement of acute spinal cord injury – a systematic review from a clinicalperspective. Spinal Cord 2000; 38: 273–86
See multiple choice questions 94–96.
Anaesthesia and acute spinal cord injury
British Journal of Anaesthesia | CEPD Reviews | Volume 2 Number 5 2002 143
Anaesthesia for spinal surgery in adults
D. A. Raw1*, J. K. Beattie2 and J. M. Hunter1
1University Department Anaesthesia, University Clinical Department, The Duncan Building, Daulby Street,Liverpool, L69 3GA, UK. 2Royal Liverpool and Broadgreen University Hospitals NHS Trust, Prescot Road,
When assessing patients before spinal surgery, particular
care should be given to the respiratory, cardiovascular, and
neurological systems; all may be affected by the pathology
for which the spinal surgery is proposed.
Airway assessment
The potential for dif®culty in airway management should
always be considered, particularly in those patients pre-
senting for surgery of the upper thoracic or cervical spine. A
careful assessment should be made for previous dif®culty in
intubation, restriction of neck movement, and the stability
or otherwise of the cervical spine. Stability is de®ned as the
ability of the spine, under physiological loads, to resist
displacement, which causes neurological injury. It is
essential to discuss preoperatively the stability of the
spine with the surgeon. The cervical spine may be assessed
clinically (presence of pain or neurological de®cits), and
Fig 1 (A) Thoracolumbar scoliosis and measurement of the Cobb angle. A perpendicular line is drawn from the end plate of the most caudal vertebrae
involved, whose inferior end plate tilts maximally to the concavity of the curve. A second perpendicular line is drawn from the end plate of the most
cephalad vertebrae, whose superior end plate tilts maximally to the concavity of the curve. The curve value is the number of degrees formed by the
angle of intersection of these two lines. (B) Thoracolumbar scoliosis after surgery, showing long rods and pedicle screws. (C) Dislocation of the 5th
and 6th cervical vertebrae after trauma; (D) same patient's MRI scan, and (E) after surgery to stabilize the cervical spine. SC, spinal cord; C6, sixth
cervical vertebrae.
Raw et al.
888
radiographically (lateral or ¯exion/extension plain ®lms,
computer aided tomography, and magnetic resonance
imaging). The stability of the cervical spine is dependent
on ligamental and vertebral elements. Damage to these
elements may not be detectable by plain x-rays alone. The
adult cervical spine below C2 is unstable or on the brink of
instability when one of the following conditions are met: (i)
all the anterior or all the posterior elements are destroyed;
(ii) there is >3.5 mm horizontal displacement of one
vertebra in relation to an adjacent one on a lateral x-ray; or
(iii) there is more than 11° of rotation of one vertebra to an
adjacent one.119 Above the level of C2, examples of
unstable injuries include: disruption of the transverse
ligament of the atlas (a distance of greater than 3 mm in
adults between the posterior corpus of the anterior arch of
C1 and the anterior border of the odontoid process, when
measured on a lateral plain x-ray ®lm, is diagnostic); and a
Jefferson burst fracture of the atlas following axial loading,
which causes atlantoaxial instability. Disruption of the
tectorial and alar ligaments and some occipital condylar
fractures also cause atlanto-occipital instability.
Some inherited disorders such as DMD may lead to
glossal hypertrophy, and previous radiotherapy to tumours
of the head and neck can cause dif®culty in direct
laryngoscopy. A decision must be made, whether to intubate
the patient awake or asleep.
Respiratory system
Patients presenting for spinal surgery frequently have
impaired respiratory function. Those who have sustained
cervical or high thoracic trauma or who have multiple
injuries may be arti®cially ventilated preoperatively. Others
have recurrent chest infections.
Preoperatively, respiratory function should be assessed
by a thorough history, focusing on functional impairment,
physical examination, and appropriate investigations
(Table 2). Scoliosis causes a restrictive pulmonary de®cit,
with reduced vital capacity and reduced total lung capacity
(TLC). The residual volume is unchanged. The severity of
functional impairment is related to the angle of the scoliosis,
the number of vertebrae involved, a cephalad location of the
curve, and a loss of the normal thoracic kyphosis.53 The
extent of functional impairment cannot, therefore, be
directly inferred from the angle of scoliosis alone. The
most common blood-gas abnormality is a reduced arterial
oxygen tension with a normal arterial carbon dioxide
tension, as a result of the mismatch between ventilation
and perfusion in hypoventilated lung units.48 Respiratory
function should be optimized by treating any reversible
cause of pulmonary dysfunction, including infection, with
physiotherapy and nebulized bronchodilators as indicated.
There is controversy over whether surgery for idiopathic
scoliosis improves,55 59 or worsens14 63 pulmonary function.
However, the type of surgery proposed may have a
signi®cant in¯uence upon postoperative pulmonary func-
tion, and may explain the contradictory ®ndings in studies of
non-homogenous groups of patients. Surgery involving the
thorax (anterior approach, combined approach, or rib
resection) was associated with an initial decline in forced
vital capacity (FVC, 19% of baseline values), forced
expiratory volume in 1 s (FEV1, 13%), and TLC (11%) at
3 months.117 This was followed by subsequent improvement
to preoperative baseline values at 2 yr postoperatively.
Surgery involving an exclusively posterior approach, how-
ever, was associated with an improvement in pulmonary
function tests by 3 months (although not reaching statistical
signi®cance); and an improvement that was statistically
signi®cant at 2-yr follow-up: FVC (14% increase from
baseline), FEV1 (14%), TLC (5%).
Older studies have reported that if preoperative vital
capacity is less than 30±35% of predicted, postoperative
ventilation is likely to be required.45 A history of depend-
ence on continuous nasal positive airways pressure at night
is also a sign of severe functional impairment and of
reduced physiological reserve. These ®ndings should
prompt serious consideration as to whether surgery repre-
Table 2 Suggested preoperative investigations before major spinal surgery
Minimum investigations Optional investigations
Airway Cervical spine lateral x-rays with
¯exion/extension views (for patients with
rheumatoid arthritis)
CT scan
Respiratory
system
Plain chest radiograph Pulmonary function tests (bronchodilator
reversibility)
Arterial blood gas analysis Pulmonary diffusion capacity
and vibration senses. The primary sensory neurone, with its cell body in
the dorsal root ganglion of the spinal cord, sends ®bres in the dorsal
aspect of the ipsilateral spinal cord to the medulla oblongata where they
synapse. The second order sensory neurone projects ®bres to the
thalamus after crossing the midline. After synapsing with the tertiary
sensory neurone in the thalamus, ®bres are projected to the primary
somatosensory cortex. This pathway must be functionally intact in order
for SSEPs to be recorded.
Anaesthesia for spinal surgery in adults
895
and the response to this command noted. If the patient can
move their legs, anaesthesia is deepened and surgery
recommenced. If the patient is unable to move their legs,
corrective measures are instituted immediately.
A wake-up test should be as easy and as rapid to institute
as possible. This necessitates an anaesthetic technique that
is reliable, but which may be quickly antagonized as many
times as the surgeon requires. Wakening should also be
smooth to minimize the risk of tracheal extubation.
Furthermore, the patient should not experience any pain
during the test and have no subsequent recall of intraopera-
tive events.
A number of different anaesthetic techniques for the
Stagnara wake-up test have been advocated, including
volatile-based anaesthesia. A Danish group,58 in a
randomized trial involving 40 patients, described the
successful use of a midazolam-based anaesthetic,
antagonized by ¯umazenil at the time of the wake-up
test, compared with a propofol infusion technique. The
midazolam/¯umazenil group was found to have a shorter
intraoperative wake-up time (mean 2.9 vs 16 min in the
propofol group), shorter postoperative wake-up times
(1.8 vs 13.9 min, respectively), and a better quality of
intraoperative arousal. Five patients in the midazolam
group, however, became resedated in the recovery room
and required further doses of ¯umazenil. Remifentanil is
a potent m-receptor agonist. Its ester linkage renders it
susceptible to hydrolysis by tissue esterases, producing a
half-life at its site of action of less than 10 min. It
therefore has a pharmacokinetic pro®le suitable for use
when a wake-up test must be performed. Preliminary
reports using remifentanil suggest a delay between the
surgeon's request for a wake-up test and adequate
conditions for neurological assessment of only 5 min.94
Despite the use of such techniques, the test has a
number of disadvantages. First, it requires the patient's
co-operation. Secondly, it poses risks to the patient of
moving on or falling from the operating table and of
tracheal extubation, often in the prone position. Thirdly,
it requires not inconsiderable operator skill on the part
of the anaesthetist. Fourthly, it is a valid measure of
motor function at only the precise moment in time the
test is instituted; it does not allow continuous IOM of
motor pathways. The onset of a change in electro-
physiological recordings and permanent neurological
injury can occur more than 20 min after the last
corrective force is applied to the spine.80 It is, therefore,
conceivable that a wake-up test could be normal after
the last corrective manoeuvre has been applied but
before the onset of the resultant neurological de®cit.
The place of the Stagnara wake-up test in spinal cord
monitoring during spinal surgery should therefore be
con®ned to situations in which electrophysiological moni-
toring techniques are not available, fail, or produce
equivocal results.
Somatosensory evoked potentials
SSEPs are elicited by stimulating electrically a mixed
peripheral nerve (usually the posterior tibial, peroneal, or
sural nerves), and recording the response from electrodes at
distant sites cephalad to the level at which surgery is
performed (Fig. 4). Guidelines on stimulation and recording
methods have been published.4 81 Typically, the stimulus is
applied to the peripheral nerve on the left and the right limb
alternately as a square wave for 0.1±0.3 ms, at a rate of 3±
7 Hz. The intensity of the stimulus varies depending upon
the electrodes and quality of skin contact, but is in the 25±40
mA range. Recording electrodes are placed in the cervical
region over the spinous processes or over the somatosensory
cortex on the scalp, or are sited during surgery in the
epidural space. Baseline data are obtained after skin
incision. This allows a stable plane of anaesthesia to be
established during baseline recordings as anaesthetic agents
affect SSEPs. During surgery, responses are recorded
repeatedly. The functional integrity of the somatosensory
pathways is determined by comparing the amplitude change
and the latency change of the responses obtained during
surgery to baseline values. A reduction in the amplitude of
the response by 50% and an increase in the latency by 10%
are considered by most workers as signi®cant.17 78 The
amplitude response is considered the primary criterion.80
The pathways involved in the recorded responses include
a peripheral nerve, the dorsomedial tracts of the spinal cord
and, depending on the electrode placement, the cerebral
cortex (Fig. 3). The physiological role of these tracts is to
Fig 4 Diagrammatic representation of typical recordings of
somatosensory and MEP. (A) Cortical SSEP recordings after stimulation
of the tibial nerve at the ankle. In accordance with international
convention, positive waves are represented by downward de¯ections and
labelled P1, P2, etc. Negative waves are represented by upward
de¯ections, labelled N1, N2, etc. (B) Cortical MEP recordings. After
magnetic stimulation of the motor cortex, compound muscle action
potentials are recorded from electrodes placed in biceps brachii under
partial neuromuscular block.
Raw et al.
896
subserve sensations of proprioception and light touch. It
must be emphasized that responses are not obtained from
motor tracts, or from the anteriolateral sensory tracts of the
spinal cord (subserving pain and temperature sensation).
This has two important rami®cations for the validity of
SSEPs. First, because of the close proximity of the
dorsomedial sensory tracts with the motor tracts in the
cord, it is assumed that when using SSEPs, any damage to
the motor tracts will be signalled by a change in SSEPs.
This, however, cannot be guaranteed. Secondly, the blood
supply of the corticospinal motor tracts differs from that of
the dorsomedial sensory tracts (Fig. 5). Hypoperfusion in
the territory of the anterior spinal artery may cause
ischaemia in the anteriolateral tracts, but not affect the
dorsomedial tracts. It is, therefore, possible to have normal
recordings from SSEPs throughout surgery, but to have a
paraplegic patient postoperatively.8 29 86 Furthermore, in
patients with pre-existing neurological disorders, reliable
data can be recorded in only 75±85% of patients.82
Effects of anaesthetic agents on SSEPs
Anaesthetic agents can have a signi®cant impact upon
SSEPs.100 Inhalation anaesthetic agents and nitrous oxide
cause a dose-dependent reduction in SSEP amplitude and an
increase in latency.60 Nitrous oxide 60% with iso¯urane 0.5
MAC or en¯urane 0.5 MAC is compatible with effective
SSEP monitoring.89 A recent retrospective study of 442
cases found that 13/60 `false-positives' (abnormal SSEPs
with no neurological de®cit postoperatively) were attribut-
able to an increased concentration of inhalation agent.83
I.V. anaesthetic agents also cause changes to SSEPs but to
a lesser degree than inhalation agents.57 69 The cortical
response appears to be most susceptible to anaesthetic
agents; subcortical, spinal, and peripheral responses are less
affected. A recent study of the use of propofol or midazolam
as a continuous i.v. infusion combined with sufentanil was
associated with maintenance of the amplitude of the cortical
SSEP from baseline values to the end of surgery (propofol
from 1.8 (0.6) to 2.2 (0.3) mV; midazolam from 1.7 (0.5) to
1.6 (0.5) mV). However, propofol and nitrous oxide used in
combination caused a signi®cant reduction in the amplitude
of cortical SSEPs (from 2.0 (0.3) to 0.6 (0.1) mV).61 The
latencies of the responses were not increased in any of the
three groups of patients, but recovery was signi®cantly
delayed in the midazolam group. The authors recommended
a propofol technique for surgery during which cortical
SSEPs are to be recorded.
Opioids such as remifentanil and fentanyl administered
via the i.v. route cause a small reduction in the amplitude
and increase in the latencies of SSEPs.97 Intrathecal opioids
have little effect on SSEPs.30 Neuromuscular blocking
agents, as may be expected, cause no change in SSEPs.101
Fig 5 Diagrammatic representation of a transverse section through the spinal cord at the level of the sixth thoracic vertebra. Motor ®bres subserving
voluntary movement descend the spinal cord as the lateral (crossed) and anterior (uncrossed) corticospinal tracts. Sensory ®bres subserving
discriminatory touch, proprioception and vibration sense ascend the spinal cord as the fasciculus gracilis and fasciculus cuneatus, which together are
termed the dorsomedial columns. The f. gracilis conveys sensory ®bres, which originate from sacral, lumbar and lower thoracic levels. The f. cuneatus
conveys sensory ®bres, which originate from upper thoracic and cervical levels of the spinal cord. The blood supply of the spinal cord is from the
anterior spinal artery (formed by the union of a branch from each vertebral artery), which supplies the anterior two-thirds of the spinal cord including
the corticospinal tracts (unshaded area), and from the posterior spinal arteries (derived from the posterior cerebellar arteries) which supply the
posterior third of the cord including the dorsomedial columns (shaded area). These arteries are reinforced by a variable number of medullary feeding
vessels from the vertebral arteries in the cervical area, and vessels (including the Artery of Adamkiewicz) from the aorta in the thoracic and lumbar
areas.
Anaesthesia for spinal surgery in adults
897
Effect of controlled hypotension on SSEP
MAP during spinal surgery is usually maintained at lower
than pre-induction values in order to minimize blood
3 Allain J, Akehurst RL, Hunter JM. Autologous transfusion, 3 yronÐwhat is new? What has happened? Second ConsensusConference on autologous transfusion held at the Royal Collegeof Physicians, Edinburgh, November 11, 1998. Br J Anaesth 1999;82: 783±4
4 American EEG Society. Guidelines for intraoperative monitoringof sensory-evoked potentials. J Clin Neurophysiol 1987; 4: 397±416
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Brain protection by anesthetic a
gentsInes P. Koerner and Ansgar M. Brambrink
Purpose of review
Patients at risk for perioperative stroke, or those who have
suffered recent cerebral injury, may benefit from
neuroprotective properties of anesthetic agents during
surgery. This manuscript reviews recent clinical and
experimental evidence for neuroprotective effects of
common anesthetic agents, and presents potential
mechanisms involved in anesthetic neuroprotection.
Recent findings
Although strong experimental data support a
neuroprotective potential of several anesthetic agents,
specifically isoflurane and xenon, consistent long-term
protection by either agent has not been demonstrated.
Unfortunately, there is a lack of clinical studies that would
support the use of any one anesthetic agent over the others.
Mechanisms of neuroprotection by anesthetic agents
appear to involve suppression of excitatory
neurotransmission, and potentiation of inhibitory activity,
which may contribute to the reduction of excitotoxic injury.
Activation of intracellular signaling cascades that lead to
altered expression of protective genes may also be involved.
Summary
Solid experimental evidence supports neuroprotection by
anesthetic agents. It is too early to recommend any specific
agent for clinical use as a neuroprotectant, however. Further
study is warranted to unravel relevant mechanisms and to
appreciate the potential clinical relevance of experimental
Curr Opin Anaesthesiol 19:481–486. � 2006 Lippincott Williams & Wilkins.
Department of Anesthesiology and Peri-Operative Medicine, Oregon Health andScience University, Portland, Oregon, USA
Correspondence to Ansgar M. Brambrink, MD, PhD, Department of Anesthesiologyand Peri-Operative Medicine, Oregon Health and Science University, Mail Code:UHS-2, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USATel: +503 494 7641; fax: +503 494 3082; e-mail: [email protected]
Current Opinion in Anaesthesiology 2006, 19:481–486
mine sedation with fentanyl or sufentanil after traumatic
brain injury, however, failed to find effects on functional
outcome after 6 months. Similarly, the addition of
Sþ-ketamine to propofol/remifentanyl anesthesia during
open heart surgery in a clinical study [40] including
106 patients had no effects on neurobehavioral outcome
tests one and 10 weeks after the intervention.
LidocaineNeuroprotection by lidocaine has been attributed to
Naþ-channel blockade. A recent in-vitro study [12] found
that postinsult administration of lidocaine to hippo-
campal slice cultures reduces cell death after OGD.
Another study [41] identified a reduction in infarct size
24 h after focal ischemia in rats that was associated with
reduced early release of cytochrome c release and cas-
pase-3 activation. Protection of hippocampal slices from
OGD was associated with preservation of mitochondrial
integrity [42].
Neurotoxic effects of anestheticsWhile several lines of clear evidence suggest a distinct
neuroprotective potential for various anesthetics, others
have reported neurotoxic effects of the very same drugs.
NMDA-receptor blockade during synaptogenesis in
the immature brain can induce widespread neuronal
degeneration [16], and it was suggested that NMDA-
antagonistic anesthetics cause cerebral damage in neo-
nates [17]. A recent study [43] on cultured rat forebrain
neurons showed evidence of apoptotic cell death and
increased expression of bax and the NR1 NMDA recep-
tor subunit after 48 h of ketamine exposure. Ketamine
also increased death in nonhuman primate forebrain
cultures, which was associated with increased NFkB
translocation [44].
Another recent study [18��] adds new evidence to this
discussion. Sixty minutes of isoflurane anesthesia (1.8%
in oxygen) was found to induce severe hypoglycemia in
10-day-old mice, which was more pronounced after
60 min of hypoxia/ischemia. Isoflurane induced hypogly-
cemia in newborn mice is an interesting observation, as it
may contribute to the neurodegeneration observed in
newborn rodents after long-term (6-h) exposure to
rized reproduction of this article is prohibited.
C
Brain protection by anesthetic agents Koerner and Brambrink 485
volatile anesthetics [17]. These findings emphasize
that complete monitoring and control of physiologic
parameters, although technically challenging, is a neces-
sary prerequisite if clinically meaningful results are to
be obtained from these kinds of experiments [19,20��].
Recent evidence [45] suggests that lidocaine can also
exert neurotoxic effects in animal and human spinal cord.
This appears to be unrelated to Naþ channel blockade,
but the precise mechanism remains unclear.
ConclusionRecommending the use of a specific agent for the care of
patients at risk for perioperative cerebral ischemia, or in
the immediate postinjury period seems premature. Iso-
flurane appears to be the most promising candidate for a
protective agent, but this may be a selection bias, as it is
among the most commonly used and studied agents, both
clinically and experimentally. Potential negative effects
of isoflurane and ketamine in very young and elderly
people require more careful study using appropriate, well
controlled models. At this point, it seems reasonable to
recommend that the anesthesia provider use standard
evaluation to choose the anesthetic regimen that is most
appropriate for the individual patient, judging by clinical
status and co-morbidities. As always, anesthesiologists
should strive to provide the best care possible, which
may include using techniques they are familiar with,
rather than choosing a regimen they are less comfortable
with, based on less-than-convincing experimental data.
References and recommended readingPapers of particular interest, published within the annual period of review, havebeen highlighted as:� of special interest�� of outstanding interest
Additional references related to this topic can also be found in the CurrentWorld Literature section in this issue (p. 579).
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13
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18
��Loepke AW, McCann JC, Kurth CD, McAuliffe JJ. The physiologic effects ofisoflurane anesthesia in neonatal mice. Anesth Analg 2006; 102:75–80.
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An excellent review that weighs the experimental evidence for neurotoxic effects ofanesthetics in immature animals against the clinical evidence for benefits fromanesthesia for painful procedures in very immature infants. The methodologicalshortcomings of several experimental studies are emphasized, and the develop-mental differences between rodents and humans that complicate translation of theexperimental findings are summarized.
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22
�Zhan X, Fahlman CS, Bickler PE. Isoflurane neuroprotection in rat hippo-campal slices decreases with aging: changes in intracellular Ca2þ regulationand N-methyl-D-aspartate receptor-mediated Ca2þ influx. Anesthesiology2006; 104:995–1003.
Isoflurane failed to protect slices from aging brains against oxygen–glucosedeprivation. Slices from aging animals exhibited neuronal death after isofluraneexposure, suggesting that age influences neuronal effects of isoflurane.
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orized reproduction of this article is prohibited.
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486 Neuroanaesthesia
27 Haelewyn B, Yvon A, Hanouz JL, et al. Desflurane affords greater protectionthan halothane against focal cerebral ischaemia in the rat. Br J Anaesth 2003;91:390–396.
28
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30
�Ma D, Hossain M, Pettet GK, et al. Xenon preconditioning reduces braindamage from neonatal asphyxia in rats. J Cereb Blood Flow Metab 2006;26:199–208.
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31
�Ma D, Hossain M, Chow A, et al. Xenon and hypothermia combine to provideneuroprotection from neonatal asphyxia. Ann Neurol 2005; 58:182–193.
Posttreatment with a subanesthetic dose of xenon in combination with hypother-mia improves functional outcome after hypoxic–ischemic injury in neonatal rats,suggesting therapeutic potential for the treatment of perinatal asphyxia (multimodalneuroprotection concept).
32
��Kawaguchi M, Furuya H, Patel PM. Neuroprotective effects of anestheticagents. J Anesth 2005; 19:150–156.
This excellent review gives a detailed discussion of the differential effects ofanesthetic agents on excitotoxic injury, but not apoptotic death.
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35 Feiner JR, Bickler PE, Estrada S, et al. Mild hypothermia, but not propofol, isneuroprotective in organotypic hippocampal cultures. Anesth Analg 2005;100:215–225.
36 Adembri C, Venturi L, Tani A, et al. Neuroprotective effects of propofol inmodels of cerebral ischemia: inhibition of mitochondrial swelling as a possiblemechanism. Anesthesiology 2006; 104:80–89.
37 Kanbak M, Saricaoglu F, Avci A, et al. Propofol offers no advantage overisoflurane anesthesia for cerebral protection during cardiopulmonary bypass:a preliminary study of S-100beta protein levels. Can J Anaesth 2004;51:712–717.
38 Basagan-Mogol E, Buyukuysal RL, Korfali G. Effects of ketamine andthiopental on ischemia reoxygenation-induced LDH leakage and aminoacid release from rat striatal slices. J Neurosurg Anesthesiol 2005; 17:20–26.
39
��Himmelseher S, Durieux ME. Revising a dogma: ketamine for patients withneurological injury? Anesth Analg 2005; 101:524–534.
This review emphasizes the tolerability of ketamine for neurologically impairedpatients. A neuroprotective effect is likely, but was only found in studies with short-term outcome.
40 Nagels W, Demeyere R, Van Hemelrijck J, et al. Evaluation of the neuropro-tective effects of S(þ)-ketamine during open-heart surgery. Anesth Analg2004; 98:1595–1603.
41 Lei B, Popp S, Capuano-Waters C, et al. Lidocaine attenuates apoptosis inthe ischemic penumbra and reduces infarct size after transient focal cerebralischemia in rats. Neuroscience 2004; 125:691–701.
42 Niiyama S, Tanaka E, Tsuji S, et al. Neuroprotective mechanisms of lidocaineagainst in vitro ischemic insult of the rat hippocampal CA1 pyramidal neurons.Neurosci Res 2005; 53:271–278.
43 Wang C, Sadovova N, Fu X, et al. The role of the N-methyl-D-aspartatereceptor in ketamine-induced apoptosis in rat forebrain culture. Neuroscience2005; 132:967–977.
44 Wang C, Sadovova N, Hotchkiss C, et al. Blockade of N-methyl-D-aspartatereceptors by ketamine produces loss of postnatal day 3 monkey frontalcortical neurons in culture. Toxicol Sci 2006; 91:192–201.
45 Johnson ME. Neurotoxicity of lidocaine: implications for spinal anesthesia andneuroprotection. J Neurosurg Anesthesiol 2004; 16:80–83.
rized reproduction of this article is prohibited.
Cerebral protection
S. Fukuda1 and D. S. Warner1–3*
1Department of Anesthesiology, 2Department of Neurobiology and 3Department of Surgery, Duke University
Medical Center, Box 3094, Durham, NC 27710, USA
*Corresponding author: Department of Anesthesiology, Duke University Medical Center, Box 3094,
Cerebral ischaemia/hypoxia can occur in a variety of peri-
operative circumstances. Outcomes from such events range
from sub-clinical neurocognitive deficits to catastrophic
neurological morbidity or death. Although certain surgical
procedures present greater risk for ischaemic/hypoxic
brain injury, most insults are not presaged but instead arise
as unintended complications of either the surgical pro-
cedure or the anaesthetic.
It has been the investigative interest of surgeons and
anaesthesiologists to reduce perioperative brain injury
for more than 60 yr.12 Classically, such intervention has
been categorized as either neuroprotection or neuro-
resuscitation. Neuroprotection was defined as treatment
initiated before onset of ischaemia, intended to modify
intra-ischaemic cellular and vascular biological responses
to deprivation of energy supply so as to increase tolerance
of tissue to ischaemia resulting in improved outcome.
Neuroresuscitation, in contrast, implied treatment begun
after the ischaemic insult had occurred with the intent of
optimizing reperfusion.
However, it has become increasingly clear that an
ischaemic/hypoxic insult does not simply constitute energy
failure with consequent interruption of ongoing metabolic
events. Indeed this does occur. In addition, though, ischae-
mia and hypoxia stimulate active responses in the brain,
which persist long after substrate delivery has been
restored. These responses include activation of transcrip-
tion factors which up-regulate expression of genes contri-
buting to apoptosis and inflammation, inhibition of protein
synthesis, sustained oxidative stress, and neurogenesis.
Although some of these responses may have a teleological
advantage [e.g. elimination of dead or dysfunctional
tissue or increased tolerance to a subsequent insult (pre-
conditioning)], most responses aggravate damage caused
by the primary insult. Consequently, the concept that neu-
roprotection can be extended well into the reperfusion
phase seems appropriate, albeit with different targets other
than preservation of energy stores. This possibility may, in
part, explain the efficacy of various experimental post-
ischaemic interventions, which have manifested either as
# The Board of Management and Trustees of the British Journal of Anaesthesia 2007. All rights reserved. For Permissions, please e-mail: [email protected]
British Journal of Anaesthesia 99 (1): 10–17 (2007)
doi:10.1093/bja/aem140
clinically available therapies (e.g. mild hypothermia) or
instead as promising candidates for future clinical use tar-
geting events, such as oxidative stress, apoptosis, and
neurogenesis.
The above logic is presented as a taste of where we are
going with investigations aimed at ameliorating long-term
improvement from an ischaemic/hypoxic insult that may
occur in the perioperative period. However, the rest of this
article will focus on the opportunities and limitations of
currently available interventions (Table 1).
Anaesthetics
Barbiturates
It has been postulated for more than 50 yr that anaesthetics
increase the tolerance of brain to an ischaemic insult.28 The
logic is simple. Most drugs selected to be anaesthetics sup-
press neurotransmission. This suppression reduces energy
requirement, and reduction in energy requirement should
allow tissue better to preserve energy balance during a tran-
sient interruption of substrate delivery. Since adenosine tri-
phosphate (ATP) synthesis recovers rapidly after restoration
of substrate delivery, anaesthetics would be expected to be
protective if present during ischaemia but not if given after
restoration of substrate delivery. It would also follow that
efficacy of an anaesthetic is dependent upon the severity of
the ischaemic insult. If the insult were sufficiently severe to
cause loss of all electrical activity, there would be no
activity for anaesthetics to suppress and thus no mechanism
for such drugs to increase tolerance to ischaemia. In
contrast, in less severe insults, suppression of activity by
the anaesthetic before onset of ischaemia should delay
decay of ATP concentrations and thus also delay loss of
ionic gradients and calcium influx.
Many studies have supported this logic. Indeed, during
abrupt onset of hypoxaemia, barbiturates and isoflurane
slow deterioration of ATP concentrations.43 48 Furthermore,
post-ischaemic treatment with either barbiturates or volatile
anaesthetics has no effect on outcome.1 59 Surprisingly,
irrefutable data supporting efficacy of pre-treatment with
anaesthetics have proved difficult to acquire.
Early work testing intra-ischaemic anaesthetic efficacy
was confounded by poor physiological control of exper-
imental subjects. It was recognized later in the evolution of
anaesthetic efficacy studies that factors such as blood
glucose, brain temperature, and perfusion pressure were
important determinants of ischaemic outcome and that
anaesthetics independently modulated these factors. In
addition, early studies typically compared one anaesthetic
against another. The assumption was that the ‘control’
anaesthetic was not protective and thus failure to improve
outcome by the ‘test’ anaesthetic indicated lack of a pro-
tective state. However, little work was done to confirm that
the ‘control’ anaesthetic was not protective. Subsequent
studies, which became feasible as experimental models
evolved, often found considerable protection from the
‘control’ anaesthetic when compared with an awake state.
Thus, the field remained confused for more than a
decade and insufficient data were generated to warrant
human trials of anaesthetic efficacy when employed intra-
operatively. Even then, the early results were mixed. One
Table 1 Evidence-based status of plausible interventions to reduce perioperative ischaemic brain injury. þþ, Repeated physiologically controlled studies in
animals/randomized, prospective, adequately powered clinical trials; þ, consistent suggestion by case series/retrospective or prospective small sample size trials,
or data extrapolated from other paradigms; 2/þ, inconsistent findings in clinical trials; may be dependent on characteristics of insult; 2, well-defined absence of
benefit; 22, absence of evidence in physiologically controlled studies in animals/randomized, prospective, adequately powered clinical trials; 222, evidence
of potential harm; *, out-of-hospital ventricular fibrillation cardiac arrest
Intervention Pre-ischaemic
efficacy in
experimentalanimals
Post-ischaemic
efficacy in
experimentalanimals
Pre-ischaemic
efficacy in
humans
Post-ischaemic
efficacy in
humans
Sustained
protection in
experimentalanimals
Sustained
protection
in humans
Moderate
hypothermia
þþ þþ 2/þ þþ* þþ þþ
Mild
hyperthermia
222 222 22 22 222 22
Hyperventilation 22 22 22 22 22 22
Normoglycaemia þþ 22 þ þ þþ 22
Hyperbaric
oxygen
þþ 22 22 2/þ 22 22
Barbiturates þþ 2 þ 2 22 22
Propofol þþ þ 2 22 22 2
Etomidate 222 22 22 22 22 22
Nitrous oxide 2 22 22 22 22 22
Isoflurane þþ 22 22 22 þþ 22
Sevoflurane 22 22 22 þþ 22
Desflurane þþ 22 22 22 22 22
Lidocaine þþ 22 þ 22 22 22
Ketamine þþ 22 22 22 22 22
Glucocorticoids 222 22 22 22 22 22
Cerebral protection
11
study found efficacy from thiopental when given in
cardiac surgical patients, whereas another did not.50 67
However, only short-term outcomes were assessed, which
prevented assessment of the full evolution of the ischae-
mic injury. Furthermore, surgical procedures and cardio-
pulmonary bypass conditions were markedly different
between the two trials. Numerous other explanations have
been offered, but perhaps the overall potency of barbitu-
rates as neuroprotective agents is weak in the face of
severe ischaemic insults.65
One problem with barbiturates is their prolonged dur-
ation of action. It was believed that optimal protection
would be present only when massive doses were adminis-
tered to abolish electroencephalographic (EEG) activity,
thereby eliciting maximal suppression of cerebral meta-
bolic rate (CMR) before onset of the insult. Some
practitioners still adhere to this principle when using bar-
biturates to protect the brain but such large doses can
markedly delay anaesthesia emergence, which has limited
their clinical application. Although it is unlikely that these
massive doses are necessary to obtain maximal efficacy,65
recognition that volatile anaesthetics can also produce
EEG isoelectricity at doses which still allow rapid anaes-
thesia emergence was greeted with optimism because such
compounds could be more widely applied in clinical
settings.
Volatile anaesthetics
The efficacy of volatile anaesthetics as neuroprotective
agents has undergone more than 30 yr of scrutiny and still
no human outcome trials have been conducted to guide
clinical practice. We know the following facts from the
laboratory. Volatile anaesthetics provide major improve-
ment in ischaemic outcome. The dose required to obtain
this protection is within a clinically relevant range, with
anaesthetics protect against both focal (e.g. obstruction of
flow distal to the circle of Willis) and global (e.g. com-
plete cessation of blood flow to the brain or forebrain)
ischaemia. However, the improvement in outcome is tran-
sient in global ischaemia,23 whereas it is persistent in
focal ischaemia.58 Sevoflurane has also been shown to
provide long-term protection in one experimental model.51
The mechanism by which volatile anaesthetics protect is,
in part, attributable to suppression of energy require-
ments.47 Both inhibition of excitatory neurotransmission
and potentiation of inhibitory receptors are likely to be
involved.15 22 30 It is also likely that volatile anaesthetics
have other important effects that include regulation of
intracellular calcium responses during ischaemia,29 and
activation of TREK-1 two-pore-domain Kþ channels.25
Although a great deal has been learned from the labora-
tory, in the absence of human outcome data, it cannot be
stated that volatile anaesthetics improve outcome from
perioperative ischaemic insults. However, if an anaesthetic
is required for a surgical procedure, inclusion of volatile
anaesthetics can be considered. Isoflurane and sevoflurane
carry the largest data set to this decision. Desflurane also
offers promise,33 38 but has been insufficiently studied to
determine whether it should be equally considered in this
class of potential neuroprotective compounds.
Other anaesthetics
Other anaesthetics possess properties that suggest potential
for intra-ischaemic neuroprotection. These include propo-
fol, etomidate, and lidocaine. Study of these drugs has not
been as extensive as for either barbiturates or volatile
anaesthetics. The principle feature of propofol and etomi-
date is suppression of CMR by inhibition of synaptic
activity.19 35 Propofol may also have free radical scaven-
ging and anti-inflammatory properties.57 Propofol appears
unique among anaesthetics in the laboratory setting
because it offers efficacy with post-ischaemic therapy
onset, although such treatment provides only transient pro-
tection.9 Propofol appears to offer efficacy similar to bar-
biturates but a dose-dependent study of its efficacy has not
been completed, leaving little guidance for potential clini-
cal use. Furthermore, propofol infused to induce EEG
burst suppression failed to improve outcome in cardiac
valve surgery patients.56 Etomidate, although initially her-
alded as a substitute for barbiturates,8 has never met rigor-
ous evaluation for neuroprotective properties. In fact,
some work has indicated that etomidate may paradoxically
exacerbate ischaemic injury by inhibiting nitric oxide
synthase, thereby intensifying the ischaemic insult.21 As a
result of this and other studies, the use of etomidate for
neuroprotection has fallen out of favour in clinical
settings.
Lidocaine also suppresses CMR, but this effect is only
meaningful at doses beyond those typically employed in
clinical environments. Numerous laboratory studies have
found efficacy for lidocaine, with perhaps its principle
mechanism of action relating to inhibition of apoptosis.39
The efficacy of lidocaine appears dependent on dose, with
doses in the range used to manage cardiac dysrhythmias
having greatest efficacy.61 There have been no long-term
outcome studies of lidocaine efficacy in experimental
stroke. One small human trial found benefit from low-dose
lidocaine infusion during cardiac surgery on long-term
neuropsychological impairment.44 Lidocaine should be
further evaluated for neuroprotective properties since its
use is supported by a litany of laboratory successes such
as short-duration of action and ease of use. However,
because it has not been evaluated in a large-scale clinical
trial, efficacy in clinical environments remains speculative.
Ketamine offers potent inhibition of glutamatergic
neurotransmission at the N-methyl-D-aspartate (NMDA)
receptor. There is a long history of NMDA receptor antag-
onists as potential neuroprotective agents but, overall, such
compounds offer little or no protection against global
Fukuda and Warner
12
insults. Protection against focal insults is substantial, but
only if the drug is given before ischaemia onset. Because
ketamine is clinically available, it is tempting to argue that
it should be considered when a focal ischaemic insult is
anticipated. To date, however, there are no human data
supporting this practice. Little is also known about dose–
response properties, even in animals. Thus, it is difficult to
recommend ketamine for the purposes of neuroprotection
in the clinical environment at this time.
Physiological management
Temperature
Hypothermia has been proposed to offer therapeutic
benefit for more than 60 yr.24 Early investigators examined
its effects in both neurosurgery and cardiac surgery
patients. In the same era, it was also considered to offer
benefit in survivors of cardiac arrest and hypoxic insults.10
It remains unclear why hypothermia fell out of favour
in subsequent decades. One factor may have been its
apparent lack of efficacy, which reduced enthusiasm for
the logistical issues necessary routinely to cool and
re-warm a large patient population. Another factor may
have been the influence of mechanistic studies conducted
in the laboratory.42 That work examined effects of
hypothermia on brain energy metabolism and found
hypothermia to reduce CMR in a temperature-dependent
fashion, which became the presumed mechanism of
action. The most impressive effects on CMR were at very
low temperatures, and those temperatures required use of
cardiopulmonary bypass. The effects of mild (32–358C)
hypothermia on CMR were negligible. In contrast, barbitu-
rates can reduce CMR by 50–60% without the use of car-
diopulmonary bypass and were therefore viewed as having
a greater potential benefit. Perhaps for those reasons, the
use of perioperative hypothermia persisted only in the
context of caring for some cardiac surgical patients.
There is no doubt that deep hypothermia (e.g. 18–
228C) is highly neuroprotective. We know that only a few
minutes of complete global ischaemia will cause neuronal
death in normothermic brain. This has been best examined
in the laboratory, but human evidence is consistent with
those findings.53 In contrast, it is widely observed that
induction of deep hypothermia before circulatory arrest
routinely allows the brain to tolerate intervals of no-flow
exceeding 40 min, and substantially greater intervals of
arrest with complete or near-complete neurological recov-
ery are frequently reported. As a result of this prima facie
evidence, the efficacy of deep hypothermia has not been
subjected to randomized controlled trials. However, there
is still much to be learned with respect to optimizing
cooling and re-warming methods, optimal magnitude of
hypothermia, determination of brain temperature using sur-
rogate sites, and defining within individual patients when
the duration of circulatory arrest approaches the limits of
deep hypothermic neuroprotection.
The story might have ended there had it not been for
several laboratory studies that ignored the CMR hypoth-
esis. Those studies re-visited the possibility that mild
hypothermia could protect the brain against ischaemia
insults.14 40 To most people’s surprise, reduction in brain
temperature by only a few degree Celsius provided major
protection. These findings stimulated numerous clinical
trials in both adults and newborns, which have since pro-
vided a scientific basis defining the opportunities and
limitations of using off-bypass hypothermia to provide
meaningful neuroprotection.
The first reported work related to traumatic brain injury
(TBI). Three pilot studies provided suggestive evidence
that mild hypothermia improved either brain physiology or
outcome. However, those studies employed small sample
sizes and more definitive evidence was needed. Thus, a
large-scale prospective human trial was conducted, but
disappointing results were obtained.18 Cooling TBI
patients within the first several hours after injury failed to
improve outcome. The design and conduct of this trial
have been vigorously debated but what is clear is that
induced hypothermia is not a panacea for TBI. If it is
proven effective in later trials, it will probably be shown
to have efficacy only in certain patient populations and
only when conducted with specific protocols. Such work
is ongoing.
If the TBI study had been performed in isolation,
perhaps off-bypass hypothermia would have been aban-
doned in the clinic again. However, other studies were
already underway, two of which markedly altered the
mood of the investigative community. Both studies were
reported simultaneously and used similar experimental
designs wherein comatose survivors of out-of-hospital
cardiac arrest were randomized to normothermia or mild
hypothermia, which involved rapid surface cooling as
soon as spontaneous circulation was restored.2 11 Both
studies found significantly more patients with good
outcome in the hypothermia group and negligible adverse
events. Finally, convincing evidence is available that off-
bypass hypothermia can appreciably improve outcome
from at least cardiac arrest in humans.
These findings have prompted publication of guidelines
recommending that comatose survivors of out-of-hospital
cardiac arrest undergo cooling after restoration of spon-
taneous circulation.3 49 The extent to which the efficacy of
induced hypothermia can be extrapolated to other con-
ditions of cardiac arrest (loss of airway, asphyxia, and
drowning) may never be known given the sporadic and
relatively rare nature of those events. However, such inter-
vention may be considered.41
In addition, there is an increasing evidence that peripar-
tum neonatal asphyxial brain injury favourably responds to
treatment with hypothermia. Two trials have been
reported. The first employed selective head cooling and
Cerebral protection
13
could only find a beneficial effect of hypothermia in a
subset of the study population.27 The second employed
total body cooling.60 In this study, the benefit of induced
mild hypothermia was clear. Despite this, some feel
additional trials are required before such intervention can
be widely advocated.32
In the course of defining hypothermia efficacy, it has
also become apparent that hyperthermia has adverse effects
on post-ischaemic brain. Spontaneous post-ischaemic
hyperthermia is common4 and, in animals, intra-ischaemic
or even delayed post-ischaemic hyperthermia dramatically
worsens outcome. Spontaneous hyperthermia has also been
associated with poor outcome in humans.36 These facts
provide sufficient evidence to advocate frequent tempera-
ture monitoring in patients with cerebral injury (and those
at risk for cerebral injury). Aggressive treatment of
hyperthermia should be considered.
Glucose
Glucose is a fundamental substrate for brain energy metab-
olism. Deprivation of glucose in the presence of oxygen
can result in neuronal necrosis, but the presence of
glucose in the absence of oxygen carries a worse fate. The
mechanistic basis for this dichotomy remains unclear. The
most persistent hypothesis is that glucose, in the absence
of oxygen, undergoes anaerobic glycolysis resulting in
intracellular acidosis, which amplifies the severity of other
deleterious cascades initiated by the ischaemic insult.
Many animal studies have demonstrated adverse effects of
hyperglycaemia from a wide variety of brain insults.
Human studies remain principally correlative in nature,
that is, patients having worse outcomes from stroke, TBI,
etc. also tend to have higher blood glucose concentrations
on hospital admission. For some time, it was unclear
whether admission hyperglycaemia simply represented a
stress response to the brain insult, or instead was contribut-
ing to a worsened injury. The animal data clearly favour
the latter interpretation. More importantly, human research
has demonstrated more rapid expansion of ischaemic
lesions in hyperglycaemic, compared with normoglycaemic
patients.6 52 In addition, there is accumulating evidence that
regulation of blood glucose yields a higher incidence of
good outcome in stroke patients.26 For all of these reasons,
it is rational to maintain normoglycaemia in all patients at
risk for, or recovering from acute brain injury.
Arterial carbon dioxide partial pressure (PaCO2)
Because cerebral blood flow and PaCO2are linearly related
within physiologically relevant ranges, hyperventilation
had become an entrenched practice in cerebral resuscita-
tion. Reduction in PaCO2was presumed to augment cer-
ebral perfusion pressure favourably by reducing the
cross-sectional diameter of the arterial circulation and thus
cerebral blood volume. This would offset increases in
intracranial pressure. Although the logic behind this
practice can be appreciated, in fact, it is contradicted by
direct examination of cerebral well being. The most salient
evidence is derived from TBI investigations. These studies
support a different concept, that being worsening of per-
fusion by hyperventilation-induced vasoconstriction in
ischaemic tissue. Indeed, the volume of ischaemic tissue,
elegantly assessed with positron emission tomography in
TBI patients, was markedly increased when moderate hypo-
capnia was induced.20 This is consistent with the only pro-
spective trial of hyperventilation on TBI outcome, which
observed a decreased number of patients with good or mod-
erate disability outcomes when chronic hyperventilation
was employed.45 It remains unevaluated whether acute
hyperventilation improves outcome from pending transten-
torial herniation or when rapid surgical decompression of a
haematoma (e.g. epidural) is anticipated. Within the
context of focal ischaemic stroke, clinical trials have found
no benefit from induced hypocapnia,17 62 although hyper-
ventilation is sometimes employed in cases of refractory
brain oedema. Use of hyperventilation during cardiopul-
monary resuscitation may serve to increase mean intrathor-
acic pressure thereby decreasing perfusion pressure and is
not advocated.5 Consequently, there are few data to support
use of hyperventilation in the context of cerebral
resuscitation.
Arterial oxygen partial pressure
It makes sense that optimization of oxygen delivery to
ischaemic tissue should improve outcome. Indeed, oxygen
deprivation is the fundamental fault leading to tissue
demise. However, reperfusion presents deranged oxygen
metabolism with the opportunity to increase formation of
reactive oxygen species that plausibly induce secondary
insults, thereby worsening outcome. There are few human
data regarding the effects of normobaric hyperoxaemia in
human resuscitation. One retrospective perinatal resuscita-
tion analysis found worse long-term outcome in children
when either hyperoxaemia or hypocapnia was present
during resuscitation or early recovery.37 Others found more
rapid normalization of Apgar scores when 40% oxygen
compared with 100% oxygen was used for resuscitation.31
In animal models, it is becoming evident that the effect
of hyperoxaemia is dependent on the nature of the ischae-
mic insult. Rats subjected to middle cerebral artery occlu-
sion had smaller infarcts when normobaric hyperoxaemia
was present during both ischaemia and reperfusion. This is
consistent with the demonstrated efficacy of hyperbaric
oxygen (HBO) in rats undergoing a similar focal ischaemic
insult.63 Evidence for HBO efficacy in humans is weak.16
In contrast, in dogs subjected to cardiac arrest, it has been
repeatedly observed that outcome is worsened by normoba-
ric hyperoxaemia present during early recirculation.64 This
has been attributed to oxidation and decreased pyruvate
dehydrogenase activity, the enzymatic link between anaero-
bic and aerobic glycolysis.55 Management of oxygen
Fukuda and Warner
14
delivery after restoration of spontaneous circulation, so as
to maintain pulse oximeter values within the range of
94–96, optimized short-term neurological outcome.7 These
compelling data should serve as a stimulus for a random-
ized clinical trial and stimulates re-consideration of the
necessity for hyperoxaemia in the early post-resuscitation
interval.
Steroids
Steroids such as dexamethasone reduce oedema surround-
ing brain tumours. Beyond that, evidence for benefit from
the use of steroids is weak. Evidence that methylpredniso-
lone improves outcome from acute spinal cord trauma is
controversial,13 but some surgeons have extended this
observation to intraoperative use in spinal cord surgery.
There is insufficient evidence to define the role of gluco-
corticoids in focal ischaemic stroke.54 A large retrospec-
tive analysis found no benefit from glucocorticoid
treatment in patients with cardiac arrest.34 In fact, there is
animal evidence that such glucocorticoids exacerbate
injury from global ischaemia by increasing plasma glucose
concentration.66 Given the potential adverse effects of
steroids and lack of demonstrable efficacy in ischaemic
brain, their use cannot be advocated.
Conclusion
Ischaemic brain injury remains a potentially devastating
disorder, although progress is being made in resuscitation
science. Two key advances occurred in the past decade.
The first was repeated demonstration that induced mild
hypothermia reduces neurological morbidity and mortality
associated with out-of-hospital ventricular fibrillation
cardiac arrest. Beyond the immediate potential to apply
this intervention is the larger message that post-ischaemic
intervention can favourably influence outcome in humans.
The second advance was recognition that efficacy of mild
hypothermia depends at least in part upon the type of
ischaemic lesion being treated. Trauma and focal ischae-
mia could not be shown to be amenable to hypothermic
intervention, at least within the bounds of the clinical trial
protocols employed.
Other than the use of mild hypothermia for ventricular
fibrillation cardiac arrest, practice of clinical neuroprotection
rests on extrapolation from animal studies and weak
clinical trials. Review of these data allows some recommen-
dations to be made (Table 2). Such recommendations are
likely to be advanced with increased understanding of
cellular responses to ischaemia and appropriately conducted
clinical trials.
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3 Part 7.5: Postresuscitation support. Circulation 2005; 112: IV84–84 Albrecht RF 2nd, Wass CT, Lanier WL. Occurrence of potentially
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Table 2 Considerations when anticipating or managing a perioperative
ischaemic insult
Assure absence of hyperthermia
Manage blood glucose with insulin to induce normoglycaemia
Optimize haemoglobin-oxygen saturation (increasing concern that
hyperoxaemia may be adverse in global ischaemia)
Establish normocapnia
Consider the use of volatile anaesthetics if surgery ongoing (consistent
sustained benefit in experimental animal studies, reversible allowing
neurological examination, human trials not performed)
Resist the use of glucorticoids (no evidence of efficacy, preclinical evidence
of adverse effect in global ischaemia)
Consider the use of postoperative sustained induced moderate hypothermia if
global ischaemia (not tested by clinical trials in perioperative environment,
but supported by consistent evidence of efficacy when used in out-of-hospital
ventricular fibrillation cardiac arrest)
Cerebral protection
15
16 Carson S, McDonagh M, Russman B, Helfand M. Hyperbaricoxygen therapy for stroke: a systematic review of the evidence.Clin Rehabil 2005; 19: 819–33
(stroke) treated with or without prolonged artificialhyperventilation. 1. Cerebral circulation, clinical course, andcause of death. Stroke 1973; 4: 568–631
18 Clifton GL, Miller ER, Choi SC, et al. Lack of effect of induction
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19 Cold GE, Eskesen V, Eriksen H, Blatt Lyon B. Changes in CMRO2,EEG and concentration of etomidate in serum and brain tissueduring craniotomy with continuous etomidate supplemented with
N2O and fentanyl. Acta Anaesthesiol Scand 1986; 30: 159–6320 Coles JP, Fryer TD, Coleman MR, et al. Hyperventilation following
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21 Drummond JC, McKay LD, Cole DJ, Patel PM. The role of nitric
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22 Elsersy H, Mixco J, Sheng H, Pearlstein RD, Warner DS. Selectivegamma-aminobutyric acid type A receptor antagonism reverses iso-
Decreased mortality by normalizing blood glucose after acuteischemic stroke. Acad Emerg Med 2006; 13: 174–80
27 Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head
cooling with mild systemic hypothermia after neonatal encephalo-pathy: multicentre randomised trial. Lancet 2005; 365: 663–70
28 Goldstein A, Jr, Wells BA, Keats AS. Increased tolerance tocerebral anoxia by pentobarbital. Arch Int Pharmacodyn Ther 1966;161: 138–43
29 Gray JJ, Bickler PE, Fahlman CS, Zhan X, Schuyler JA. Isofluraneneuroprotection in hypoxic hippocampal slice cultures involvesincreases in intracellular Ca2þ and mitogen-activated proteinkinases. Anesthesiology 2005; 102: 606–15
30 Harada H, Kelly PJ, Cole DJ, Drummond JC, Patel PM. Isofluranereduces N-methyl-D-aspartate toxicity in vivo in the rat cerebralcortex. Anesth Analg 1999; 89: 1442–7
31 Hellstrom-Westas L, Forsblad K, Sjors G, et al. Earlier Apgarscore increase in severely depressed term infants cared for in
Swedish level III units with 40% oxygen versus 100% oxygenresuscitation strategies: a population-based register study.Pediatrics 2006; 118: e1798–804
32 Higgins RD, Raju TN, Perlman J, et al. Hypothermia and perinatalasphyxia: executive summary of the National Institute of Child
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35 Kaisti KK, Langsjo JW, Aalto S, et al. Effects of sevoflurane, pro-
pofol, and adjunct nitrous oxide on regional cerebral blood flow,oxygen consumption, and blood volume in humans. Anesthesiology2003; 99: 603–13
36 Kammersgaard LP, Jorgensen HS, Rungby JA, et al. Admission
body temperature predicts long-term mortality after acutestroke: the Copenhagen Stroke Study. Stroke 2002; 33: 1759–62
37 Klinger G, Beyene J, Shah P, Perlman M. Do hyperoxaemia andhypocapnia add to the risk of brain injury after intrapartumasphyxia? Arch Dis Child Fetal Neonatal Ed 2005; 90: F49–52
38 Kurth CD, Priestley M, Watzman HM, McCann J, Golden J.Desflurane confers neurologic protection for deep hypothermiccirculatory arrest in newborn pigs. Anesthesiology 2001; 95: 959–64
39 Lei B, Popp S, Capuano-Waters C, Cottrell JE, Kass IS. Lidocaineattenuates apoptosis in the ischemic penumbra and reduces
infarct size after transient focal cerebral ischemia in rats.Neuroscience 2004; 125: 691–701
40 Leonov Y, Sterz F, Safar P, et al. Mild cerebral hypothermia duringand after cardiac arrest improves neurologic outcome in dogs.J Cereb Blood Flow Metab 1990; 10: 57–70
41 McDonagh DL, Allen IN, Keifer JC, Warner DS. Induction ofhypothermia after intraoperative hypoxic brain insult. AnesthAnalg 2006; 103: 180–1
42 Michenfelder J, Terry HJ, Daw E, Uihlein A. Induced hypothermia:
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47 Nellgard B, Mackensen GB, Pineda J, Wellons JC 3rd, Pearlstein RD,Warner DS. Anesthetic effects on cerebral metabolic rate predict
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406–11
Cerebral protection
17
New Age Neurosurgery: Avoiding Complications in Interventional Neuroradiology
William L. Young, M.D. San Francisco, California
311 Page 1
This talk will outline the roles of the Anesthesiologist in the Interventional Neuroradiology (INR) suite with an emphasis on management strategies to prevent complications and minimize their effects if they occur. We will discuss fundamental management principles of affording "protection," of which direct pharmacological protection is perhaps the least important. Planning the anesthetic and perioperative management is predicated on understanding the goals of the therapeutic intervention and anticipating potential problems. Endovascular neurosurgery / INR is firmly established in the management of cerebrovascular disease, most notably in the management of intracranial aneurysms.1 For the overall management approach to the patient with cerebrovascular disease, there is accelerating interest and discussion in appropriate management of asymptomatic or unruptured lesions.2,3 There are several anesthetic concerns that are particularly important for INR procedures, including: (1) maintaining immobility during the procedure to facilitate imaging; (2) rapid recovery from anesthesia at the end of the case to facilitate neurological examination and monitoring, or provide for intermittent evaluation of neurological function during the procedure; (3) managing anticoagulation; (4) treating and managing sudden unexpected procedure-specific complications during the procedure, i.e., hemorrhage or vascular occlusion, which may involve manipulating systemic or regional blood pressures; (5) guiding the medical management of critical care patients during transport to and from the radiology suites; (6) self-protection issues related to radiation safety.4,5 PRE-OPERATIVE PLANNING AND PATIENT PREPARATION Baseline blood pressure and cardiovascular reserve should be assessed carefully. This almost axiomatic statement is particularly important for several reasons. Blood pressure manipulation is commonly required and treatment-related perturbations should be anticipated. Therefore, a clear sense of “where the patient lives” needs to be established. One must keep in mind that “autoregulation” as presented in the textbooks is a description of a population; individual patients are likely to vary considerably, a concept based on the historical observations that underlie our modern notions of autoregulatory behavior.6,7 In those cases where intra-arterial catheters are used, the concordance between blood pressure cuff and intra-arterial readings needs to be considered; pre-operative blood pressure range is likely to be known through blood pressure cuff values. Pre-operative calcium channel blockers for prophylaxis for cerebral ischemia may be used and can affect hemodynamic management. In addition, these agents or trans-dermal nitroglycerin are sometimes used to lessen the incidence of catheter-induced vasospasm. For cases managed with an unsecured airway, routine evaluation of the potential ease of laryngoscopy in an emergent situation should take into account that direct access to the airway may be limited by table or room logistics. Recent pterional craniotomy can sometimes result in impaired tempomandicular joint mobility. For i.v. sedation cases, careful padding of pressure points and working with the patient to obtain final comfortable positioning may assist in the patient’s ability to tolerate a long period of lying supine and motionless, decreasing the requirement for sedation, anxiolysis, and analgesia. The possibility of pregnancy in female patients and a history of adverse reactions to radiographic contrast agents should be explored. Secure intravenous (iv) access should be available with adequate extension tubing to allow drug and fluid administration at maximal distance from the image intensifier during fluoroscopy. Access to intravenous or arterial catheters can be difficult when the patient is draped and the arms are restrained at the sides; connections should be secure. Infusions of anticoagulant, primary anesthetics or vasoactive agents should be through proximal ports with minimal dead space. In addition to standard monitors, capnography sampling via the sampling port of nasal cannula is useful for i.v. sedation cases. A pulse oximeter probe can be placed on the great toe of the leg that will receive the femoral introducer sheath to provide an early warning of femoral artery obstruction or distal thromboembolism. For intracranial procedures and post-operative care, beat-to-beat arterial pressure monitoring and blood sampling can be facilitated by an arterial line. A side port of the femoral artery introducer sheath can be used, but the sheath is usually removed immediately after the procedure. In a patient who requires continuous blood pressure monitoring post-operatively or frequent blood sampling, it is convenient to have a separate radial arterial blood pressure catheter. Using a co-axial or tri-axial catheter system, arterial pressure at the carotid artery, vertebral artery, and the
311 Page 2 distal cerebral circulation can be measured. Pressures in these distal cathethers usually underestimate systolic and overestimates diastolic pressure; however, mean pressures are reliable. Bladder catheters assist in fluid management as well as patient comfort. A significant volume of heparinized flush solution and radiographic contrast is may be used. Radiation Safety is a critical part of pre-operative planning. It is probably reasonable to assume that the x-ray machine is always on. There are three sources of radiation in the INR suite: direct radiation from the X-ray tube, leakage (through the collimators' protective shielding), and scattered (reflected from the patients and the area surrounding the body part to be imaged). A fundamental knowledge of radiation safety is essential for all staff members working in an INR suite. The amount of exposure decreases proportionally to the inverse of the square of the distance from the source of radiation (inverse square law). Digital subtraction angiography (DSA) delivers considerably more radiation than fluoroscopy. Optimal protection would dictate that all personnel should wear lead aprons, thyroid shields, and radiation exposure badges. The lead aprons should be periodically evaluated for any cracks in the lead lining that may allow accidental radiation exposure. Movable lead glass screens may provide additional protection for the anesthesia team. Clear communication between the INR and anesthesia teams is also crucial for limiting radiation exposure. With proper precautions the anesthesia team should be exposed to far less than the annual recommended limit for health care workers (see URL http://pdg.lbl.gov/). ANESTHETIC TECHNIQUE Choice of Anesthetic Technique Most centers routinely involved use general endotracheal anesthesia for aneurysm coiling and endovascular treatment of vasospasm. Choice of anesthetic technique varies between centers with no clear superior method. General Anesthesia A primary reason for employing general anesthesia is to minimize motion artifacts and to improve the quality of image. Relative normocapnia or modest hypocapnia consistent with the safe conduct of positive pressure ventilation should be maintained unless intracranial pressure is a concern. The specific choice of anesthesia may be guided primarily by other cardio- and cerebrovascular considerations. Total intravenous anesthetic techniques, or combinations of inhalational and intravenous methods, may optimize rapid emergence. To date, pharmacological protection against ischemic injury during neurosurgical procedures has not been proven. A theoretical argument could be made for eschewing the use of N2O because of the possibility of introducing air emboli into the cerebral circulation and reports that it worsens outcome after experimental brain injury. Intravenous Sedation Intravenous sedation in aneurysm management is used most often for patients coming for interim follow-up angiography to assess the necessity for retreatment after primary coiling. If further treatment is indicated, the technique can be converted to a general anesthetic. Goals of anesthetic choice for intravenous sedation are to alleviate pain, anxiety, and discomfort, provide patient immobility and allow rapid recovery. There may be a discomfort associated with injection of contrast into the cerebral arteries (burning) and with distention or traction on them (headache). A long period of lying can cause significant discomfort. A variety of sedation regimens are available, and specific choices are based on the experience of the practitioner and the goals of anesthetic management. Common to all intravenous sedation techniques is the potential for upper airway obstruction. Placement of nasopharyngeal airways may cause troublesome bleeding in anticoagulated patients and is generally avoided. Dexmetetomidine is a new agent that may have applicability in the setting of INR. It is a potent, selective alpha2-agonist with sedative, anxiolytic, and analgesic properties, with recent regulatory approval for sedation. Dexmedetomidine is especially noteworthy for its ability to produce a state of patient tranquility without depressing respiration. However, there are two caveats to consider. First, there are still unclear effects on cerebral perfusion.8 More importantly, there is a tendency for patients managed with dexmedetomidine to have relatively low blood pressure in the post-anesthesia recovery period.9 Because patients with aneurismal subarachnoid hemorrhage may be critically dependent on adequate collateral perfusion pressure, use of regimens that may result in blood pressure decreases should be used with great caution.
311 Page 3 ANTICOAGULATION Heparin: Careful management of coagulation is required to prevent thromboembolic complications during and after the procedure. Generally, after a baseline activated clotting time (ACT) is obtained, intravenous heparin (70 units/kg) is given to a target prolongation of 2 ~ 3 times of baseline. Then heparin can be given continuously or as an intermittent bolus with hourly monitoring of ACT. Occasionally, a patient may be refractory to attempts to obtain adequate anticoagulation. Switching from bovine to porcine heparin or vice versa should be considered. If antithrombin III deficiency is suspected, administration of fresh frozen plasma may be necessary. Direct Thrombin Inhibitors: Heparin-induced thrombocytopenia (HIT) is a potentially devastating prothrombotic syndrome caused by heparin dependent antibodies after exposure. Direct thrombin inhibitors may be used in patients with or at risk of HIT, although they entail their own risks, including a small risk of anaphylaxis. They inhibit thrombin both in the free form or bound to the clot. Monitoring of action is done by measuring the aPTT, or ACT. Lepirudin is FDA-approved for anticoagulation in patients with HIT. The half-life of lepirudin is 40 to 120 minutes, and it undergoes renal elimination. For HIT patients with renal impairment, Argatroban, predominantly metabolized in the liver, may be preferrable. Bivalirudin, a synthetic derivative of lepirudin, has a short half-life of about 25 minutes. Since bivalirudin is partially renally eliminated, dose adjustments may be needed in patients with renal dysfunction. A recent report described bivalirudin as a potential alternative during INR procedures to heparin for intravenous anticoagulation and intra-arterial thrombolysis.10 Antiplatelet agents: Antiplatelet agents (aspirin, the glycoprotein IIb/IIIa receptor antagonists and the thienopyridine derivatives) are increasingly being used for cerebrovascular disease management, as well as rescue from thromboembolic complications.11,12 Activation of the platelet membrane glycoprotein (GP) IIb/IIIa leads to fibrinogen binding and is a final common pathway for platelet aggregation. Abciximab, eptifibatide and tirofiban are glycoprotein IIb/IIIa receptor antagonists. The long duration and potent effect of Abciximab also increase the likelihood of major bleeding. The smaller molecule agents, eptifibatide and tirofiban, are competitive blockers and have a shorter half-life (about 2 hours). Thienopyridine derivatives (ticlopidine and clopidogrel) bind to the platelet’s ADP receptors and permanently alter the receptor; therefore, the duration of action is the life span of the platelet. The addition of clopidogrel to the antiplatelet regimen is used when stent-assisted coiling is anticipated, and also for management of unruptured aneurysms. Reversal of Anticoagulation: At the end of the procedure or at occurrence of hemorrhagic complication, heparin may be reversed with protamine. Since there is no specific antidote for the direct thrombin inhibitors or the antiplatelet agents, the biological half-life is one of the major considerations in drug choice and platelet transfusion is a non-specific therapy, should reversal be indicated. There is no currently available accurate test to measure platelet function in patients taking the newer antiplatelet drugs. Desmopressin (DDAVP) has been reported to shorten the prolonged bleeding time of individuals taking antiplatelet agents such as aspirin and ticlopidine. There are also increasing recent reports on using specific clotting factors, including recombinant factor VIIa and factor IX complex, to rescue severe life-threatening bleeding, including intracranial hemorrhage uncontrolled by standard transfusion therapy. The safety and efficacy of these coagulation factors remain to be investigated. DELIBERATE HYPERTENSION During acute arterial occlusion or vasospasm, the only practical way to increase collateral blood flow may be an augmentation of the collateral perfusion pressure by raising the systemic blood pressure. The Circle of Willis is a primary collateral pathway in cerebral circulation. However, in as many as 21% of otherwise normal subjects, the circle may not be complete. There are also secondary collateral channels that bridge adjacent major vascular territories, most importantly for the long circumferential arteries that supply the hemispheric convexities. These pathways are known as the pial-to-pial collateral or leptomeningeal pathways. The extent to which the blood pressure has to be raised depends on the condition of the patient and the nature of the disease. Typically, during deliberate hypertension the systemic blood pressure is raised by 30-40% above the baseline, in the absence of some direct outcome measure such as resolution of ischemic symptoms or imaging evidence of improved perfusion. Phenylephrine is usually the first line agent for deliberate hypertension and is
311 Page 4 titrated to achieve the desired level of blood pressure. The risk of causing hemorrhage into the ischemic area must be weighed against the benefits of improving perfusion, but augmentation of blood pressure in the face of acute cerebral ischemia is probably protective in most settings. DELIBERATE HYPOTENSION The two primary indications for induced hypotension are: (1) to test cerebrovascular reserve in patients undergoing carotid occlusion, and (2) to slow flow in a feeding artery of BAVMs before glue injection. The most important factor in choosing a hypotensive agent is the ability to safely and expeditiously achieve the desired reduction in blood pressure while maintaining the patient physiologically stable. The choice of agent should be determined by the experience of the practitioner, the patient's medical condition, and the goals of the blood pressure reduction in a particular clinical setting. Intravenous adenosine has been used to induce transient cardiac pause and may be a viable method of partial flow arrest.13 MANAGEMENT OF NEUROLOGICAL AND PROCEDURAL CRISES A well thought-out plan, coupled with rapid and effective communication between the anesthesia and radiology teams, is critical for good outcomes. The primary responsibility of the anesthesia team is to preserve gas exchange and, if indicated, secure the airway. Simultaneous with airway management, the first branch in the decision-making algorithm is for the anesthesiologist to communicate with the INR team and determine whether the problem is hemorrhagic or occlusive. In the setting of vascular occlusion, the goal is to increase distal perfusion by blood pressure augmentation with or without direct thrombolysis. If the problem is hemorrhagic, immediate cessation of heparin and reversal with protamine is indicated. As an emergency reversal dose, 1 mg protamine can be given for each 100 units of initial heparin dosage that resulted in therapeutic anticoagulation. The ACT can then be used to fine-tune the final protamine dose. Complications of protamine administration include hypotension, true analphylaxis and pulmonary hypertension. With the advent of new long-acting direct thrombin inhibitors such as bivalirudin, new strategies for emergent reversal of anticoagulation will need to be developed. Bleeding catastrophes are usually heralded by headache, nausea, vomiting and vascular pain related to the area of perforation. Sudden loss of consciousness is not always due to intracranial hemorrhage. Seizures, as a result of contrast reaction or transient ischemia, and the resulting post-ictal state can also result in an obtunded patient. In the anesthetized or comatose patient, the sudden onset of bradycardia and hypertension (Cushing response) or the endovascular therapist’s diagnosis of extravasation of contrast may be the only clues to a developing hemorrhage. Most cases of vascular rupture can be managed in the angiography suite. The INR team can attempt to seal the rupture site endovascularly and abort the procedure; a ventriculostomy catheter may be placed emergently in the angiography suite. Patients with suspected rupture will require emergent CT scan, but emergent craniotomy is usually not indicated. SPECIFIC PROCEDURES Intracranial Aneurysm Ablation The two basic approaches for INR therapy of cerebral aneurysms are occlusion of proximal parent arteries and obliteration of the aneurysmal sac. With the publication of the ISAT trial,14 coil embolization of intracranial aneurysms has become a routine first choice therapy for many lesions. The anesthesiologist should be prepared for aneurysmal rupture and acute SAH at all times, either from spontaneous rupture of a leaky sac or direct injury of the aneurysm wall by the vascular manipulation. There is great interest in the development of stent-assisted coiling methods. The stent can provide protection of the parent vessel. Stent placement requires a greater degree of instrumentation and manipulation, probably increasing the ever-present intra-procedural risk of parent vessel occlusion, thromboembolism or vascular rupture. Angioplasty of Cerebral Vasospasm from Aneurysmal SAH Roughly 1 out of 4 patients with SAH will develop symptomatic vasospasm. Angioplasty, either mechanical (balloon) or pharmacological (intraarterial vasodilators), may be used as a treatment.15 Angioplasty is ideally done in patients that have already had the symptomatic lesion surgically clipped and for patients in the early course of symptomatic ischemia in order to prevent hemorrhagic transformation of an ischemia region. A balloon catheter is guided under fluoroscopy into the spastic segment and inflated to mechanically distend the constricted area. It is also possible to perform a “pharmacologic” angioplasty by direct intra-arterial infusion. There
311 Page 5 is the greatest experience with papaverine, but there are potential CNS toxic effects.16 Other agents such as calcium channel blockers (nicardipine and verapamil) are being used.17 Intraarterial vasodilators may have systemic effects (bradycardia and hypotension). Patients who come for angioplasty are often critically ill with a variety of challenging co-morbidities, including neurocardiac injury, volume overload from “triple-H” therapy, hydrocephalus, brain injury from recent craniotomy, and residual effects of the presenting hemorrhage. Procedural complications include arterial rupture, reperfusion hemorrhage, thromboembolism, and arterial dissection. Carotid Test Occlusion and Therapeutic Carotid Occlusion Large or otherwise unclippable aneurysms may be partly or completely treated by proximal vessel occlusion. In order to assess the consequences of carotid occlusion in anticipation of surgery, the patient may be scheduled for a test occlusion in which cerebrovascular reserve is evaluated in several ways. A multimodal combination of angiographic, clinical, and physiologic tests can be used to arrive at the safest course of action for a given patient’s clinical circumstances. The judicious use of deliberate hypotension can increase the sensitivity of the test.18 The most important factor in choosing a hypotensive agent is the ability to safely and expeditiously achieve the desired reduction in blood pressure while maintaining the patient physiologically stable. The choice of agent should be determined by the experience of the practitioner, the patient's medical condition and the goals of the blood pressure reduction in a particular clinical setting. Brain Arteriovenous Malformations (BAVMs) Also called cerebral or pial AVMs, these are typically large, complex lesions made up of a tangle of abnormal vessels (called the nidus) frequently containing several discrete fistulae served by multiple feeding arteries and draining veins. The goal of the therapeutic embolization is to obliterate as many of the fistulae and their respective feeding arteries as possible. BAVM embolization is usually an adjunct for surgery or radiotherapy. The cyanoacrylate glues offer relatively “permanent” closure of abnormal vessels. Passage of glue into a draining vein can result in acute hemorrhage; in smaller patients, pulmonary embolism of glue can be symptomatic. For these reasons, deliberate hypotension may increase safety of glue delivery. Although less durable, polyvinyl alcohol microsphere embolization is also commonly used. If surgery is planned within days after PVA embolization, the rate of recanalization is low. Dural AVMs Dural AVM is considered an acquired lesion resulting from venous dural sinus stenosis or occlusion, opening of potential AV shunts, and subsequent recanalization. Symptoms are variable according to which sinus is involved. Venous hypertension of pial veins is a risk factor for intracranial hemorrhage. Dural AVMs may be fed by multiple meningeal vessels, and therefore, multi-staged embolization is often necessary. Dural AV fistulas can induce markedly increased venous pressure and decrease net cerebral perfusion pressure. Therefore, presence of venous hypertension should be factored into management of systemic arterial and cerebral perfusion pressure. Angioplasty and Stenting for Atherosclerotic Lesion Angioplasty and stenting for atherosclerosis for treatment of atherosclerotic disease involving the cervical and intracranial arteries continue to supplant open surgical management.19,20 Risk of distal thromboembolism is a major issue in this procedure. Catheter systems employing some kind of trapping system distal to the angioplasty balloon are being developed. There are multiple ongoing trials to compare the utility of stenting to carotid endarterctomy for extracranial carotid disease. It is likely that use of stenting will continue to increase as favorable data supporting its safety and efficacy emerge. Preparation for anesthetic management may include placement of transcutaneous pacing leads, in case of severe bradycardia or asystole from carotid body stimulation during angioplasty. Intravenous atropine or glycopyrrolate may be also used in an attempt to mitigate against bradycardia, which almost invariably occurs to some degree with inflation of the balloon. This powerful chronotropic response may be difficult or impossible to prevent or control by conventional means. Adverse effects of increasing myocardial oxygen demand need to be considered in anti-bradycardia interventions.
311 Page 6 Potential complications include vessel occlusion, perforation, dissection, spasm, thrombo-emboli, occlusion of adjacent vessels, transient ischemic episodes, and stroke. Similar to carotid endarterectomy, there is about a 5% risk of symptomatic cerebral hemorrhage and/or brain swelling after carotid angioplasty.21 Although the etiology of this syndrome is unknown, it has been associated with cerebral hyperperfusion, and it may be related to poor post-operative blood pressure control. Thrombolysis of Acute Thromboembolic Stroke In acute occlusive stroke, it is possible to recanalize the occluded vessel by superselective intra-arterial thrombolytic therapy. Thrombolytic agents can be delivered in high concentration by a microcatheter navigated close to the clot. Neurological deficits may be reversed without additional risk of secondary hemorrhage if treatment is completed within 4-6 hours from the onset of carotid territory ischemia and 24 hours in vertebrobasilar territory. One of the impediments in development in this area has been the fear of increasing the risk of hemorrhagic transformation of the acute infarction patient. Despite an increased frequency of early symptomatic hemorrhagic complications, treatment with intra-arterial pro-urokinase within 6 hours of the onset of acute ischemic stroke with MCA occlusion significantly improved clinical outcome at 90 days.22 Details of anesthetic management are reviewed elsewhere.23 POST-OPERATIVE MANAGEMENT Endovascular surgery patients pass the immediate post-operative period in a monitored setting, to watch for signs of hemodynamic instability or neurologic deterioration. Control of blood pressure may be necssary during transport and post-operative recovery, e.g., induced hypertension, if indicated. Abrupt restoration of normal systemic pressure to a chronically hypotensive (ischemic) vascular bed may overwhelm autoregulatory capacity and result in hemorrhage or swelling (normal perfusion pressure breakthrough, NPPB). In the absence of collateral perfusion pressure inadequacy, fastidious attention to preventing hypertension is warranted. Complicated cases may go first to CT or some other kind of tomographic imaging; critical care management may need to be extended during transport and imaging. References: 1. A. J. Molyneux, et al., Lancet 366, 809-17 (2005) 2. C. Stapf, et al., Curr Opin Neurol 19, 63-68 (2006) 3. D. O. Wiebers, et al., Lancet 362, 103-10 (2003) 4. W. L. Young, et al., Anesthesiology 80, 427-456 (1994) 5. W. L. Young, et al., Anesthesiology Clinics of North America 15(3), 631-653 (1997) 6. S. Strandgaard, et al., Br Med J 1, 507-510 (1973) 7. J. C. Drummond, et al., Anesthesiology 86, 1431-1433 (1997) 8. R. C. Prielipp, et al., Anesth Analg 95, 1052-9, table of contents (2002) 9. S. R. Arain, et al., Anesth Analg 95, 461-6, table of contents (2002) 10. M. R. Harrigan, et al., Neurosurgery 54, 218-22; discussion 222-3 (2004) 11. T. Hashimoto, et al., Anesthesiol Clin North America 20, 347-59, vi (2002) 12. D. Fiorella, et al., Neurosurgery 54, 1089-98 (2004) 13. T. Hashimoto, et al., Anesthesiology 93, 998-1001 (2000) 14. A. Molyneux, et al., Lancet 360, 1267-74 (2002) 15. D. W. Newell, et al., J Neurosurg 71, 654-660 (1989) 16. W. S. Smith, et al., Stroke 35, 2518-22 (2004) 17. L. Feng, et al., AJNR Am J Neuroradiol 23, 1284-1290 (2002) 18. R. S. Marshall, et al., Brain 124, 1208-17 (2001) 19. R. T. Higashida, et al., AJNR Am J Neuroradiol 26, 2323-7 (2005) 20. P. P. Goodney, et al., J Vasc Surg 43, 406-11 (2006) 21. P. M. Meyers, et al., Neurosurgery 47, 335-43; discussion 343-5 (2000) 22. A. Furlan, et al., Jama 282, 2003-11 (1999) 23. C. Z. Lee, et al., J Vasc Interv Radiol 15 (1), S13-S19 (2004)
Interventional neuroradiology—anesthetic
considerations
Tomoki Hashimoto, MDa,d, Dhanesh K. Gupta, MDa,d,William L. Young, MDa,b,c,d,*
aDepartment of Anesthesia and Perioperative Care, University of California,
San Francisco, CA 94110, USAbDepartment of Neurological Surgery, University of California, San Francisco, CA 94110, USA
cDepartment of Neurology, University of California, San Francisco, CA 94110, USAdCenter for Cerebrovascular Research, University of California, San Francisco,
San Francisco General Hospital, 1001 Potrero Avenue, Room 3C-38,
San Francisco, CA 94110, USA
Interventional neuroradiology (INR) is a hybrid of traditional neurosurgery
and neuroradiology, with certain overlaps with aspects of head-and-neck
surgery. It can be broadly defined as treatment of central nervous system (CNS)
disease by endovascular access for the purpose of delivering therapeutic
agents, including both drugs and devices [1]. Because of a recent advance-
ment in the field of INR [2], more anesthesiologists are involved in care of
patients undergoing INR procedures. Anesthesiologists have several important
concerns when providing care to patients who undergo INR procedures,
including (1) maintenance of patient immobility and physiologic stability; (2)
manipulating systemic or regional blood flow; (3) managing anticoagulation;
(4) treating and managing sudden unexpected complications during the pro-
cedure; (5) guiding the medical management of critical care patients during
transport to and from the radiology suites; and (6) rapid recovery from
anesthesia and sedation during or immediately after the procedure to facilitate
neurologic examination and monitoring [3,4]. To achieve these goals, anes-
thesiologists should be familiar with specific radiological procedures and their
potential complications.
0889-8537/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.
PII: S0889 -8537 (01 )00005 -0
This work is supported in part by National Institutes of Health, Grants K24-NS02091 (W.L.Y.).
* Corresponding author. Center for Cerebrovascular Research, University of California, San
Francisco General Hospital, 1001 Potrero Ave., Room 3C-38, San Francisco, CA 94110, USA.
administration: effect on regional cerebral blood flow in patients with arteriovenous malforma-
tions. J Neurosurg 1996;85:395–402.
[19] Roberts JT, Pile-Spellman J, Joseph M, et al. A patient with massive oral-facial venous malfor-
mation. J Clin Anesth 1991;3:76–9.
[20] Higashida RT, Tsai FY, Halbach VV, et al. Transluminal angioplasty for atherosclerotic disease of
the vertebral and basilar arteries. J Neurosurg 1993;78:192–8.
[21] Tsai FY, Matovich V, Hieshima G, et al. Percutaneous transluminal angioplasty of the carotid
artery. AJNR Am J Neuroradiol 1986;7:349–58.
[22] Theron J, Courtheoux P, Alachkar F, et al. New triple coaxial catheter system for carotid
angioplasty with cerebral protection [followed with Commentary by Ferguson R: Getting it right
the first time, p. 875–7]. AJNR Am J Neuroradiol 1990;11:869–74.
[23] Meyers PM, Higashida RT, Phatouros CC, et al. Cerebral hyperperfusion syndrome after percu-
taneous transluminal stenting of the craniocervical arteries [In Process Citation]. Neurosurgery
2000;47:335–43; discussion 343–5.
[24] Furlan A, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischemic stroke.
The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboem-
bolism. JAMA 1999;282:2003–11.
T. Hashimoto et al. / Anesthesiology Clin N Am 20 (2002) 347–359 359
CommentaryCommentaire
It is time to clear the confusion about the utility ofsteroids in cases of acute spinal cord injury. A com-mittee of Canadian neurosurgical and orthopedic
spine specialists, emergency physicians and physiatrists(listed at the end of the article) has reviewed the evidenceand concluded that high-dose methylprednisolone infu-sion is not an evidence-based standard of care for patientswith such an injury.1
The consequences of a spinal cord injury are often deva-stating, and any possibility of mitigating neurologic loss is attractive. To this end, management of acute spinal cord in-juries has included the use of steroids for the past 30 years,based in large part on physiological hypotheses with limitedclinical support.2,3 Mechanical injury to the spinal cord initi-ates a cascade of secondary events that include ischemia, in-flammation and calcium-mediated cell injury. Animal ex-periments have shown that methylprednisolone exhibitspotential neuroprotective effects through its inhibition oflipid peroxidation and calcium influx and through its anti-inflammatory effects.4,5 Three well-designed, large, random-ized clinical trials (the National Acute Spinal Cord InjuryStudies [NASCIS I, II and III]) examined the effect of steroidadministration in patients with acute spinal cord injury.6–11
NASCIS I examined the change in motor function inspecific muscles and changes in light touch and pinpricksensation from baseline.6,7 The study detected no benefitfrom methylprednisolone, but the dose was considered tobe below the therapeutic threshold determined from ani-mal experiments. Therefore, NASCIS II used a muchhigher dose, and patients were randomly assigned to re-ceive a 24-hour infusion of methylprednisolone, naloxoneor placebo within 12 hours after acute spinal cord injury.8,9
Again, there was no benefit overall in the methylpred-nisolone group; however, post hoc analyses detected a smallgain in the total motor and sensory score in a subgroup ofpatients who had received the drug within 8 hours aftertheir injury. As a result, this 24-hour, high-dose methyl-prednisolone infusion, if started within 8 hours after injury,quickly became an implied standard of care despite consid-erable criticism of the validity of such a post hoc analysis.
Subsequent clinical trials have provided conflicting evi-dence about steroid treatment in acute spinal cord injury. AJapanese study attempted to replicate the results seen in the8-hour subgroup from NASCIS II and reported improvedfunction at 6 months in a larger number of muscles and
sensory dermatomes among subjects who received high-dose methylprednisolone infusion than among those whoreceived only low doses of the drug or no drug.12 However,the study lacked detail about randomization and outcomemeasures, and it included only 74% of the enrolled subjectsin the outcome analysis. Conversely, an underpoweredprospective randomized trial that used a methylpred-nisolone regimen similar to that used in NASCIS II foundno improvement in motor and sensory scores at 1 year.13,14
NASCIS III compared a 48-hour infusion of methylpred-nisolone with a 24-hour infusion started within 8 hours af-ter injury and found no benefit from extending the infusionbeyond 24 hours. Again, only post hoc analysis showed abenefit from extending the infusion to 48 hours when treat-ment was started between 3 and 8 hours after injury. Noother study has verified the primary outcome of 48 hoursversus 24 hours or the post hoc conclusion of benefit fromstarting treatment between 3 and 8 hours after injury.
A meta-analysis of all of the trials concluded, on the basisof the controversial subgroup post hoc analyses in NASCISII and III and the data from the Japanese study, that a 24-hour high-dose methylprednisolone infusion within 8 hoursafter injury is efficacious.15 Despite this meta-analysis, theefficacy of such a regimen remains uncertain and will re-quire further study. The controversy about the post hocanalyses of NASCIS data continues,16–23 and unfortunatelythe studies that could have clarified the efficacy of such aregimen have lacked the rigour to do so.
Steroid therapy is not without risk. Most patients withacute spinal cord injury are treated in intensive care units,have polytrauma, have impaired lung capacity and are vul-nerable to sepsis. In all 3 NASCIS studies and other,smaller studies, the incidence of sepsis and pneumonia washigher in the high-dose methylprednisolone groups than inthe placebo or other treatment groups;6–11,24–26 the differ-ences were not significant except in NASCIS III. Hyper-glycemia and gastrointestinal complications were alsoreported following high-dose methylprednisolone treat-ment.13,24 Therefore, it has been proposed that, withoutcompelling evidence for its efficacy, methylprednisoloneshould be used with caution and may even be harmful, par-ticularly if infusion goes beyond 24 hours.17
The cost of a 24-hour methylprednisolone infusion is notprohibitive, and a gain of antigravity strength in one ormore muscles below a spinal segment can provide an impor-
Methylprednisolone for acute spinal cord injury: not a standard of care
tant functional gain, especially for patients with cervicalspinal cord injuries. Therefore, even the small improvementobserved in the NASCIS subgroups could be viewed as abenefit in cases of complete or incomplete cervical cord in-jury. Despite the risk of complications and as long as theoutcomes in the NASCIS subgroups remain a possibility,physicians may still opt to administer a high-dose methyl-prednisolone infusion within 8 hours after injury. However,they should no longer feel compelled to do so. Physicianswho conduct the initial triage and resuscitation of patientswith acute spinal cord injury should consult their specialistcolleagues who will be continuing the care of these patientsregarding their preference for methylprednisolone infusion.
The Canadian Neurosurgical Society, the CanadianSpine Society and the Canadian Association of EmergencyPhysicians have adopted the committee’s recommendationthat a high-dose, 24-hour infusion of methylprednisolonestarted within 8 hours after an acute closed spinal cord in-jury is not a standard treatment nor a guideline for treat-ment but, rather, a treatment option, for which there is veryweak level II and III evidence.27
References
1. Hugenholtz H, Cass DE, Dvorak MF, Fewer DH, Fox RJ, Izukawa DMS, etal. High-dose methylprednisolone for acute closed spinal cord injury — onlya treatment option. Can J Neurol Sci 2002;29(3):227-35.
2. Tator CH. Acute spinal cord injury: a review of recent studies of treatmentand pathophysiology. CMAJ 1972;107(2):143-5.
3. Green BA, Kahn T, Klose KJ. A comparative study of steroid therapy in acuteexperimental spinal cord injury. Surg Neurol 1980;13(2):91-7.
4. Braughler JM, Hall ED. Lactate and pyruvate metabolism in injured catspinal cord before and after a single large intravenous dose of methylpred-nisolone. J Neurosurg 1983;59:256-61.
5. Hall ED. The neuroprotective pharmacology of methylprednisolone. J Neu-rosurg 1992;76:13-22.
6. Bracken MB, Collins WF, Freeman DF, Shepard MJ, Wagner FW, SiltenRM, et al. Efficacy of methylprednisolone in acute spinal cord injury. JAMA1984;251(1):45-52.
7. Bracken MB, Shepard MJ, Hellenbrand KG, Collins WF, Leo LS, FreemanDF, et al. Methylprednisolone and neurological function 1 year after spinalcord injury. Results of the National Acute Spinal Cord Injury Study. J Neuro-surg 1985;63(5):704-13.
8. Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS,et al. A randomized, controlled trial of methylprednisolone or naloxone in thetreatment of acute spinal-cord injury. Results of the Second National AcuteSpinal Cord Injury Study. N Engl J Med 1990;322(20):1405-11.
9. Bracken MB, Shepard MJ, Collins WF Jr, Holford TR, Baskin DS, EisenbergHM, et al. Methylprednisolone or naloxone treatment after acute spinal cordinjury: 1-year follow-up data. Results of the second National Acute SpinalCord Injury Study. J Neurosurg 1992;76(1):23-31.
10. Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, FazlM, et al. Administration of methylprednisolone for 24 or 48 hours or tirilazadmesylate for 48 hours in the treatment of acute spinal cord injury. Results ofthe Third National Acute Spinal Cord Injury Randomized Controlled Trial.National Acute Spinal Cord Injury Study. JAMA 1997;277(20):1597-604.
11. Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M,et al. Methylprednisolone or tirilazad mesylate administration after acutespinal cord injury: 1-year follow up. Results of the third National Acute Spinal
cial effect of methylprednisolone sodium succinate in the treatment of acutespinal cord injury. Sekitsui Sekizui J 1996;7:633-47.
13. Petitjean ME, Pointillart V, Dixmerias F, Wiart L, Sztark F, Lassie P, et al.Medical treatment of spinal cord injury in the acute stage. Ann Fr Anesth Re-anim 1998;17(2):114-22.
14. American Spinal Cord Injury Association. Standard for neurological classificationof spinal cord patients. Chicago: The Association; 1992.
15. Bracken MB. Pharmacological intervention for acute spinal cord injury[Cochrane review]. In: The Cochrane Library; Issue 1, 2001. Oxford: UpdateSoftware.
16. Coleman WP, Benzel D, Cahill DW, Ducker T, Geisler F, Green B, et al. Acritical appraisal of the reporting of the National Acute Spinal Cord InjuryStudies (II and III) of methylprednisolone in acute spinal cord injury. J SpinalDisord 2000;13(3):185-99.
17. Hurlbert RJ. Methylprednisolone for acute spinal cord injury: an inappropri-ate standard of care. J Neurosurg 2000;93(Suppl 1):1-7.
18. Nesathurai S. Steroids and spinal cord injury: revisiting the NASCIS 2 andNASCIS 3 trials. J Trauma 1998;45(6):1088-93.
19. Short DJ, El Masry WS, Jones PW. High dose methylprednisolone in themanagement of acute spinal cord injury — a systematic review from a clinicalperspective [review]. Spinal Cord 2000;38(5):273-86.
20. Section on disorders of the spine and peripheral nerves of the American Asso-ciation of Neurological Surgeons and the Congress of Neurological Sur-geons. Guidelines for the management of acute cervical spine and spinal cordinjuries. Neurosurgery 2002;50(Suppl 3):S67-72.
21. Oxman AD, Guyatt GH. A consumer’s guide to subgroup analyses. Ann In-tern Med 1992;116:78-84.
22. Fehlings MG. Summary statement: the use of methylprednisolone in acutespinal cord injury. Spine 2001;26(Suppl 24):S55.
23. Fehlings MG. Recommendations regarding the use of methylprednisolone inacute spinal cord injury: making sense out of the controversy [editorial]. Spine2001;26(Suppl 24):S56-7.
24. Matsumoto T, Tamaki T, Kawakami M, Yoshida M, Ando M, Yamada H. Earlycomplications of high-dose methylprednisolone sodium succinate treatment inthe follow-up of acute cervical spinal cord injury. Spine 2001;26(4):426-30.
25. Galandiuk S, Raque G, Appel S, Polk HC Jr. The two-edged sword of large-dosesteroids for spinal cord trauma. Ann Surg 1993;218(4):419-25; discussion 425-7.
27. Canadian Task Force on the Periodic Health Examination. The periodichealth examination. 1. Introduction. CMAJ 1986;134(7):721-9.
Commentaire
1146 JAMC • 29 AVR. 2003; 168 (9)
This article has been peer reviewed.
Competing interests: None declared.
Dr. Hugenholtz is with the Division of Neurosurgery, Queen Elizabeth II HealthSciences Centre, Halifax, NS.
Correspondence to: Dr. Herman Hugenholtz, New HalifaxInfirmary, Rm. 3808, 1796 Summer St., Halifax NS B3H 3A7; fax 902 473-8912
Members of the Committee of the Canadian Spine Society andthe Canadian Neurosurgical Society to Review the Role ofMethylprednisolone in Acute Spinal Cord Injury: HermanHugenholtz (chair), Division of Neurosurgery, Queen Elizabeth IIHealth Sciences Centre, Halifax, NS; Nirmala D. Bharatwal,Toronto Rehabilitation Institute, Toronto, Ont.; Dan E. Cass,Director of Emergency Services, St. Michael’s Hospital, Toronto,Ont.; Marcel F. Dvorak, Medical Director, Combined SpineProgram, Vancouver Hospital and Health Sciences Centre,Vancouver, BC; Derek Fewer, Section of Neurosurgery, HealthSciences Centre, Winnipeg, Man.; Richard J. Fox, Department ofNeurosurgery, Walter C. Mackenzie Health Science Centre,University Hospital, Edmonton, Alta.; Dennis M.S. Izukawa,Department of Neurosurgery, Trillium Health Centre,Mississauga, Ont.; Joel Lexchin, Emergency Department,University Health Network, Toronto, Ont.; Christine Short, NovaScotia Rehabilitation Centre, Halifax, NS; and Sagun Tuli,Department of Neurosurgery, Brigham and Women’s Hospital,Boston, Mass.
CC
Neuroprotection in traumatic br
ain injury: a complex struggle
against the biology of natureJoost W. Schouten
Purpose of review
Translating the efficacy of neuroprotective agents in
experimental traumatic brain injury to clinical benefit has
proven an extremely complex and, to date, unsuccessful
undertaking. The focus of this review is on neuroprotective
agents that have recently been evaluated in clinical trials
and are currently under clinical evaluation, as well as on
those that appear promising and are likely to undergo
clinical evaluation in the near future.
Recent findings
Excitatory neurotransmitter blockage and magnesium have
recently been evaluated in phase III clinical trials, but
showed no neuroprotective efficacy. Cyclosporin A,
erythropoietin, progesterone and bradykinin antagonists are
currently under clinical investigation, and appear promising.
Summary
Traumatic brain injury is a complex disease, and
development of clinically effective neuroprotective agents is
a difficult task. Experimental traumatic brain injury has
provided numerous promising compounds, but to date
these have not been translated into successful clinical trials.
Continued research efforts are required to identify and test
new neuroprotective agents, to develop a better
understanding of the sequential activity of pathophysiologic
mechanisms, and to improve the design and analysis of
clinical trials, thereby optimizing chances for showing
benefit in future clinical trials.
Keywords
clinical trial, head injury, neuroprotection, neurotrauma,
traumatic brain injury
Curr Opin Crit Care 13:134–142. � 2007 Lippincott Williams & Wilkins.
Department of Neurosurgery, Erasmus Medical Center, Rotterdam, TheNetherlands
Correspondence to Joost W. Schouten, MD, Department of Neurosurgery, ErasmusMedical Center, Postbus 2040, 3000 CA, Rotterdam, The NetherlandsE-mail: [email protected]
Current Opinion in Critical Care 2007, 13:134–142
Abbreviations
CSF c
opyrigopyrig
134
erebrospinal fluid
iNOS in ducible nitric oxide synthase NMDA N -methyl-D-aspartic acid NOS n itric oxide synthase TBI tr aumatic brain injury
Table 1 Neuroprotective strategies evaluated in experimental traum
Pharmacological target Remarks
Excitatory amino acids Numerous compounds have been evadifferent pharmacological profiles (e
Calcium channels Extensively studied, also in clinical TBinjury seems to limit further clinical
Scavenging oxygen radicals Tirilazad Mesylate, PEG-SOD and Lubcompounds are at least promising i
Inflammation A double-edged sword in TBI, both dis a high potential target for neuropand nitroxides.
Caspases Caspases are important enzymes in amatter of debate whether apoptosis
Calpains Calcium-dependent proteases involveTBI reduce damage to fiber tracts,
Hormonal treatment Progesterone is currently being evaluapast. Experimental compounds attrathyrotropin-releasing hormone and t
Neurotransmission Widespread changes in neurotransmiserotonin, histamine, g-aminobutyricpotential interest following TBI. Cogwhich might benefit from this appro
Neurotrophic factors These growth/survival factors effectiveTBI. Many questions about dosage,
Coagulation Recombinant human factor VII has befollowing TBI, relate to outcome, antreatment of microvascular thrombo
Anticonvulsants Seizures occur frequently following TBacute administration can be neurop
Immunophilin ligands Cyclosporin A is currently being evaluinvestigation.
Minocycline Minocycline is a broad-spectrum antibOthers In experimental research additional ho
improvement of axonal outgrowth aclinical trial in pediatric TBI has bee
TBI, traumatic brain injury. Neuroprotective strategies are discussed more e
clinical trials join a growing list of neuroprotective agents
without proven clinical benefit (Table 2 [14–24]). The
focus of this review is on neuroprotective agents that
have recently been evaluated in clinical trials and are
currently under clinical evaluation, as well as on those
that appear promising and are likely to undergo clinical
evaluation in the near future.
Excitatory neurotransmitter antagonismDisturbances in neurotransmitter concentration occur
frequently following TBI. Excitotoxicity refers to an
excessive release of excitatory neurotransmitters
(primarily glutamate) initiating various pathophysiologic
processes including excessive calcium influx in neurons,
resulting in neuronal cell death [10]. High concentrations
of extracellular glutamate have been demonstrated in
both experimental models and clinical patients with TBI.
Experimental research has elucidated many aspects of
excitotoxicity and identified a number of glutamate
antagonists acting either pre- or postsynaptically on
5-methyl-4-isoxazolyl-propionic acid (AMPA)/kainate or
metabotropic receptors, in a competitive, noncompetitive
or modulating way. However, glutamate receptors are of
utmost importance to normal functioning, so antagonism
of excessive excitotoxic activity must be achieved
orized reproduction of this article is prohibited.
atic brain injury
luated and reviewed elsewhere [8��,10]. New compounds with.g. memantine) require further experimental evaluation.I (Nimodipine and SNX-111); the short time frame followinguse.eluzole have been clinically evaluated; many new
n experimental TBI.etrimental and beneficial. The massive inflammatory responserotection, with special attention for NO inhibitors, nitrones
poptotic cell death known to occur following TBI. It is however still ais a good or bad thing compared to necrosis following TBI.
d in cytoskeletal remodeling. Calpain inhibitors in experimentaland therefore are of major interest in axonal injury.ted in a clinical trial. Steroids have been extensively studied in thecting a lot of attention are dehydroepiandrosterone,heir analogs.tters occur following TBI. All compounds interfering in cathecholamine,
acid (GABA) and acetylcholine metabolism are therefore ofnitive problems and depression frequently present following TBI,ach, although a rationale for more acute administration exists.ly reduce apoptosis and improve functional outcome in experimentaltime-window and route of administration remain to be answered.
en evaluated in a clinical trial. Coagulation disorders are commond will be a hot topic for future research. Controversies regardingsis and progressive hemorrhagic contusions require attention [11].I, and anticonvulsants may reduce early seizures. In addition,
rotective [12,13].ated in a clinical trial, other compounds are under experimental
iotic, shown to be neuroprotective in experimental studies.t topics far from translation into clinical trials are neurogenesis,nd stem-cell transplantation, although for the latter a smalln initiated.
tective agent in the injured brain should be required,
ensuring adequate tissue penetration once the agent is
studied in efficacy trials. A more sensitive analysis of
outcome in new types of clinical trials is advocated,
with an important role for surrogate outcome measures
as well as new types of outcome analysis. Further
standardization in treatment is likely to benefit from
further development of evidence-based treatment
guidelines. Implementation of these suggestions, even
though a complex challenge, is likely to improve the
chance that experimentally effective agents will show
positive results in future clinical trials.
References and recommended readingPapers of particular interest, published within the annual period of review, havebeen highlighted as:� of special interest�� of outstanding interest
Additional references related to this topic can also be found in the CurrentWorld Literature section in this issue (pp. 226–227).
1
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8
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C
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38
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43 Yatsiv I, Grigoriadis N, Simeonidou C, et al. Erythropoietin is neuroprotective,improves functional recovery, and reduces neuronal apoptosis and inflamma-tion in a rodent model of experimental closed head injury. FASEB J 2005;19:1701–1703.
44 Ehrenreich H, Hasselblatt M, Dembowski C, et al. Erythropoietin therapy foracute stroke is both safe and beneficial. Mol Med 2002; 8:495–505.
45 Xenocostas A, Cheung WK, Farrell F, et al. The pharmacokinetics oferythropoietin in the cerebrospinal fluid after intravenous administration ofrecombinant human erythropoietin. Eur J Clin Pharmacol 2005; 61:189–195.
46 Mushkudiani N, Engel DC, Steyerberg EW, et al. The prognostic valueof demographic characteristics in traumatic brain injury: results from theIMPACT� study. J Neurotrauma (in press).
47 Stein DG, Hoffman SW. Estrogen and progesterone as neuroprotectiveagents in the treatment of acute brain injuries. Pediatr Rehabil 2003;6:13–22.
49 Robertson CL, Puskar A, Hoffman GE, et al. Physiologic progesteronereduces mitochondrial dysfunction and hippocampal cell loss after traumaticbrain injury in female rats. Exp Neurol 2006; 197:235–243.
50 He J, Hoffman SW, Stein DG. Allopregnanolone, a progesterone metabolite,enhances behavioral recovery and decreases neuronal loss after traumaticbrain injury. Restor Neurol Neurosci 2004; 22:19–31.
51 Djebaili M, Guo Q, Pettus EH, et al. The neurosteroids progesterone andallopregnanolone reduce cell death, gliosis, and functional deficits aftertraumatic brain injury in rats. J Neurotrauma 2005; 22:106–118.
52 Wright DW, Ritchie JC, Mullins RE, et al. Steady-state serum concentrationsof progesterone following continuous intravenous infusion in patients withacute moderate to severe traumatic brain injury. J Clin Pharmacol 2005;45:640–648.
53 Wright DW, Kellermann AL, Hertzberg VS, et al. ProTECT: A randomizedclinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med2006 [epub ahead of print].
54 Marmarou A, Guy M, Murphey L, et al. A single dose, three-arm, placebo-controlled, phase I study of the bradykinin B2 receptor antagonist Anatibant(LF16-0687Ms) in patients with severe traumatic brain injury. J Neurotrauma2005; 22:1444–1455.
55 Wada K, Chatzipanteli K, Busto R, Dietrich WD. Role of nitric oxide intraumatic brain injury in the rat. J Neurosurg 1998; 89:807–818.
57 Guix FX, Uribesalgo I, Coma M, Munoz FJ. The physiology and pathophysiol-ogy of nitric oxide in the brain. Prog Neurobiol 2005; 76:126–152.
58 Clark RSB, Kochanek PM, Obrist WD, et al. Cerebrospinal fluid and plasmanitrite and nitrate concentrations after head injury in humans. Crit Care Med1996; 24:1243–1251.
59 Pou S, Pou WS, Bredt DS, et al. Generation of superoxide by purified brainnitric oxide synthase. J Biol Chem 1992; 267:24173–24176.
60 Stuehr D, Pou S, Rosen GM. Oxygen reduction by nitric-oxide synthases.J Biol Chem 2001; 276:14533–14536.
61 Gahm C, Holmin S, Wiklund PN, et al. Neuroprotection by selective inhibitionof inducible nitric oxide synthase after experimental brain contusion. J Neuro-trauma 2006; 23:1343–1354.
62 Werner ER, Schmidt HH. Nitric oxide synthase inhibitors: pterin antagonistsand antipterins. In Handbook of experimental pharmacology. Berlin: SpringerVerlag; 2000: pp.137–157.
63 Morales DM, Marklund M, Lebold D, et al. Experimental models of traumaticbrain injury: do we really need to build a better mousetrap? Neuroscience2005; 136:971–989.
64 Doppenberg EM, Choi SC, Bullock R. Clinical trials in traumatic brain injury:lessons for the future. J Neurosurg Anesthesiol 2004; 16:87–94.
65 Hillered L, Persson L, Nilsson P, et al. Continuous monitoring of cerebralmetabolism in traumatic brain injury: a focus on cerebral microdialysis. CurrOpin Crit Care 2006; 12:112–118.
orized reproduction of this article is prohibited.
This is a brief review with the same topic as the current review. There is someoverlap in the drugs discussed, some points of view are different.
67 Murray GD, Barer D, Choi S, et al. Design and analysis of phase III trials withordered outcome scales: the concept of the sliding dichotomy. J Neurotrauma2005; 22:511–517.
68 Clifton GL, Miller ER, Choi SC, et al. Lack of effect of induction of hypothermiaafter acute brain injury. N Engl J Med 2001; 344:556–563.
69 Hukkelhoven CW, Steyerberg EW, Farace E, et al. Regional differences inpatient characteristics, case management, and outcomes in traumaticbrain injury: experience from the tirilazad trials. J Neurosurg 2002; 97:549–557.
Airway Management in Adults after Cervical Spine TraumaEdward T. Crosby, M.D., F.R.C.P.C.*
This article has been selected for the AnesthesiologyCME Program. After reading the article, go to http://www.asahq.org/journal-cme to take the test and apply forCategory 1 credit. Complete instructions may be found inthe CME section at the back of this issue.
Cervical spinal injury occurs in 2% of victims of blunt trau-ma; the incidence is increased if the Glasgow Coma Scale scoreis less than 8 or if there is a focal neurologic deficit. Immobili-zation of the spine after trauma is advocated as a standard ofcare. A three-view x-ray series supplemented with computedtomography imaging is an effective imaging strategy to rule outcervical spinal injury. Secondary neurologic injury occurs in2–10% of patients after cervical spinal injury; it seems to be aninevitable consequence of the primary injury in a subpopula-tion of patients. All airway interventions cause spinal move-ment; immobilization may have a modest effect in limitingspinal movement during airway maneuvers. Many anesthesiol-ogists state a preference for the fiberoptic bronchoscope tofacilitate airway management, although there is considerable,favorable experience with the direct laryngoscope in cervicalspinal injury patients. There are no outcome data that wouldsupport a recommendation for a particular practice option forairway management; a number of options seem appropriateand acceptable.
THE provision of acute medical care to patients withcervical spinal injuries (CSIs) is a complex, challenging,and rewarding task. It is also an anxiety-provoking en-deavor because care is provided in a milieu where thereis constant concern about medical interventions result-ing in the conversion of a spinal injury without neuro-logic sequelae to one in which the two are now concur-rent. It is also a topic of continuous debate because careproviders struggle in an environment of limited data andincomplete answers to try to craft clinical care para-digms designed to optimize preservation and return ofneurologic function, while minimizing the risk of creat-ing additional injury and neurologic compromise. Manyquestions regarding the initial care of these patients,particularly as they relate to airway management, remain
unresolved, but there has been great effort, energy, andenthusiasm expended during the past two decadessearching for these answers. This article reviews theliterature that has been generated on the topic of airwaymanagement after CSI, particularly that published in thepast 10 yr, identifying new areas of knowledge andevolving practice patterns. It also attempts to addressand resolve controversy surrounding areas of care thathave proven more contentious, most particularly the useof the direct laryngoscope to facilitate direct trachealintubation in these patients.
The Adult Cervical Spine: Stability, Injury,and Instability
Movement and Stability of the Upper Cervical SpineFlexion–extension occurs in the upper cervical spine
at both the atlanto-occipital and atlantoaxial articula-tions, and a combined 24° of motion may be achieved.1
Flexion is limited by contact between the odontoid pro-cess and the anterior border of the foramen magnum atthe atlanto-occipital articulation and by the tectorialmembrane and posterior elements at the Cl–C2 level.Extension is limited by the contact of the posterior archof the atlas with the occiput superiorly and with the archof the axis inferiorly. The distance from the posteriorarch of the atlas to the occiput is termed the atlanto-occipital gap, and a narrow atlanto-occipital gap hasbeen cited as being a cause of difficult intubation.2 Ni-chol and Zuck2 suggested that attempts to extend thehead in patients with a narrow atlanto-occipital gapresults in anterior bowing of the cervical spine, forwarddisplacement of the larynx, and a poor view duringlaryngoscopy. This concept, although offering an elegantanatomical explanation for the clinical experience ofdifficult laryngoscopy, has yet to be validated, and thetruth may be simpler. Calder et al.3 have reported thatlimited separation of the occiput from the atlas and theatlas from the axis yields an immobile upper spine andreduces both cervical spine extension and mouth open-ing, resulting in difficult direct laryngoscopy.
The ligaments contributing to the stability of the uppercomplex are the transverse, apical, and alar ligamentsas well as the superior terminations of the anterior andposterior longitudinal ligaments (fig. 1). In adults, thetransverse ligament normally allows no more than 3mm of anteroposterior translation between the dens and
* Professor.
Received from the Department of Anesthesiology, University of Ottawa, Ot-tawa, Ontario, Canada. Submitted for publication March 10, 2005. Accepted forpublication October 24, 2005. Support was provided solely from institutionaland/or departmental sources.
Address correspondence to Dr. Crosby: Department of Anesthesiology, TheOttawa Hospital–General Campus, Room 2600, 501 Smyth Road, Ottawa, On-tario, Canada, K1H 8L6. [email protected]. Individual article reprints may bepurchased through the Journal Web site, www.anesthesiology.org.
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the anterior arch of the atlas. This may be measured onlateral radiographs of the neck and is termed the atlas–dens interval. If the transverse ligament alone is dis-rupted and the alar and apical ligaments remain intact,up to 5 mm of movement may be seen. If all the liga-ments have been disrupted, 10 mm or more of displace-ment may be seen. Destruction of these ligaments is acommon consequence of severe and long-standing rheu-matoid arthritis.4
Significant posterior displacement of the dens reducesthe space available for the spinal cord (SAC) in thevertebral column. The SAC is defined as the diameter ofthe spinal canal measured in the anteroposterior plane,at the Cl level, that is not occupied by the odontoidprocess. The SAC represents the area composed of bothcord and space. The area of the spinal canal at Cl may bedivided into one third odontoid, one third cord, and onethird “space.” The one third space allows for some en-croachment of the spinal lumen without cord compro-mise. However, when this margin of safety has beenexhausted, compression of neural elements will occur;persistent compression will eventually lead to myelopa-thy and neurologic deficit. The cord occupies a greaterproportion of the available SAC in the subaxial spine; atthe C6 level, approximately 75% of the SAC is occupiedby the cord.5
Movement and Stability of the Lower CervicalSpineA further 66° of flexion–extension may be achieved in
the lower cervical spine, with the C5–C7 segments con-tributing the largest component. There is an inverserelation between age and range of motion, i.e., as ageincreases, mobility decreases. However, most of the de-crease occurs at the C5–C7 motion segments, and thisusually does not have a significant impact on the ease ofdirect laryngoscopy. With the head in the standard sniff-ing position, the cervical spine below C5 is relativelystraight; there is increasing flexion from C4 to C2, andthe occipitoatlantoaxial complex is at or near full exten-sion.
In the lower cervical spine, the structures contributing
to stability include, from anterior to posterior, the ante-rior longitudinal ligament, the intervertebral discs, theposterior longitudinal ligament, the facet joints withtheir capsular ligaments and the intertransverse liga-ments, the interspinous ligament, and the supraspi-nous ligaments (fig. 2). The posterior longitudinal lig-ament and the structures anterior to it are grouped asthe anterior elements or anterior column (fig. 3). Theposterior elements or posterior column are thosegrouped behind the posterior ligament. Motion seg-ments are defined as two adjacent vertebrae and theintervening soft tissue elements.
Fig. 1. Ligaments of the atlantoaxial joint. View is from above,with the skull removed.
Fig. 2. The ligaments of the lower cervical spine, sagittal section.
Fig. 3. Schematic representation of the two column concept ofthe spine. From White AA III, Panjabi MM: Clinical biomechan-ics of the spine. Philadelphia, JB Lippincott, 1978; used withpermission.
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Cervical Spinal Instability after Injury: Mechanismsand ConsequencesWhite et al.6 have defined stability as “the ability of the
spine to limit its pattern of displacement under physio-logic loads so as not to allow damage or irritation of thespinal cord or nerve roots.” Instability occurs whenphysiologic loading causes patterns of vertebral displace-ment that jeopardize the spinal cord or nerve roots.7
Instability may result from congenital anomalies, ac-quired conditions related to chronic disease, and acutelyafter trauma. The following discussion will primarilyrelate to traumatic instability.
One element in the injured column must be preservedto achieve spinal stability. Clinically, to ensure a marginof safety, preservation of elements in the injured columncannot be assumed, and the spine must be considered tobe potentially unstable until proven otherwise. The an-terior column contributes more to the stability of thespine in extension, and the posterior column exerts itsmajor forces in flexion. Therefore, the anterior elementstend to be disrupted in hyperextension injuries, and theposterior elements tend to be disrupted in hyperflexioninjuries. With extreme flexion or extension or if either acompressive or rotational force is added, both columnsmay be disrupted.
Flexion injuries usually cause compression of the an-terior column and distraction of the posterior column(fig. 4).5 Pure flexion trauma may result in wedge frac-ture of the vertebral body without ligamentous injuries.These injuries are stable and are rarely associated withneurologic injuries. With more extreme trauma, ele-ments of the posterior column are disrupted as well, andfacet joint dislocation may result. These injuries are un-stable and are associated with a high incidence of corddamage. Flexion–rotation injuries also commonly dis-rupt the posterior ligamentous complex and may alsoproduce facet joint dislocation. They tend to be stableand are not usually associated with spinal cord injury,although cervical root injury is common. Hyperexten-sion injuries cause compression of the posterior column
and distraction of the anterior column (fig. 4). Hyperex-tension combined with compressive forces (e.g., divinginjury) may result in injury to the lateral vertebralmasses, pedicles, and laminae. Because both anterior andposterior columns are disrupted, this injury is unstableand is associated with a high incidence of cord injury.Violent hyperextension, with fracture of the pedicles ofC2 and forward movement of C2 on C3, produces atraumatic spondylolisthesis of the axis, or hangman’sfracture. The fracture is unstable, but the degree ofneurologic compromise is highly variable, because thebilateral pedicular fractures serve to decompress thespinal cord at the site of injury.
Burst fractures are caused by compressive loading ofthe vertex of the skull in the neutral position and are notas common as flexion–extension injuries. Compressionforces in the lower cervical spine result in the explosionof intervertebral disc material into the vertebral body.Depending on the magnitude of the compression load-ing and associated angulating forces, the resulting injuryranges from loss of vertebral body height with relativelyintact margins, to complete disruption of the vertebralbody. Posterior displacement (retropulsion) of commi-nuted fragments may result, producing cord injury; thespine is usually stable. Pure distraction injuries areuncommon but, if severe, may result in ligamentousdisruption causing both cord trauma and an unstablespine.
Determining Stability of the Cervical Spine afterInjuryBecause spinal instability usually results in vertebral
displacement, it may be detected in many instances byradiography. White and Panjabi8 identified the upperlimit of vertebral displacement and that which is beyondthe physiologic range. They concluded that a normaladult spine would not permit horizontal motion greaterthan 2.7 mm between vertebrae. Therefore, if horizontaldisplacement exceeding 3.5 mm (corrected for x-raymagnification) or 20% of the vertebral body width was
Fig. 4. Injuring force mechanisms and re-sulting lesions. In A, a compression hy-perextension force has resulted in dis-traction of the elements of the anteriorcolumn and compression of posteriorcolumn elements; an avulsion fracturefrom the anterior-inferior margin of thevertebral body (small arrow 2) and afracture of the articular process (smallarrow 1) have resulted. In B, a flexion(large arrow 2), compression (large ar-row 1) force has produced a wedge frac-ture of the vertebral body (small arrow2) and an incomplete disruption of theinterspinous and supraspinous liga-ments (small arrow 1).
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found on lateral radiographs of the neck (or with flex-ion–extension views or dynamic fluoroscopy), this mo-tion was deemed abnormal and the spine was consid-ered unstable. With respect to angular displacement, theupper limit of physiologic angular displacement of avertebral body compared with adjacent vertebrae was11°. If there is greater angulation of the vertebra inquestion demonstrated on imaging studies, the spine isdeemed unstable at the site of the excessively rotatedvertebra.
The ligamentous structures, intervertebral discs, andosseous articulations have been extensively studied, andtheir major role in determining clinical stability has beendemonstrated.7 Although the muscles in the neck exertsome stabilizing forces, the contribution that they maketoward clinical stability has not been studied. The re-peated observation that secondary neurologic injuriesoccur frequently in spine-injured patients who are notimmobilized suggests that muscle splinting is not highlyprotective after injury.9,10
Not all cervical spine injuries result in clinical instabil-ity. Generally, fractures are considered to be clinicallyinsignificant if failing to identify them would be unlikelyto result in harm to the patient or, alternatively, recog-nizing the injury would prompt no specific treatment.Two groups have categorized, by expert consensus, anumber of injuries as not clinically important.11,12 TheNational Emergency X-Radiography Utilization Study(NEXUS) group identified the following injuries as notclinically significant: spinous process fractures, wedgecompression fractures with loss of 25% or less of bodyheight, isolated avulsion fractures without ligament in-jury, type 1 odontoid fractures, end-plate fractures, iso-lated osteophyte fractures, trabecular fractures, and iso-lated transverse process fractures.11 Similarly, theCanadian CT Head and Cervical Spine Study group iden-tified the following injuries as not significant: simpleosteophyte fractures, transverse process fractures, spi-nous process fractures, and compression fractures withloss of less than 25% of body height.12
Mechanisms of Spinal Cord InjuryThere are a number of mechanisms implicated in pri-
mary spinal cord injuries. Immediate neural damage mayresult from shear, compressive, ballistic, or distractingforces, which primarily avulse and devitalize tissues.Persistent cord compression from fracture–dislocationmay lead to ischemia. The cord may be injured by bonefragment or missile injury with resultant laceration, con-tusion or concussion.13 Secondary and progressive in-jury may also result from local perfusion deficits due tovascular compression by deranged anatomy (e.g., tissuedamage or edema) or from global perfusion compromisecaused by systemic hypotension. In addition, tissue hy-poxemia leading to secondary injury may also occur as aresult of hypoventilation caused by head or cord injury
or by primary lung trauma. Finally, there are multiplemechanisms at the cellular and subcellular level that mayresult in exacerbation of the injury resulting in an exten-sion of the clinical deficit.14
The impact of persistent cord compression and thebenefits of urgent decompression of injured cord havebeen assessed by a number of authors. Carlson et al.15
determined the relation between the duration of sus-tained spinal cord compression and the extent of spinalcord injury and the capacity for functional recovery afterimmediate decompression. Sixteen dogs underwent spi-nal cord compression for 30 or 180 min. Sustained cordcompression was associated with a gradual decline inthe amplitude of evoked potentials. Within 1 h of de-compression, dogs that had experienced 30 min of com-pression had recovery of the evoked potentials, but noanimal that had been subjected to 180 min of compres-sion had similar recovery. Motor tests demonstratedrapid recovery of hind-limb function in the 30-mingroup, but there was considerable impairment in the180-min group, and this impairment was persistent. In asimilar model, Delamarter et al.16 demonstrated thatneurologic recovery after 1 h of cord compression oc-curred after immediate decompression but not whencord compression persisted for 6 h or more.
Despite the basic science support for early decompres-sion after spinal cord injury, two recent reviews haveconcluded that the evidence supports decompression asa practice option only.17,18 The authors of these reviewsconcluded that the data assessing the impact of earlydecompression on neurologic outcomes was limited,consisted of primarily class III (case series, retrospectivereviews, and opinion) and limited class II (prospectivecohort studies or controlled studies with comparisoncohorts) evidence, and demonstrated a possible benefitto patients with incomplete injury only. Both early de-compression and conservative management were asso-ciated with neurologic improvement in some patientsand deterioration in others. Both groups of authors ac-knowledged the need for randomized, controlled trialsto better delineate the role of surgery in the managementof acute spinal cord injury.17,18
Biomechanics of the Spinal Cord and CanalFor proper functioning of the spinal cord, a minimum
canal lumen is required, both at rest and during move-ment. Cord compromise will result if the canal space isless than that required for cord function; neurologicinjury will occur if this reduction in canal space is per-sistent. The neurologic injury results from sustained me-chanical pressure on the cord leading to both anatomicaldeformation and ischemia. A reduction in canal size isoften seen with age-related changes in spinal anatomysuch as disc degeneration, osteophyte formation, hyper-trophy of the ligaments of the spinal column, and thevertebral subluxations common in the chronic arthriti-
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des. Canal size may also be reduced acutely with trau-matic injury to the spinal column. Although neurologicdeficits do not directly correlate with the degree ofposttraumatic reduction of the spinal canal, canal im-pingement is more commonly observed in patients withboth spinal injury and neurologic deficit than in patientswho do not have a deficit after spinal injury.19
The functional size of the spinal canal may be furtherreduced with movement. The spinal canal is a column ofrelatively fixed volume.20 As it lengthens, its cross-sec-tional area will be reduced, and as it is shortened, its areawill be increased; this behavior is termed the Poissoneffect. With flexion, the canal length is increased and itsarea is reduced; the cord is stretched. This occurs be-cause the axis of rotation of the spine is centered in thevertebral body.21 As the spine flexes, the rotation pointswill transcribe an arc; posterior spinal elements, includ-ing the canal, will also transcribe an arc, but that of alarger circle and will axially lengthen (fig. 5).22 ThePoisson effect dictates that both the lumen of the canaland the spinal cord will narrow as they lengthen. Thecord will tolerate a degree of elastic deformation whilemaintaining normal neurologic function.20 It may befurther stretched and deformed if there is a local anom-aly such as an osteophyte, prolapsed disc, or subluxedvertebral body projecting into the canal. These deforma-tions may, over time, result in the application of strainand shear forces to the cord and ultimately result inaxonal injury and myelopathy.23
With extension, the canal length is decreased and itsarea is increased; the cord is shortened. Again, this is aneffect of the axis of rotation being centered in the ver-tebral bodies and the posterior spinal elements includingthe canal now transcribing the arc of a smaller circle; thePoisson effect will dictate canal widening. However, theshortening and folding of the cord when the spine is inextension may result in a relative increase in the ratio ofcord size to canal lumen, despite the potential increasein the lumen. As well, there is posterior protrusion of thedisc annulus and buckling of the ligamentum flavum inextension, which may further reduce canal dimensionsand the space available for the cord at any given verte-
bral level. A number of age-related pathologic processes,including osteophyte formation and ossification of theposterior longitudinal ligament, may lead to further im-pingement on the canal lumen; these typically manifesta greater impact during spinal extension.
Ching et al.24 measured the impact of different posi-tioning on canal occlusion in a cervical spine burstfracture model. Extension increased the canal occlusionto levels normally associated with the onset of neuro-logic injury. Flexion did not result in a significant in-crease in canal occlusion. These observations run coun-terintuitive to what might be expected on the basis ofthe Poisson effect and are likely manifestations of boththe soft tissue buckling and bone fragment retropulsionwhich occur during extension. Prone positioning is alsooften associated with modest degrees of extension, andthere is evidence that canal stenosis is increased withpatients with cervical myelopathy who are positionedprone compared with supine positioning.25 Again, this islikely a manifestation of the soft tissue encroachment onthe spinal canal with extension and aggravated by thepreexistent canal compromise. The clinical relevance ofthese findings is that a persistent malposition of an ab-normal neck may result in a degree of cord compression.If the abnormality is modest, it is likely that the malpo-sition will need to be of greater magnitude and moreprolonged to cause harm; as the anatomical derange-ment is increased, the duration of positional stress re-quired to cause harm is shortened.15,26 Prone position-ing is also associated with increases in vena cavalpressures that may further reduce cord blood flow al-ready compromised by cord compression.27
Dominguez et al.28 reported the occurrence of irre-versible tetraplegia in a 21-yr-old woman without cervi-cal pathology whose neck was maintained in extremeflexion after tracheal reconstruction; a magnetic reso-nance imaging (MRI) study was consistent with cordinfarction. Deem et al.29 reported the occurrence ofquadriparesis in a 60-yr-old man with severe cervicalstenosis after thoracolumbar surgery in the prone posi-tion. The patient’s trachea was intubated, and he waspositioned prone while still awake; anesthesia was in-
Fig. 5. The Poisson effect: schematic rep-resentation. The axis of rotation is indi-cated by the small squares superimposedon the vertebral bodies. In the neutralposition (A), the gentle arc of the normallordotic curve is transcribed. In exten-sion (B), the elements posterior to thebodies, including the canal, transcribethe arc of a smaller circle than that of thevertebral bodies, indicated by the smallcircles. In flexion (C), the opposite effectis seen, and the arc of a larger circle istranscribed by the posterior elements.The Poisson effect dictates that as thelength increases (the arc is of a largercircle), the cross-sectional area (lumen)of the column will decrease.
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duced after his cervical spinal positioning was ascer-tained to be near neutral, and neurologic examinationresults were deemed normal. When he awoke from an-esthesia after 6 h of surgery, there was evidence of acentral cord syndrome. The authors acknowledge thepossibility that, even though extreme degrees of flexionand extension were avoided, more subtle degrees ofmalpositioning may have been present. Unfortunately,cord injury may occur when positions detrimental tocanal architecture are persistent; the greater the degreeof underlying spinal pathology is, the lesser the magni-tude of malpositioning required to cause harm is. Theprone position may be especially threatening in theseinstances for the reasons already outlined.
Patients with severe cervical spondylosis may manifestsuch severe positional intolerance that they developsymptoms of cord compromise with degrees of malpo-sition that may be imperceptible to the caregivers. Milleret al.30 described exacerbation of neurologic symptomsin a 74-yr-old women with an osseous bar at C3–C4 whopresented with signs of cord compression and wasbooked for cervical laminectomy. On the first surgicaloccasion, after awake tracheal intubation accomplishedwith sedation, she was considerably weaker than beforeintubation. Surgery was cancelled, and her trachea wasextubated; her neurologic condition returned to baselinewithin 2 h. Four days later, she presented for surgery inhalo traction, and after sedation with intravenous diaze-pam, her neurologic condition deteriorated. A joint de-cision was made to induce anesthesia and proceed withtracheal intubation and surgical laminectomy at theC3–C5 spinal levels. Although she awoke with signs ofneurologic deterioration, she recovered to her baselinecondition by the fourth hour. The authors of this reportpostulated that the increased neurologic symptoms werean effect of the medications administered to facilitateawake intubation. Whether the drugs actually causeddeterioration in the patient’s neurologic status or madethe neurologic assessment less reliable is not certain.Equally unknown is whether, in general, patients mightbe more likely to overlook or underreport neurologicchanges that occur if they were sedated during awakeintubation. The reliability of a neurologic assessment ina sedated patient might be questioned, especially if oneis seeking evidence of subtle changes.
Bejjani et al.31 reported the case of a 54-yr-old womanwith cervical spondylosis and canal stenosis from C4 toC7 who developed signs of cord compression while herhead was restrained in a plastic head-holder for thepurpose of cerebral angiography. Approximately 45 minafter the procedure had begun, she reported neck painand upper extremity weakness; her symptoms were at-tributed to anxiety, and she was sedated. At the termi-nation of the procedure, she was hemiparetic on the leftside; an MRI study revealed a high-signal lesion consis-tent with edema. She recovered completely over the
next 6 weeks. The potential for general anesthesia topermit positioning for MRI in postures not tolerated byawake patients with resultant neurologic injury has alsobeen reported.32
Magnaes33 measured cerebral spinal fluid pressurewith the neck in the extended position for trachealintubation, in eight patients with a compromised spinalcanal due to cervical spondylosis. Pressures up to ap-proximately 140 cm H2O were recorded. Longitudinalskeletal traction with the tong placed frontally signifi-cantly reduced the pressure on the spinal cord in allpatients. This finding would suggest that there is likely abenefit, in terms of decreased intracanal pressures, inmaintaining the compromised cervical spine in as closeto the neutral position as possible at all times after injury.As has already been noted, it may be very difficult todetermine neutral position in some patients.
Persistent severe malpositioning at the extremes of thespinal range of motion has the potential to cause harmeven in the normal spine–cord complex. In patientswith disease processes that result in spinal canal com-promise, minor degrees of malpositioning may also re-sult in severe stress to the cord. If these positions areenforced, especially for prolonged periods, neurologicinjury may result. As well, the use of sedation or anes-thesia to allow patients to be maintained in positions thatare neurologically intolerable to them while awake mayalso result in neurologic injury.
The Incidence of Cervical Spinal Injury after BluntTraumaThe incidence of CSI in victims of blunt trauma is
estimated to be 0.9–3%, with a weighted average of1.8%.34 Many of these previously published studies eval-uating CSI after blunt trauma involved data from individ-ual institutions or limited populations of trauma victims;there have been few data available regarding injury pat-terns at a national level. A substudy of NEXUS wasdesigned to provide such data regarding the prevalence,spectrum, and distribution of CSI after blunt trauma.35 Atotal of 34,069 patients with blunt trauma undergoingcervical spine radiography at 21 US institutions wereenrolled. Consistent with past reports, 818 (2.4%) oftrauma victims had a total of 1,496 distinct CSIs. Thesecond cervical vertebra (C2) was the most commonlevel of injury (24.0% of all fractures), and 39.3% offractures occurred in the two lowest cervical vertebrae(C6, C7). The vertebral body was the most frequentanatomical site of fracture; nearly one third of all injuries(29.3%) were considered clinically insignificant.
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Cervical Spine Injury and AssociatedCraniocerebral TraumaAlthough it has been reported that patients with
craniocerebral trauma had an incidence of CSI similar tothat of the general trauma population, review of thelarge databases evolving at major trauma centers nowdispute this finding. Holly et al. 36 reviewed 447 consec-utive, moderately to severely head-injured patients pre-senting to two level l trauma centers. Twenty-four pa-tients (5.4%) had a CSI; patients with an initial GlasgowComa Scale (GCS) score less than 8 were more likely tosustain both a CSI and a cord injury than those withhigher scores. Demetriades et al.37 conducted a similarreview of all CSI patients admitted over a 5-yr period ata major trauma center. During the study period, therewere 14,755 admissions and 292 patients with CSI, foran overall incidence of 2.0%. Again, the incidence of CSIvaried with the GCS score, being 1.4% if the GCS scorewas 13–15, 6.8% when it was 9–12, and 10.2% when itwas less than 8. Hackl et al.38 used a large computerizeddatabase to assess the association between CSI and facialinjuries in 3,083 patients with facial injuries. Two hun-dred six (6.7%) of these patients had experienced aconcomitant CSI, an incidence substantially higher thanwould be expected after blunt trauma. Blackmore etal.39 reviewed their institutional experience with 472patients with trauma (168 with cervical fractures, 302without fractures) to delineate the clinical characteris-tics of trauma patients with cervical fracture. The clinicalpredictors of cervical spine injury included severe headinjury (odds ratio, 8.5; 95% confidence interval [CI],4–17) and focal neurologic deficit (odds ratio, 58; 95%CI, 12–283). In patients with head injury, those whowere persistently unconscious had an even higher like-lihood of spinal injury (odds ratio, 14; 95% CI, 6–35)than those with head injury who were not unconscious.Therefore, new evidence has emerged that consistentlysuggests a higher incidence of cervical injury in patientswho have experienced craniocerebral trauma, especiallyamong those with increasing severity of craniocerebralinjury as determined by low GCS score and unconscious-ness. The finding of a focal neurologic deficit has beenidentified as a highly important clinical finding predict-ing spinal injury.39
Systemic Injuries Associated with Cervical SpineInjuryThe majority of patients with CSI also have other
injuries; in only 20% of instances are traumatic injuriesrestricted to the cervical spine.40 Although 2–10% ofpatients with craniocerebral trauma have CSI, 25–50% ofpatients with CSI have an associated head injury. Patientswith additional injuries are more likely to experiencehypoxia and hypotension, both of which may not onlyprompt urgent airway intervention, but may also predis-pose to secondary neurologic injury. There is data to
suggest reduced neurologic recovery and increased mor-tality in cord-injured patients who have concurrent in-jury. It is not clear whether these patients experiencedmore severe primary injury or whether they are morelikely to experience secondary injury leading to thepoorer outcome.
Defining the Low-risk Trauma PatientThe National Emergency X-Radiography Utiliza-
tion Study. The majority of patients who have experi-enced a blunt traumatic injury do not have a CSI. Enor-mous resources are currently expended to clear thespine (determine the absence of injury when injury doesnot exist) in these patients. The NEXUS project at-tempted to derive a set of clinical criteria to identifyblunt trauma victims at low risk for CSI.41 The decisioninstrument required patients to meet five criteria to beclassified as having a low probability of injury: (1) nomidline cervical tenderness; (2) no focal neurologic def-icit; (3) normal alertness; (4) no intoxication; and (5) nopainful, distracting injury. Distracting injuries were de-fined as including long bone fractures; visceral injuriesrequiring surgical consultation; large lacerations; burns;degloving or crush injuries; or any injury that mightimpair the patient’s ability to participate in a generalphysical, mental, or neurologic examination. The deci-sion instrument was applied to 34,069 patients and iden-tified as high risk all but 8 of the 818 patients who hada CSI (sensitivity, 99%; 95% CI, 98–99.6%). The negativepredictive value was 99.8% (95% CI, 99.6 –100%),the specificity was 12.9%, and the positive predictivevalue was 2.7%. Only two of the eight patients missedby the screening protocol had a clinically significantinjury. In the NEXUS study, plain radiographs alonerevealed 932 injuries in 498 patients but missed 564injuries in 320 patients.42 The majority of missed in-juries (436 injuries in 237 patients) occurred in casesin which plain radiographs were interpreted as abnor-mal (but not diagnostic of injury) or inadequate. How-ever, 23 patients had 35 injuries (including three po-tentially unstable injuries) that were not visualized onadequate plain film imaging. In the absence of all fiveclinical risk factors identified by the NEXUS study aspredicting an increased risk of CSI, the likelihood of asignificant injury is low. The practice of withholdingimaging for patients who meet these exclusionarycriteria has been endorsed by recent neurosurgicalguidelines.43
The Canadian C-Spine Rule for Radiography afterTrauma. The Canadian CT Head and Cervical SpineStudy Group attempted to derive an optimally sensitiveclinical decision rule to allow for selectivity in the use ofradiography in alert and stable trauma patients.12 A pro-spective cohort study was conducted in 10 large Cana-dian hospitals and included 8,924 consecutive adult pa-tients presenting to emergency departments after
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sustaining acute blunt trauma to the head or neck. Pa-tients were eligible for enrollment if they were alert(GCS of 15), if they had stable vitals signs, and if they hadeither neck pain after injury or had no neck pain butvisible injury above the clavicles after a dangerous mech-anism of injury. The patients were assessed using 20standardized clinical findings from the history, generalphysical examination, and an assessment of neurologicstatus. Patients then underwent diagnostic imaging atthe discretion of the treating physician; this imagingconsisted of a minimum of three views of the cervicalspine.
Among the study sample, 151 patients (1.7%) had animportant cervical injury. The resultant rule that wasderived comprises three questions: (1) Is there any high-risk factor present that mandates radiography? (2) Arethere low-risk factors that would allow a safe assessmentof a range of motion? and (3) Is the patient able toactively rotate the neck 45° to the left and to the right?When applied to the study population, the derived rulehad 100% sensitivity and 42.5% specificity for identifyingpatients with clinically important injuries. The rule alsoidentified 27 of 28 patients with clinically unimportantcervical injuries (primarily avulsion fractures), defined asthose not requiring stabilization or follow-up.
The NEXUS Low-Risk Criteria were compared prospec-tively with the Canadian C-Spine Rule in 8,283 patientspresenting to Canadian hospital emergency departmentsafter trauma.44 Two percent of patients had clinicallyimportant cervical injuries, and the C-Spine Rule wasboth more sensitive than the NEXUS criteria (99.4% vs.90.7%) and more specific (45.1% vs. 36.8%) for injury.The C-Spine Rule would have missed one patient, andthe NEXUS criteria would have missed 16 patients withimportant injuries.
Strategies to define a low-risk clinical population con-tinue to evolve. It must be emphasized that the primaryfocus and utility of these strategies is to allow for selec-tive use of diagnostic imaging in patients who have alow-risk of injury, thus reducing imaging use and patientexposure, conserving resources, and allowing for expe-dited and simplified care for this patient group. A criti-cism leveled at the NEXUS protocol is that applicationwould have a limited impact in reducing imaging be-cause only 12.9% of patients presenting after traumawould be deferred; most would not meet at least onedeferral criteria.45 Application of the C-Spine Rule wouldallow for the exclusion of 42.5% of trauma patients fromradiographic imaging. The original rationale for the der-ivation of the protocols, to provide more efficient careand conserve imaging resources, is satisfied to a verylimited degree by the NEXUS protocol but to a greaterdegree by the C-Spine Rule. Application of either proto-col will still demand imaging in a large portion of thetrauma patient population at low risk for CSI.
There will be a small population of patients presenting
for urgent surgical intervention after minor injury whoare fully evaluable using either the NEXUS criteria(12.9%) or the C-Spine Rule (42.5%); it is likely notnecessary to delay surgery to clear the cervical spine ofthese patients with detailed imaging. Unfortunately,many patients presenting for urgent operative interven-tions after trauma will manifest more severe injuries; itwill not be possible to clinically rule out injury in thispatient cohort, and they will still require diagnostic im-aging. As well, application of these protocols is compli-cated by the fact that there is a lack of agreement on thedefinitions of both distracting injury and intoxication.Failure to appreciate the degree of both distraction andintoxication may reduce the clinical index of suspicionfor injury, resulting in missed diagnosis.
Patterns of Practice in Evaluating and Clearing theCervical Spine after TraumaTwo authors have recently reported descriptions of
patterns of practice in the United States and the UnitedKingdom obtained through postal surveys regardingevaluation and clearance of the cervical spine after trau-ma.46,47 Grossmann et al.46 surveyed 165 US traumacenters and reported that between 26 and 73% hadwritten protocols for cervical spine clearance aftertrauma. It was more common for level I and academiccenters to have protocols. In most instances where aprotocol existed, it also described the radiographic ap-proach to clearance; most centers did not consider thateither computerized tomography (CT) or MRI was thestandard of care in this setting. The use of a five-viewseries was moderately prevalent in response to specificscenarios, and the problem of visualizing the cervicotho-racic junction was dealt with in most centers (68%) usingan axillary/swimmer’s radiographic view. For patientswith a head injury who are comatose or who havealtered mental status and who have normal plain films,21% of level II and 10% of level I centers advocatedremoval of the cervical collar without further testingbeyond a five-view series.
Jones et al.47 surveyed 27 United Kingdom neurosur-gical and spine injury units to determine the methods ofcervical spine clearance used in unconscious, adulttrauma patients and the point at which immobilizationwas discontinued. Most centers did not have either awritten protocol to perform clearance or one regardingdiscontinuing cervical immobilization (78%). All unitsrelied to some degree on plain radiography for clear-ance; 10 units (37%) performed only a single lateral viewas the initial evaluation, and the remainder performedtwo more views. Five units routinely used CT imaging,and 17 units (63%) made no use of CT to screen forcervical injury. If the initial investigations were normal,12 units (44%) would discontinue immobilization, and10 units continued it until the patient could be evaluated
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clinically irregardless as to the results of the screeningimaging.
The Eastern Association for the Surgery of Traumarecently reported the results of a survey of 31 largeAmerican and Canadian trauma centers.† Centers wereasked to identify their routine practice for determiningcervical spinal stability in obtunded or comatose patients.Twenty-four centers (77%) reported using three views ofthe cervical spine (lateral, odontoid, and antero-posteriorviews) supplemented by CT through suspicious or poorlyvisualized areas. Three centers (9.7%) relied on three viewsonly, and three centers (9.7%) added a swimmer’s view tovisualize the lower cervical spine and the cervicothoracicjunction.
There is considerable variation in the approach thatdifferent centers take in the performance of radiographicevaluation of at-risk patients, making the determinationthat the spine has been cleared, and reaching the deci-sion that immobilizing devices can be safely removed.The most common pattern of practice in North Ameri-can centers is to rely on multiple (at least three views)plain radiographs; the use of supplementary CT is alsocommon.
Radiographic Assessment after Blunt Trauma:Evolving a Best PracticeAn evaluative approach that would provide timely and
accurate assessment of cervical stability in patients whomay not be reliably examined clinically so that immobi-lizing devices can be safely removed is desirable. Thiswould minimize the potential for sequelae related toprolonged immobilization. The reader is referred tothree excellent reviews on the topic of evaluating andclearing the cervical spine in high-risk patients; thesereviews form the basis of the subsequent discus-sion.45,48,49
The cross-table lateral radiograph, of acceptable qual-ity and interpreted by an expert, will disclose the major-ity of injuries. However, the sensitivity of the cross-tableview is such that up to 20% of patients with cervicalinjury will have a normal study. Half of cross-table viewsare deemed inadequate to properly assess the entirecervical anatomy; injuries at both the craniocervical andthe cervicothoracic junctions are often not well visual-ized in the cross-table view. Too many injuries aremissed when only a cross-table view is used for it to beconsidered an acceptable study to rule out injury in ahigh-risk patient. The sensitivity of three views (cervicalseries) approximates 90%; the cervical series was longregarded as an acceptable radiologic evaluation in pa-tients deemed at risk for CSI. Similar technical concerns
apply to the cervical series as to the cross-table lateralview with respect to both anatomical limitations at thecervical junctions and inadequate studies being issues. Itis estimated that 1% of clinically important injuries willbe missed even with a technically adequate cervicalseries.
A three-view cervical series supplemented by CTthrough areas that are either difficult to visualize orsuspicious on plain radiography will detect most spinalinjuries. The negative predictive value of this combina-tion of studies is reported to be 99–100% in several classII and III evidence studies.45,48,49 In the obtunded pa-tient with a normal cervical series and appropriate sup-plemental CT of the cervical spine, the incidence ofsignificant spine injury is less than 1%. High-resolutionCT scanning with sagittal reconstruction of the entirecervical spine rather than directed scanning of only at-risk areas may be even more effective in capturing vir-tually all injuries.
The use of MRI in addition to plain radiography andsupplemental CT has been advocated to perform spinalclearance; the significance of a positive MRI study in thesetting of negative CT imaging is currently unclear be-cause many false-positive findings are reported withMRI. As well, MRI is less sensitive than CT for injuries inthe upper and posterior cervical spine. Shuster et al.50
studied the role of MRI in assessing the spines of patientswith persistent cervical pain and no motor deficits aftertrauma when the CT imaging was negative for injury.Ninety-three patients (3.4%) had a normal admissionmotor examination, a CT result negative for trauma, andpersistent cervical spine pain; they underwent MRI ex-amination. All MRI examinations were negative for clin-ically significant injury, and no patient subsequently ex-perienced a neurologic deterioration. Hogan51 assessedthe role of magnetic resonance imaging in 366 obtundedor unreliable patients who had normal CT imaging aftertrauma. Magnetic resonance images were negative foracute injury in 354 of 366 patients; the most commoninjury seen was a cervical cord contusion, identified in 7patients. Magnetic resonance images were also negativefor spinal ligament injuries in 362 of 366 patients; 4patients had ligament injuries, but in all cases, the injurywas limited to the ligaments of a single column. CT hadnegative predictive values of 98.9% for ligament injuryand 100% predictive value for unstable cervical injury;MRI identified a small number of patients with ligamentinjuries not diagnosed with CT, but none of these weredeemed to be unstable injuries.
In summary, in a patient at high risk for cervical injury,who cannot be evaluated clinically, a three-view cervicalseries supplemented by high-resolution CT scanningwith sagittal reconstruction will reduce the likelihood ofan occult fracture to less than 1%. After a technicallyadequate imaging series has been reviewed and clearedby a radiologist, it is prudent to remove cervical immo-
† Eastern Association for the Surgery of Trauma: Determination of cervicalspine stability in trauma patients. Winston-Salem, North Carolina, EAST, 2000.Available at: www.east.org/tpg/chap3u.pdf. Accessed October 27, 2005.
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bilization. If there is evidence of a neurologic deficitreferable to the cervical spine despite the finding ofnormal cervical radiography and CT imaging, MRI shouldbe considered.
Spinal Ligament Injuries and Spinal Cord Injurywithout Radiographic AbnormalitySpinal ligament injuries are of particular concern be-
cause of the high incidence of resultant spinal instability,the potential for cord injury, and the hemodynamicinstability common at presentation in this subpopula-tion. In Demetriades’37 review of CSI patients admittedduring 5 yr to a major trauma center, 31 patients (10.6%)had a ligament injury (subluxation without fracture), and11 patients (3.8%) had an isolated spinal cord injurywithout fracture or subluxation (spinal cord injury with-out radiographic abnormality [SCIWORA]). Of the 31patients with ligament injury, one third required trachealintubation before clinical evaluation of the spine wascompleted. Of the 11 patients with spinal cord injurywithout radiographic abnormality, 27.3% required intu-bation before spinal evaluation occurred. The diagnosisof cord injury was made on admission in only 5 patients(45.5%) with spinal cord injury without radiographicabnormality. In 3 patients, the neurologic examinationon admission was normal, and neurologic deficits ap-peared a few hours later. In the remaining 3 patients (2intubated, 1 intoxicated), the diagnosis was missed ini-tially. Patients who required urgent airway interventionwere less likely to have had a complete neurologic eval-uation and were more likely to have neurologic injurythan those who did not require urgent interventions.Chiu et al.52 also investigated the incidence of cervicalspinal ligament injury in 14,577 blunt trauma victims. Sixhundred fourteen patients (4.2%) had CSI, and 87 (14%of CSI) had dislocation without evidence of fracture.There were 2,605 (18%) patients who could not beassessed for symptoms, and 143 (5.5%) of these unreli-able patients had a CSI; 129 (90%) had a fracture, and 14had no fracture.
Trauma patients with greater severity of injury aremore likely to have had a CSI; clinical evaluation is moredifficult in these patients, typically because of depressedconsciousness. Patients with ligament injury of the cer-vical spine without fractures frequently require urgentintubation, and not uncommonly, clinical evaluation iseither not possible or not complete at the time thatintervention is required; delay in the diagnosis of injuryis common in these patients.
Failure to Diagnose Cervical Spine Injury at InitialAssessment: Factors and ConsequencesPatients with decreased mental status from trauma,
alcohol, or drugs and patients with other painful ordistracting injuries have an unreliable history andphysical examination for CSI; patients with these char-
acteristics have spinal injuries that are also more likelyto be missed on initial presentation. The commonestreasons for missed diagnosis are failure to obtainradiographs, poor quality of the imaging study, ormisinterpretation of the radiographs.9,10 Inadequateradiographic studies are more likely in patients withhemodynamic compromise on admission or in thosepatients urgently requiring intervention for operativetreatment of associated injuries. Unfortunately, missedinjuries are often unstable, and secondary neurologiclesions occur in 10 –29% of patients whose injuries arenot diagnosed at initial evaluation.9,10 Failure to im-mobilize the spine in patients whose injuries aremissed at the initial assessment is considered to be aleading cause of secondary injury.
Poonnoose et al.53 conducted a detailed review of theexperience of a specialty spinal cord injury unit to de-termine both the incidence of missed injury and theclinical mismanagement that occurred in the setting ofmissed injury. The medical records of 569 patients withneurologic deficits secondary to traumatic spinal cordinjury were reviewed. In 52 instances (9.1%), the diag-nosis was initially missed, and 26 of these patients (50%)had evidence of neurologic deterioration after admissionto care. The median time to recognition of the injury was4 days. Therapeutic interventions were performed in 34patients that were deemed inappropriate to their condi-tion before the diagnosis was made. In 19 patients, therewere significant neurologic findings present on initialassessment, and in 7, the initial neurologic deficit wasminimal. Nine patients eventually developed paralysis,and 6 died with the deaths attributed to the delay indiagnosis. Again, the major cause for delayed diagnosiswas related to radiographic assessments: In 18 cases, theinitial images were of poor quality; in 11 patients, thearea of concern was not adequately visualized; in 10cases, an obvious fracture was missed; in 11 cases, facetjoint malalignment was not recognized; and in 10 cases,prevertebral hematoma went undetected. It was com-mon for the clinicians to consider the spine clearedwhen the radiographs “failed” to reveal injury and toattribute neurologic findings to either preexistent con-ditions (e.g., ankylosing spondylitis) or peripheral trau-matic injuries. As well, 7 patients with evidence of neu-rologic deficits were initially labeled as “hysterical” andnot managed as at-risk.
It is unfortunately the case that patients with CSI arefrequently not correctly diagnosed at the time of initialpresentation.9,10,53,54 This may occur in a small percent-age of CSI patients because the injury is a ligamentousone and the screening imaging seems on initial review tobe negative.37,54 However, it more commonly occursbecause there is a low index of suspicion for injurydespite high-risk mechanisms, inadequate radiographicstudies are deemed acceptable, and neurologic signs orsymptoms are either attributed to other causes or ig-
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nored entirely. Delayed diagnosis is associated with avery high incidence of secondary injury, and the magni-tude of that injury is often considerable.9,10,53,54
Secondary Neurologic Injury after Cervical SpineInjurySecondary injury may be precipitated in CSI victims
when management is suboptimal, and in particular whenthe injured spine is not immobilized. However, there isalso evidence that neurologic deterioration occurs afteracute injury despite appropriate management para-digms; the reported incidence of neurologic deteriora-tion in this setting ranges from 2 to 10%.55 Frankel56
reported the occurrence of an ascending myelopathy2–18 days after spinal cord injury despite appropriateclinical management. Only patients with ascension ofinjury level of at least four levels were included in thisanalysis; despite the high threshold for inclusion, thismagnitude of secondary injury occurred in 1% of 808patients admitted to the center. Frankel attributed thedeterioration to either vascular catastrophes (arterial in-sufficiency or venous thrombosis) or inflammation; thisreport predated MRI, so no imaging is available in thesepatients to support the clinical conjecture. Marshall etal.55 reported a prospective study assessing neurologicdeterioration in cord-injured patients conducted in fiveUS trauma centers. Deterioration occurred in 4.9% ofpatients and was consistent across the five centers. Al-though the deterioration was often associated with aspecific intervention (surgery in 4 patients, traction ap-plication in 3, halo vest application in 2, Stryker framerotation in 2, and rotobed rotation in 1), there was noevidence that these procedures were performed poorlyor that they could have been performed in an alteredfashion to prevent the deterioration. There were 375such interventions recorded among the 283 patients.The authors concluded that deterioration is an inevitableconsequence of providing care to cord-injured patientsand will occur in some patients despite acceptable carepractices.
Farmer et al.57 reported the experience of a US re-gional spinal cord center regarding neurologic deterio-ration after cervical cord injury. Deterioration was evi-dent in 1.84% of 1,031 patients assessed. The averagetime from injury to deterioration was 3.95 days, anddeteriorations were associated with early surgery (� 5days after injury), sepsis, ankylosing spondylitis, andtracheal intubation. Tracheal intubation was associatedwith two minor and two major deteriorations, but nofurther details were offered regarding this cohort; it ispossible that the intubation was necessitated by theneurologic deterioration and not the cause of it. In thepatients who experienced deterioration and survived,92% of patients eventually had improvement in theirneurologic status. Harrop et al.58 analyzed the cases of
12 of 186 patients (6%) with acute traumatic cord inju-ries who demonstrated neurologic ascension within 30days after injury. Three subgroups were defined: an earlydeterioration group who worsened within 24 h, a de-layed deterioration group (1–7 days), and a late (beyond7 days) deterioration group. Two patients in the lategroup had vertebral artery injury; vertebral artery injuryis common after midcervical injury, and its clinical sig-nificance is uncertain.59,60
Yablon et al.61 described 14 cases of ascending my-elopathy (involving 1–4 levels) that occurred in the first4 weeks after injury. These cases were attributed tospinal cord edema; MRI studies demonstrated evidenceof this as well as diffuse intrathecal hemorrhage. Be-langer et al.62 identified a similar occurrence of ascend-ing myelopathy, which they labeled as subacute post-traumatic ascending myelopathy, occurring within thefirst 2 weeks after injury. This syndrome occurred inthree patients who experienced neurologic deteriora-tion with a secondary injury ascending six or more levels(6, 9, and 17 levels) from the initial level after an un-eventful early course. No etiologic factors could be iden-tified. In all three patients, T2 weighted MRI studiesrevealed a high signal intensity located centrally withinthe cord and extending rostrally from the site of injury.T2-weighted images are sensitive to the presence ofedema and effectively distinguish pathologic from nor-mal tissue; the high signal intensity identified indicatesinjury and edema.
The above reports suggest that there is a progressivepostinjury course in some patients leading to a second-ary neurologic injury and ascension of injury level, some-times to a striking degree. In some instances, this dete-rioration has been associated with clinical interventions,including immobilization, traction, surgery, intubation,and sepsis. In other instances, no clear factors are asso-ciated, and in particular, both extrinsic cord compres-sion and vascular interruptions have been excluded. Thissyndrome, when witnessed early in the course afterinjury, has usually been attributed to vascular perturba-tions or cord edema and inflammation; MRI studies havebeen consistent with this attribution. More recent workhas also suggested a role for apoptosis in the causationand progression of ascending myelopathy.63 A diagnosisof ascending myelopathy must be considered when asecondary injury has occurred; there is natural tempta-tion to attribute the deterioration to temporally relatedclinical interventions but, in fact, these interventions arerarely associated with neurologic sequelae. Progressiveneurologic injury after CSI may be inevitable in somepatients because of pathophysiologic processes initiatedat the time of the application of the injuring forces andmay occur despite the provision of appropriate manage-ment paradigms and interventions.
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Clinical Care of the Spine-injured Patient
Spinal Immobilization in Trauma Patients: TheOverviewDuring the past 30 yr, the neurologic status of spinal
cord–injured patients arriving in emergency depart-ments has dramatically improved, and the odds of dyingduring the first year after injury have been significantlyreduced.64,65 The improvement in the neurologic statusof patients has been attributed to improved initial careand retrieval systems, recognition of the importance ofinstituting prehospital spinal immobilization, maintain-ing immobilization until clearance is obtained or defini-tive therapy is applied, and hospital practices designedto prevent secondary injury. The routine use of spineimmobilization for all trauma patients, particularly thosewith a low likelihood of spinal injury, has been chal-lenged on the basis that it is unlikely that all patientsrescued from the scene of an accident or site of trau-matic injury require spine immobilization.66 A Cochranesystematic review also concluded that the impact ofimmobilization on mortality, neurologic injury, and spi-nal stability was uncertain and that direct evidence link-ing immobilization to improved outcomes was lacking.67
The Cochrane review further concluded that the poten-tial for immobilization to actually increase morbidity ormortality could not be excluded based on a review of theliterature. However, the current consensus among ex-perts remains that all patients with the potential for a CSIafter trauma should be treated with spinal column im-mobilization until injury has been excluded or definitivemanagement for CSI has been initiated.64
The benefits, consequences, and sequelae of spinalimmobilization in at-risk patients have been recentlyanalyzed, and the reader is referred to these reviews formore detailed discussions.64,68,69 The chief concern dur-ing the initial management of patients with potential CSIis that neurologic function may be further compromisedby pathologic motion of the injured vertebrae. Manage-ment of the potentially traumatized spine emphasizesthree principles: (1) restoration and maintenance of spi-nal alignment, (2) protection of the cord with preserva-tion of intact pathways, and (3) establishment of spinalstability. To achieve these principles, immobilization ofthe cervical spine before radiographic assessment andclearance is the accepted standard of care. The rationalebehind early immobilization is the prevention of neuro-logic injury in the patient with an unstable spine. Insti-tution of a clinical care paradigm that features immobi-lization as a core element has resulted in improvedneurologic outcomes in spine-injured patients during thepast three decades.64,65 Failure to immobilize in thecontext of missed or delayed diagnosis is also associatedwith an increased incidence of neurologic injury.9,10,53
Lack of immobilization has been cited as a cause ofneurologic deterioration among acutely injured trauma
patients being transported to medical facilities for defin-itive care.70
A number of complications to prolonged immobiliza-tion have been identified.64,68,69 Cutaneous ulcerations(pressure sores) are common, and the incidence in-creases when immobilization is prolonged beyond48–72 h. Airway management, central venous accessand line care, provision of oral care, enteral nutrition,and physiotherapy regimes are all made more difficultwhen immobilization must be maintained. The need formultiple staff to allow for safe positioning and transfer ofimmobilized patients makes barrier nursing more diffi-cult and may result in higher rates of cross-contamina-tion and infection in high-dependency units.
The application of cervical collars has also been asso-ciated with increased intracranial pressure (ICP) in bothinjured patients and healthy volunteers. Davies71 pro-spectively analyzed ICP in a series of injured patientstreated with a rigid collar. The ICP increased a mean of4.5 mmHg when the collar was firmly in place. Kolb72
also examined changes in ICP after the application of arigid Philadelphia collar in 20 adult patients. ICP aver-aged 17.68 cm H2O initially and increased to an averageof 20.15 cm H2O after collar placement. Although thedifference in ICP of 2.47 mm H2O was statistically sig-nificant, it remains uncertain that it has clinical rele-vance. Nonetheless, this modest increase in pressuremay be magnified in patients who already have increasedICP and poor intracranial compliance. The potential forcomplications should not discourage the use of immobi-lization where indicated. Rather, because many of thecomplications are time dependent, they should encour-age attempts to promptly assess the patient for cervicalinjury to expedite the discontinuance of immobilizationin those patients whose spines can be cleared.
Techniques and Devices for Preadmission SpinalImmobilizationThe position in which the injured spine should be
placed and held immobile, the “neutral position,” ispoorly defined. De Lorenzo et al.,73 in an MRI study of 19adults, found that 2 cm of occiput elevation produced afavorable increase in spinal canal/spinal cord ratio at theC5 and C6 levels, a region of frequent unstable cervicalspine injuries. Podolsky et al.74 evaluated the efficacy ofcervical spine immobilization techniques. Hard foam andhard plastic collars were better at limiting cervical spinemotion than soft foam collars, although the use of collarsalone did not effectively restrict spinal motion. The useof sandbag-tape immobilization was more effective atreducing spinal movement than any of the other individ-ual methods tested. Adding a Philadelphia collar to thesandbag–tape construct reduced neck extension but hadno effect on any other motion of the cervical spine.These authors found that sandbags and tape combinedwith a rigid cervical collar was the most effective con-
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struct of those evaluated to limit cervical spine motion,restricting movement to approximately 5% of the normalrange. The sandbag–tape–backboard–collar and varia-tions thereof have become the most commonly usedextrication and transport assembly in prehospital traumacare to provide spinal immobilization.
Bednar75 assessed the efficacy of soft, semirigid, andhard collars to immobilize the neck in a destabilizedelderly cadaver model. Bednar’s experiment involvedcreation of unstable motion segments at the C3–C4,C4–C5, or C5–C6 levels; isolated posterior column, com-bined column, and then anterior column injuries weresequentially assessed. Soft, semirigid, and rigid collarswere used in an attempt to restrict neck movements, andthen the spines were subjected to unrestrained gravita-tional forces with flexion, lateral side-bending, and ex-tension. The collars were not effective in reducing spinalmovement; in fact, there was evidence for increasedspinal movement. Bednar hypothesized that the in-creased movement resulted from the levering of themobile head and proximal cadaver neck over the collaredge. The model described allowed for the applicationof forces that would rarely be applied or permitted inclinical settings but did emphasize the very limited rolethat collars would play in limiting spinal movement if thespine were subjected to very hostile forces.
Goutcher and Lochhead76 measured maximal mouthopening (interincisor distance) in 52 volunteers, beforeand after the application of a semirigid cervical collar.Three collars were assessed: the Stifneck (Laerdal Medi-cal Corp., Wappinger’s Falls, NY), the Miami J (JeromeMedical, Moorestown, NJ) and the Philadelphia (Phila-delphia Cervical Collar Co., Thorofare, NJ). Applicationof a collar significantly reduced interincisor distancefrom a mean of 41 � 7 mm in the control state to 26 �8 mm with the Stifneck, 29 � 9 mm with the Miami J,and 29 � 9 mm with the Philadelphia. There was a widevariation between subjects, and a significant proportionhad an interincisor distance reduced to less than 20 mmafter application of the collar (Stifneck, 25%; Miami J,21%; Philadelphia, 21%). Goutcher and Lochhead con-cluded that the presence of a semirigid collar signifi-cantly reduced mouth opening and would likely ofteninterfere with airway management; removal of the ante-rior portion of the collar before attempts at trachealintubation was encouraged by these authors.
Manual In-line ImmobilizationThe goal of manual in-line immobilization (MILI) is to
apply sufficient forces to the head and neck to limit themovement which might result during medical interven-tions, most notably, airway management. MILI is typi-cally provided by an assistant positioned either at thehead of the bed or, alternatively, at the side of thestretcher facing the head of the bed. The patient ispositioned supine with the head and the neck in neutral
position. Assistants either grasp the mastoid processedwith their fingertips and cradle the occiput in the palmsof their hands (head-of-bed assistant) or cradle the mas-toids and grasp the occiput (side-of-bed assistant). WhenMILI is in place, the anterior portion of the cervical collarcan be removed to allow for greater mouth opening,facilitating airway interventions. During laryngoscopy,the assistant ideally applies forces that are equal in forceand opposite in direction to those being generated bythe laryngoscopist to keep the head and neck in theneutral position.
Avoiding traction forces during the application of MILImay be particularly important when there is a seriousligamentous injury resulting in gross spinal instability.Lennarson et al.77 noted excess distraction at the site ofa complete ligamentous injury when traction forceswere applied for the purposes of spinal stabilizationduring direct laryngoscopy. Similarly, Kaufmann et al.78
demonstrated that in-line traction applied for the pur-poses of radiographic evaluation resulted in spinal col-umn lengthening and distraction at the site of injury infour patients with ligamentous disruptions. Bivins etal.79 reported that traction applied during orotrachealintubation in four victims of blunt traumatic arrest withunstable spinal injuries resulted in both distraction andposterior subluxation at the fracture site. It is possiblethat the fracture site distraction that was observed re-sulted from application of traction forces not appropri-ately axially aligned.
Majernick et al.80 demonstrated that MILI reduced totalspinal movement during the process of laryngoscopyand tracheal intubation; movement was not reduced to asimilar degree by collars. Similarly, Watts et al.81 mea-sured a reduction of spinal movement with the applica-tion of MILI during tracheal intubation in patients withnormal spines during general anesthesia. However, Len-narson et al.82 were unable to demonstrate that applica-tion of MILI resulted in any significant reduction inmovement during intubation in a cadaver model with aposterior column injury. In a cadaver model with com-plete ligamentous instability, Lennarson et al.77 reportedthat application of MILI minimized distraction and angu-lation at the injured level but had no effect on subluxa-tion at the site of injury.
Manual in-line immobilization may be effective in re-ducing overall spinal movements recorded during airwaymaneuvers but may have lesser restraining effects at theactual point of injury. This may be because spinal move-ment is restricted by the weight of the torso at the caudalend and the MILI forces at the cephalad end but isunrestricted by any force at its cervical midpoint. It ispossible that application of traction forces during MILIwould also reduce midcervical movement in some pa-tients, but traction forces may also result in distraction atthe site of injury; the use of such forces during applica-
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tion of in-line immobilization continues to be discour-aged.
Impact of MILI on the View Obtained atLaryngoscopyThe application of MILI during airway maneuvers may
result in decreases in overall spinal movement, but theevidence also suggests modest, if any, effect at individualmotion segments.77,82 However, the use of MILI mayhave lesser impact on the view obtained during directlaryngoscopy than relying on other immobilization tech-niques, such as axial traction or a cervical collar, tape,and sandbags. Heath83 examined the effect on laryngos-copy of two different immobilization techniques in 50patients. A grade 3 or 4 laryngoscopic view (partial or noview of the glottic structures) was obtained in 64% ofpatients immobilized with a collar, tape, and sandbagscompared with 22% of patients stabilized with MILI. Thelaryngeal view improved by one grade in 56% of patientsand by two grades in 10% when MILI was substituted forthe collar, tape, and sandbags. The main factor contrib-uting to the increased difficulty of laryngoscopy whenpatients were wearing cervical collars was reducedmouth opening. Gerling et al.84 reported the findings ofan analogous study using a cadaver model with a C5–C6destabilization and arrived at similar findings. MILI al-lowed less spinal movement than did cervical collarimmobilization during laryngoscopy and intubation andwas associated with improved laryngeal visualization.
Hastings and Wood85 measured the degree of headextension required to expose the arytenoid cartilagesand glottis and determined the impact of applied MILI.The subjects were 31 anesthetized patients (24 study, 7control) with normal cervical spines and Mallampati 1views on preoperative airway assessment. Two methodsof immobilization were assessed. Either axial tractionwas applied, wherein the assistant pulled the head in acaudal to cephalad direction as strongly as he or shethought was necessary to immobilize the neck, or forcewas applied to the head in a downward direction to holdthe head onto the table. Without stabilization, the bestview of the glottis was achieved with 10°–15° of headextension. Head immobilization reduced extension an-gles of 4°–5° compared with no stabilization, and it wasmore effective than axial traction immobilization in lim-iting extension. In 4 of the 24 study patients (17%), 2 ineach immobilization group, the laryngoscopic view de-teriorated from grade I or II to grade III with the appli-cation of immobilizing forces. Therefore, the use of MILIreduced the amount of head extension that was neces-sary for laryngoscopy but resulted in a poorer view in aportion of the patients studied.
Although MILI seems to have the least impact of allimmobilization techniques on airway management, itmay make direct laryngoscopy more difficult in somepatients than if no immobilizing forces are being applied.
Nolan and Wilson86 assessed the impact of MILI withcricoid pressure on the view obtained at laryngoscopy in157 normal patients and compared it with the viewobtained in the same patients while in the sniffing posi-tion. With application of MILI and cricoid pressure, theview remained the same in 86 patients (54.8%), wasworse by one grade in 56 (35.6%), and was worse by twogrades in 15 (9.5%). A grade 3 view (partial glottic view)was obtained in 34 restrained patients (21.6%) comparedwith 2 (1.3%) in the sniffing position. Wood et al.87 alsostudied the effect of cervical stabilization maneuvers onthe view obtained at laryngoscopy in 78 uninjured, elec-tive surgical patients and concluded that cervical immo-bilization commonly worsened laryngoscopic view. Theeffects of MILI on laryngeal view were in a similar direc-tion to those reported by Hastings but occurred morecommonly in Wood’s study. Anterior laryngeal or cricoidpressure often improved the view of the larynx whenthe neck was immobilized. Concern has been expressedin the past regarding the use of anterior cervical pressurein patients at risk for CSI, but Donaldson et al.88 reportedthat application of cricoid pressure did not result inmovement in an injured upper cervical spine in a ca-daver model.
Manual in-line immobilization may have lesser impacton airway interventions than do other forms of immobi-lization. The experience supports routinely removing atleast the anterior portion of collars to facilitate airwayinterventions provided that cervical spinal immobiliza-tion is maintained by MILI. Removal of the anteriorportion of the collar improves mouth opening and facil-itates airway management; reapplication of the mechan-ical immobilization should occur promptly when airwayinterventions are complete. MILI may increase laryngo-scopic grade in some patients; this may be counteredwith anterior laryngeal or cricoid pressure.
Spinal Movement during Airway InterventionsThe early biomechanical analyses of spinal motion typ-
ically used static radiography to determine the relationsbetween the vertebral elements of the cervical spine andto quantify spinal movements. Unfortunately, no stan-dardized technique of measurement has been used in theworks since published, which have evaluated spinalmovement during airway interventions. Both static radi-ography and dynamic fluoroscopy have been used; studyfindings have been reported movement as absolute dis-tances, relative distances (typically a percentage of ver-tebral body width), and degrees of motion and havefurther been categorized relative to individual motionsegments or upper and lower cervical spinal divisions orsummated across the entire cervical spine. There is alsolittle guidance available as to the clinical importance ofthe movements recorded, especially as they relate to theinjured spine. Those spinal movements that fall withinphysiologic ranges have usually been considered to be
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nonthreatening to the cord; whether they are in fact andremain so in a spine with a canal lumen already compro-mised by an acute, a chronic, or an acute superimposedon chronic anatomical derangement is by no meanscertain. Unfortunately, as we analyze the publishedworks, we typically find ourselves in the position ofcomparing the recorded results with physiologic normsand then drawing an empiric conclusion as to the po-tential risk of such movements.
The Effects of Basic Airway Maneuvers on theInjured Neck. Aprahamian89 studied the effect of bothairway maneuvers on a human cadaver, unstable spinemodel. The anterior and most of the posterior columnwere surgically disrupted; the interspinous and supraspi-nous ligaments were spared. Lateral cervical spine radio-graphs were taken during both basic and advanced air-way maneuvers. Basic maneuvers included chin lift, jawthrust, head tilt, and placement of both oral and esoph-ageal airways. Advanced maneuvers included placementof the following: an esophageal obturator airway; anorotracheal tube placed with both a straight and acurved laryngoscopic blade; and a nasotracheal tube,blindly placed. Chin lift and jaw thrust resulted in ex-pansion of the disc space more than 5 mm at the site ofinjury. When blind nasotracheal intubation was facili-tated by anterior pressure to stabilize the airway, 5 mmof posterior subluxation occurred at the site of injury.The other advanced airway maneuvers produced 3–4mm of disc space enlargement. The study was repeatedafter the application of both soft and semirigid cervicalcollars; collars did not effectively immobilize the neckfor either basic or advanced airway maneuvers.
Hauswald90 also determined the impact of basic airwaymaneuvers on cervical spine movement. Eight humantraumatic arrest victims were studied within 40 min ofdeath. All subjects were ventilated by mask, and theirtracheas were intubated orally with a direct laryngo-scope, over a lighted oral stylet and using a flexiblelaryngoscope, and nasally. Cinefluoroscopic measure-ment of maximum cervical displacement during eachprocedure was made with the subjects supine and im-mobilized by a hard collar, backboard, and tape. Themean maximum cervical spine displacement was foundto be 2.93 mm for mask ventilation, 1.51 mm for oralintubation, 1.85 mm for guided oral intubation, and 1.20mm for nasal intubation. Ventilation by mask causedmore cervical spine displacement than the other proce-dures studied. It was concluded that mask ventilationmoves the cervical spine more than any of the com-monly used methods of tracheal intubation.
Airway maneuvers will result in some degree of neckmovement, both in general and specifically at the sites ofinjury. The amounts of movement are small, typicallywell within physiologic ranges, and their impact onsecondary neurologic injury has not been defined. How-ever, as will be subsequently discussed, airway interven-
tions are frequently performed on at-risk trauma pa-tients, and there seems to be a very low incidence ofsecondary injury in these patients associated with airwayclinical interventions.
Cervical Spinal Movement during Direct Laryn-goscopy in Normal Patients. Sawin et al.91 deter-mined the nature, extent, and distribution of segmentalcervical motion produced by direct laryngoscopy andorotracheal intubation in normal human subjects. Tenpatients underwent laryngoscopy while paralyzed andduring general anesthesia. Minimal displacement of theskull base and cervical vertebral bodies was observedduring laryngoscope blade insertion; elevation of thelaryngoscope blade to achieve laryngeal visualizationcaused superior rotation of the occiput and Cl and mildinferior rotation of C3–C5. The largest magnitude mo-tions were at the atlanto-occipital and atlantoaxial joints,but there was extension at each motion segment as-sessed. Tracheal intubation created slight additional su-perior rotation at the craniocervical junction but causedlittle alteration in the postures of C3–C5. Horton et al.92
conducted a similar experiment in volunteers duringtopical anesthesia only. Subjects in a supine, sniffingposition underwent direct laryngoscopy, and at full glot-tic exposure, a lateral radiograph of the head and neckwas performed. The radiographs indicated that exten-sion at the craniocervical junction was near maximal andthat there was progressively increasing extension fromC4 to the base of the skull, but that the position of thelower cervical spine remained static during laryngos-copy. Both Sawin et al. and Horton et al. agreed that,during laryngoscopy, in both awake and unconscioussubjects, most cervical motion occurs at the craniocer-vical junction; the subaxial cervical segments subjacentto and including C4 are minimally displaced (fig. 6).91,92
Spinal Movement during Laryngoscopy in In-jured Spine Models. Donaldson et al.88 studied themotion that occurred during intubation in a cadavermodel with an unstable C1–C2 segment. The followingwere measured in the intact specimen and then againafter creation of the unstable segment: angulation, dis-traction, and the space available for the cord (SAC). Withmaximum flexion and extension, the SAC was narrowed
Fig. 6. Impact of direct laryngoscopy and tracheal intubation oncervical spine movement.91,92
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1.49 mm in the intact cervical spine but 6.06 mm in theunstable spine. Chin lift and jaw thrust reduced the SACby 1 mm and 2.5 mm, respectively; oral intubation andnasal intubation created a similar (1.6 mm) reduction ofSAC. Distraction at the unstable injured level was similarfor chin lift, jaw thrust, and crash intubation (1–2 mm);distraction during gentle oral intubation and nasal intu-bation was less than 1 mm. Chin lift and jaw thrustcreated similar angulations (4°–5°) to those of the oralintubation techniques, but nasal intubation caused less(2.5°). Cricoid pressure resulted in no significant move-ments when it was applied in either the stable or unsta-ble model. Donaldson et al. concluded that (1) the SACwas narrowed to a greater degree by preintubation ma-neuvers than it was by intubation techniques, (2) nasaland oral intubation techniques resulted in similaramounts of SAC narrowing, and (3) application of cri-coid pressure produced no significant movement at thecraniocervical junction.
Stabilization during Airway Interventions in Ca-daver Models of an Injured Spine. Lennarson et al.82
evaluated the impact of commonly used immobilizationtechniques in limiting spinal motion in an injured-spinemodel; the model involved the creation of a posteriorligamentous injury at the C5 level and compared theeffects of MILI and Gardner-Wells traction. The predom-inant motion measured at all spinal levels during laryn-goscopy and intubation in the intact spine was exten-sion; this was consistent with the findings of Donaldsonet al.,88 Sawin et al.,91 and Horton et al.92 Subluxation inthe anterior–posterior dimension remained less than 1mm in both the intact and the partially destabilizedspine; rotatory or angular movements were the onlysignificant movement recorded. Application of Gardner-Wells traction limited rotatory motion at the craniocer-vical junction after destabilization; MILI did not have asimilar effect.
Lennarson et al.77 conducted a similar experimentassessing the efficacy of immobilization maneuvers in amodel of complete C4–C5 segmental instability. Move-ment was measured at the injured level during the ap-plication of traction, during MILI, and without stabiliza-tion. Traction resulted in distraction at the site of injurywhen instability was complete; the magnitude of thesemovements was not reduced by MILI, although theyremained within physiologic limits. Gerling et al.84 alsoevaluated the effect of both MILI and cervical collarimmobilization on spinal movement during direct laryn-goscopy in an unstable C5–C6 cadaver model. Althoughthere was less displacement (2 mm) measured withapplication of MILI compared with collars, the magni-tude of movement was small overall and within physio-logic ranges.
Brimacombe et al.93 assessed spinal movement in acadaver model with a posterior injury at C3, with MILIapplied as various airway interventions (facemask venti-
lation, direct laryngoscopy and tracheal intubation, fiber-optic nasal intubation, laryngeal mask insertion, intubat-ing laryngeal mask airway insertion followed byfiberoptic intubation, and insertion of a Combitube)were performed. Posterior displacement was less whenintubation was performed nasally with a flexible scope(0.1 � 0.7 mm) than for any other maneuver; mostmaneuvers caused 2–3 mm of displacement.
Influence of Laryngoscope Blade Type on SpinalMovement during Direct Laryngoscopy. Three au-thors have assessed the influence of the type of laryngo-scope blade on the spinal movements generated duringdirect laryngoscopy. MacIntyre et al.94 compared theMacintosh and McCoy blades in patients with normalspines during general anesthesia with cervical collarsapplied. There were no significant differences betweenthe two blades with respect to the amount of spinalmovement generated during intubation. Hastings et al.95
compared head movement occurring during laryngos-copy in patients with normal spines using Macintosh andMiller laryngoscopes, and again, there were no differ-ences in the amount of movement measured. Finally,Gerling et al.84 compared spine movement in a cadavermodel with a C5–C6 transection injury while performinglaryngoscopy with Miller, Macintosh, and McCoy-typeblades. There was no difference in the movements re-corded with the different blades with regard to eitheranteroposterior displacement or angular rotation. Lessaxial distraction was measured with the Miller bladecompared with the other two blade types; in absoluteterms, the differences was 1.7 mm. Overall, there seemsto be little difference in the spinal movement resultingfrom direct laryngoscopy relative to the type of bladeused during laryngoscopy.
Cervical Spinal Movement with Indirect Rigid Fi-beroptic Laryngoscopes. Watts et al.81 compared cer-vical spine extension and time to intubation with theBullard (ACMI Corp., Southborough, MA) and Macintoshlaryngoscopes during a simulated emergency with cervi-cal spine precautions taken. Twenty-nine patients wereplaced on a rigid board, and anesthesia was induced.Laryngoscopy was performed on four occasions, twiceeach with the Bullard and Macintosh laryngoscopes,both with and without MILI applied (MILI was appliedwith cricoid pressure). Cervical spine extension (fromthe occiput to C5) was greatest with the Macintosh andwas reduced both when the Macintosh was used withMILI and when the Bullard was used with or withoutstabilization. Times to intubation were similar for theMacintosh with MILI and for the Bullard without MILI.MILI applied during laryngoscopy with the Bullard re-sulted in further reduction in cervical spine extensionbut a prolonged the time to intubation, although it stillwas achieved in less than a minute. In a study designsimilar to that of Watts et al., Hastings et al.95 found thatcervical spine extension from the occiput to C4 was
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decreased when comparing the Bullard with both theMacintosh and the Miller laryngoscope blades.
The times to achieve intubation using the Bullard la-ryngoscope, in the study of Watts et al.,81 are similar toothers reported in the literature. Twenty-two of 29 pa-tients (76%) were intubated in less than 30s when usingthe Bullard under standard conditions.81 In a study usingthe dedicated intubating stylet, Cooper et al.96 found70% of patients were intubated in less than 30 s. Therewas also better exposure of the larynx during laryngos-copy with the Bullard than with the direct laryngoscope.Application of MILI resulted in deterioration in the gradeview of the larynx when using the Macintosh in 19 of 29patients (65%). In contrast, only 2 patients (7%) pre-sented an inferior view of the larynx after application ofMILI and cricoid pressure when using the Bullard laryn-goscope.
Rudolph et al.97 compared movement in the uppercervical spine in 20 patients scheduled to undergo elec-tive surgery, when laryngoscopy was performed withthe Bonfils intubation fiberscope (Karl Storz EndoscopyLtd., Tuttlingen, Germany) and the Macintosh laryngo-scope. With the patient’s head in neutral position on thetable and no pillow used, a baseline lateral radiographwas taken. The head was extended, laryngoscopy wasperformed using the Macintosh, a second radiographwas taken, and the head was returned to the neutralposition. Laryngoscopy was then performed with theBonfils fiberscope, and the trachea was intubated. Withthe Macintosh, views at laryngoscopy were class I in 8patients, II in 5, and III in 7; all views obtained with theBonfils fiberscope were class I. The time between inser-tion of the instrument and achievement of optimumview was similar for both instruments. Laryngoscopywith the Macintosh resulted in spinal movement thatwas greater in magnitude than that measured duringBonfils fiberscopy.
The Glidescope (Saturn Biomedical Systems, Burnaby,British Columbia, Canada) is a new video laryngoscopethat incorporates a high resolution digital camera in theblade tip; the image is transmitted to a liquid crystaldisplay monitor via a dedicated video cable. Agro et al.98
compared the laryngeal view obtained initially with aMacintosh and then with the Glidescope in 15 normalpatients presenting for general anesthesia who werewearing cervical collars. The laryngeal view was reducedby one Cormack grade in 14 of the 15 patients (93%)studied when the Glidescope was used compared withthe Macintosh; the average time to intubation with theGlidescope was 38 s. Turkstra et al.99 compared cervicalspine movement, measured fluoroscopically, during in-tubation with a Macintosh, a light wand, and the Glide-scope. In-line immobilization was achieved by taping thepatients’ heads into a Mayfield-type headrest; movementwas measured at the Oc–C1, C1–C2, C2–C5, and C5–Thlevels. The largest amount of motion measured was at
the Oc–C1 complex with all devices. Cervical spinalmovement was reduced 57% overall (all segments com-bined) comparing the light wand with the Macintosh;reduced movement was apparent at each level. Spinalmovement was reduced only at the C2–C5 segmentwhen the Glidescope was compared with the Macin-tosh; 6.9° � 5.2° of flexion was measured during Macin-tosh laryngoscopy, and this was reduced by 50% usingthe Glidescope. Motion was not significantly altered atthe three other segments studied. The time to intubationwas longest with the Glidescope (27 � 12 s) but similarwith the light wand (14 � 9 s) and the Macintosh (16 �7 s).
Cervical spine movements are generally less whenrigid indirect laryngoscopes are used compared with theML direct laryngoscope. Visualization of the glottis is alsoimproved with the use of the rigid laryngoscopes, butthe time to achieve the best view is somewhat longer;these times tend to be short, and the difference com-pared with the direct laryngoscope is likely to be of littleclinical relevance.
Cervical Spinal Movement and Laryngeal MaskAirways. Kihara et al.100 measured cervical movementproduced by the intubating laryngeal mask airway dur-ing MILI in 20 anesthetized patients with cervical pathol-ogy undergoing cervical spine surgery. During the inser-tion of the intubating laryngeal mask airway, C5 andsuperior segmental levels were flexed by less than 2°.During intubation, C4 and superior segmental levelswere flexed by 3° or less, and C3 and levels above wereflexed by an average of 1° during removal. There wassome posterior displacement at the C2–C5 levels duringinsertion and intubation but not during removal.
Keller et al.101 implanted microchip sensors into thepharyngeal surfaces of C2 and C3 in 20 cadavers todetermine the pressures exerted against the cervicalvertebrae by both the standard laryngeal mask airwayand the intubating laryngeal mask airway during inser-tion and manipulation. The impact of these pressures oncervical spine movement was also determined. Keller etal. concluded that laryngeal mask devices exert highpressures against the upper cervical vertebrae duringinsertion, during inflation, and while in situ; these pres-sures could produce posterior displacement of the up-per cervical C-spine. The clinical relevance of thesefindings as they relate to CSI has yet to be clarified.
Cervical Spinal Movement during Surgical Crico-thyrotomy. Surgical cricothyrotomy was initially advo-cated as a preferred airway intervention in patients atrisk for CSI compared with orotracheal intubation andnow is deemed to be an appropriate alternative if oral ornasal routes cannot be used or are unsuccessful. Al-though long considered safe in the presence of a CSI, itsapplication in this scenario has not been well studiedwith respect to either spinal movements or neurologicoutcomes. Gerling et al.102 used a cadaver model to
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quantify movement during cricothyrotomy. Standardopen cricothyrotomy was performed in 13 cadavers withcomplete C5–C6 transection injuries, and cervical spineimages were recorded fluoroscopically during the pro-cedure. Peak axial distraction was measured at 4.5% ofthe C5 width, amounting to 1–2 mm of axial compres-sion; peak antero-posterior displacement was measuredat 6.3% of the C5 width, equivalent to 1–2 mm of dis-placement. Although these values were statistically sig-nificant, there clinical relevance has yet to be deter-mined.
The Clinical Practice of Airway Management inPatients with Cervical Spine InjurySurveys of Patterns of Clinical Practice Regarding
Airway Management after Cervical Spine Injury.Four authors have surveyed North American anesthesi-ologists as to their preferred methods of airway manage-ment in patients with cervical spine trauma or disease.Lord et al.103 compared practice preferences amongsurgical members of the Eastern Association for the Sur-gery of Trauma with anesthesiologists in US anesthesiol-ogy training programs. In the elective situation (CSI butbreathing spontaneously with stable vital signs), anesthe-siologists stated that they were less likely to use nasotra-cheal intubation (53% vs. 69%), equally likely to useorotracheal intubation, and more likely to use the fiber-optic bronchoscope than were trauma surgeons. In theurgent scenario (patient with unstable vital signs), anes-thesiologists tended to use both nasotracheal and orotra-cheal intubation in a manner similar to that of the sur-geons but more frequently (16%) preferred thebronchoscope. In an emergency situation (apneic pa-tient with unstable vital signs), both anesthesiologistsand surgeons relied extensively on the direct laryngo-scope (78% and 81%); anesthesiologists were more likelyto use the bronchoscope (15%) than were surgeons butused a surgical airway less frequently than did the sur-geons (7% vs. 19%).
Rosenblatt et al.104 received 472 responses from 1,000active members of the American Society of Anesthesiol-ogists who were surveyed as to their preferences formanagement methods for the difficult airway in cooper-ative adult patients. With respect to patients with CSI,78% of respondents expressed a preference for an awakeintubation and the use of bronchoscope; the bulk of theremainder induced general anesthesia and used a directlaryngoscope. Rosenblatt et al. did not request informa-tion regarding the levels of experience attained with thedevices preferred but did ascertain that they were avail-able to the practitioners who stated that they would usethem. Jenkins et al.105 collected 833 responses from1,702 members of the Canadian Anesthesiologists’ Soci-ety surveyed regarding their management choices forthe difficult airway in Canada. When faced with a patientwith a cervical cord compression and neurologic deficit
presenting for discectomy, 67% expressed a preferencefor awake intubation, and most (63%) stated that theywould use a bronchoscope. Thirty-one percent wouldinduce general anesthesia before airway intervention,and slightly more would use a direct laryngoscope thanpreferred a lighted stylet in this setting. Jenkins et al. didnot solicit information regarding the level of experiencewith the methods identified as being preferred by thesurvey respondents.
Ezri et al.106 surveyed 452 American-trained AmericanSociety of Anesthesiologists members attending the 1999Annual Meeting. When faced with a cooperative adultpatient with cervical spine disease (rheumatoid arthritisor ankylosing spondylitis) presenting for elective sur-gery, awake fiberoptic intubation was preferred by most.Although 75% stated that they would use it in some ofthe scenarios outlined, only 59% or respondents re-ported skill in the use of the bronchoscope.
The surveys are consistent in revealing that manyNorth American anesthesiologists express a preferencefor the use of a fiberoptic bronchoscope during airwaymanagement in patients with cervical spine disease orinjury including in apneic trauma scenarios. This prefer-ence persists despite the fact that some who state thispreference also acknowledge that they are not confidentregarding their skill levels with the bronchoscope. De-pending on the setting and the perceived urgency of thesituation, direct laryngoscopy is still commonly used,and use of the lightwand is preferred by a significantminority of anesthesiologists, at least in Canada.
Airway Management of Cervical Spine–injuredPatients: The Experience and Outcomes Reported.Meschino et al.107 reviewed their experience with 454patients with critical cervical cord or spine injuries orboth. One hundred sixty-five patients underwent awaketracheal intubation within 2 months of injury; 289 didnot require intubation during the same period. The di-rect laryngoscope was used in 36 patients (22%), thefiberoptic bronchoscope was used in 76 (46%), and 51patients (32%) underwent blind nasal intubation. Pa-tients undergoing intubation were more severely im-paired than those who did not require intubation. De-spite this, there was no difference in the incidence ofneurologic deterioration over time between the twogroups, and tracheal intubation was not associated withneurologic deterioration in any patient. Holley and Jor-dan108 conducted a retrospective analysis of traumatic,unstable cervical spine fractures requiring operativemanagement to determine both the airway managementtechniques used and the incidence of neurologic com-plications. One hundred thirty-three patients with 140fractures were reviewed. Ninety-four patients under-went nasal intubation in the operating room, and 29were intubated with direct laryngoscopy and in-line sta-bilization. No neurologic complications were recognizedin any patient.
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Rhee et al.109 analyzed their experience with 21 pa-tients with cervical cord or spine injury who underwenttracheal intubation in the emergency room. Orotrachealintubation was used in 81% of CSI patients; neuromus-cular blockers were used in 82% of these intubations.The authors concluded that no injury was recognized tobe caused or exacerbated by airway maneuvers. How-ever, one patient with a C7–T1 dislocation and a C7 cordtransection was noted to have absent sensation belowthe nipples before intubation (T4 level) and motor andsensory examination results consistent with a C7 cordtransection after intubation. Whether this disparity re-flect an ascension in the level of injury from T4 to C7 orthe difference in findings between an emergency roomscreening neurologic exam and a more precise examina-tion performed later is not certain; the authors’ conclu-sions seem to prefer the latter explanation. Scanell etal.110 reviewed their experience with 81 patients withCSI, including 58 with unstable fractures, who receivedemergency orotracheal intubations performed by expe-rienced anesthesiologists. Neurologic assessment wasdocumented before and after intubation, and in no in-stance was there a recognized deterioration of neuro-logic functions after tracheal intubation. Shatney et al.111
reviewed their experience with 81 patients with 98fractures who were neurologically intact on initial pre-sentations. Orotracheal intubation was performed in 48patients, and no neurologic deteriorations were recog-nized. In-line immobilization was used during the airwaymaneuvers, and agitated or combative patients weresedated, paralyzed, or both. Talucci et al.112 reviewedtheir experience with 335 patients requiring urgent in-tubations. Seven patients with unstable CSI underwentorotracheal intubation after induction of anesthesia andparalysis; none experienced neurologic compromise as aresult of airway management.
Suderman et al.113 reviewed the experience of 150patients with traumatic CSI and well-preserved neuro-logic function presenting for operative stabilization.General anesthesia before intubation was induced in 83patients, of whom 65 had their tracheas intubated withthe direct laryngoscope; 22 patients were intubatedwhile awake using the direct laryngoscope. The remain-der had tracheal intubation performed with a variety ofalternatives to the direct laryngoscope, most commonlythe bronchoscope; the majority of those latter intuba-tions were performed with the patient awake. Two pa-tients experienced new neurologic deficits; one had awire passed through the cervical cord accidentally dur-ing operative stabilization and was rendered quadriple-gic, the second recovered from a new single level radic-ulopathy attributed to the operative decompression.Both of these patients had their tracheas intubated witha direct laryngoscope while anesthetized. McCrory114
performed a similar retrospective analysis of the recordsof 45 patients who presented for operative stabilization
of cervical injuries resulting from trauma. Tracheal intu-bation was performed after induction of general anesthe-sia with neuromuscular block in 40% of cases; in theremainder, intubation was performed with a broncho-scope while the patient was awake. One awake trachealintubation was abandoned as a result of patient noncom-pliance; this patient’s trachea was intubated after induc-tion of general anesthesia. Weighted traction was used inall cases to immobilize the spine. No patient developedeither a new neurologic finding or worsening of a pre-existent deficit.
Wright et al.115 reviewed the records of 987 blunttrauma patients; 60 of the patients had a cervical frac-ture, and 53 of these were deemed to be unstable.Twenty-six patients’ tracheas were intubated orally, 25were intubated nasally, and two were intubated by cri-cothyrotomy. One patient who underwent nasotrachealintubation experienced a neurologic deterioration. Lordet al.103 reviewed the case records of 102 patients whohad a CSI and were admitted to their center after trauma.Sixty-two patients required airway management. Themost common method used was orotracheal intubationfacilitated by direct laryngoscopy (43%), followed bybronchoscope-assisted intubation (27%), nasotracheal in-tubation (22%), and tracheostomy (2%); in 4%, themethod could not be determined. No patient was recog-nized to have experienced a neurologic deteriorationassociated with airway management. Other authors havereported similar findings in smaller series of trauma pa-tients with CSI.112,116
These studies are limited by both their small samplesize and their retrospective nature. However, they doreveal that neurologic deterioration in CSI patients isuncommon after airway management, even in high-riskpatients undergoing urgent tracheal intubation. They arenot sufficient to rule out the potential that airway man-agement provided in isolation or as part of a more com-plex clinical intervention, even provided with the ut-most care, may rarely result in neurologic injury. To doso would require a study of enormous proportions. Asnoted previously, progressive neurologic deteriorationoccurs in a minority of CSI patients. If this incidence wasset at 2% and a study was designed to prove that anairway intervention did not double this baseline inci-dence, approximately 1,800 patients would need to bestudied. No method of airway intervention has beenevaluated with such a study, or anything close to it, andtherefore, statements comparing the relative safety ofdifferent methods have tenuous evidentiary support.
The Use of the Direct Laryngoscope after CervicalSpine Injury: The Debate. As part of the early effortsaimed at reducing secondary injuries in spine-injuredpatients, a hypothesis was generated that the tracheas ofpatients with unstable cervical spines could not be safelymanaged by direct laryngoscopy and oral intubation.117
Oral intubation was deemed dangerous because it alleg-
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edly caused excessive spinal movement, and this move-ment could lead to secondary injury. Such secondaryinjury could theoretically be avoided by the careful per-formance of nasotracheal intubation or cricothyrotomy.These techniques were advocated as the emergencyairway maneuvers of choice in patients at risk for spinalinjury. There were no data at that time to support thisthesis, and the data collected since seem to suggest thatsecondary neurologic injury associated with any form ofairway management is exceedingly rare. The early Ad-vanced Trauma Life Support protocols for airway man-agement were consistent in their support for the nasalintubation/cricothyrotomy strategy, implying a lack ofsupport for the use of direct laryngoscopy in this clinicalsetting. Not all practitioners agreed that the use of directlaryngoscopy was contraindicated in patients at risk forcervical injury. There was evidence made available soonafter publication of these protocols that some experi-enced trauma centers (including our own) were ignoringthe Advanced Trauma Life Support recommendationsand performing direct laryngoscopy in at-risk popula-tions.107,113,118
McLeod and Calder119 examined the association be-tween the use of the direct laryngoscope in patients andsubsequent spinal injury or pathology. They suggestedthat the following five case features would add credenceto the diagnosis of a laryngoscopy-induced cord injury:(1) a short period of unconsciousness, (2) myelopathypresent on recovery, (3) autonomic disturbances afterlaryngoscopy, (4) difficult laryngoscopy, and (5) cranio-cervical disease or gross instability below C3. Thesecriteria were then used to evaluate the likelihood thatlaryngoscopy was the causative factor for neurologicdeterioration in the reports. Although they do makeintuitive sense, whether these criteria discriminate wellin assigning cause to injury recognized after intubation isnot established. Six reports dealing with 10 patients inwhich it was alleged that direct laryngoscopy contrib-uted to a neurologic injury were reviewed.57,120–124
With the possible exception of one case, they concludedafter review and analysis of the case reports, that thereports did not provide sufficient data to allow them tomake the determination that the use of the direct laryn-goscope was the cause of the neurologic injuries re-ported.
The first report analyzed was that of Farmer et al.,57
who reviewed their institutional experience with cord-injured patients. They reported that four patients hadneurologic deteriorations associated with tracheal intu-bation. Two deteriorations were classified as minor andtwo were classified as major, but no further details wereprovided regarding the cases or the intubations. Thesecond report was that of Muckart et al.,120 who re-ported two cases of neurologic deterioration after clini-cal interventions. The first patient was a 45-yr-old maninvolved in a motor vehicle accident who sustained
bilateral femoral fractures and a closed head injury. De-spite the mechanism of injury, a period of unconscious-ness, and the presence of neck pain, no imaging wasperformed, and his spine was not immobilized. He un-derwent anesthesia for operative repair of the femoralfractures and was quadriplegic on awakening; a C2 frac-ture–dislocation was subsequently diagnosed, and herecovered completely. The second patient was a 22-yr-old man with multiple gunshot wounds to the neck; hearrived in the hospital neurologically intact. Imaging ofthe neck revealed no apparent injury to the cervicalspine to a level of C5; the radiograph showed only theupper five vertebrae. He underwent emergency surgeryduring general anesthesia without neck immobilizationand was quadriplegic after. A CT scan demonstrated aburst fracture of C6 with a retropulsed fragment imping-ing on the canal. He was placed in traction, had opera-tive fixation, and recovered completely. Although directlaryngoscopy and tracheal intubation were componentparts of the care of both patients, they were not the soleinterventions; the lack of immobilization and the poten-tial for malpositioning cannot be excluded as significantrisk factors in both cases. The complete recovery in bothpatients suggests that malpositioning may have been anetiologic factor inducing a transient, compressive neura-praxia-like injury.
The third report analyzed was that of Redl,121 whodescribed the case of an 18-yr-old man with undiagnosedspondyloepiphyseal dysplasia congenita resulting in un-recognized craniocervical instability. He underwent gen-eral anesthesia and direct laryngoscopy with trachealintubation for removal of retained knee hardware. Theintraoperative and early postoperative course was un-eventful, but he developed a spastic quadriparesis theday after surgery. A CT scan demonstrated a congenitallyabnormal craniocervical junction with an os odontoi-deum (congenitally nonfused odontoid process) in theforamen magnum compressing the spinal cord. Al-though he made a full recovery, he awoke quadriplegicafter a subsequent craniocervical stabilization procedurefor which his trachea was intubated using a fiberopticbronchoscope. The precise role of the laryngoscopy inthe development of transient neurologic symptoms in apatient with a congenitally abnormal and unstable spineis uncertain; the development of symptoms on the dayafter laryngoscopy reduces the strength of a causativeassociation. The fourth report reviewed is that of Yanand Diggan,122 who described the occurrence of a cen-tral cord syndrome in a 42-yr-old woman with acquiredimmune deficiency syndrome who underwent urgentlaryngoscopy and intubation for respiratory failure. Be-fore her admission, she was using a walker and wheel-chair to ambulate. Following the recognition of upperextremity weakness after intubation and resuscitation,she underwent imaging and evaluation of her central andperipheral nervous system. There was no evidence of
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spinal anomaly or instability; there was imaging evidenceof marked and generalized cerebral atrophy and a spinalcord contusion and electrodiagnostic evidence of bothcentral and peripheral neuropathy. The etiology of injurywas attributed to hyperextension, but there was alsoevidence of advanced neurologic disease likely related toinfection with human immunodeficiency virus. The fifthreport was that by Yaszemski et al.,123 who reported thecase of a 59-yr-old woman with advanced rheumatoidarthritis. She underwent a right wrist fusion during gen-eral anesthesia, and her trachea was intubated with abronchoscope while she was awake. Her trachea wasextubated at the end of the procedure, and the earlypostoperative course was uneventful. She had a cardiacarrest 10 h postoperatively and was intubated with di-rect laryngoscopy, but could not be resuscitated. Atautopsy, she was confirmed to have atlantoaxial instabil-ity (recognized preoperatively), and there was micro-scopic evidence of focal areas of ischemia and infarctionin the upper cord and lower medulla oblongata. Theauthors attributed the damage and the cause of death tothe resuscitation intubation, although she was alreadydead at the time of that intubation. Further, the patho-logic finding of infarction suggests that the injury likelytook place remotely from the time of death, perhapsduring the surgery, and may well have been a position-ing injury that was progressive.
The case that MacLeod and Calder cited as being mostlikely (four of five features present) a laryngoscopy-in-duced cord injury was that reported by Hastings andKelley.124 They reported of the case of a 65-yr-old manadmitted to hospital after a motor vehicle accident. De-spite reporting neck pain and exhibiting left arm weak-ness, CSI was not ruled out, nor was spinal immobiliza-tion enforced. His condition deteriorated some hourssubsequently, and after repeated, failed attempts at di-rect laryngoscopy without spinal immobilization, he un-derwent cricothyrotomy; 3 h later, he was found to beparaplegic. A review of the original cervical spine radio-graph demonstrated a widened disc space at C6–C7suggesting disruption of the anterior longitudinal liga-ment. CT scans confirmed that finding as well as notingcongenital spinal stenosis from C3 to C7, osteophytefragments in the spinal canal at C6, a fracture of theC6–C7 facet joint, a C7 laminar fracture, and a C6 spi-nous fracture. The constellation of symptoms could notbe attributed to a single cord lesion, and he was diag-nosed as having both an anterior cord syndrome affect-ing the T11 and subjacent levels and a central cordsyndrome at the cervical level. No MRI study was per-formed to detail the nature of the cord injuries, and it ispossible that his neurologic deterioration was inevitableand perhaps the cause of his respiratory insufficiency.However, at no time from admission until the occur-rence of his neurologic deterioration was his spine im-mobilized.
Two additional cases of intubation-associated neuro-logic injury not reviewed by MacLeod and Calder havebeen reported.125,126 Liang et al.125 reported a case sim-ilar to that of Hastings and Kelley of a man involved in amotor vehicle accident with a suspected CSI who wasleft quadriplegic after airway management. Despite theevidence of a CSI (nature of injury not reported) and aneurologic deficit (limited movement in both upper ex-tremities), repeated and failed attempts were made atboth nasal (five attempts) and then oral intubation witha direct laryngoscopy (five attempts). The last threeattempts at oral intubation were made after removal ofthe cervical collar, but MILI was not used. The tracheawas eventually intubated via a surgical airway. There isno discussion of the care afforded after intubation withrespect to the spine injury or any description of subse-quent imaging studies performed. The next day, it wasrecognized that he was quadriplegic. Powell andHeath126 reported the case of 59-yr-old man found col-lapsed and unconscious. Paramedics found him to beapneic, cyanosed, and unresponsive and attempted butfailed to intubate his trachea. Tracheal intubation wasperformed in the emergency room, and then the spinewas immobilized. A lateral cervical radiograph revealedan odontoid peg fracture, and the patient’s conditionwas consistent with a complete cord injury at the C2level. Although it was inferred that the cord injury mayhave been caused or aggravated by the airway manage-ment, it was acknowledged by the authors that the injurywas probably sustained at the time of the accident.
A number of reports detailing a relation between air-way management and the occurrence of secondary neu-rologic injury in CSI patients have been reviewed. Thesereports consist typically of observations made in a singlepatient or in a small series of patients admitted to a singleinstitution. Although the deterioration has often beenassociated temporally with airway management, in mostcases, it is impossible to determine with certainty thecause of the deterioration because confounding factorsare typically present and acknowledged by the reportingauthors. As well, it is possible in some instances that theassociation between airway management and a worsen-ing neurologic state arises not because of cause andeffect but because the airway intervention was madenecessary by a progressively deteriorating clinical condi-tion such as an ascending myelopathy. It may well bethat the magnitude of the deterioration does not be-comes apparent until after clinical interventions, atwhich time they, themselves, become suspect culprits.As unsatisfactory as it might be, determining the truenature of the association (causal or otherwise) betweenairway management and adverse neurologic outcomes inCSI patients is not possible at this time, given the currentstate of our knowledge.
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The Use of the Flexible Fiberoptic Bronchoscopein Cervical Spine Injury. There is considerable enthu-siasm, particularly among anesthesiologists, for the useof the fiberoptic bronchoscope in patients at risk forcervical spine disease. The advantages are its potentialfor use in awake patients, the minimal cervical move-ment required to achieve tracheal intubation, and theability to perform postintubation neurologic assessmentsin cooperative and cognitively intact patients. However,there have been have been relatively few reports recog-nized in the literature regarding the use of the broncho-scope in the emergency management of the airway aftertrauma.127 The overall success rate for intubation usingthe bronchoscope in the trauma setting has been cited at83.3% (95% CI, 72–94.6%).127 There is a report detailingthe successful use of the bronchoscope to facilitateawake intubation in 327 consecutive patients presentingfor elective cervical spine surgery; the bulk of the pro-cedures were surgeries for cervical disc prolapse, andthere were no patients with traumatic injuries includedin the review.128 Although the procedure was well tol-erated by the majority of the patients, 38 (12%) devel-oped low oxygen saturations; in this group, the meanoxygen saturation measured by pulse oximetry was 84 �4% (range, 72–89%). The potential for desaturation dur-ing bronchoscope-facilitated intubation seems to be asgreat or greater in CSI patients compromised by trau-matic injury as in these elective surgical patients; theincidence and magnitude of hypoxemia in a series ofCSI-trauma patients undergoing such management hasnot been reported.
There are no published data in the English literaturethat would indicate that the cited advantages of thefiberoptic bronchoscope translate into improved out-comes among CSI patients compared with other intuba-tion techniques. As well, Ezri et al.106 reported, after asurvey of American anesthesiologists, that more than40% of respondents acknowledged that they were notcomfortable using a bronchoscope for airway manage-ment. McGuire and El-Beheiry129 reported two cases ofcomplete airway obstruction during elective awakebronchoscope-assisted intubation in patients with unsta-ble cervical spine fractures; both patients were salvagedwith emergency surgical airways. In patients with braininjury, a common concurrent injury to CSI, the use of thebronchoscope is associated with significant increases inICP that are not prevented by the administration ofmorphine, midazolam, and nebulized lidocaine.130
Comparing Rigid and Flexible Fiberoptic Endo-scopes in At-risk Populations. Cohn and Zornow131
compared the fiberoptic bronchoscope and the Bullardlaryngoscope with respect to rapidity of glottic visualiza-tion and intubation in patients requiring cervical immo-bility during tracheal intubation. Seventeen adult pa-tients scheduled to undergo neurosurgical correction ofa cervical spine problem were studied. Each patient was
considered at risk for neurologic injury during trachealintubation based on a request for awake fiberoptic tra-cheal intubation by the neurosurgical team, or radicularsymptoms initiated or exacerbated by neck extension.Most showed evidence of spinal canal impingement on apreoperative MRI. Patients were allocated randomly toone of two study groups for tracheal intubation with theBullard (n � 8) or the fiberoptic bronchoscope (n � 9);before intubation, glottic visualization was performedusing the alternative technique. All intubations wereperformed with the neck in a comfortable position forthe patient and with any preexisting immobilization de-vice (e.g., collar, traction) in place. Glottic visualizationwas uniformly successful on the first attempt in bothgroups. Tracheal intubation was also uniformly success-ful, although one intubation in the bronchoscope grouptook 183 s because of difficulty passing the endotrachealtube through the glottis after an easy laryngoscopy. Nonew neurologic deficits were observed after trachealintubation in either group.
Practice Options for Airway Management afterCervical Spine Injury. There is discordant opinionexpressed in the literature regarding the optimal meansof securing the airway in patients with CSI. Enthusiasmis expressed by some neuroanesthesia experts for theexclusive use of the fiberoptic bronchoscope to facilitatetracheal intubation in spine-injured patients.132 Thereare a number of theoretical factors that would supportsuch a choice. The head and neck may be left in a neutralposition, and little spinal movement is required toachieve laryngeal visualization and tracheal intubation.The patient’s protective reflexes are largely left intact,and the potential for deleterious movements and posi-tioning is perhaps reduced. A neurologic assessment canbe made after intubation to ensure that there has beenno change in the patient’s status, although the accuracyof this evaluation may be diminished by sedation. Finally,the patient could be positioned awake to increase thelikelihood that potentially injurious position could beavoided. These considerations support the use of thetracheal intubation facilitated by a fiberoptic broncho-scope and performed by an experienced care provider asa practice option in the management of the airway inspine-injured patients. Survey evidence also supports theconclusion that many anesthesiologists are of the opin-ion that it is the preferred option, especially in electivescenarios. This preference persists even among physi-cians who acknowledge limited skills with the device.However, there are no data to suggest that better neu-rologic outcomes are achieved with its use. In fact, theapplication of a technique by practitioners not expert inits use may carry risk. Failed awake intubation has beenidentified as a cause of morbidity and mortality in thelatest analysis of difficult airway claims by the AmericanSociety of Anesthesiologists’ Closed Claims Project.133
The use of a direct laryngoscope after induction of
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anesthesia is also deemed an acceptable practice optionby the American College of Surgeons as outlined in thestudent manual of the Advanced Trauma Life SupportProgram for Doctors; by experts in trauma, anesthesiol-ogy, and neurosurgery; and by the Eastern Associationfor the Surgery of Trauma.3,107,109,119,127,134–143 Theprinciple advantages of the direct laryngoscope are thatanesthesiologists are very experienced in its use and thatit is a highly effective tool; many anesthesiologists do notconsider themselves similarly skilled with other practiceoptions.106 Direct laryngoscopy can also be performedmore quickly than some, but not all, alternative tech-niques, and it does not require time to obtain and set upspecialized equipment. However, it has the potential tocause greater spinal movement than indirect techniques.In addition, if laryngoscopy is performed after the induc-tion of general anesthesia, the potential for difficult ven-tilation, a failed intubation, and a cannot-intubate, can-not-ventilate scenario cannot be excluded. Finally, ifthere is underlying severe, chronic cervical spinal pa-thology, difficult laryngoscopy should be anticipated be-cause it is more likely to occur.3 This is particularly trueif the upper cervical spine is severely impacted by thedisease process.
The use of the direct laryngoscope is a practice optionaccepted by expert practitioners; its use is commonlyencouraged in urgent or emergent situations. Otherpractice options, such as light wands, rigid fiberopticlaryngoscopes, and laryngeal mask airways, are alsodeemed appropriate. There is no published evidencethat would indicate that one intubation option is supe-rior to others with respect to outcomes in general and, inparticular, with respect to neurologic outcomes. Anycomparative study that could or would support a singlepractice option would have to be very large to be per-suasive.
Summary of the Literature
There is an incidence of CSI approximating 2% amongvictims of blunt trauma, and this incidence is trebled ifthe patient presents unconscious or with a GCS scorereduced to 8 or below. A finding of a focal neurologicdeficit also significantly increases the likelihood of acervical injury. The need to evaluate all at-risk patientswith a complete and technically adequate imaging seriesseems to be accepted as the standard of care, althoughthere is debate as to what constitutes the at-risk popula-tion and an acceptable imaging series. A three-viewspine series (lateral, antero-posterior, and odontoidviews) supplemented by computerized tomographic im-aging through areas that are difficult to visualize or sus-picious is effective in ruling out injury in both coopera-tive and noncooperative patients. MRI studies may beuseful in patients with neurologic symptoms but nega-
tive radiography and CT imaging; they seem to add littleto the evaluation of patients with persistent pain but anormal neurologic examination and negative imaging. Aswell, although MRI may identify CSI not captured by CT,these injuries are not usually unstable. Failure to diag-nose the injury at time of presentation is associated witha worse neurologic outcome; it occurs most commonlyas a result of either failure to appropriately image thespine or misinterpretation of appropriate imaging.
Immobilization of the spine in at-risk patients at thetime of first system contact and maintenance of theimmobilization until the spine is cleared is accepted byexpert consensus as the standard of care. However,there is some debate about the need for immobilizationin patients at low risk. Prolonged spinal immobilizationis costly in terms of system resources and not withoutrisk to the patient. Strategies that permit efficient andprudent spine clearance are available and their use isencouraged so as to reduce costs, conserve resources,and, most importantly, to prevent harm.
Secondary neurologic injury occurs after CSI and maybe associated with clinical care interventions. There isnow recognized a syndrome of progressive, ascendingmyelopathy that occurs in some patients and that ischaracterized by a widely distributed cord injury. It mayoccur after a period of relative clinical stability and in theabsence of both mechanical instability and canal com-promise at the spinal levels to which the injury hasascended. The use of MRI (especially T2-weighted stud-ies) has been instrumental in documenting both theoccurrence and the nature of this injury. It may alsopresent at a time when clinical interventions are ongoingto treat the original traumatic injuries. Although therehas been a past tendency to attribute many secondaryinjuries to clinical interventions, especially in a medical–legal context, critical examination of these cases, sup-plemented with MRI evaluations, may reveal that some,and perhaps most, are an inevitable consequence of theprimary injury.
The routine use of some form of immobilization duringairway maneuvers in at-risk patients is accepted as thestandard of care. All airway maneuvers will result insome degree of neck movement, both in general andspecifically at the sites of injury. The amounts of move-ment are small and may be restrained by in-line immo-bilization, but they are not eliminated. The available dataand the accumulated clinical experience support a con-clusion at the current time that these movements areunlikely to result in neurologic injury provided that rea-sonable care is taken during airway interventions. How-ever, a study of sufficient size to validate this statementhas not been performed.
The most appropriate technique for performing tra-cheal intubation in patients with cervical spine injurycontinues to be debated. There are no clinical outcomedata that suggest better neurologic outcomes with any
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particular technique, and it is acknowledged that a verylarge study would be required to furnish such data.Surveys indicate that the majority of American anesthe-siologists would prefer to use a fiberoptic bronchoscopeto intubate the trachea of at-risk patients and to do sowith the patient awake. A significant proportion of thosesharing this preference acknowledge limited skills withthe bronchoscope. As well, failed awake intubation hasbeen associated with morbidity and mortality in recentanalyses of closed claims. Surprisingly, there are no re-ports of series of CSI patients treated in this fashion, andso it is not possible to comment on the outcomes of thisstrategy.
There are a large number of reports that confirm thatrapid sequence induction of general anesthesia followedby direct laryngoscopy and tracheal intubation is widelyperformed in patients at risk for and with confirmed CSI;the resulting neurologic outcomes compare favorably tosimilar patient populations undergoing awake trachealintubation and to patients who do not require airwayintervention after traumatic injury. This technique doesnot seem to be associated with a higher incidence ofsecondary injury when compared with any other tech-nique of intubation. Unfortunately, these reports arelimited by small sample size and their retrospective na-ture. The current evidence and opinion expressed in theliterature support the use of a range of practice optionsin the management of the airway in CSI patients.
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1317AIRWAY MANAGEMENT AFTER CERVICAL SPINE INJURY
Anesthesiology, V 104, No 6, Jun 2006
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cooperation among the different disciplines involved.
References and recommended readingPapers of particular interest, published within the annual period of review, havebeen highlighted as:� of special interest�� of outstanding interest
1 Kotob F, Twersky RS. Anesthesia outside the operating room: general over-view and monitoring standards. Int Anesthesiol Clin 2003; 41:1–15.
2 Alspach D, Falleroni M. Monitoring patients during procedures conductedoutside the operating room. Int Anesthesiol Clin 2004; 42:95–111.
3 Castagnini HE, van Eijs F, Salevsky FC, Nathanson MH. Sevoflurane forinterventional neuroradiology procedures is associated with more rapid earlyrecovery than propofol. Can J Anaesth 2004; 51:486–491.
�Holmstrom A, Akeson J. Desflurane increases intracranial pressure more andsevoflurane less than isoflurane in pigs subjected to intracranial hypertension.J Neurosurg Anesthesiol 2004; 16:136–143.
One of the many papers describing the effect of volatile agents on cerebralhemodynamics in the year reviewed.
6 Sponheim S, Skraastad Ø, Helseth E, et al. Effects of 0.5 and 1.0 MACisoflurane, sevoflurane and desflurane on intracranial and cerebral perfusionpressures in children. Acta Anaesthesiol Scand 2003; 47:932–938.
7 Hall JE, Uhrich TD, Barney JA, et al. Sedative, amnestic, and analgesicproperties of small-dose dexmedetomidine infusions. Anesth Analg 2000;90:699–705.
8 Bekker AY, Kaufman B, Samir H, Doyle W. The use of dexmedetomidineinfusion for awake craniotomy. Anesth Analg 2001; 92:1251–1253.
9 Ard J, Doyle W, Bekker A. Awake craniotomy with dexmedetomidine inpediatric patients. J Neurosurg Anesthesiol 2003; 15:263–266.
10 Bustillo MA, Lazar RM, Finck AD, et al.Dexmedetomidine may impair cognitivetesting during endovascular embolization of cerebral arteriovenous malforma-tions: a retrospective case report series. J Neurosurg Anesthesiol 2002;14:209–212.
11 Soeda A, Sakai N, Sakai H, et al. Thromboembolic events associated withGuglielmi detachable coil embolization of asymptomatic cerebral aneurysms:evaluation of 66 consecutive cases with use of diffusion-weighted MRimaging. Am J Neuroradiol 2003; 24:127–132.
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13 Kubalek R, Berlis A, Schwab M, et al. Activated clotting time or activatedpartial thromboplastin time as the method of choice for patients undergoingneuroradiological intervention. Neuroradiology 2003; 45:325–327.
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29
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This is an excellent review of the recent advances in the field of interventionalneuroradiology.
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Anesthesia for neuroradiology See and Manninen 441
Spinal cord injury is a devastating event, often
resulting in long-term disability. The injury may
occur in isolation or in conjunction with other
injuries. A thorough understanding of the patho-
physiological processes involved aids manage-
ment. This article aims to provide advice on
understanding and managing some of the prob-
lems encountered by the anaesthetist.
Aetiology and incidenceThere are approximately 1000 new cases of
spinal cord injury per year in the UK, predomi-
nantly young males. Over 50% of spinal cord
injuries occur as a result of road traffic accidents,
the other major causes are sports injuries, assaults
and industrial accidents.
ClassificationLevel
Spinal cord injury may occur at any level (Table
1) but certain areas, particularly the lower cervi-
cal spine and the thoracolumbar junction, are
structurally more vulnerable. The level of the
injury determines the extent of the neurological
deficit with higher cervical lesions having the
most serious consequences.
Stability
Anatomically, the vertebral column is described
as being composed of anterior, middle and poste-
rior columns. These columns include bony and
ligamentous structures which are both important
for maintaining stability. An isolated anterior or
posterior column injury will be stable but injuries
involving more than one column are not.
In the cervical spine, C1–C2 and C5–C7 cervi-
cal vertebrae are the most vulnerable to injury.
These injuries are often unstable requiring immo-
bilisation to prevent further damage. Although
injuries of the cervical vertebral column are more
common, the spinal canal is relatively spacious at
this level and cord injury is not inevitable.
However, the mid-thoracic region is much less
mobile and the small circular vertebral canal
leaves little space around the spinal cord making
cord compression more likely. The same princi-
ple of immobilisation should be adhered to for
thoracic and lumbar spine injuries, although, in
general, these injuries are more stable.
Instability allows actual or potential abnormal
movement of one vertebral segment upon anoth-
er, thereby compromising neural structures.
Defining the stability of a vertebral column injury
is important, as it may influence the anaesthetic
and surgical management. All spinal injuries
should be treated as potentially unstable until
proven otherwise.
Neurological deficit
In general, a spinal cord injury can be described
as being complete or incomplete. An incomplete
spinal cord injury is defined by partial preserva-
tion of neurological function more than one level
below the level of spinal cord injury. Sacral spar-
ing and preserved sensory or motor function are
examples of incomplete lesions. There are sever-
al recognised patterns of incomplete lesions (e.g.
anterior cord syndrome, Brown-Sequard syn-
drome, cauda equina syndrome). If a lesion is
complete there is absence of motor and sensory
function below the level of the lesion. Complete
transection occurs in approximately 50% of
spinal cord injuries.
Anaesthesia and acute spinal cordinjury
Philippa Veale BSc MBBS FRCAJoanne Lamb MBBS FRCA
139British Journal of Anaesthesia | CEPD Reviews | Volume 2 Number 5 2002
Lu J,Ashwell KWS,Waite P.Advances in secondary spinal cord injury: role ofapoptosis. Spine 2000; 25: 1859–66
Mcleod A, Calder I. Spinal cord injury and direct laryngoscopy – the legendlives on. Br J Anaesth 2000; 84: 705–9
Short DJ, El Masry WS, Jones PW. High dose methylprednisolone in the man-agement of acute spinal cord injury – a systematic review from a clinicalperspective. Spinal Cord 2000; 38: 273–86
See multiple choice questions 94–96.
Anaesthesia and acute spinal cord injury
British Journal of Anaesthesia | CEPD Reviews | Volume 2 Number 5 2002 143
Anaesthesia for spinal surgery in adults
D. A. Raw1*, J. K. Beattie2 and J. M. Hunter1
1University Department Anaesthesia, University Clinical Department, The Duncan Building, Daulby Street,Liverpool, L69 3GA, UK. 2Royal Liverpool and Broadgreen University Hospitals NHS Trust, Prescot Road,
When assessing patients before spinal surgery, particular
care should be given to the respiratory, cardiovascular, and
neurological systems; all may be affected by the pathology
for which the spinal surgery is proposed.
Airway assessment
The potential for dif®culty in airway management should
always be considered, particularly in those patients pre-
senting for surgery of the upper thoracic or cervical spine. A
careful assessment should be made for previous dif®culty in
intubation, restriction of neck movement, and the stability
or otherwise of the cervical spine. Stability is de®ned as the
ability of the spine, under physiological loads, to resist
displacement, which causes neurological injury. It is
essential to discuss preoperatively the stability of the
spine with the surgeon. The cervical spine may be assessed
clinically (presence of pain or neurological de®cits), and
Fig 1 (A) Thoracolumbar scoliosis and measurement of the Cobb angle. A perpendicular line is drawn from the end plate of the most caudal vertebrae
involved, whose inferior end plate tilts maximally to the concavity of the curve. A second perpendicular line is drawn from the end plate of the most
cephalad vertebrae, whose superior end plate tilts maximally to the concavity of the curve. The curve value is the number of degrees formed by the
angle of intersection of these two lines. (B) Thoracolumbar scoliosis after surgery, showing long rods and pedicle screws. (C) Dislocation of the 5th
and 6th cervical vertebrae after trauma; (D) same patient's MRI scan, and (E) after surgery to stabilize the cervical spine. SC, spinal cord; C6, sixth
cervical vertebrae.
Raw et al.
888
radiographically (lateral or ¯exion/extension plain ®lms,
computer aided tomography, and magnetic resonance
imaging). The stability of the cervical spine is dependent
on ligamental and vertebral elements. Damage to these
elements may not be detectable by plain x-rays alone. The
adult cervical spine below C2 is unstable or on the brink of
instability when one of the following conditions are met: (i)
all the anterior or all the posterior elements are destroyed;
(ii) there is >3.5 mm horizontal displacement of one
vertebra in relation to an adjacent one on a lateral x-ray; or
(iii) there is more than 11° of rotation of one vertebra to an
adjacent one.119 Above the level of C2, examples of
unstable injuries include: disruption of the transverse
ligament of the atlas (a distance of greater than 3 mm in
adults between the posterior corpus of the anterior arch of
C1 and the anterior border of the odontoid process, when
measured on a lateral plain x-ray ®lm, is diagnostic); and a
Jefferson burst fracture of the atlas following axial loading,
which causes atlantoaxial instability. Disruption of the
tectorial and alar ligaments and some occipital condylar
fractures also cause atlanto-occipital instability.
Some inherited disorders such as DMD may lead to
glossal hypertrophy, and previous radiotherapy to tumours
of the head and neck can cause dif®culty in direct
laryngoscopy. A decision must be made, whether to intubate
the patient awake or asleep.
Respiratory system
Patients presenting for spinal surgery frequently have
impaired respiratory function. Those who have sustained
cervical or high thoracic trauma or who have multiple
injuries may be arti®cially ventilated preoperatively. Others
have recurrent chest infections.
Preoperatively, respiratory function should be assessed
by a thorough history, focusing on functional impairment,
physical examination, and appropriate investigations
(Table 2). Scoliosis causes a restrictive pulmonary de®cit,
with reduced vital capacity and reduced total lung capacity
(TLC). The residual volume is unchanged. The severity of
functional impairment is related to the angle of the scoliosis,
the number of vertebrae involved, a cephalad location of the
curve, and a loss of the normal thoracic kyphosis.53 The
extent of functional impairment cannot, therefore, be
directly inferred from the angle of scoliosis alone. The
most common blood-gas abnormality is a reduced arterial
oxygen tension with a normal arterial carbon dioxide
tension, as a result of the mismatch between ventilation
and perfusion in hypoventilated lung units.48 Respiratory
function should be optimized by treating any reversible
cause of pulmonary dysfunction, including infection, with
physiotherapy and nebulized bronchodilators as indicated.
There is controversy over whether surgery for idiopathic
scoliosis improves,55 59 or worsens14 63 pulmonary function.
However, the type of surgery proposed may have a
signi®cant in¯uence upon postoperative pulmonary func-
tion, and may explain the contradictory ®ndings in studies of
non-homogenous groups of patients. Surgery involving the
thorax (anterior approach, combined approach, or rib
resection) was associated with an initial decline in forced
vital capacity (FVC, 19% of baseline values), forced
expiratory volume in 1 s (FEV1, 13%), and TLC (11%) at
3 months.117 This was followed by subsequent improvement
to preoperative baseline values at 2 yr postoperatively.
Surgery involving an exclusively posterior approach, how-
ever, was associated with an improvement in pulmonary
function tests by 3 months (although not reaching statistical
signi®cance); and an improvement that was statistically
signi®cant at 2-yr follow-up: FVC (14% increase from
baseline), FEV1 (14%), TLC (5%).
Older studies have reported that if preoperative vital
capacity is less than 30±35% of predicted, postoperative
ventilation is likely to be required.45 A history of depend-
ence on continuous nasal positive airways pressure at night
is also a sign of severe functional impairment and of
reduced physiological reserve. These ®ndings should
prompt serious consideration as to whether surgery repre-
Table 2 Suggested preoperative investigations before major spinal surgery
Minimum investigations Optional investigations
Airway Cervical spine lateral x-rays with
¯exion/extension views (for patients with
rheumatoid arthritis)
CT scan
Respiratory
system
Plain chest radiograph Pulmonary function tests (bronchodilator
reversibility)
Arterial blood gas analysis Pulmonary diffusion capacity
and vibration senses. The primary sensory neurone, with its cell body in
the dorsal root ganglion of the spinal cord, sends ®bres in the dorsal
aspect of the ipsilateral spinal cord to the medulla oblongata where they
synapse. The second order sensory neurone projects ®bres to the
thalamus after crossing the midline. After synapsing with the tertiary
sensory neurone in the thalamus, ®bres are projected to the primary
somatosensory cortex. This pathway must be functionally intact in order
for SSEPs to be recorded.
Anaesthesia for spinal surgery in adults
895
and the response to this command noted. If the patient can
move their legs, anaesthesia is deepened and surgery
recommenced. If the patient is unable to move their legs,
corrective measures are instituted immediately.
A wake-up test should be as easy and as rapid to institute
as possible. This necessitates an anaesthetic technique that
is reliable, but which may be quickly antagonized as many
times as the surgeon requires. Wakening should also be
smooth to minimize the risk of tracheal extubation.
Furthermore, the patient should not experience any pain
during the test and have no subsequent recall of intraopera-
tive events.
A number of different anaesthetic techniques for the
Stagnara wake-up test have been advocated, including
volatile-based anaesthesia. A Danish group,58 in a
randomized trial involving 40 patients, described the
successful use of a midazolam-based anaesthetic,
antagonized by ¯umazenil at the time of the wake-up
test, compared with a propofol infusion technique. The
midazolam/¯umazenil group was found to have a shorter
intraoperative wake-up time (mean 2.9 vs 16 min in the
propofol group), shorter postoperative wake-up times
(1.8 vs 13.9 min, respectively), and a better quality of
intraoperative arousal. Five patients in the midazolam
group, however, became resedated in the recovery room
and required further doses of ¯umazenil. Remifentanil is
a potent m-receptor agonist. Its ester linkage renders it
susceptible to hydrolysis by tissue esterases, producing a
half-life at its site of action of less than 10 min. It
therefore has a pharmacokinetic pro®le suitable for use
when a wake-up test must be performed. Preliminary
reports using remifentanil suggest a delay between the
surgeon's request for a wake-up test and adequate
conditions for neurological assessment of only 5 min.94
Despite the use of such techniques, the test has a
number of disadvantages. First, it requires the patient's
co-operation. Secondly, it poses risks to the patient of
moving on or falling from the operating table and of
tracheal extubation, often in the prone position. Thirdly,
it requires not inconsiderable operator skill on the part
of the anaesthetist. Fourthly, it is a valid measure of
motor function at only the precise moment in time the
test is instituted; it does not allow continuous IOM of
motor pathways. The onset of a change in electro-
physiological recordings and permanent neurological
injury can occur more than 20 min after the last
corrective force is applied to the spine.80 It is, therefore,
conceivable that a wake-up test could be normal after
the last corrective manoeuvre has been applied but
before the onset of the resultant neurological de®cit.
The place of the Stagnara wake-up test in spinal cord
monitoring during spinal surgery should therefore be
con®ned to situations in which electrophysiological moni-
toring techniques are not available, fail, or produce
equivocal results.
Somatosensory evoked potentials
SSEPs are elicited by stimulating electrically a mixed
peripheral nerve (usually the posterior tibial, peroneal, or
sural nerves), and recording the response from electrodes at
distant sites cephalad to the level at which surgery is
performed (Fig. 4). Guidelines on stimulation and recording
methods have been published.4 81 Typically, the stimulus is
applied to the peripheral nerve on the left and the right limb
alternately as a square wave for 0.1±0.3 ms, at a rate of 3±
7 Hz. The intensity of the stimulus varies depending upon
the electrodes and quality of skin contact, but is in the 25±40
mA range. Recording electrodes are placed in the cervical
region over the spinous processes or over the somatosensory
cortex on the scalp, or are sited during surgery in the
epidural space. Baseline data are obtained after skin
incision. This allows a stable plane of anaesthesia to be
established during baseline recordings as anaesthetic agents
affect SSEPs. During surgery, responses are recorded
repeatedly. The functional integrity of the somatosensory
pathways is determined by comparing the amplitude change
and the latency change of the responses obtained during
surgery to baseline values. A reduction in the amplitude of
the response by 50% and an increase in the latency by 10%
are considered by most workers as signi®cant.17 78 The
amplitude response is considered the primary criterion.80
The pathways involved in the recorded responses include
a peripheral nerve, the dorsomedial tracts of the spinal cord
and, depending on the electrode placement, the cerebral
cortex (Fig. 3). The physiological role of these tracts is to
Fig 4 Diagrammatic representation of typical recordings of
somatosensory and MEP. (A) Cortical SSEP recordings after stimulation
of the tibial nerve at the ankle. In accordance with international
convention, positive waves are represented by downward de¯ections and
labelled P1, P2, etc. Negative waves are represented by upward
de¯ections, labelled N1, N2, etc. (B) Cortical MEP recordings. After
magnetic stimulation of the motor cortex, compound muscle action
potentials are recorded from electrodes placed in biceps brachii under
partial neuromuscular block.
Raw et al.
896
subserve sensations of proprioception and light touch. It
must be emphasized that responses are not obtained from
motor tracts, or from the anteriolateral sensory tracts of the
spinal cord (subserving pain and temperature sensation).
This has two important rami®cations for the validity of
SSEPs. First, because of the close proximity of the
dorsomedial sensory tracts with the motor tracts in the
cord, it is assumed that when using SSEPs, any damage to
the motor tracts will be signalled by a change in SSEPs.
This, however, cannot be guaranteed. Secondly, the blood
supply of the corticospinal motor tracts differs from that of
the dorsomedial sensory tracts (Fig. 5). Hypoperfusion in
the territory of the anterior spinal artery may cause
ischaemia in the anteriolateral tracts, but not affect the
dorsomedial tracts. It is, therefore, possible to have normal
recordings from SSEPs throughout surgery, but to have a
paraplegic patient postoperatively.8 29 86 Furthermore, in
patients with pre-existing neurological disorders, reliable
data can be recorded in only 75±85% of patients.82
Effects of anaesthetic agents on SSEPs
Anaesthetic agents can have a signi®cant impact upon
SSEPs.100 Inhalation anaesthetic agents and nitrous oxide
cause a dose-dependent reduction in SSEP amplitude and an
increase in latency.60 Nitrous oxide 60% with iso¯urane 0.5
MAC or en¯urane 0.5 MAC is compatible with effective
SSEP monitoring.89 A recent retrospective study of 442
cases found that 13/60 `false-positives' (abnormal SSEPs
with no neurological de®cit postoperatively) were attribut-
able to an increased concentration of inhalation agent.83
I.V. anaesthetic agents also cause changes to SSEPs but to
a lesser degree than inhalation agents.57 69 The cortical
response appears to be most susceptible to anaesthetic
agents; subcortical, spinal, and peripheral responses are less
affected. A recent study of the use of propofol or midazolam
as a continuous i.v. infusion combined with sufentanil was
associated with maintenance of the amplitude of the cortical
SSEP from baseline values to the end of surgery (propofol
from 1.8 (0.6) to 2.2 (0.3) mV; midazolam from 1.7 (0.5) to
1.6 (0.5) mV). However, propofol and nitrous oxide used in
combination caused a signi®cant reduction in the amplitude
of cortical SSEPs (from 2.0 (0.3) to 0.6 (0.1) mV).61 The
latencies of the responses were not increased in any of the
three groups of patients, but recovery was signi®cantly
delayed in the midazolam group. The authors recommended
a propofol technique for surgery during which cortical
SSEPs are to be recorded.
Opioids such as remifentanil and fentanyl administered
via the i.v. route cause a small reduction in the amplitude
and increase in the latencies of SSEPs.97 Intrathecal opioids
have little effect on SSEPs.30 Neuromuscular blocking
agents, as may be expected, cause no change in SSEPs.101
Fig 5 Diagrammatic representation of a transverse section through the spinal cord at the level of the sixth thoracic vertebra. Motor ®bres subserving
voluntary movement descend the spinal cord as the lateral (crossed) and anterior (uncrossed) corticospinal tracts. Sensory ®bres subserving
discriminatory touch, proprioception and vibration sense ascend the spinal cord as the fasciculus gracilis and fasciculus cuneatus, which together are
termed the dorsomedial columns. The f. gracilis conveys sensory ®bres, which originate from sacral, lumbar and lower thoracic levels. The f. cuneatus
conveys sensory ®bres, which originate from upper thoracic and cervical levels of the spinal cord. The blood supply of the spinal cord is from the
anterior spinal artery (formed by the union of a branch from each vertebral artery), which supplies the anterior two-thirds of the spinal cord including
the corticospinal tracts (unshaded area), and from the posterior spinal arteries (derived from the posterior cerebellar arteries) which supply the
posterior third of the cord including the dorsomedial columns (shaded area). These arteries are reinforced by a variable number of medullary feeding
vessels from the vertebral arteries in the cervical area, and vessels (including the Artery of Adamkiewicz) from the aorta in the thoracic and lumbar
areas.
Anaesthesia for spinal surgery in adults
897
Effect of controlled hypotension on SSEP
MAP during spinal surgery is usually maintained at lower
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Raw et al.
904
Cerebral protection
S. Fukuda1 and D. S. Warner1–3*
1Department of Anesthesiology, 2Department of Neurobiology and 3Department of Surgery, Duke University
Medical Center, Box 3094, Durham, NC 27710, USA
*Corresponding author: Department of Anesthesiology, Duke University Medical Center, Box 3094,
Cerebral ischaemia/hypoxia can occur in a variety of peri-
operative circumstances. Outcomes from such events range
from sub-clinical neurocognitive deficits to catastrophic
neurological morbidity or death. Although certain surgical
procedures present greater risk for ischaemic/hypoxic
brain injury, most insults are not presaged but instead arise
as unintended complications of either the surgical pro-
cedure or the anaesthetic.
It has been the investigative interest of surgeons and
anaesthesiologists to reduce perioperative brain injury
for more than 60 yr.12 Classically, such intervention has
been categorized as either neuroprotection or neuro-
resuscitation. Neuroprotection was defined as treatment
initiated before onset of ischaemia, intended to modify
intra-ischaemic cellular and vascular biological responses
to deprivation of energy supply so as to increase tolerance
of tissue to ischaemia resulting in improved outcome.
Neuroresuscitation, in contrast, implied treatment begun
after the ischaemic insult had occurred with the intent of
optimizing reperfusion.
However, it has become increasingly clear that an
ischaemic/hypoxic insult does not simply constitute energy
failure with consequent interruption of ongoing metabolic
events. Indeed this does occur. In addition, though, ischae-
mia and hypoxia stimulate active responses in the brain,
which persist long after substrate delivery has been
restored. These responses include activation of transcrip-
tion factors which up-regulate expression of genes contri-
buting to apoptosis and inflammation, inhibition of protein
synthesis, sustained oxidative stress, and neurogenesis.
Although some of these responses may have a teleological
advantage [e.g. elimination of dead or dysfunctional
tissue or increased tolerance to a subsequent insult (pre-
conditioning)], most responses aggravate damage caused
by the primary insult. Consequently, the concept that neu-
roprotection can be extended well into the reperfusion
phase seems appropriate, albeit with different targets other
than preservation of energy stores. This possibility may, in
part, explain the efficacy of various experimental post-
ischaemic interventions, which have manifested either as
# The Board of Management and Trustees of the British Journal of Anaesthesia 2007. All rights reserved. For Permissions, please e-mail: [email protected]
British Journal of Anaesthesia 99 (1): 10–17 (2007)
doi:10.1093/bja/aem140
clinically available therapies (e.g. mild hypothermia) or
instead as promising candidates for future clinical use tar-
geting events, such as oxidative stress, apoptosis, and
neurogenesis.
The above logic is presented as a taste of where we are
going with investigations aimed at ameliorating long-term
improvement from an ischaemic/hypoxic insult that may
occur in the perioperative period. However, the rest of this
article will focus on the opportunities and limitations of
currently available interventions (Table 1).
Anaesthetics
Barbiturates
It has been postulated for more than 50 yr that anaesthetics
increase the tolerance of brain to an ischaemic insult.28 The
logic is simple. Most drugs selected to be anaesthetics sup-
press neurotransmission. This suppression reduces energy
requirement, and reduction in energy requirement should
allow tissue better to preserve energy balance during a tran-
sient interruption of substrate delivery. Since adenosine tri-
phosphate (ATP) synthesis recovers rapidly after restoration
of substrate delivery, anaesthetics would be expected to be
protective if present during ischaemia but not if given after
restoration of substrate delivery. It would also follow that
efficacy of an anaesthetic is dependent upon the severity of
the ischaemic insult. If the insult were sufficiently severe to
cause loss of all electrical activity, there would be no
activity for anaesthetics to suppress and thus no mechanism
for such drugs to increase tolerance to ischaemia. In
contrast, in less severe insults, suppression of activity by
the anaesthetic before onset of ischaemia should delay
decay of ATP concentrations and thus also delay loss of
ionic gradients and calcium influx.
Many studies have supported this logic. Indeed, during
abrupt onset of hypoxaemia, barbiturates and isoflurane
slow deterioration of ATP concentrations.43 48 Furthermore,
post-ischaemic treatment with either barbiturates or volatile
anaesthetics has no effect on outcome.1 59 Surprisingly,
irrefutable data supporting efficacy of pre-treatment with
anaesthetics have proved difficult to acquire.
Early work testing intra-ischaemic anaesthetic efficacy
was confounded by poor physiological control of exper-
imental subjects. It was recognized later in the evolution of
anaesthetic efficacy studies that factors such as blood
glucose, brain temperature, and perfusion pressure were
important determinants of ischaemic outcome and that
anaesthetics independently modulated these factors. In
addition, early studies typically compared one anaesthetic
against another. The assumption was that the ‘control’
anaesthetic was not protective and thus failure to improve
outcome by the ‘test’ anaesthetic indicated lack of a pro-
tective state. However, little work was done to confirm that
the ‘control’ anaesthetic was not protective. Subsequent
studies, which became feasible as experimental models
evolved, often found considerable protection from the
‘control’ anaesthetic when compared with an awake state.
Thus, the field remained confused for more than a
decade and insufficient data were generated to warrant
human trials of anaesthetic efficacy when employed intra-
operatively. Even then, the early results were mixed. One
Table 1 Evidence-based status of plausible interventions to reduce perioperative ischaemic brain injury. þþ, Repeated physiologically controlled studies in
animals/randomized, prospective, adequately powered clinical trials; þ, consistent suggestion by case series/retrospective or prospective small sample size trials,
or data extrapolated from other paradigms; 2/þ, inconsistent findings in clinical trials; may be dependent on characteristics of insult; 2, well-defined absence of
benefit; 22, absence of evidence in physiologically controlled studies in animals/randomized, prospective, adequately powered clinical trials; 222, evidence
of potential harm; *, out-of-hospital ventricular fibrillation cardiac arrest
Intervention Pre-ischaemic
efficacy in
experimentalanimals
Post-ischaemic
efficacy in
experimentalanimals
Pre-ischaemic
efficacy in
humans
Post-ischaemic
efficacy in
humans
Sustained
protection in
experimentalanimals
Sustained
protection
in humans
Moderate
hypothermia
þþ þþ 2/þ þþ* þþ þþ
Mild
hyperthermia
222 222 22 22 222 22
Hyperventilation 22 22 22 22 22 22
Normoglycaemia þþ 22 þ þ þþ 22
Hyperbaric
oxygen
þþ 22 22 2/þ 22 22
Barbiturates þþ 2 þ 2 22 22
Propofol þþ þ 2 22 22 2
Etomidate 222 22 22 22 22 22
Nitrous oxide 2 22 22 22 22 22
Isoflurane þþ 22 22 22 þþ 22
Sevoflurane 22 22 22 þþ 22
Desflurane þþ 22 22 22 22 22
Lidocaine þþ 22 þ 22 22 22
Ketamine þþ 22 22 22 22 22
Glucocorticoids 222 22 22 22 22 22
Cerebral protection
11
study found efficacy from thiopental when given in
cardiac surgical patients, whereas another did not.50 67
However, only short-term outcomes were assessed, which
prevented assessment of the full evolution of the ischae-
mic injury. Furthermore, surgical procedures and cardio-
pulmonary bypass conditions were markedly different
between the two trials. Numerous other explanations have
been offered, but perhaps the overall potency of barbitu-
rates as neuroprotective agents is weak in the face of
severe ischaemic insults.65
One problem with barbiturates is their prolonged dur-
ation of action. It was believed that optimal protection
would be present only when massive doses were adminis-
tered to abolish electroencephalographic (EEG) activity,
thereby eliciting maximal suppression of cerebral meta-
bolic rate (CMR) before onset of the insult. Some
practitioners still adhere to this principle when using bar-
biturates to protect the brain but such large doses can
markedly delay anaesthesia emergence, which has limited
their clinical application. Although it is unlikely that these
massive doses are necessary to obtain maximal efficacy,65
recognition that volatile anaesthetics can also produce
EEG isoelectricity at doses which still allow rapid anaes-
thesia emergence was greeted with optimism because such
compounds could be more widely applied in clinical
settings.
Volatile anaesthetics
The efficacy of volatile anaesthetics as neuroprotective
agents has undergone more than 30 yr of scrutiny and still
no human outcome trials have been conducted to guide
clinical practice. We know the following facts from the
laboratory. Volatile anaesthetics provide major improve-
ment in ischaemic outcome. The dose required to obtain
this protection is within a clinically relevant range, with
anaesthetics protect against both focal (e.g. obstruction of
flow distal to the circle of Willis) and global (e.g. com-
plete cessation of blood flow to the brain or forebrain)
ischaemia. However, the improvement in outcome is tran-
sient in global ischaemia,23 whereas it is persistent in
focal ischaemia.58 Sevoflurane has also been shown to
provide long-term protection in one experimental model.51
The mechanism by which volatile anaesthetics protect is,
in part, attributable to suppression of energy require-
ments.47 Both inhibition of excitatory neurotransmission
and potentiation of inhibitory receptors are likely to be
involved.15 22 30 It is also likely that volatile anaesthetics
have other important effects that include regulation of
intracellular calcium responses during ischaemia,29 and
activation of TREK-1 two-pore-domain Kþ channels.25
Although a great deal has been learned from the labora-
tory, in the absence of human outcome data, it cannot be
stated that volatile anaesthetics improve outcome from
perioperative ischaemic insults. However, if an anaesthetic
is required for a surgical procedure, inclusion of volatile
anaesthetics can be considered. Isoflurane and sevoflurane
carry the largest data set to this decision. Desflurane also
offers promise,33 38 but has been insufficiently studied to
determine whether it should be equally considered in this
class of potential neuroprotective compounds.
Other anaesthetics
Other anaesthetics possess properties that suggest potential
for intra-ischaemic neuroprotection. These include propo-
fol, etomidate, and lidocaine. Study of these drugs has not
been as extensive as for either barbiturates or volatile
anaesthetics. The principle feature of propofol and etomi-
date is suppression of CMR by inhibition of synaptic
activity.19 35 Propofol may also have free radical scaven-
ging and anti-inflammatory properties.57 Propofol appears
unique among anaesthetics in the laboratory setting
because it offers efficacy with post-ischaemic therapy
onset, although such treatment provides only transient pro-
tection.9 Propofol appears to offer efficacy similar to bar-
biturates but a dose-dependent study of its efficacy has not
been completed, leaving little guidance for potential clini-
cal use. Furthermore, propofol infused to induce EEG
burst suppression failed to improve outcome in cardiac
valve surgery patients.56 Etomidate, although initially her-
alded as a substitute for barbiturates,8 has never met rigor-
ous evaluation for neuroprotective properties. In fact,
some work has indicated that etomidate may paradoxically
exacerbate ischaemic injury by inhibiting nitric oxide
synthase, thereby intensifying the ischaemic insult.21 As a
result of this and other studies, the use of etomidate for
neuroprotection has fallen out of favour in clinical
settings.
Lidocaine also suppresses CMR, but this effect is only
meaningful at doses beyond those typically employed in
clinical environments. Numerous laboratory studies have
found efficacy for lidocaine, with perhaps its principle
mechanism of action relating to inhibition of apoptosis.39
The efficacy of lidocaine appears dependent on dose, with
doses in the range used to manage cardiac dysrhythmias
having greatest efficacy.61 There have been no long-term
outcome studies of lidocaine efficacy in experimental
stroke. One small human trial found benefit from low-dose
lidocaine infusion during cardiac surgery on long-term
neuropsychological impairment.44 Lidocaine should be
further evaluated for neuroprotective properties since its
use is supported by a litany of laboratory successes such
as short-duration of action and ease of use. However,
because it has not been evaluated in a large-scale clinical
trial, efficacy in clinical environments remains speculative.
Ketamine offers potent inhibition of glutamatergic
neurotransmission at the N-methyl-D-aspartate (NMDA)
receptor. There is a long history of NMDA receptor antag-
onists as potential neuroprotective agents but, overall, such
compounds offer little or no protection against global
Fukuda and Warner
12
insults. Protection against focal insults is substantial, but
only if the drug is given before ischaemia onset. Because
ketamine is clinically available, it is tempting to argue that
it should be considered when a focal ischaemic insult is
anticipated. To date, however, there are no human data
supporting this practice. Little is also known about dose–
response properties, even in animals. Thus, it is difficult to
recommend ketamine for the purposes of neuroprotection
in the clinical environment at this time.
Physiological management
Temperature
Hypothermia has been proposed to offer therapeutic
benefit for more than 60 yr.24 Early investigators examined
its effects in both neurosurgery and cardiac surgery
patients. In the same era, it was also considered to offer
benefit in survivors of cardiac arrest and hypoxic insults.10
It remains unclear why hypothermia fell out of favour
in subsequent decades. One factor may have been its
apparent lack of efficacy, which reduced enthusiasm for
the logistical issues necessary routinely to cool and
re-warm a large patient population. Another factor may
have been the influence of mechanistic studies conducted
in the laboratory.42 That work examined effects of
hypothermia on brain energy metabolism and found
hypothermia to reduce CMR in a temperature-dependent
fashion, which became the presumed mechanism of
action. The most impressive effects on CMR were at very
low temperatures, and those temperatures required use of
cardiopulmonary bypass. The effects of mild (32–358C)
hypothermia on CMR were negligible. In contrast, barbitu-
rates can reduce CMR by 50–60% without the use of car-
diopulmonary bypass and were therefore viewed as having
a greater potential benefit. Perhaps for those reasons, the
use of perioperative hypothermia persisted only in the
context of caring for some cardiac surgical patients.
There is no doubt that deep hypothermia (e.g. 18–
228C) is highly neuroprotective. We know that only a few
minutes of complete global ischaemia will cause neuronal
death in normothermic brain. This has been best examined
in the laboratory, but human evidence is consistent with
those findings.53 In contrast, it is widely observed that
induction of deep hypothermia before circulatory arrest
routinely allows the brain to tolerate intervals of no-flow
exceeding 40 min, and substantially greater intervals of
arrest with complete or near-complete neurological recov-
ery are frequently reported. As a result of this prima facie
evidence, the efficacy of deep hypothermia has not been
subjected to randomized controlled trials. However, there
is still much to be learned with respect to optimizing
cooling and re-warming methods, optimal magnitude of
hypothermia, determination of brain temperature using sur-
rogate sites, and defining within individual patients when
the duration of circulatory arrest approaches the limits of
deep hypothermic neuroprotection.
The story might have ended there had it not been for
several laboratory studies that ignored the CMR hypoth-
esis. Those studies re-visited the possibility that mild
hypothermia could protect the brain against ischaemia
insults.14 40 To most people’s surprise, reduction in brain
temperature by only a few degree Celsius provided major
protection. These findings stimulated numerous clinical
trials in both adults and newborns, which have since pro-
vided a scientific basis defining the opportunities and
limitations of using off-bypass hypothermia to provide
meaningful neuroprotection.
The first reported work related to traumatic brain injury
(TBI). Three pilot studies provided suggestive evidence
that mild hypothermia improved either brain physiology or
outcome. However, those studies employed small sample
sizes and more definitive evidence was needed. Thus, a
large-scale prospective human trial was conducted, but
disappointing results were obtained.18 Cooling TBI
patients within the first several hours after injury failed to
improve outcome. The design and conduct of this trial
have been vigorously debated but what is clear is that
induced hypothermia is not a panacea for TBI. If it is
proven effective in later trials, it will probably be shown
to have efficacy only in certain patient populations and
only when conducted with specific protocols. Such work
is ongoing.
If the TBI study had been performed in isolation,
perhaps off-bypass hypothermia would have been aban-
doned in the clinic again. However, other studies were
already underway, two of which markedly altered the
mood of the investigative community. Both studies were
reported simultaneously and used similar experimental
designs wherein comatose survivors of out-of-hospital
cardiac arrest were randomized to normothermia or mild
hypothermia, which involved rapid surface cooling as
soon as spontaneous circulation was restored.2 11 Both
studies found significantly more patients with good
outcome in the hypothermia group and negligible adverse
events. Finally, convincing evidence is available that off-
bypass hypothermia can appreciably improve outcome
from at least cardiac arrest in humans.
These findings have prompted publication of guidelines
recommending that comatose survivors of out-of-hospital
cardiac arrest undergo cooling after restoration of spon-
taneous circulation.3 49 The extent to which the efficacy of
induced hypothermia can be extrapolated to other con-
ditions of cardiac arrest (loss of airway, asphyxia, and
drowning) may never be known given the sporadic and
relatively rare nature of those events. However, such inter-
vention may be considered.41
In addition, there is an increasing evidence that peripar-
tum neonatal asphyxial brain injury favourably responds to
treatment with hypothermia. Two trials have been
reported. The first employed selective head cooling and
Cerebral protection
13
could only find a beneficial effect of hypothermia in a
subset of the study population.27 The second employed
total body cooling.60 In this study, the benefit of induced
mild hypothermia was clear. Despite this, some feel
additional trials are required before such intervention can
be widely advocated.32
In the course of defining hypothermia efficacy, it has
also become apparent that hyperthermia has adverse effects
on post-ischaemic brain. Spontaneous post-ischaemic
hyperthermia is common4 and, in animals, intra-ischaemic
or even delayed post-ischaemic hyperthermia dramatically
worsens outcome. Spontaneous hyperthermia has also been
associated with poor outcome in humans.36 These facts
provide sufficient evidence to advocate frequent tempera-
ture monitoring in patients with cerebral injury (and those
at risk for cerebral injury). Aggressive treatment of
hyperthermia should be considered.
Glucose
Glucose is a fundamental substrate for brain energy metab-
olism. Deprivation of glucose in the presence of oxygen
can result in neuronal necrosis, but the presence of
glucose in the absence of oxygen carries a worse fate. The
mechanistic basis for this dichotomy remains unclear. The
most persistent hypothesis is that glucose, in the absence
of oxygen, undergoes anaerobic glycolysis resulting in
intracellular acidosis, which amplifies the severity of other
deleterious cascades initiated by the ischaemic insult.
Many animal studies have demonstrated adverse effects of
hyperglycaemia from a wide variety of brain insults.
Human studies remain principally correlative in nature,
that is, patients having worse outcomes from stroke, TBI,
etc. also tend to have higher blood glucose concentrations
on hospital admission. For some time, it was unclear
whether admission hyperglycaemia simply represented a
stress response to the brain insult, or instead was contribut-
ing to a worsened injury. The animal data clearly favour
the latter interpretation. More importantly, human research
has demonstrated more rapid expansion of ischaemic
lesions in hyperglycaemic, compared with normoglycaemic
patients.6 52 In addition, there is accumulating evidence that
regulation of blood glucose yields a higher incidence of
good outcome in stroke patients.26 For all of these reasons,
it is rational to maintain normoglycaemia in all patients at
risk for, or recovering from acute brain injury.
Arterial carbon dioxide partial pressure (PaCO2)
Because cerebral blood flow and PaCO2are linearly related
within physiologically relevant ranges, hyperventilation
had become an entrenched practice in cerebral resuscita-
tion. Reduction in PaCO2was presumed to augment cer-
ebral perfusion pressure favourably by reducing the
cross-sectional diameter of the arterial circulation and thus
cerebral blood volume. This would offset increases in
intracranial pressure. Although the logic behind this
practice can be appreciated, in fact, it is contradicted by
direct examination of cerebral well being. The most salient
evidence is derived from TBI investigations. These studies
support a different concept, that being worsening of per-
fusion by hyperventilation-induced vasoconstriction in
ischaemic tissue. Indeed, the volume of ischaemic tissue,
elegantly assessed with positron emission tomography in
TBI patients, was markedly increased when moderate hypo-
capnia was induced.20 This is consistent with the only pro-
spective trial of hyperventilation on TBI outcome, which
observed a decreased number of patients with good or mod-
erate disability outcomes when chronic hyperventilation
was employed.45 It remains unevaluated whether acute
hyperventilation improves outcome from pending transten-
torial herniation or when rapid surgical decompression of a
haematoma (e.g. epidural) is anticipated. Within the
context of focal ischaemic stroke, clinical trials have found
no benefit from induced hypocapnia,17 62 although hyper-
ventilation is sometimes employed in cases of refractory
brain oedema. Use of hyperventilation during cardiopul-
monary resuscitation may serve to increase mean intrathor-
acic pressure thereby decreasing perfusion pressure and is
not advocated.5 Consequently, there are few data to support
use of hyperventilation in the context of cerebral
resuscitation.
Arterial oxygen partial pressure
It makes sense that optimization of oxygen delivery to
ischaemic tissue should improve outcome. Indeed, oxygen
deprivation is the fundamental fault leading to tissue
demise. However, reperfusion presents deranged oxygen
metabolism with the opportunity to increase formation of
reactive oxygen species that plausibly induce secondary
insults, thereby worsening outcome. There are few human
data regarding the effects of normobaric hyperoxaemia in
human resuscitation. One retrospective perinatal resuscita-
tion analysis found worse long-term outcome in children
when either hyperoxaemia or hypocapnia was present
during resuscitation or early recovery.37 Others found more
rapid normalization of Apgar scores when 40% oxygen
compared with 100% oxygen was used for resuscitation.31
In animal models, it is becoming evident that the effect
of hyperoxaemia is dependent on the nature of the ischae-
mic insult. Rats subjected to middle cerebral artery occlu-
sion had smaller infarcts when normobaric hyperoxaemia
was present during both ischaemia and reperfusion. This is
consistent with the demonstrated efficacy of hyperbaric
oxygen (HBO) in rats undergoing a similar focal ischaemic
insult.63 Evidence for HBO efficacy in humans is weak.16
In contrast, in dogs subjected to cardiac arrest, it has been
repeatedly observed that outcome is worsened by normoba-
ric hyperoxaemia present during early recirculation.64 This
has been attributed to oxidation and decreased pyruvate
dehydrogenase activity, the enzymatic link between anaero-
bic and aerobic glycolysis.55 Management of oxygen
Fukuda and Warner
14
delivery after restoration of spontaneous circulation, so as
to maintain pulse oximeter values within the range of
94–96, optimized short-term neurological outcome.7 These
compelling data should serve as a stimulus for a random-
ized clinical trial and stimulates re-consideration of the
necessity for hyperoxaemia in the early post-resuscitation
interval.
Steroids
Steroids such as dexamethasone reduce oedema surround-
ing brain tumours. Beyond that, evidence for benefit from
the use of steroids is weak. Evidence that methylpredniso-
lone improves outcome from acute spinal cord trauma is
controversial,13 but some surgeons have extended this
observation to intraoperative use in spinal cord surgery.
There is insufficient evidence to define the role of gluco-
corticoids in focal ischaemic stroke.54 A large retrospec-
tive analysis found no benefit from glucocorticoid
treatment in patients with cardiac arrest.34 In fact, there is
animal evidence that such glucocorticoids exacerbate
injury from global ischaemia by increasing plasma glucose
concentration.66 Given the potential adverse effects of
steroids and lack of demonstrable efficacy in ischaemic
brain, their use cannot be advocated.
Conclusion
Ischaemic brain injury remains a potentially devastating
disorder, although progress is being made in resuscitation
science. Two key advances occurred in the past decade.
The first was repeated demonstration that induced mild
hypothermia reduces neurological morbidity and mortality
associated with out-of-hospital ventricular fibrillation
cardiac arrest. Beyond the immediate potential to apply
this intervention is the larger message that post-ischaemic
intervention can favourably influence outcome in humans.
The second advance was recognition that efficacy of mild
hypothermia depends at least in part upon the type of
ischaemic lesion being treated. Trauma and focal ischae-
mia could not be shown to be amenable to hypothermic
intervention, at least within the bounds of the clinical trial
protocols employed.
Other than the use of mild hypothermia for ventricular
fibrillation cardiac arrest, practice of clinical neuroprotection
rests on extrapolation from animal studies and weak
clinical trials. Review of these data allows some recommen-
dations to be made (Table 2). Such recommendations are
likely to be advanced with increased understanding of
cellular responses to ischaemia and appropriately conducted
clinical trials.
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ance of brain temperature in cerebral ischemic injury. Stroke1989; 20: 1113–14
15 Canas PT, Velly LJ, Labrande CN, et al. Sevoflurane protects rat
mixed cerebrocortical neuronal-glial cell cultures against transientoxygen-glucose deprivation: involvement of glutamate uptake andreactive oxygen species. Anesthesiology 2006; 105: 990–8
Table 2 Considerations when anticipating or managing a perioperative
ischaemic insult
Assure absence of hyperthermia
Manage blood glucose with insulin to induce normoglycaemia
Optimize haemoglobin-oxygen saturation (increasing concern that
hyperoxaemia may be adverse in global ischaemia)
Establish normocapnia
Consider the use of volatile anaesthetics if surgery ongoing (consistent
sustained benefit in experimental animal studies, reversible allowing
neurological examination, human trials not performed)
Resist the use of glucorticoids (no evidence of efficacy, preclinical evidence
of adverse effect in global ischaemia)
Consider the use of postoperative sustained induced moderate hypothermia if
global ischaemia (not tested by clinical trials in perioperative environment,
but supported by consistent evidence of efficacy when used in out-of-hospital
ventricular fibrillation cardiac arrest)
Cerebral protection
15
16 Carson S, McDonagh M, Russman B, Helfand M. Hyperbaricoxygen therapy for stroke: a systematic review of the evidence.Clin Rehabil 2005; 19: 819–33
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18 Clifton GL, Miller ER, Choi SC, et al. Lack of effect of induction
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19 Cold GE, Eskesen V, Eriksen H, Blatt Lyon B. Changes in CMRO2,EEG and concentration of etomidate in serum and brain tissueduring craniotomy with continuous etomidate supplemented with
N2O and fentanyl. Acta Anaesthesiol Scand 1986; 30: 159–6320 Coles JP, Fryer TD, Coleman MR, et al. Hyperventilation following
head injury: effect on ischemic burden and cerebral oxidativemetabolism. Crit Care Med 2007; 35: 568–78
21 Drummond JC, McKay LD, Cole DJ, Patel PM. The role of nitric
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22 Elsersy H, Mixco J, Sheng H, Pearlstein RD, Warner DS. Selectivegamma-aminobutyric acid type A receptor antagonism reverses iso-
Decreased mortality by normalizing blood glucose after acuteischemic stroke. Acad Emerg Med 2006; 13: 174–80
27 Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head
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28 Goldstein A, Jr, Wells BA, Keats AS. Increased tolerance tocerebral anoxia by pentobarbital. Arch Int Pharmacodyn Ther 1966;161: 138–43
29 Gray JJ, Bickler PE, Fahlman CS, Zhan X, Schuyler JA. Isofluraneneuroprotection in hypoxic hippocampal slice cultures involvesincreases in intracellular Ca2þ and mitogen-activated proteinkinases. Anesthesiology 2005; 102: 606–15
30 Harada H, Kelly PJ, Cole DJ, Drummond JC, Patel PM. Isofluranereduces N-methyl-D-aspartate toxicity in vivo in the rat cerebralcortex. Anesth Analg 1999; 89: 1442–7
31 Hellstrom-Westas L, Forsblad K, Sjors G, et al. Earlier Apgarscore increase in severely depressed term infants cared for in
Swedish level III units with 40% oxygen versus 100% oxygenresuscitation strategies: a population-based register study.Pediatrics 2006; 118: e1798–804
32 Higgins RD, Raju TN, Perlman J, et al. Hypothermia and perinatalasphyxia: executive summary of the National Institute of Child
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35 Kaisti KK, Langsjo JW, Aalto S, et al. Effects of sevoflurane, pro-
pofol, and adjunct nitrous oxide on regional cerebral blood flow,oxygen consumption, and blood volume in humans. Anesthesiology2003; 99: 603–13
36 Kammersgaard LP, Jorgensen HS, Rungby JA, et al. Admission
body temperature predicts long-term mortality after acutestroke: the Copenhagen Stroke Study. Stroke 2002; 33: 1759–62
37 Klinger G, Beyene J, Shah P, Perlman M. Do hyperoxaemia andhypocapnia add to the risk of brain injury after intrapartumasphyxia? Arch Dis Child Fetal Neonatal Ed 2005; 90: F49–52
38 Kurth CD, Priestley M, Watzman HM, McCann J, Golden J.Desflurane confers neurologic protection for deep hypothermiccirculatory arrest in newborn pigs. Anesthesiology 2001; 95: 959–64
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406–11
Cerebral protection
17
New Age Neurosurgery: Avoiding Complications in Interventional Neuroradiology
William L. Young, M.D. San Francisco, California
311 Page 1
This talk will outline the roles of the Anesthesiologist in the Interventional Neuroradiology (INR) suite with an emphasis on management strategies to prevent complications and minimize their effects if they occur. We will discuss fundamental management principles of affording "protection," of which direct pharmacological protection is perhaps the least important. Planning the anesthetic and perioperative management is predicated on understanding the goals of the therapeutic intervention and anticipating potential problems. Endovascular neurosurgery / INR is firmly established in the management of cerebrovascular disease, most notably in the management of intracranial aneurysms.1 For the overall management approach to the patient with cerebrovascular disease, there is accelerating interest and discussion in appropriate management of asymptomatic or unruptured lesions.2,3 There are several anesthetic concerns that are particularly important for INR procedures, including: (1) maintaining immobility during the procedure to facilitate imaging; (2) rapid recovery from anesthesia at the end of the case to facilitate neurological examination and monitoring, or provide for intermittent evaluation of neurological function during the procedure; (3) managing anticoagulation; (4) treating and managing sudden unexpected procedure-specific complications during the procedure, i.e., hemorrhage or vascular occlusion, which may involve manipulating systemic or regional blood pressures; (5) guiding the medical management of critical care patients during transport to and from the radiology suites; (6) self-protection issues related to radiation safety.4,5 PRE-OPERATIVE PLANNING AND PATIENT PREPARATION Baseline blood pressure and cardiovascular reserve should be assessed carefully. This almost axiomatic statement is particularly important for several reasons. Blood pressure manipulation is commonly required and treatment-related perturbations should be anticipated. Therefore, a clear sense of “where the patient lives” needs to be established. One must keep in mind that “autoregulation” as presented in the textbooks is a description of a population; individual patients are likely to vary considerably, a concept based on the historical observations that underlie our modern notions of autoregulatory behavior.6,7 In those cases where intra-arterial catheters are used, the concordance between blood pressure cuff and intra-arterial readings needs to be considered; pre-operative blood pressure range is likely to be known through blood pressure cuff values. Pre-operative calcium channel blockers for prophylaxis for cerebral ischemia may be used and can affect hemodynamic management. In addition, these agents or trans-dermal nitroglycerin are sometimes used to lessen the incidence of catheter-induced vasospasm. For cases managed with an unsecured airway, routine evaluation of the potential ease of laryngoscopy in an emergent situation should take into account that direct access to the airway may be limited by table or room logistics. Recent pterional craniotomy can sometimes result in impaired tempomandicular joint mobility. For i.v. sedation cases, careful padding of pressure points and working with the patient to obtain final comfortable positioning may assist in the patient’s ability to tolerate a long period of lying supine and motionless, decreasing the requirement for sedation, anxiolysis, and analgesia. The possibility of pregnancy in female patients and a history of adverse reactions to radiographic contrast agents should be explored. Secure intravenous (iv) access should be available with adequate extension tubing to allow drug and fluid administration at maximal distance from the image intensifier during fluoroscopy. Access to intravenous or arterial catheters can be difficult when the patient is draped and the arms are restrained at the sides; connections should be secure. Infusions of anticoagulant, primary anesthetics or vasoactive agents should be through proximal ports with minimal dead space. In addition to standard monitors, capnography sampling via the sampling port of nasal cannula is useful for i.v. sedation cases. A pulse oximeter probe can be placed on the great toe of the leg that will receive the femoral introducer sheath to provide an early warning of femoral artery obstruction or distal thromboembolism. For intracranial procedures and post-operative care, beat-to-beat arterial pressure monitoring and blood sampling can be facilitated by an arterial line. A side port of the femoral artery introducer sheath can be used, but the sheath is usually removed immediately after the procedure. In a patient who requires continuous blood pressure monitoring post-operatively or frequent blood sampling, it is convenient to have a separate radial arterial blood pressure catheter. Using a co-axial or tri-axial catheter system, arterial pressure at the carotid artery, vertebral artery, and the
311 Page 2 distal cerebral circulation can be measured. Pressures in these distal cathethers usually underestimate systolic and overestimates diastolic pressure; however, mean pressures are reliable. Bladder catheters assist in fluid management as well as patient comfort. A significant volume of heparinized flush solution and radiographic contrast is may be used. Radiation Safety is a critical part of pre-operative planning. It is probably reasonable to assume that the x-ray machine is always on. There are three sources of radiation in the INR suite: direct radiation from the X-ray tube, leakage (through the collimators' protective shielding), and scattered (reflected from the patients and the area surrounding the body part to be imaged). A fundamental knowledge of radiation safety is essential for all staff members working in an INR suite. The amount of exposure decreases proportionally to the inverse of the square of the distance from the source of radiation (inverse square law). Digital subtraction angiography (DSA) delivers considerably more radiation than fluoroscopy. Optimal protection would dictate that all personnel should wear lead aprons, thyroid shields, and radiation exposure badges. The lead aprons should be periodically evaluated for any cracks in the lead lining that may allow accidental radiation exposure. Movable lead glass screens may provide additional protection for the anesthesia team. Clear communication between the INR and anesthesia teams is also crucial for limiting radiation exposure. With proper precautions the anesthesia team should be exposed to far less than the annual recommended limit for health care workers (see URL http://pdg.lbl.gov/). ANESTHETIC TECHNIQUE Choice of Anesthetic Technique Most centers routinely involved use general endotracheal anesthesia for aneurysm coiling and endovascular treatment of vasospasm. Choice of anesthetic technique varies between centers with no clear superior method. General Anesthesia A primary reason for employing general anesthesia is to minimize motion artifacts and to improve the quality of image. Relative normocapnia or modest hypocapnia consistent with the safe conduct of positive pressure ventilation should be maintained unless intracranial pressure is a concern. The specific choice of anesthesia may be guided primarily by other cardio- and cerebrovascular considerations. Total intravenous anesthetic techniques, or combinations of inhalational and intravenous methods, may optimize rapid emergence. To date, pharmacological protection against ischemic injury during neurosurgical procedures has not been proven. A theoretical argument could be made for eschewing the use of N2O because of the possibility of introducing air emboli into the cerebral circulation and reports that it worsens outcome after experimental brain injury. Intravenous Sedation Intravenous sedation in aneurysm management is used most often for patients coming for interim follow-up angiography to assess the necessity for retreatment after primary coiling. If further treatment is indicated, the technique can be converted to a general anesthetic. Goals of anesthetic choice for intravenous sedation are to alleviate pain, anxiety, and discomfort, provide patient immobility and allow rapid recovery. There may be a discomfort associated with injection of contrast into the cerebral arteries (burning) and with distention or traction on them (headache). A long period of lying can cause significant discomfort. A variety of sedation regimens are available, and specific choices are based on the experience of the practitioner and the goals of anesthetic management. Common to all intravenous sedation techniques is the potential for upper airway obstruction. Placement of nasopharyngeal airways may cause troublesome bleeding in anticoagulated patients and is generally avoided. Dexmetetomidine is a new agent that may have applicability in the setting of INR. It is a potent, selective alpha2-agonist with sedative, anxiolytic, and analgesic properties, with recent regulatory approval for sedation. Dexmedetomidine is especially noteworthy for its ability to produce a state of patient tranquility without depressing respiration. However, there are two caveats to consider. First, there are still unclear effects on cerebral perfusion.8 More importantly, there is a tendency for patients managed with dexmedetomidine to have relatively low blood pressure in the post-anesthesia recovery period.9 Because patients with aneurismal subarachnoid hemorrhage may be critically dependent on adequate collateral perfusion pressure, use of regimens that may result in blood pressure decreases should be used with great caution.
311 Page 3 ANTICOAGULATION Heparin: Careful management of coagulation is required to prevent thromboembolic complications during and after the procedure. Generally, after a baseline activated clotting time (ACT) is obtained, intravenous heparin (70 units/kg) is given to a target prolongation of 2 ~ 3 times of baseline. Then heparin can be given continuously or as an intermittent bolus with hourly monitoring of ACT. Occasionally, a patient may be refractory to attempts to obtain adequate anticoagulation. Switching from bovine to porcine heparin or vice versa should be considered. If antithrombin III deficiency is suspected, administration of fresh frozen plasma may be necessary. Direct Thrombin Inhibitors: Heparin-induced thrombocytopenia (HIT) is a potentially devastating prothrombotic syndrome caused by heparin dependent antibodies after exposure. Direct thrombin inhibitors may be used in patients with or at risk of HIT, although they entail their own risks, including a small risk of anaphylaxis. They inhibit thrombin both in the free form or bound to the clot. Monitoring of action is done by measuring the aPTT, or ACT. Lepirudin is FDA-approved for anticoagulation in patients with HIT. The half-life of lepirudin is 40 to 120 minutes, and it undergoes renal elimination. For HIT patients with renal impairment, Argatroban, predominantly metabolized in the liver, may be preferrable. Bivalirudin, a synthetic derivative of lepirudin, has a short half-life of about 25 minutes. Since bivalirudin is partially renally eliminated, dose adjustments may be needed in patients with renal dysfunction. A recent report described bivalirudin as a potential alternative during INR procedures to heparin for intravenous anticoagulation and intra-arterial thrombolysis.10 Antiplatelet agents: Antiplatelet agents (aspirin, the glycoprotein IIb/IIIa receptor antagonists and the thienopyridine derivatives) are increasingly being used for cerebrovascular disease management, as well as rescue from thromboembolic complications.11,12 Activation of the platelet membrane glycoprotein (GP) IIb/IIIa leads to fibrinogen binding and is a final common pathway for platelet aggregation. Abciximab, eptifibatide and tirofiban are glycoprotein IIb/IIIa receptor antagonists. The long duration and potent effect of Abciximab also increase the likelihood of major bleeding. The smaller molecule agents, eptifibatide and tirofiban, are competitive blockers and have a shorter half-life (about 2 hours). Thienopyridine derivatives (ticlopidine and clopidogrel) bind to the platelet’s ADP receptors and permanently alter the receptor; therefore, the duration of action is the life span of the platelet. The addition of clopidogrel to the antiplatelet regimen is used when stent-assisted coiling is anticipated, and also for management of unruptured aneurysms. Reversal of Anticoagulation: At the end of the procedure or at occurrence of hemorrhagic complication, heparin may be reversed with protamine. Since there is no specific antidote for the direct thrombin inhibitors or the antiplatelet agents, the biological half-life is one of the major considerations in drug choice and platelet transfusion is a non-specific therapy, should reversal be indicated. There is no currently available accurate test to measure platelet function in patients taking the newer antiplatelet drugs. Desmopressin (DDAVP) has been reported to shorten the prolonged bleeding time of individuals taking antiplatelet agents such as aspirin and ticlopidine. There are also increasing recent reports on using specific clotting factors, including recombinant factor VIIa and factor IX complex, to rescue severe life-threatening bleeding, including intracranial hemorrhage uncontrolled by standard transfusion therapy. The safety and efficacy of these coagulation factors remain to be investigated. DELIBERATE HYPERTENSION During acute arterial occlusion or vasospasm, the only practical way to increase collateral blood flow may be an augmentation of the collateral perfusion pressure by raising the systemic blood pressure. The Circle of Willis is a primary collateral pathway in cerebral circulation. However, in as many as 21% of otherwise normal subjects, the circle may not be complete. There are also secondary collateral channels that bridge adjacent major vascular territories, most importantly for the long circumferential arteries that supply the hemispheric convexities. These pathways are known as the pial-to-pial collateral or leptomeningeal pathways. The extent to which the blood pressure has to be raised depends on the condition of the patient and the nature of the disease. Typically, during deliberate hypertension the systemic blood pressure is raised by 30-40% above the baseline, in the absence of some direct outcome measure such as resolution of ischemic symptoms or imaging evidence of improved perfusion. Phenylephrine is usually the first line agent for deliberate hypertension and is
311 Page 4 titrated to achieve the desired level of blood pressure. The risk of causing hemorrhage into the ischemic area must be weighed against the benefits of improving perfusion, but augmentation of blood pressure in the face of acute cerebral ischemia is probably protective in most settings. DELIBERATE HYPOTENSION The two primary indications for induced hypotension are: (1) to test cerebrovascular reserve in patients undergoing carotid occlusion, and (2) to slow flow in a feeding artery of BAVMs before glue injection. The most important factor in choosing a hypotensive agent is the ability to safely and expeditiously achieve the desired reduction in blood pressure while maintaining the patient physiologically stable. The choice of agent should be determined by the experience of the practitioner, the patient's medical condition, and the goals of the blood pressure reduction in a particular clinical setting. Intravenous adenosine has been used to induce transient cardiac pause and may be a viable method of partial flow arrest.13 MANAGEMENT OF NEUROLOGICAL AND PROCEDURAL CRISES A well thought-out plan, coupled with rapid and effective communication between the anesthesia and radiology teams, is critical for good outcomes. The primary responsibility of the anesthesia team is to preserve gas exchange and, if indicated, secure the airway. Simultaneous with airway management, the first branch in the decision-making algorithm is for the anesthesiologist to communicate with the INR team and determine whether the problem is hemorrhagic or occlusive. In the setting of vascular occlusion, the goal is to increase distal perfusion by blood pressure augmentation with or without direct thrombolysis. If the problem is hemorrhagic, immediate cessation of heparin and reversal with protamine is indicated. As an emergency reversal dose, 1 mg protamine can be given for each 100 units of initial heparin dosage that resulted in therapeutic anticoagulation. The ACT can then be used to fine-tune the final protamine dose. Complications of protamine administration include hypotension, true analphylaxis and pulmonary hypertension. With the advent of new long-acting direct thrombin inhibitors such as bivalirudin, new strategies for emergent reversal of anticoagulation will need to be developed. Bleeding catastrophes are usually heralded by headache, nausea, vomiting and vascular pain related to the area of perforation. Sudden loss of consciousness is not always due to intracranial hemorrhage. Seizures, as a result of contrast reaction or transient ischemia, and the resulting post-ictal state can also result in an obtunded patient. In the anesthetized or comatose patient, the sudden onset of bradycardia and hypertension (Cushing response) or the endovascular therapist’s diagnosis of extravasation of contrast may be the only clues to a developing hemorrhage. Most cases of vascular rupture can be managed in the angiography suite. The INR team can attempt to seal the rupture site endovascularly and abort the procedure; a ventriculostomy catheter may be placed emergently in the angiography suite. Patients with suspected rupture will require emergent CT scan, but emergent craniotomy is usually not indicated. SPECIFIC PROCEDURES Intracranial Aneurysm Ablation The two basic approaches for INR therapy of cerebral aneurysms are occlusion of proximal parent arteries and obliteration of the aneurysmal sac. With the publication of the ISAT trial,14 coil embolization of intracranial aneurysms has become a routine first choice therapy for many lesions. The anesthesiologist should be prepared for aneurysmal rupture and acute SAH at all times, either from spontaneous rupture of a leaky sac or direct injury of the aneurysm wall by the vascular manipulation. There is great interest in the development of stent-assisted coiling methods. The stent can provide protection of the parent vessel. Stent placement requires a greater degree of instrumentation and manipulation, probably increasing the ever-present intra-procedural risk of parent vessel occlusion, thromboembolism or vascular rupture. Angioplasty of Cerebral Vasospasm from Aneurysmal SAH Roughly 1 out of 4 patients with SAH will develop symptomatic vasospasm. Angioplasty, either mechanical (balloon) or pharmacological (intraarterial vasodilators), may be used as a treatment.15 Angioplasty is ideally done in patients that have already had the symptomatic lesion surgically clipped and for patients in the early course of symptomatic ischemia in order to prevent hemorrhagic transformation of an ischemia region. A balloon catheter is guided under fluoroscopy into the spastic segment and inflated to mechanically distend the constricted area. It is also possible to perform a “pharmacologic” angioplasty by direct intra-arterial infusion. There
311 Page 5 is the greatest experience with papaverine, but there are potential CNS toxic effects.16 Other agents such as calcium channel blockers (nicardipine and verapamil) are being used.17 Intraarterial vasodilators may have systemic effects (bradycardia and hypotension). Patients who come for angioplasty are often critically ill with a variety of challenging co-morbidities, including neurocardiac injury, volume overload from “triple-H” therapy, hydrocephalus, brain injury from recent craniotomy, and residual effects of the presenting hemorrhage. Procedural complications include arterial rupture, reperfusion hemorrhage, thromboembolism, and arterial dissection. Carotid Test Occlusion and Therapeutic Carotid Occlusion Large or otherwise unclippable aneurysms may be partly or completely treated by proximal vessel occlusion. In order to assess the consequences of carotid occlusion in anticipation of surgery, the patient may be scheduled for a test occlusion in which cerebrovascular reserve is evaluated in several ways. A multimodal combination of angiographic, clinical, and physiologic tests can be used to arrive at the safest course of action for a given patient’s clinical circumstances. The judicious use of deliberate hypotension can increase the sensitivity of the test.18 The most important factor in choosing a hypotensive agent is the ability to safely and expeditiously achieve the desired reduction in blood pressure while maintaining the patient physiologically stable. The choice of agent should be determined by the experience of the practitioner, the patient's medical condition and the goals of the blood pressure reduction in a particular clinical setting. Brain Arteriovenous Malformations (BAVMs) Also called cerebral or pial AVMs, these are typically large, complex lesions made up of a tangle of abnormal vessels (called the nidus) frequently containing several discrete fistulae served by multiple feeding arteries and draining veins. The goal of the therapeutic embolization is to obliterate as many of the fistulae and their respective feeding arteries as possible. BAVM embolization is usually an adjunct for surgery or radiotherapy. The cyanoacrylate glues offer relatively “permanent” closure of abnormal vessels. Passage of glue into a draining vein can result in acute hemorrhage; in smaller patients, pulmonary embolism of glue can be symptomatic. For these reasons, deliberate hypotension may increase safety of glue delivery. Although less durable, polyvinyl alcohol microsphere embolization is also commonly used. If surgery is planned within days after PVA embolization, the rate of recanalization is low. Dural AVMs Dural AVM is considered an acquired lesion resulting from venous dural sinus stenosis or occlusion, opening of potential AV shunts, and subsequent recanalization. Symptoms are variable according to which sinus is involved. Venous hypertension of pial veins is a risk factor for intracranial hemorrhage. Dural AVMs may be fed by multiple meningeal vessels, and therefore, multi-staged embolization is often necessary. Dural AV fistulas can induce markedly increased venous pressure and decrease net cerebral perfusion pressure. Therefore, presence of venous hypertension should be factored into management of systemic arterial and cerebral perfusion pressure. Angioplasty and Stenting for Atherosclerotic Lesion Angioplasty and stenting for atherosclerosis for treatment of atherosclerotic disease involving the cervical and intracranial arteries continue to supplant open surgical management.19,20 Risk of distal thromboembolism is a major issue in this procedure. Catheter systems employing some kind of trapping system distal to the angioplasty balloon are being developed. There are multiple ongoing trials to compare the utility of stenting to carotid endarterctomy for extracranial carotid disease. It is likely that use of stenting will continue to increase as favorable data supporting its safety and efficacy emerge. Preparation for anesthetic management may include placement of transcutaneous pacing leads, in case of severe bradycardia or asystole from carotid body stimulation during angioplasty. Intravenous atropine or glycopyrrolate may be also used in an attempt to mitigate against bradycardia, which almost invariably occurs to some degree with inflation of the balloon. This powerful chronotropic response may be difficult or impossible to prevent or control by conventional means. Adverse effects of increasing myocardial oxygen demand need to be considered in anti-bradycardia interventions.
311 Page 6 Potential complications include vessel occlusion, perforation, dissection, spasm, thrombo-emboli, occlusion of adjacent vessels, transient ischemic episodes, and stroke. Similar to carotid endarterectomy, there is about a 5% risk of symptomatic cerebral hemorrhage and/or brain swelling after carotid angioplasty.21 Although the etiology of this syndrome is unknown, it has been associated with cerebral hyperperfusion, and it may be related to poor post-operative blood pressure control. Thrombolysis of Acute Thromboembolic Stroke In acute occlusive stroke, it is possible to recanalize the occluded vessel by superselective intra-arterial thrombolytic therapy. Thrombolytic agents can be delivered in high concentration by a microcatheter navigated close to the clot. Neurological deficits may be reversed without additional risk of secondary hemorrhage if treatment is completed within 4-6 hours from the onset of carotid territory ischemia and 24 hours in vertebrobasilar territory. One of the impediments in development in this area has been the fear of increasing the risk of hemorrhagic transformation of the acute infarction patient. Despite an increased frequency of early symptomatic hemorrhagic complications, treatment with intra-arterial pro-urokinase within 6 hours of the onset of acute ischemic stroke with MCA occlusion significantly improved clinical outcome at 90 days.22 Details of anesthetic management are reviewed elsewhere.23 POST-OPERATIVE MANAGEMENT Endovascular surgery patients pass the immediate post-operative period in a monitored setting, to watch for signs of hemodynamic instability or neurologic deterioration. Control of blood pressure may be necssary during transport and post-operative recovery, e.g., induced hypertension, if indicated. Abrupt restoration of normal systemic pressure to a chronically hypotensive (ischemic) vascular bed may overwhelm autoregulatory capacity and result in hemorrhage or swelling (normal perfusion pressure breakthrough, NPPB). In the absence of collateral perfusion pressure inadequacy, fastidious attention to preventing hypertension is warranted. Complicated cases may go first to CT or some other kind of tomographic imaging; critical care management may need to be extended during transport and imaging. References: 1. A. J. Molyneux, et al., Lancet 366, 809-17 (2005) 2. C. Stapf, et al., Curr Opin Neurol 19, 63-68 (2006) 3. D. O. Wiebers, et al., Lancet 362, 103-10 (2003) 4. W. L. Young, et al., Anesthesiology 80, 427-456 (1994) 5. W. L. Young, et al., Anesthesiology Clinics of North America 15(3), 631-653 (1997) 6. S. Strandgaard, et al., Br Med J 1, 507-510 (1973) 7. J. C. Drummond, et al., Anesthesiology 86, 1431-1433 (1997) 8. R. C. Prielipp, et al., Anesth Analg 95, 1052-9, table of contents (2002) 9. S. R. Arain, et al., Anesth Analg 95, 461-6, table of contents (2002) 10. M. R. Harrigan, et al., Neurosurgery 54, 218-22; discussion 222-3 (2004) 11. T. Hashimoto, et al., Anesthesiol Clin North America 20, 347-59, vi (2002) 12. D. Fiorella, et al., Neurosurgery 54, 1089-98 (2004) 13. T. Hashimoto, et al., Anesthesiology 93, 998-1001 (2000) 14. A. Molyneux, et al., Lancet 360, 1267-74 (2002) 15. D. W. Newell, et al., J Neurosurg 71, 654-660 (1989) 16. W. S. Smith, et al., Stroke 35, 2518-22 (2004) 17. L. Feng, et al., AJNR Am J Neuroradiol 23, 1284-1290 (2002) 18. R. S. Marshall, et al., Brain 124, 1208-17 (2001) 19. R. T. Higashida, et al., AJNR Am J Neuroradiol 26, 2323-7 (2005) 20. P. P. Goodney, et al., J Vasc Surg 43, 406-11 (2006) 21. P. M. Meyers, et al., Neurosurgery 47, 335-43; discussion 343-5 (2000) 22. A. Furlan, et al., Jama 282, 2003-11 (1999) 23. C. Z. Lee, et al., J Vasc Interv Radiol 15 (1), S13-S19 (2004)
Interventional neuroradiology—anesthetic
considerations
Tomoki Hashimoto, MDa,d, Dhanesh K. Gupta, MDa,d,William L. Young, MDa,b,c,d,*
aDepartment of Anesthesia and Perioperative Care, University of California,
San Francisco, CA 94110, USAbDepartment of Neurological Surgery, University of California, San Francisco, CA 94110, USA
cDepartment of Neurology, University of California, San Francisco, CA 94110, USAdCenter for Cerebrovascular Research, University of California, San Francisco,
San Francisco General Hospital, 1001 Potrero Avenue, Room 3C-38,
San Francisco, CA 94110, USA
Interventional neuroradiology (INR) is a hybrid of traditional neurosurgery
and neuroradiology, with certain overlaps with aspects of head-and-neck
surgery. It can be broadly defined as treatment of central nervous system (CNS)
disease by endovascular access for the purpose of delivering therapeutic
agents, including both drugs and devices [1]. Because of a recent advance-
ment in the field of INR [2], more anesthesiologists are involved in care of
patients undergoing INR procedures. Anesthesiologists have several important
concerns when providing care to patients who undergo INR procedures,
including (1) maintenance of patient immobility and physiologic stability; (2)
manipulating systemic or regional blood flow; (3) managing anticoagulation;
(4) treating and managing sudden unexpected complications during the pro-
cedure; (5) guiding the medical management of critical care patients during
transport to and from the radiology suites; and (6) rapid recovery from
anesthesia and sedation during or immediately after the procedure to facilitate
neurologic examination and monitoring [3,4]. To achieve these goals, anes-
thesiologists should be familiar with specific radiological procedures and their
potential complications.
0889-8537/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved.
PII: S0889 -8537 (01 )00005 -0
This work is supported in part by National Institutes of Health, Grants K24-NS02091 (W.L.Y.).
* Corresponding author. Center for Cerebrovascular Research, University of California, San
Francisco General Hospital, 1001 Potrero Ave., Room 3C-38, San Francisco, CA 94110, USA.
administration: effect on regional cerebral blood flow in patients with arteriovenous malforma-
tions. J Neurosurg 1996;85:395–402.
[19] Roberts JT, Pile-Spellman J, Joseph M, et al. A patient with massive oral-facial venous malfor-
mation. J Clin Anesth 1991;3:76–9.
[20] Higashida RT, Tsai FY, Halbach VV, et al. Transluminal angioplasty for atherosclerotic disease of
the vertebral and basilar arteries. J Neurosurg 1993;78:192–8.
[21] Tsai FY, Matovich V, Hieshima G, et al. Percutaneous transluminal angioplasty of the carotid
artery. AJNR Am J Neuroradiol 1986;7:349–58.
[22] Theron J, Courtheoux P, Alachkar F, et al. New triple coaxial catheter system for carotid
angioplasty with cerebral protection [followed with Commentary by Ferguson R: Getting it right
the first time, p. 875–7]. AJNR Am J Neuroradiol 1990;11:869–74.
[23] Meyers PM, Higashida RT, Phatouros CC, et al. Cerebral hyperperfusion syndrome after percu-
taneous transluminal stenting of the craniocervical arteries [In Process Citation]. Neurosurgery
2000;47:335–43; discussion 343–5.
[24] Furlan A, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischemic stroke.
The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboem-
bolism. JAMA 1999;282:2003–11.
T. Hashimoto et al. / Anesthesiology Clin N Am 20 (2002) 347–359 359
CommentaryCommentaire
It is time to clear the confusion about the utility ofsteroids in cases of acute spinal cord injury. A com-mittee of Canadian neurosurgical and orthopedic
spine specialists, emergency physicians and physiatrists(listed at the end of the article) has reviewed the evidenceand concluded that high-dose methylprednisolone infu-sion is not an evidence-based standard of care for patientswith such an injury.1
The consequences of a spinal cord injury are often deva-stating, and any possibility of mitigating neurologic loss is attractive. To this end, management of acute spinal cord in-juries has included the use of steroids for the past 30 years,based in large part on physiological hypotheses with limitedclinical support.2,3 Mechanical injury to the spinal cord initi-ates a cascade of secondary events that include ischemia, in-flammation and calcium-mediated cell injury. Animal ex-periments have shown that methylprednisolone exhibitspotential neuroprotective effects through its inhibition oflipid peroxidation and calcium influx and through its anti-inflammatory effects.4,5 Three well-designed, large, random-ized clinical trials (the National Acute Spinal Cord InjuryStudies [NASCIS I, II and III]) examined the effect of steroidadministration in patients with acute spinal cord injury.6–11
NASCIS I examined the change in motor function inspecific muscles and changes in light touch and pinpricksensation from baseline.6,7 The study detected no benefitfrom methylprednisolone, but the dose was considered tobe below the therapeutic threshold determined from ani-mal experiments. Therefore, NASCIS II used a muchhigher dose, and patients were randomly assigned to re-ceive a 24-hour infusion of methylprednisolone, naloxoneor placebo within 12 hours after acute spinal cord injury.8,9
Again, there was no benefit overall in the methylpred-nisolone group; however, post hoc analyses detected a smallgain in the total motor and sensory score in a subgroup ofpatients who had received the drug within 8 hours aftertheir injury. As a result, this 24-hour, high-dose methyl-prednisolone infusion, if started within 8 hours after injury,quickly became an implied standard of care despite consid-erable criticism of the validity of such a post hoc analysis.
Subsequent clinical trials have provided conflicting evi-dence about steroid treatment in acute spinal cord injury. AJapanese study attempted to replicate the results seen in the8-hour subgroup from NASCIS II and reported improvedfunction at 6 months in a larger number of muscles and
sensory dermatomes among subjects who received high-dose methylprednisolone infusion than among those whoreceived only low doses of the drug or no drug.12 However,the study lacked detail about randomization and outcomemeasures, and it included only 74% of the enrolled subjectsin the outcome analysis. Conversely, an underpoweredprospective randomized trial that used a methylpred-nisolone regimen similar to that used in NASCIS II foundno improvement in motor and sensory scores at 1 year.13,14
NASCIS III compared a 48-hour infusion of methylpred-nisolone with a 24-hour infusion started within 8 hours af-ter injury and found no benefit from extending the infusionbeyond 24 hours. Again, only post hoc analysis showed abenefit from extending the infusion to 48 hours when treat-ment was started between 3 and 8 hours after injury. Noother study has verified the primary outcome of 48 hoursversus 24 hours or the post hoc conclusion of benefit fromstarting treatment between 3 and 8 hours after injury.
A meta-analysis of all of the trials concluded, on the basisof the controversial subgroup post hoc analyses in NASCISII and III and the data from the Japanese study, that a 24-hour high-dose methylprednisolone infusion within 8 hoursafter injury is efficacious.15 Despite this meta-analysis, theefficacy of such a regimen remains uncertain and will re-quire further study. The controversy about the post hocanalyses of NASCIS data continues,16–23 and unfortunatelythe studies that could have clarified the efficacy of such aregimen have lacked the rigour to do so.
Steroid therapy is not without risk. Most patients withacute spinal cord injury are treated in intensive care units,have polytrauma, have impaired lung capacity and are vul-nerable to sepsis. In all 3 NASCIS studies and other,smaller studies, the incidence of sepsis and pneumonia washigher in the high-dose methylprednisolone groups than inthe placebo or other treatment groups;6–11,24–26 the differ-ences were not significant except in NASCIS III. Hyper-glycemia and gastrointestinal complications were alsoreported following high-dose methylprednisolone treat-ment.13,24 Therefore, it has been proposed that, withoutcompelling evidence for its efficacy, methylprednisoloneshould be used with caution and may even be harmful, par-ticularly if infusion goes beyond 24 hours.17
The cost of a 24-hour methylprednisolone infusion is notprohibitive, and a gain of antigravity strength in one ormore muscles below a spinal segment can provide an impor-
Methylprednisolone for acute spinal cord injury: not a standard of care
tant functional gain, especially for patients with cervicalspinal cord injuries. Therefore, even the small improvementobserved in the NASCIS subgroups could be viewed as abenefit in cases of complete or incomplete cervical cord in-jury. Despite the risk of complications and as long as theoutcomes in the NASCIS subgroups remain a possibility,physicians may still opt to administer a high-dose methyl-prednisolone infusion within 8 hours after injury. However,they should no longer feel compelled to do so. Physicianswho conduct the initial triage and resuscitation of patientswith acute spinal cord injury should consult their specialistcolleagues who will be continuing the care of these patientsregarding their preference for methylprednisolone infusion.
The Canadian Neurosurgical Society, the CanadianSpine Society and the Canadian Association of EmergencyPhysicians have adopted the committee’s recommendationthat a high-dose, 24-hour infusion of methylprednisolonestarted within 8 hours after an acute closed spinal cord in-jury is not a standard treatment nor a guideline for treat-ment but, rather, a treatment option, for which there is veryweak level II and III evidence.27
References
1. Hugenholtz H, Cass DE, Dvorak MF, Fewer DH, Fox RJ, Izukawa DMS, etal. High-dose methylprednisolone for acute closed spinal cord injury — onlya treatment option. Can J Neurol Sci 2002;29(3):227-35.
2. Tator CH. Acute spinal cord injury: a review of recent studies of treatmentand pathophysiology. CMAJ 1972;107(2):143-5.
3. Green BA, Kahn T, Klose KJ. A comparative study of steroid therapy in acuteexperimental spinal cord injury. Surg Neurol 1980;13(2):91-7.
4. Braughler JM, Hall ED. Lactate and pyruvate metabolism in injured catspinal cord before and after a single large intravenous dose of methylpred-nisolone. J Neurosurg 1983;59:256-61.
5. Hall ED. The neuroprotective pharmacology of methylprednisolone. J Neu-rosurg 1992;76:13-22.
6. Bracken MB, Collins WF, Freeman DF, Shepard MJ, Wagner FW, SiltenRM, et al. Efficacy of methylprednisolone in acute spinal cord injury. JAMA1984;251(1):45-52.
7. Bracken MB, Shepard MJ, Hellenbrand KG, Collins WF, Leo LS, FreemanDF, et al. Methylprednisolone and neurological function 1 year after spinalcord injury. Results of the National Acute Spinal Cord Injury Study. J Neuro-surg 1985;63(5):704-13.
8. Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS,et al. A randomized, controlled trial of methylprednisolone or naloxone in thetreatment of acute spinal-cord injury. Results of the Second National AcuteSpinal Cord Injury Study. N Engl J Med 1990;322(20):1405-11.
9. Bracken MB, Shepard MJ, Collins WF Jr, Holford TR, Baskin DS, EisenbergHM, et al. Methylprednisolone or naloxone treatment after acute spinal cordinjury: 1-year follow-up data. Results of the second National Acute SpinalCord Injury Study. J Neurosurg 1992;76(1):23-31.
10. Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, FazlM, et al. Administration of methylprednisolone for 24 or 48 hours or tirilazadmesylate for 48 hours in the treatment of acute spinal cord injury. Results ofthe Third National Acute Spinal Cord Injury Randomized Controlled Trial.National Acute Spinal Cord Injury Study. JAMA 1997;277(20):1597-604.
11. Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M,et al. Methylprednisolone or tirilazad mesylate administration after acutespinal cord injury: 1-year follow up. Results of the third National Acute Spinal
cial effect of methylprednisolone sodium succinate in the treatment of acutespinal cord injury. Sekitsui Sekizui J 1996;7:633-47.
13. Petitjean ME, Pointillart V, Dixmerias F, Wiart L, Sztark F, Lassie P, et al.Medical treatment of spinal cord injury in the acute stage. Ann Fr Anesth Re-anim 1998;17(2):114-22.
14. American Spinal Cord Injury Association. Standard for neurological classificationof spinal cord patients. Chicago: The Association; 1992.
15. Bracken MB. Pharmacological intervention for acute spinal cord injury[Cochrane review]. In: The Cochrane Library; Issue 1, 2001. Oxford: UpdateSoftware.
16. Coleman WP, Benzel D, Cahill DW, Ducker T, Geisler F, Green B, et al. Acritical appraisal of the reporting of the National Acute Spinal Cord InjuryStudies (II and III) of methylprednisolone in acute spinal cord injury. J SpinalDisord 2000;13(3):185-99.
17. Hurlbert RJ. Methylprednisolone for acute spinal cord injury: an inappropri-ate standard of care. J Neurosurg 2000;93(Suppl 1):1-7.
18. Nesathurai S. Steroids and spinal cord injury: revisiting the NASCIS 2 andNASCIS 3 trials. J Trauma 1998;45(6):1088-93.
19. Short DJ, El Masry WS, Jones PW. High dose methylprednisolone in themanagement of acute spinal cord injury — a systematic review from a clinicalperspective [review]. Spinal Cord 2000;38(5):273-86.
20. Section on disorders of the spine and peripheral nerves of the American Asso-ciation of Neurological Surgeons and the Congress of Neurological Sur-geons. Guidelines for the management of acute cervical spine and spinal cordinjuries. Neurosurgery 2002;50(Suppl 3):S67-72.
21. Oxman AD, Guyatt GH. A consumer’s guide to subgroup analyses. Ann In-tern Med 1992;116:78-84.
22. Fehlings MG. Summary statement: the use of methylprednisolone in acutespinal cord injury. Spine 2001;26(Suppl 24):S55.
23. Fehlings MG. Recommendations regarding the use of methylprednisolone inacute spinal cord injury: making sense out of the controversy [editorial]. Spine2001;26(Suppl 24):S56-7.
24. Matsumoto T, Tamaki T, Kawakami M, Yoshida M, Ando M, Yamada H. Earlycomplications of high-dose methylprednisolone sodium succinate treatment inthe follow-up of acute cervical spinal cord injury. Spine 2001;26(4):426-30.
25. Galandiuk S, Raque G, Appel S, Polk HC Jr. The two-edged sword of large-dosesteroids for spinal cord trauma. Ann Surg 1993;218(4):419-25; discussion 425-7.
27. Canadian Task Force on the Periodic Health Examination. The periodichealth examination. 1. Introduction. CMAJ 1986;134(7):721-9.
Commentaire
1146 JAMC • 29 AVR. 2003; 168 (9)
This article has been peer reviewed.
Competing interests: None declared.
Dr. Hugenholtz is with the Division of Neurosurgery, Queen Elizabeth II HealthSciences Centre, Halifax, NS.
Correspondence to: Dr. Herman Hugenholtz, New HalifaxInfirmary, Rm. 3808, 1796 Summer St., Halifax NS B3H 3A7; fax 902 473-8912
Members of the Committee of the Canadian Spine Society andthe Canadian Neurosurgical Society to Review the Role ofMethylprednisolone in Acute Spinal Cord Injury: HermanHugenholtz (chair), Division of Neurosurgery, Queen Elizabeth IIHealth Sciences Centre, Halifax, NS; Nirmala D. Bharatwal,Toronto Rehabilitation Institute, Toronto, Ont.; Dan E. Cass,Director of Emergency Services, St. Michael’s Hospital, Toronto,Ont.; Marcel F. Dvorak, Medical Director, Combined SpineProgram, Vancouver Hospital and Health Sciences Centre,Vancouver, BC; Derek Fewer, Section of Neurosurgery, HealthSciences Centre, Winnipeg, Man.; Richard J. Fox, Department ofNeurosurgery, Walter C. Mackenzie Health Science Centre,University Hospital, Edmonton, Alta.; Dennis M.S. Izukawa,Department of Neurosurgery, Trillium Health Centre,Mississauga, Ont.; Joel Lexchin, Emergency Department,University Health Network, Toronto, Ont.; Christine Short, NovaScotia Rehabilitation Centre, Halifax, NS; and Sagun Tuli,Department of Neurosurgery, Brigham and Women’s Hospital,Boston, Mass.
SPINAL CORD MONITORING AND PROTECTION DURING SPINAL SURGERY
A. Travers Pathogenesis of spinal cord injury during spinal surgery Patients at risk for persistent neurological injury following spinal surgery are those with preoperative neurological deficit (tumour, spinal stenosis, disc herniation). Operative procedures associated with greater risk for spinal injury include the passage of sub laminar wires, thoracic pedicle screws, distraction derotation manoeuvres, osteotomies, segmental vessel ligation, and combined anterior-posterior fusioni, ii, iii, iv For example, an inappropriately sized laminar hook or the osteotome may cause direct contusion to the spinal cord. Sub laminar wires can cause direct cord trauma. The risk of neurological damage with pedicle screw placement increases the higher up in the spinal column surgery is performed. Furthermore, rotational deformities make placement of pedicle screws more difficult. During scoliosis surgery the application of corrective forces is another potential cause of cord damage. Furthermore, neurological complications are more likely in longer cases and those with large blood losses. Large time-temperature integrals are linked to complications, suggesting that it is the quantity of hypothermia rather than the nadir temperature that is a risk factor.v In summary, mechanisms of spinal cord injury include ischaemia, compression and over distraction / rotation.vi Nerve root injury (C5 injury has an incidence as high as 12.9% after laminectomy) is attributed to posterior migration and expansion of the spinal cord and oedema of the affected root.vii Anatomy relevant to spinal cord monitoring Figure 1: Motor and sensory pathways of the spinal cord.
The lateral and anterior corticospinal tracts subserve voluntary movement. From the primary motor cortex the upper motor neuron axon descends via the internal capsule to the medulla oblongata. 85% of the motor fibres cross the midline at the pyramidal decussation to descend contralaterally as the lateral corticospinal tract. 15% do not cross the midline and descend ipsilaterally as the anterior spinal tract. A functional corticospinal tract is necessary for recording motor evoked potentials (MEPs) and the Stagnara wake-up test. The dorso-medial sensory tracts subserve touch, proprioception and vibration. From the dorsal root ganglion the primary sensory neuron runs ipsilaterally in the dorsal aspect of the spinal cord to the medulla oblongata. After synapsing the second order neuron crosses the midline and projects to the thalamus. From here the third order neurons project to the primary somatosensory cortex. This path must be intact to record somatosensory evoked potentials (SSEPs). Figure 2: Transverse section through spinal cord at T6. The blood supply of the spinal cord is from the anterior spinal artery (formed by the union of a branch from each vertebral artery), which supplies the anterior two thirds of the cord including the corticospinal tracts (unshaded area fig 2). The posterior spinal arteries (derived from the posterior cerebellar arteries) supply the posterior third of the cord including the dorsomedial columns (shaded area fig 2). These arteries are reinforced by a variable number of medullary feeding arteries from the vertebral arteries in the cervical region, and vessels from the aorta in the thoracic and lumbar regions (including the Artery of Adamkiewicz). Spinal cord monitoring The incidence of motor deficit or paraplegia after scoliosis surgery without spinal cord monitoring is between 3.7 and 6.9% I, ii iii, viii, ix This figure may be reduced to 0.5% when intraoperative monitoring (IOM) is used.x Ideally, IOM should detect changes in spinal cord function early, allowing the surgeon and anaesthesiologist to take action to prevent irreversible damage. The disturbing fact is that the time between onset of changes in electrophysiological recordings and permanent ischaemic damage of the cord with over distension is only 5 – 6 minutes in animal studies. xi
A. Clinical tests
1. Ankle clonus test
This test is performed during emergence at the end of surgery or during the wake-up test. The foot is sharply dorsiflexed at the ankle joint. Spinal cord injury is indicated by complete absence of clonus. The test is based on a number of physiological principles: In the awake individual, higher cortical centres have a descending inhibitory influence on the reflex, and clonus is not elicited on ankle joint dorsiflexion. During anaesthesia there is a loss of this descending inhibition, and clonus can be elicited during emergence in the neurologically intact individual. Spinal cord injury results in a period of spinal shock with a loss of reflex activity and consequently a flaccid paralysis – no ankle clonus can be elicited. Obviously neuromuscular paralysis must be completely reversed before performing this test. Although this test has both a high sensitivity (100%) and specificity (99.7%) xii, there are a number of problems. The test can only be performed intermittently. Advances in surgical methods have changed the period of neural risk from one identifiable event (distraction) to multiple, potentially deleterious events (sub laminar wires, multiple hooks, pedicle screws). A more continuous form of monitoring has become mandatory. Furthermore, the absence of clonus has other causes besides cord damage: inadequate or too great a depth of anaesthesia. xiii
2. Stagnara wake-up test In 1973 this test was described by Vauzelle and Stagnaraxiv and evaluates the functional integrity of the motor pathways (lower + upper motor neurons and muscles). Integrity of peripheral sensory function is not assessed. Preoperatively the patient is told that he will be woken and asked to perform a motor function. Usually they are instructed to first perform an action involving muscle groups above the level of potential cord damage e.g. grip the anaesthesiologist’s fingers. Following a positive response, the patient is subsequently instructed to move his legs. If the patient is unable to respond corrective measures are instituted immediately. The technique has a number of disadvantages. It requires the patient’s co-operation and poses risks to the patient of falling from the operating table and of tracheal extubation. It requires skill from the anaesthesiologist. As with the ankle clonus test, it does not allow continuous IOM of motor pathways. The onset of a change in electrophysiological recordings and permanent neurological injury can occur more than 20 minutes after the last corrective force is applied to the spine.xv Because of the limitations of the wake-up test, neurophysiologic monitoring of the spinal cord has become a preferred method of optimising safety during spinal surgery. If reliable monitoring is in place, the wake-up test can be omitted.xv
B. Neurophysiologic monitoring Neurophysiologic monitoring methods are based on evoking electrical potentials and quantifying these potentials as an assessment of an otherwise silent neural tract. These evoked electrical potentials are extremely small, necessitating digital signal averaging to resolve them from the much longer EEG and ECG activity. This method entails repeatedly stimulating the nervous system and measuring the response for a set window of time (needed to resolve the evoked neural activity from other electrical activity). The evoked response becomes apparent because this unwanted background activity is unrelated to the stimulus and thus averaged out. The peaks and valleys of the evoked response are thought to arise from specific neural generators (often more than one neural structure per peak) and therefore can be used to follow the response at various points along the stimulated tract. xiii Several studies have confirmed the efficacy and cost effectiveness of intraoperative monitoring. The American Academy of Neurology has concluded that “considerable evidence favours the use of monitoring as a safe and efficacious tool in clinical situations where there is a significant nervous system risk, provided its limitations are appreciated.” xvi
1. Somatosensory evoked potentials (SSEP) This is the electrophysiological technique that is probably used most extensively for spinal cord monitoring. SSEP are elicited by stimulating electrically a mixed peripheral nerve (usually post. tibial, peroneal, ulnar or median), and recording the response from electrodes at sites cephalad to the level at which the surgery is performed. Dermatomal, rather than mixed nerve stimulation is less frequently used. In these cases, electrodes are applied that stimulate the sensory fibres innervating the skin surface, or alternatively the underlying muscle groups. In theory, proper placement of electrodes will monitor responses mediated by a single nerve root.
With mixed nerve SSEP stimulation sites are chosen because of easily identifiable anatomical landmarks. To stimulate the median nerve, the cathode of the stimulating pair of electrodes is placed 2 – 4 cm proximal to the wrist crease between the tendons of flexor carpi radialis and palmaris longus. The anode is placed 2 – 3 cm distal to cathode to avoid anodal block. For ulnar nerve stimulation the cathode is placed 2 – 4 cm proximal to the wrist crease on either side of the tendon of flexor carpi ulnaris. Stimulation of the posterior tibial nerve is done at the ankle between the medial malleolus and the Achilles tendon. To stimulate the peroneal nerve the cathode is placed distal to the lateral aspect of the knee and slightly medial to the head of the fibula.xvii
Typically the stimulus is applied to the peripheral nerve on the left and the right limb alternately as a square wave for 0.1 – 0.3 ms, at a rate of 3 – 5 Hz. The intensity varies, depending on the electrodes and quality of skin contact, a current of 25 – 40 mA is used.
Recording electrodes are placed in the cervical region over the spinous processes or over the somatosensory cortex on the scalp, or are sited during surgery in the epidural space. Baseline values are obtained after skin incision to ensure a stable plane of anaesthesia as anaesthetic agents affect SSEPs.
Responses are recorded repeatedly during surgery and the functional integrity of the somatosensory pathways is determined by comparing amplitude and latency changes of the responses obtained during surgery to baseline values. A significant response is considered one in which a 50% reduction in amplitude and 10% increase in latency is recorded. x
The pathways involved in the recorded responses include a peripheral nerve, the dorsomedial tracts of the spinal cord, and the cerebral cortex (when cortex electrodes are used). It is currently thought that upper limb SSEP represents primarily the activity in the spinal pathways of proprioception and vibration (posterior column) The response from the lower limbs probably includes a contribution from the antero-lateral spinal cord (pain + temperature) dorsal spino cerebellar pathways in addition to posterior column activity. Because of the close proximity of the dorsomedial sensory tracts with the motor tracts in the cord, it is assumed that when using SSEPs, any damage to the motor tracts will be signalled by a change in SSEPs. THIS CANNOT BE GUARANTEED. Furthermore, the blood supply of the anteriorly situated corticospinal tracts comes from the anterior spinal artery, while the posteriorly situated dorsomedial tracts are supplied by the posterior spinal arteries. It is, therefore, possible to have normal SSEP recordings throughout surgery, but have a paraplegic patient postoperatively.xviii Another limitation is that in patients with pre-existing neurological disorders reliable data can only be collected in 75 – 85% of patients.xix
For monitoring purposes TIVA is the best choice. When SSEP’s alone and no motor evoked potentials are monitored, an alternative is inhalational agent at <0.5 MAC without N2O. Effectiveness of SSEP A large retrospective study including over 51 000 cases, showed SSEP to have a sensitivity of 92% and specificity of 98.9% x The false negative rate was 0.127% (normal SSEP throughout the procedure but neurological deficit post op) The false positive rate was 1.5% (SSEP changed, but no new neurological deficit post op). SSEP is currently the “gold-standard” of spinal cord monitoring with a proven record. It is a reliable technique with a high sensitivity and specificity for early detection of neurological deficit.
2. Motor evoked potentials (MEP) MEPs are neuroelectric events elicited from descending motor pathways:
peripheral nerves → skeletal muscle innervated by alpha motor neurons. In contrast to the white matter-mediated sensory neurons monitored with SSEP, the corticospinal axons that originate in the motor cortex enter the spinal cord grey matter. In the grey matter corticospinal tract axons interact with spinal interneurons that synapse with alpha motor neurons that innervate skeletal muscles. MEP monitoring techniques are subdivided according to: Site of stimulation:
Motor cortex or spinal cord Method of stimulation: Electrical potential
Magnetic fields Site of recording: Spinal cord
Peripheral mixed nerve Muscle
The principles of all the above techniques are similar: Stimulation cranial to the site of surgery causes prodromic stimulation of motor tracts in the spinal cord, and of peripheral nerve and muscle caudal to the site of surgery.xx A compromised motor pathway results in a reduction in amplitude and an increase in latency of the recorded response.
The motor cortex can be stimulated by electrical or magnetic means.xxi, xxii Magnetic stimulation equipment is bulky but has the advantage of not being affected by the quality of electrode contact.
Recorded responses may be either myogenic or neurogenic. Myogenic responses result from the summed EMG activity in a muscle in response to stimulation. Neurogenic recordings result from the summed electrical activity in a peripheral nerve or the spinal cord. Responses recorded from the spine consist of a direct or D wave representing the direct activation of the corticospinal tract cells by the transcranial stimulus. In awake or lightly anaesthetised patients, the D wave is followed by a series of I waves (indirect waves) generated by cortical synapses.
The advantage of recording EMG responses is their large amplitude, but the main disadvantage is the variable morphology of EMG waves. When EMG recording is done, the depth of neuromuscular relaxation is critical: if too deep no response is obtained; if residual block only, violent movement in response to stimulation could cause injury. It is therefore recommended that neuromuscular blocking agents be administered by continuous infusion. The depth of blockade should be maintained at first twitch of train-of-four at 10 – 20% of control.
Neurogenic responses are not affected by neuromuscular blockade, and are more reliable in terms of morphology.
Spontaneous EMG (spEMG) can be used to monitor for injury to spinal nerve roots. In this case the stimulus is involuntary: decompression, hook / screw insertion, removal of bony fragments, tumour resection or traction on a spinal root will provoke ion depolarisation, and the resultant motor unit potential can be recorded from the muscle innervated by that specific nerve root. These events are observed as discrete EMG “bursts”.
Stimulus evoked electromyography (stEMG) is another useful technique during pedicular screw placement. The technique involves applying an electrical stimulus to the pedicle screw and recording EMG activity from muscles innervated by the nerve root adjacent to the pedicle. If the pedicle wall is fractured, the nerve root will depolarise at a much lower current (< 7mA) compared with an intact pedicle.
A TIVA technique using propofol and an opioid (fentanyl or remifentanil) has been advocated for providing adequate MEP recording in 7% of cases when multiple pulse stimulation is used.xxx
Effectiveness of MEPs MEP monitoring is less reliable in patients with preoperative neurological deficit. Sensitivity of MEP is not 100%, especially when neurogenic MEPs are used. Neurogenic spinal evoked potentials are mediated through pathways that are responsible for SSEPs, thus measuring sensory rather than motor function, and offering an explanation for the false negative cases. xxxii MEP is complementary to SSEP, rather than a replacement. The wake-up test is reserved for situations where neurophysiological monitoring is not available / possible, or responses are significantly compromised. Conclusion The detection of emerging injury through intraoperative neurological monitoring is the best way to prevent neurologic injury during spinal surgery. Intraoperative care in the ideal setting should include neurological monitoring and interpretation by a team comprising the anaesthesiologist, neurophysiologist and surgeon. i Mooney III J.F, Bernstein R., Hennrikus W.L. Neurologic risk management in scoliosis surgery. J Pediatr Orthop 2002;22:683-
9.
ii Drummond D.S., Schwartz D.M., Johnson D.R. et al. Neurological injury complicating surgery. In: De Wald R.L, Arlet V., Allen C.L. et al, editors. Spinal deformities: the comprehensive text. New York. Thieme; 2004. pp. 615 – 25.
iii Brown C.A., Lenke L.G., Bridwell K.H. et al. Complications of pediatric throacolumbar and lumbar pedicle screws. Spine 1998;23:1566 – 71.
iv Wilber R.G., Thompson G.H., Shaffer J.W. et al. Postoperative neurological deficits in segmental spinal instrumentation. A study using spinal cord monitoring. J Bone Joint Surg Am 1984 Oct;66(8):1178 – 87.
v Guest J.D., Vanri S., Silbert L. Mild hypothermia, blood loss and complications in elective spinal surgery. The Spine Journal
2004;4:130 – 137.
vi Bridwell K.H., Lenker L.G., Baldus C. et al. Major intraoperative neurologic deficits in pediatric and adult spinal deformity
patients: Incidence and etiology at one institution. Spine 1998;23:324 – 31. vii Fan D., Schwartz D.M., Vaccano A.R. et al. intraoperative neurophysiologic detection of iatrogenic C5 nerve root injury
during laminectomy for cervical compression myelopathy. Spine 2002;27(22):2499 – 2502.
viii Epstein N.E., Danto J., Nardi D. Evaluation of intraoperative somatosensory-evoked potential monitoring during 100 cervical
operations. Spine 1993;18:737-47.
ix Meyer P.R. Cotter H.B., Gireeson G.T. Operative neurological complications resulting from thoracic and lumbar spine internal
fixation. Clin Otrhop 1988;237;125-31. x Nuwer M.R., Dawson E.G., Carlson L.G. et al. Somatosensory evoked potential monitoring reduces neurological deficits after
scoliosis surgery: results of a large multicenter study.j Electroenceph. Clin Neurophysiol. 1995;96:6 – 11. xi Owen J.H, Naito M., Bridwell K.H. Relationship between duration of spinal cord ischaemia and postoperative neruologic
deficits in animals. Spine 1990;15:846-51. xii Hopperfield S., Gross A., Andrews C. The ankle clonus test for assessment of the integrity of the spinal cord during operations
for scoliosis. J Bone Joint Surg Am 1997;79:208-12.
xiii Sloan T.B. Clinical monitoring of the brain and spinal cord. In: ASA, Annual Meeting Refresher Course Lectures. 2004:402.
xiv Vauzelle L., Stagnara P. Functional monitoring of spinal cord activity during spinal surgery. Clin Orthop 1973;93:173-8.
xv Padberg A.M., Wilson-Holden T.J., Lenke L.G. et al. somatosensory and motor evoked potential monitoring without a wake-
up test during idiopathic scoliosis surgery: an accepted standard of care. Spine 1998;23:1392 – 400.
xvi Assessment: Intraoperative neurophysiology. Report of Therapeutic and Tehcnology assessment subcommittee of the
American Academy of Neurology. Neurology 1990;40:1644 – 6.
xvii Toleikis J.R. Intraoperative monitoring using somatosensory evoked potentials. A position statement by the American
Society of Neurophysiological Monitoring. J Clin Monit and Comp 2005;19:241 – 258.
xviii Pelosi L., Jardine A., Webb J.K. Neurological complications of anterior spinal surgery for kyphosis with normal
xix Owen J.M. The application of intraoperative monitoring during surgery for spinal deformity. Spine 1999;24:2649 – 62.
xx Raw D.A., Beattie J.K, Hunger J.M. Anaesthesia for spinal surgery in adults. BJA 2003;91(6):886 – 904.
xxi Calancie B., Harris W., Broton J.G. et al. “Threshold-level” multipulse transcranial electrical stimulation of motor cortex for
intraooperative monitoring of spinal motor tracts: description of methods and comparison to somatosensory evoked potential
monitoring. J Neurosurg 1998;88:457 – 70.
xxii Kitagawa H., Nakamura H., Kawagucki Y et al. Magnetic-evoked compound muscle action potential neuro monitoring in spine surgery. Spine 1995;20:2233 – 9.
SPINAL CORD MONITORING AND PROTECTION DURING SPINAL SURGERY
A. Travers Pathogenesis of spinal cord injury during spinal surgery Patients at risk for persistent neurological injury following spinal surgery are those with preoperative neurological deficit (tumour, spinal stenosis, disc herniation). Operative procedures associated with greater risk for spinal injury include the passage of sub laminar wires, thoracic pedicle screws, distraction derotation manoeuvres, osteotomies, segmental vessel ligation, and combined anterior-posterior fusioni, ii, iii, iv For example, an inappropriately sized laminar hook or the osteotome may cause direct contusion to the spinal cord. Sub laminar wires can cause direct cord trauma. The risk of neurological damage with pedicle screw placement increases the higher up in the spinal column surgery is performed. Furthermore, rotational deformities make placement of pedicle screws more difficult. During scoliosis surgery the application of corrective forces is another potential cause of cord damage. Furthermore, neurological complications are more likely in longer cases and those with large blood losses. Large time-temperature integrals are linked to complications, suggesting that it is the quantity of hypothermia rather than the nadir temperature that is a risk factor.v In summary, mechanisms of spinal cord injury include ischaemia, compression and over distraction / rotation.vi Nerve root injury (C5 injury has an incidence as high as 12.9% after laminectomy) is attributed to posterior migration and expansion of the spinal cord and oedema of the affected root.vii Anatomy relevant to spinal cord monitoring Figure 1: Motor and sensory pathways of the spinal cord.
The lateral and anterior corticospinal tracts subserve voluntary movement. From the primary motor cortex the upper motor neuron axon descends via the internal capsule to the medulla oblongata. 85% of the motor fibres cross the midline at the pyramidal decussation to descend contralaterally as the lateral corticospinal tract. 15% do not cross the midline and descend ipsilaterally as the anterior spinal tract. A functional corticospinal tract is necessary for recording motor evoked potentials (MEPs) and the Stagnara wake-up test. The dorso-medial sensory tracts subserve touch, proprioception and vibration. From the dorsal root ganglion the primary sensory neuron runs ipsilaterally in the dorsal aspect of the spinal cord to the medulla oblongata. After synapsing the second order neuron crosses the midline and projects to the thalamus. From here the third order neurons project to the primary somatosensory cortex. This path must be intact to record somatosensory evoked potentials (SSEPs). Figure 2: Transverse section through spinal cord at T6. The blood supply of the spinal cord is from the anterior spinal artery (formed by the union of a branch from each vertebral artery), which supplies the anterior two thirds of the cord including the corticospinal tracts (unshaded area fig 2). The posterior spinal arteries (derived from the posterior cerebellar arteries) supply the posterior third of the cord including the dorsomedial columns (shaded area fig 2). These arteries are reinforced by a variable number of medullary feeding arteries from the vertebral arteries in the cervical region, and vessels from the aorta in the thoracic and lumbar regions (including the Artery of Adamkiewicz). Spinal cord monitoring The incidence of motor deficit or paraplegia after scoliosis surgery without spinal cord monitoring is between 3.7 and 6.9% I, ii iii, viii, ix This figure may be reduced to 0.5% when intraoperative monitoring (IOM) is used.x Ideally, IOM should detect changes in spinal cord function early, allowing the surgeon and anaesthesiologist to take action to prevent irreversible damage. The disturbing fact is that the time between onset of changes in electrophysiological recordings and permanent ischaemic damage of the cord with over distension is only 5 – 6 minutes in animal studies. xi
A. Clinical tests
1. Ankle clonus test
This test is performed during emergence at the end of surgery or during the wake-up test. The foot is sharply dorsiflexed at the ankle joint. Spinal cord injury is indicated by complete absence of clonus. The test is based on a number of physiological principles: In the awake individual, higher cortical centres have a descending inhibitory influence on the reflex, and clonus is not elicited on ankle joint dorsiflexion. During anaesthesia there is a loss of this descending inhibition, and clonus can be elicited during emergence in the neurologically intact individual. Spinal cord injury results in a period of spinal shock with a loss of reflex activity and consequently a flaccid paralysis – no ankle clonus can be elicited. Obviously neuromuscular paralysis must be completely reversed before performing this test. Although this test has both a high sensitivity (100%) and specificity (99.7%) xii, there are a number of problems. The test can only be performed intermittently. Advances in surgical methods have changed the period of neural risk from one identifiable event (distraction) to multiple, potentially deleterious events (sub laminar wires, multiple hooks, pedicle screws). A more continuous form of monitoring has become mandatory. Furthermore, the absence of clonus has other causes besides cord damage: inadequate or too great a depth of anaesthesia. xiii
2. Stagnara wake-up test In 1973 this test was described by Vauzelle and Stagnaraxiv and evaluates the functional integrity of the motor pathways (lower + upper motor neurons and muscles). Integrity of peripheral sensory function is not assessed. Preoperatively the patient is told that he will be woken and asked to perform a motor function. Usually they are instructed to first perform an action involving muscle groups above the level of potential cord damage e.g. grip the anaesthesiologist’s fingers. Following a positive response, the patient is subsequently instructed to move his legs. If the patient is unable to respond corrective measures are instituted immediately. The technique has a number of disadvantages. It requires the patient’s co-operation and poses risks to the patient of falling from the operating table and of tracheal extubation. It requires skill from the anaesthesiologist. As with the ankle clonus test, it does not allow continuous IOM of motor pathways. The onset of a change in electrophysiological recordings and permanent neurological injury can occur more than 20 minutes after the last corrective force is applied to the spine.xv Because of the limitations of the wake-up test, neurophysiologic monitoring of the spinal cord has become a preferred method of optimising safety during spinal surgery. If reliable monitoring is in place, the wake-up test can be omitted.xv
B. Neurophysiologic monitoring Neurophysiologic monitoring methods are based on evoking electrical potentials and quantifying these potentials as an assessment of an otherwise silent neural tract. These evoked electrical potentials are extremely small, necessitating digital signal averaging to resolve them from the much longer EEG and ECG activity. This method entails repeatedly stimulating the nervous system and measuring the response for a set window of time (needed to resolve the evoked neural activity from other electrical activity). The evoked response becomes apparent because this unwanted background activity is unrelated to the stimulus and thus averaged out. The peaks and valleys of the evoked response are thought to arise from specific neural generators (often more than one neural structure per peak) and therefore can be used to follow the response at various points along the stimulated tract. xiii Several studies have confirmed the efficacy and cost effectiveness of intraoperative monitoring. The American Academy of Neurology has concluded that “considerable evidence favours the use of monitoring as a safe and efficacious tool in clinical situations where there is a significant nervous system risk, provided its limitations are appreciated.” xvi
1. Somatosensory evoked potentials (SSEP) This is the electrophysiological technique that is probably used most extensively for spinal cord monitoring. SSEP are elicited by stimulating electrically a mixed peripheral nerve (usually post. tibial, peroneal, ulnar or median), and recording the response from electrodes at sites cephalad to the level at which the surgery is performed. Dermatomal, rather than mixed nerve stimulation is less frequently used. In these cases, electrodes are applied that stimulate the sensory fibres innervating the skin surface, or alternatively the underlying muscle groups. In theory, proper placement of electrodes will monitor responses mediated by a single nerve root.
With mixed nerve SSEP stimulation sites are chosen because of easily identifiable anatomical landmarks. To stimulate the median nerve, the cathode of the stimulating pair of electrodes is placed 2 – 4 cm proximal to the wrist crease between the tendons of flexor carpi radialis and palmaris longus. The anode is placed 2 – 3 cm distal to cathode to avoid anodal block. For ulnar nerve stimulation the cathode is placed 2 – 4 cm proximal to the wrist crease on either side of the tendon of flexor carpi ulnaris. Stimulation of the posterior tibial nerve is done at the ankle between the medial malleolus and the Achilles tendon. To stimulate the peroneal nerve the cathode is placed distal to the lateral aspect of the knee and slightly medial to the head of the fibula.xvii
Typically the stimulus is applied to the peripheral nerve on the left and the right limb alternately as a square wave for 0.1 – 0.3 ms, at a rate of 3 – 5 Hz. The intensity varies, depending on the electrodes and quality of skin contact, a current of 25 – 40 mA is used.
Recording electrodes are placed in the cervical region over the spinous processes or over the somatosensory cortex on the scalp, or are sited during surgery in the epidural space. Baseline values are obtained after skin incision to ensure a stable plane of anaesthesia as anaesthetic agents affect SSEPs.
Responses are recorded repeatedly during surgery and the functional integrity of the somatosensory pathways is determined by comparing amplitude and latency changes of the responses obtained during surgery to baseline values. A significant response is considered one in which a 50% reduction in amplitude and 10% increase in latency is recorded. x
The pathways involved in the recorded responses include a peripheral nerve, the dorsomedial tracts of the spinal cord, and the cerebral cortex (when cortex electrodes are used). It is currently thought that upper limb SSEP represents primarily the activity in the spinal pathways of proprioception and vibration (posterior column) The response from the lower limbs probably includes a contribution from the antero-lateral spinal cord (pain + temperature) dorsal spino cerebellar pathways in addition to posterior column activity. Because of the close proximity of the dorsomedial sensory tracts with the motor tracts in the cord, it is assumed that when using SSEPs, any damage to the motor tracts will be signalled by a change in SSEPs. THIS CANNOT BE GUARANTEED. Furthermore, the blood supply of the anteriorly situated corticospinal tracts comes from the anterior spinal artery, while the posteriorly situated dorsomedial tracts are supplied by the posterior spinal arteries. It is, therefore, possible to have normal SSEP recordings throughout surgery, but have a paraplegic patient postoperatively.xviii Another limitation is that in patients with pre-existing neurological disorders reliable data can only be collected in 75 – 85% of patients.xix
For monitoring purposes TIVA is the best choice. When SSEP’s alone and no motor evoked potentials are monitored, an alternative is inhalational agent at <0.5 MAC without N2O. Effectiveness of SSEP A large retrospective study including over 51 000 cases, showed SSEP to have a sensitivity of 92% and specificity of 98.9% x The false negative rate was 0.127% (normal SSEP throughout the procedure but neurological deficit post op) The false positive rate was 1.5% (SSEP changed, but no new neurological deficit post op). SSEP is currently the “gold-standard” of spinal cord monitoring with a proven record. It is a reliable technique with a high sensitivity and specificity for early detection of neurological deficit.
2. Motor evoked potentials (MEP) MEPs are neuroelectric events elicited from descending motor pathways:
peripheral nerves → skeletal muscle innervated by alpha motor neurons. In contrast to the white matter-mediated sensory neurons monitored with SSEP, the corticospinal axons that originate in the motor cortex enter the spinal cord grey matter. In the grey matter corticospinal tract axons interact with spinal interneurons that synapse with alpha motor neurons that innervate skeletal muscles. MEP monitoring techniques are subdivided according to: Site of stimulation:
Motor cortex or spinal cord Method of stimulation: Electrical potential
Magnetic fields Site of recording: Spinal cord
Peripheral mixed nerve Muscle
The principles of all the above techniques are similar: Stimulation cranial to the site of surgery causes prodromic stimulation of motor tracts in the spinal cord, and of peripheral nerve and muscle caudal to the site of surgery.xx A compromised motor pathway results in a reduction in amplitude and an increase in latency of the recorded response.
The motor cortex can be stimulated by electrical or magnetic means.xxi, xxii Magnetic stimulation equipment is bulky but has the advantage of not being affected by the quality of electrode contact.
Recorded responses may be either myogenic or neurogenic. Myogenic responses result from the summed EMG activity in a muscle in response to stimulation. Neurogenic recordings result from the summed electrical activity in a peripheral nerve or the spinal cord. Responses recorded from the spine consist of a direct or D wave representing the direct activation of the corticospinal tract cells by the transcranial stimulus. In awake or lightly anaesthetised patients, the D wave is followed by a series of I waves (indirect waves) generated by cortical synapses.
The advantage of recording EMG responses is their large amplitude, but the main disadvantage is the variable morphology of EMG waves. When EMG recording is done, the depth of neuromuscular relaxation is critical: if too deep no response is obtained; if residual block only, violent movement in response to stimulation could cause injury. It is therefore recommended that neuromuscular blocking agents be administered by continuous infusion. The depth of blockade should be maintained at first twitch of train-of-four at 10 – 20% of control.
Neurogenic responses are not affected by neuromuscular blockade, and are more reliable in terms of morphology.
Spontaneous EMG (spEMG) can be used to monitor for injury to spinal nerve roots. In this case the stimulus is involuntary: decompression, hook / screw insertion, removal of bony fragments, tumour resection or traction on a spinal root will provoke ion depolarisation, and the resultant motor unit potential can be recorded from the muscle innervated by that specific nerve root. These events are observed as discrete EMG “bursts”.
Stimulus evoked electromyography (stEMG) is another useful technique during pedicular screw placement. The technique involves applying an electrical stimulus to the pedicle screw and recording EMG activity from muscles innervated by the nerve root adjacent to the pedicle. If the pedicle wall is fractured, the nerve root will depolarise at a much lower current (< 7mA) compared with an intact pedicle.
A TIVA technique using propofol and an opioid (fentanyl or remifentanil) has been advocated for providing adequate MEP recording in 7% of cases when multiple pulse stimulation is used.xxx
Effectiveness of MEPs MEP monitoring is less reliable in patients with preoperative neurological deficit. Sensitivity of MEP is not 100%, especially when neurogenic MEPs are used. Neurogenic spinal evoked potentials are mediated through pathways that are responsible for SSEPs, thus measuring sensory rather than motor function, and offering an explanation for the false negative cases. xxxii MEP is complementary to SSEP, rather than a replacement. The wake-up test is reserved for situations where neurophysiological monitoring is not available / possible, or responses are significantly compromised. Conclusion The detection of emerging injury through intraoperative neurological monitoring is the best way to prevent neurologic injury during spinal surgery. Intraoperative care in the ideal setting should include neurological monitoring and interpretation by a team comprising the anaesthesiologist, neurophysiologist and surgeon. i Mooney III J.F, Bernstein R., Hennrikus W.L. Neurologic risk management in scoliosis surgery. J Pediatr Orthop 2002;22:683-
9.
ii Drummond D.S., Schwartz D.M., Johnson D.R. et al. Neurological injury complicating surgery. In: De Wald R.L, Arlet V., Allen C.L. et al, editors. Spinal deformities: the comprehensive text. New York. Thieme; 2004. pp. 615 – 25.
iii Brown C.A., Lenke L.G., Bridwell K.H. et al. Complications of pediatric throacolumbar and lumbar pedicle screws. Spine 1998;23:1566 – 71.
iv Wilber R.G., Thompson G.H., Shaffer J.W. et al. Postoperative neurological deficits in segmental spinal instrumentation. A study using spinal cord monitoring. J Bone Joint Surg Am 1984 Oct;66(8):1178 – 87.
v Guest J.D., Vanri S., Silbert L. Mild hypothermia, blood loss and complications in elective spinal surgery. The Spine Journal
2004;4:130 – 137.
vi Bridwell K.H., Lenker L.G., Baldus C. et al. Major intraoperative neurologic deficits in pediatric and adult spinal deformity
patients: Incidence and etiology at one institution. Spine 1998;23:324 – 31. vii Fan D., Schwartz D.M., Vaccano A.R. et al. intraoperative neurophysiologic detection of iatrogenic C5 nerve root injury
during laminectomy for cervical compression myelopathy. Spine 2002;27(22):2499 – 2502.
viii Epstein N.E., Danto J., Nardi D. Evaluation of intraoperative somatosensory-evoked potential monitoring during 100 cervical
operations. Spine 1993;18:737-47.
ix Meyer P.R. Cotter H.B., Gireeson G.T. Operative neurological complications resulting from thoracic and lumbar spine internal
fixation. Clin Otrhop 1988;237;125-31. x Nuwer M.R., Dawson E.G., Carlson L.G. et al. Somatosensory evoked potential monitoring reduces neurological deficits after
scoliosis surgery: results of a large multicenter study.j Electroenceph. Clin Neurophysiol. 1995;96:6 – 11. xi Owen J.H, Naito M., Bridwell K.H. Relationship between duration of spinal cord ischaemia and postoperative neruologic
deficits in animals. Spine 1990;15:846-51. xii Hopperfield S., Gross A., Andrews C. The ankle clonus test for assessment of the integrity of the spinal cord during operations
for scoliosis. J Bone Joint Surg Am 1997;79:208-12.
xiii Sloan T.B. Clinical monitoring of the brain and spinal cord. In: ASA, Annual Meeting Refresher Course Lectures. 2004:402.
xiv Vauzelle L., Stagnara P. Functional monitoring of spinal cord activity during spinal surgery. Clin Orthop 1973;93:173-8.
xv Padberg A.M., Wilson-Holden T.J., Lenke L.G. et al. somatosensory and motor evoked potential monitoring without a wake-
up test during idiopathic scoliosis surgery: an accepted standard of care. Spine 1998;23:1392 – 400.
xvi Assessment: Intraoperative neurophysiology. Report of Therapeutic and Tehcnology assessment subcommittee of the
American Academy of Neurology. Neurology 1990;40:1644 – 6.
xvii Toleikis J.R. Intraoperative monitoring using somatosensory evoked potentials. A position statement by the American
Society of Neurophysiological Monitoring. J Clin Monit and Comp 2005;19:241 – 258.
xviii Pelosi L., Jardine A., Webb J.K. Neurological complications of anterior spinal surgery for kyphosis with normal