Come Evitare la paralisi residua e vivere felici :il sugammadex. C.Melloni Libero professionista Napoli SIA 2013
Come Evitare la paralisi residua e
vivere felici :il sugammadex.
C.Melloni
Libero professionista
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RESIDUAL NEUROMUSCULAR BLOCK
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Italian survey 2010 (Minerva Anestesiol. 2012 Jul;78(7):767-73.Neuromuscular block in Italy: a survey of
current management. Della Rocca G, Iannuccelli F, Pompei L, Pietropaoli P, Reale C, Di Marco P
Acta Anaesthesiol Scand. 2010 Mar;54(3):307-12. doi: 10.1111/j.1399-6576.2009.02131.x. Epub 2009 Oct 15.Knowledge of residual curarization: an Italian survey.
Di Marco P, Della Rocca G, Iannuccelli F, Pompei L, Reale C, Pietropaoli P.
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Only 35% of italian anesthesiologists use TOF.........
73% of italian anesthesiologists rely on clinical signs for return of muscular power
24% know that before extubation at least a TOF 0f 0.90 is needed
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What is adequate neuromuscular recovery?
Ability to breathe normally;TV,paO2,SaO2,etCO2,PEF,FEV....
maintain a patent upper airway, preserve protective airway reflexes, swallow, cough, smile, Talk. Arm and leg movements........
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TOF(R)
introduced in the early 1970s by Ali et al. Four supramaximal stimuli are delivered every 0.5 second (2 Hz) muscle response to the fourth stimulus is compared with that of the
first stimulus. Fade of force of muscle contraction in response to repetitive nerve
stimulation provides the basis for evaluation; the degree of fade is proportional to the intensity of the neuromuscular block.
Advantages:» does not require a control,prerelaxant twitch height» less pain on stimulation over tetanic stimulation» lack of posttetanic facilitation
»Threshold??????Napoli SIA 2013
TOFR=D/A
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Innervator Fisher & Paykel e TOfWatch Organon
TOFR thresholds(in the definition of residual neuromuscular block)
1970 –1977 a mean TOF ratio of 0.74 represented“acceptable recovery” from d-tubocurarine blockade.
Patients with this level of recovery were able to open eyes widely, cough, protrude the tongue, sustain head lift for 5 seconds, develop a forced vital capacity of at least 15 to 20 mL/kg, and sustain tetanic stimulation without fade for 5 seconds.
, changes in measured respiratory variables, including tidal volume, vital capacity, inspiratory force, and peak expiratory flow rate, were “negligible” until TOF ratios decreased To 0.6.
At a TOF ratio of 0.7, all patients were able to sustain eye opening, hand grasp, and tongue protrusion, whereas 9 of 10 were able to maintain a 5-second head lift
Ali HH, Kitz RJ. Evaluation of recovery from nondepolarizing neuromuscular block, using a digital neuromuscular transmission analyzer: preliminary report. Anesth Analg 1973;52:740–5.
AliHH,Wilson RS, Savarese JJ, Kitz RJ. The effect of tubocurarineon indirectly elicited train-of- four muscle response and respiratory measurements in humans. Br J Anaesth 1975;47:570–4 Brand JB, Cullen DJ, Wilson NE, Ali HH. Spontaneous recovery from nondepolarizing neuromuscular blockade: correlation between clinical and evoked
responses. Anesth Analg 1977;56:55–8.
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Train of four ratio>0.7, <=0.9
1997-2000 TOFR 0.9 to ensure optimal patient safety. pharyngeal dysfunction and an increased risk for aspiration occur at TOF ratios 0.9. Impaired inspiratory flow and partial upper airway obstruction have been observed
frequently at TOF ratios of 0.8. subtle levels of neuromuscular blockade may produce distressing symptoms in awake
patients, which may persist even at TOF ratios 0.9. These recent data suggest that the new “gold standard” for the minimal acceptable level
of neuromuscular recovery is an EMG or MMG TOF ratio of 0.9 (or perhaps 1.0 when AMG is used
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POST OPERATIVE RESIDUAL CURARIZATION
PORC
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POSTOPERATIVE RESIDUAL PARALYSIS
PORP
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POSTOPERATIVE RESIDUAL NEUROMUSCULAR BLOCKADE OR WEAKNESS
PO RE NMB ??
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Dichiarazione di assenza di conflitto di interessi
non ho alcun interesse finanziario o attività commerciale né sono supportato dalla azienda produttrice del Sugammadex(Bridion).
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PORC % nella metanalisi di Naguib Br J Anaesth. 2007 Mar;98(3):302-16.Neuromuscular monitoring and postoperative residual
curarisation: a meta-analysis.Naguib M, Kopman AF, Ensor JE.
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DtcGallapanc
vari
Atrac 0
panc
Atrac 0galla
Pancvecu Panc
vecu
panc
panc
panc
Tof<70
Tof <90
PORC % nella metanalisi di Naguib ;parte II
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Bissing
er 2
000
panc
Bissing
er 2
000
vecu
Ballar
d 20
00 v
ecu
Hayes
200
1 ve
cu
Hayes
200
1atra
c
Hayes
200
1 ve
cu
Hayes
200
1 ro
cu
Hayes
200
1 at
rac
Hayes
200
1 ro
cu
KIM 2
002
vecu
Kim 2
002
rocu
gark
e 20
02 ro
cu
Garke
200
2 ro
cu
Camm
u 20
02 c
isatra
c
Camm
u 20
02 ro
cu
Dedba
ene
2003
atra
c
Deabe
ne 2
003
vecu
Debae
ne 2
003
rocu
Kopm
an 2
004
cisat
rac
Kopm
an 2
004
rocu
Mur
phy
2005
rocu
Ballar
d 20
05 in
term
edia
Kopm
an 2
005
cisat
rac
Kopm
an 2
005
rocu
0
10
20
30
40
50
60
70
80
90
100
tof <0.70
tof < 0.90
Residual Paralysis at the Time of Tracheal ExtubationGlenn S. Murphy, Joseph W. Szokol, Jesse H. Marymont, Mark Franklin,Michael J. Avram, Jeffery S. Vender.(Anesth Analg 2005;100:1840–5)
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Midazolam,1–2 mg.; propofol 1.5–
2.5 mg/kg , fentanyl ,sevoflurane 0.5%–
3.5% in an air/oxygen mixture. neuromuscular
blockade was reversed with neostigmine 50 microg/kg
and glycopyrrolate 10 micro g/kg adequacy of neuromuscular
reversal usingstandard clinical criteria :(5-s head lift
or hand grip, eye opening on command,negative inspiratory force more than 20
cmH2 O, or vital capacity breath 15 cc/kg)
and peripheralnerve stimulation (no evidence of fade
with TOFor tetanic stimulation [50 Hz]). A 5-s
head lift (or handgrip) and the observation of an absence
of fade withperipheral nerve stimulation were the
minimal requirements
Nm block maintained at TOF 1-2
12% only with tof>0.9
120 pts
Residual Paralysis at the Time of Tracheal ExtubationGlenn S. Murphy, Joseph W. Szokol, Jesse H. Marymont, Mark Franklin,Michael J. Avram, Jeffery S. Vender.(Anesth Analg 2005;100:1840–5)
The use of a peripheral nerve stimulator in the OR may reduce, but does not eliminate, the problem of postoperative paresis.
Detection of incomplete reversal of neuromuscular blockade is difficult with standard TOF or tetanic stimulation. Experienced observers are unable to detect fade when the TOF ratio is 0.4 Viby-Mogensen J, Jensen
NH, Englbaek J, et al. Tactile and visual evaluation of the response to train-of-four nerve stimulation. Anesthesiology 1985;63:440 –3.).
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Residual Neuromuscular Block: Lessons Unlearned.Part I: Definitions, Incidence, and Adverse Physiologic
Effects of Residual Neuromuscular Block
Glenn S. Murphy, Sorin J. Brull, Anesth Analg 2010;111:120–8
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What are the factors that alter the incidence of postoperative residual paralysis?
The great variability is due to different methods: use of T4/T1 ratio of 0.7, 0.8 or 0.9 as PORP criterion use of different NMB of short, intermediate and long-term duration use of single or repeated doses, or continuous infusion of NMB assessment method of the residual NMB with or without reversal of neuromuscular blockade at the end of anesthesia with
anticholinesterase drugs with dose and interval between the anticholinesterase drugs and degree
assessment of neuromuscular blockade Age presence of kidney, cardiac or neuromuscular dysfunction drug use that can alter the pharmacodynamics and/or pharmacokinetics of NMB
(calcium channel blockers, magnesium, lithium, antibiotics, local anesthetics, inhaled anesthetics, opioids, benzodiazepines
electrolyte abnormalities, metabolic or respiratory acidosis and hypothermia.Napoli SIA 2013
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Kopman et al.Relationship of the train of four fade ratio to clinical signes and symptoms of residual
paralysis in awake volunteers.Anesthesioloogy,1997;86:765-71.
Volontari sani infusione di mivacurium monitoraggio Datex 221 NMT valutazione; stretta di mano
sollev,testa & gamba per 5 sec. Ritenzione di abbassalingua
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Osservazioni cliniche sulla relazione fra tof e correlati di forza:
disturbi visivi sempre con tof di 0.90(diplopia,diff.seguire oggetti in moto,ecc)
forza dei masseteri ridotta sempre sollev.testa e gamba sempre possibile > 0.60 stretta di mano variabile,ma 83% del basale a tof
0.90 per tof < 0.75 tutti disturbati
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Conclusioni delle correlazioni fra segni clinici di forza muscolare e tof
Capacità di ritenzione dell’abbassalingua è un test più sensibile del sollevamento del capo
tof <1 ancora residuano disturbi visivi e senso generalizzato di fatica
tof = 1 (o altri monitoraggi) per dimissione in chirurgia ambulatoriale??
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Assiomi della ripresa nm.
TOF > 0.70 sicuro indice della ripresa nm……….. Ali HH, Wilson RS, Savarese JJ, Kitz RJ: The effect of tubocurarine on indirectly elicited train-of-four muscle response and respiratory measurements in humans. Br J Anaesth 47:570-4, 1975
Brand JB, Cullen DJ, Wilson NE, Ali HH: Spontaneous recovery from nondepolarizing neuromuscular blockade: Correlation between clinical and evoked responses. Anesth Analg 56:55-8, 1977
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Mutazioni occorse
Esplosione della chirurgia ambulatoriale pressione per la diminuzione della
spesa sanitaria aumento delle persone anziane e
debilitate anche in chir amb. Disponibilità di nuovi farmaci
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Rivalutazione della pratica clinica
Età e stato di salute differiscono fra volontari sani e pazienti!
La prassi clinica e l’utilizzo dei miorilassanti variano fra i diversi centri ambulatoriali
il monitoraggio degli effetti nm non è praticato in ospedale,figurarsi nei centri ambulatoriali!
I metodi di monitoraggio usati da Kopman et al si applicano ad una ampia gamma di situazioni cliniche.
Esistono pesanti pressioni economiche per la diminuzione della spesa sanitaria.
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Implicazioni del lavoro di Kopman:1
I paz chirurgici sono in genere più anziani e ammalati dei volontari sani dello studio di Kopman/( ASA 1, entro il 15% del peso ideale,tra 23—33 anni….)
gli effetti residui dei miorilassanti è probabile possano essere + significativi nella pratica ambulatoriale con pazienti + anziani e debilitati.
Si potrebbe arguire che i paz.con sedazione residua siano meno attenti a disturbi visivi e
debolezza dei muscoli facciali;ma è anche vero che dal punto di vista della sicurezza i paz postop siano esposti a rischio maggiore di aumento della morbilità,poichè la debolezza residua nm può essere aggravata da residui dell’anestesia.
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Implicazioni del lavoro di Kopman:2
mivacurium non è rappresentativo dei miorilassanti usati in chir amb;il mercato è dominato dai miorilassanti ad azione intermedia quali vecuronium, atracurium, rocuronium, cisatracurium
se una paralisi residua permane per un’ora dopo interruzione del mivac,caratterizzato da un RI di pochi min,che succede dopo la somministrazione dei mioril a durata intermedia(RI 20-30 min )?
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Conclusioni
Esiste evidenza sperimentale e clinica che i nmb nondepolarizzanti interferiscano con il controllo della ventilazione in condizioni di ipossia,verosimilmente attraverso una depressione reversibile della attività chemorecettoriale dei corpi carotidei implicazioneclinica
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Chemorec.perif
Chemrecett.centr SNC
Ipossia
ipercapnia iperventilazione
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Corpi carotidei
Sito nicotinico
Sito muscarinico
nmb
atropina
ipossia
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Eriksson LI,Sundman E,Olsson R,NilssonL,Witt H,Ekberg O,Kuylenswtierna R. Functional Assessment of the Pharynx at Rest
and during Swallowing in Partially Paralyzed Humans: Simultaneous Videomanometry and Mechanomyography of Awake Human
Volunteers,Anesthesiology 1997;67:1035-43.
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Eriksson LI,Sundman E,Olsson R,NilssonL,Witt H,Ekberg O,Kuylenswtierna R. Functional Assessment of the Pharynx at Rest and during Swallowing in Partially Paralyzed Humans: Simultaneous Videomanometry and Mechanomyography of
Awake Human Volunteers,Anesthesiology 1997;67:1035-43.
Vecuronium induced partial paralysis(tof o.60-0.80) cause pharyngeal disfunction:
upper esophageal sphincter tone Pharynx muscle coordination Bolus transit time
–6/14 volunteers aspirated at tof<0.90
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The Incidence and Mechanisms of pharyngeal and Upper Esophageal Dysfunction in Partially Paralyzed humans.Eva Sundrnan,H anne Witt, Rolf
Olsson, Olle Ekberg, SRichard Kuylenstierna, Lars I. Eriksson.Anesthesiology 2000;92:977-84
20 healthy volunteers studied awake during liquid-contrast bolus swallowing. The incidence of pharyngeal dysfunction was studied by fluoroscopy.+
Simultaneous manometry After control recordings, an iv infusion of atracurium was administered to obtain
TOF 0.60, 0.70, and 0.80, followed by recovery to a > 0.90. The incidence of pharyngeal dysfunction increased to 28%, 17%, and 20% at TOF
0.60, 0.70, and 0.80, respectively. Pharyngeal dysfunction occurred in 74/ 444 swallows, the majority (80%) resulting
in laryngeal penetration. The initiation of the swallowing reflex was impaired during partial paralysis The pharyngeal coordination was impaired at train-of-four ratios of 0.60 and 0.70 . A marked reduction in the upper esophageal sphincter resting tone was found, as
well as a reduced contraction force in the pharyngeal constrictor muscles. The bolus transit time did not change significantly.
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Time interval between passage of bolus from the anterior faucial arches and hyoid bone
ms
Time interval between start of contraction of pharyngeal constrictor and start of relaxation of upper esophageal sphincter
ms
Resting tension of the upper esophageal sphincter
Pharyngeal constrictor muscle function
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The Incidence and Mechanisms of pharyngeal and Upper Esophageal Dysfunction in Partially
Paralyzed humans
Partial neuromuscular paralysis caused by atracurium is associated with a four- to fivefold increase in the incidence of misdirected swallowing. The mechanism behind the pharyngeal dysfunction is
1) a delayed initiation of the swallowing reflex,
2)impaired pharyngeal muscle function,
3)impaired coordination.
The majority of misdirected swallows resulted in
penetration of bolus to the larynxNapoli SIA 2013
RESIDUAL NEUROMUSCULAR BLOCK AFFECTS PULMONARY FUNCTION
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Acta Anaesthesiol Scand. 2004 Mar;48(3):365-70.Predictive value of mechanomyography and accelerometry for pulmonary
function in partially paralyzed volunteers.Eikermann M, Groeben H, Hüsing J, Peters J.
: In awake partially paralyzed volunteers spirometrically assessed pulmonary function every 5 min until recovery. Rocuronium (0.01 mg kg(-1) + 2-10 microg kg(-1) min(-1)) was administered to maintain
train-of-four (TOF)-ratios (assessed every 15 s) of approximately 0.5 and 0.8 over a period of more than 5 min.
The TOF-ratio associated with 'acceptable' pulmonary recovery [forced vital capacity (FVC) and forced inspiratory volume in 1 s (FIV1) of > or =90% of baseline] was calculated using a linear regression model. During 5-min periods of repetitive nerve stimulation we compared the squared residuals of the FVC and FIV1 estimates from TOFACM vs. TOFMMG, and compared variance of values derived from ACM and MMG using Wilcoxon's test.
RESULTS:
TOF ACM(0.56 (0.22-0.71) [mean (95%CI) and 0.6 MMG (0.28-0.74)], respectively, predict 'acceptable' (90%) recovery of FVC while FIV1 remains impaired until TOF-ratios of 0.91 (0.82-1.07) and 0.95 (0.82-1.18), respectively.
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Anesthesiology. 2012 Dec;117(6):1234-44..Residual neuromuscular blockade affects postoperative pulmonary function.
Kumar GV, Nair AP, Murthy HS, Jalaja KR, Ramachandra K, Parameshwara G.
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Heier T,. Caldwell,JE. Feiner JR, Liu, L, Ward, T, B,. Wright PMC.Relationship between Normalized Adductor PollicisTrain-of-four Ratio and Manifestations of
ResidualNeuromuscular Block A Study Using Acceleromyography during Near Steady–stateConcentrations of Mivacurium
Anesthesiology 2010 : 113 ;2010.825-832 . 12 healthy volunteers 3 steady–state levels of neuromuscular block were achieved with mivacurium infusions. TOF ratio of 0.85– 0.95
(block level 1), TOF ratio of 0.65– 0.75 (block level 2), and TOF ratio of 0.45– 0.55 (block level 3). TOF ratio was measured acceleromyographically at the adductor pollicis using a preload. Lung volume measurements and a series of clinical tests were made at each stable block and reconciled to the
normalized TOF measures. Results: None experienced airway obstruction or arterial oxygen desaturation, even at normalized TOF ratio less
than 0.4. Functional residual capacity remained unchanged whereas vital capacity decreased linearly with decreasing TOF ratio.
The ability to protrude the tongue was preserved at all times. The ability to clench the teeth was lost in one volunteer at normalized TOF ratio of 0.84 but retained in four at normalized TOF ratio less than 0.4. Four
volunteers lost the ability both to raise the head more than 5 s and to swallow, with the most sensitive individual demonstrating these effects at normalized TOF ratio of 0.60. At mean normalized TOF ratio of 0.42, the mean handgrip strength was approximately 20% of baseline value.
Conclusion: Lung vital capacity decreased linearly with decreasing TOF ratio. Responses to clinical tests of muscle function varied to a large extent among individuals at comparable TOF ratios. None of the volunteers had significant clinical effects of neuromuscular block at normalized acceleromyographic TOF ratio greater than 0.90.
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The relationship between normalized acceleromyography adductor pollicis train-of-four (AMG AP TOF) ratio and vital capacity of the lungs and between normalized AMG AP TOF ratio and handgrip strength in 12 volunteers during stable mivacurium blocks.Both vital capacity and
handgrip strength decreased significantly with decreasing AMG AP TOF ratio.Heier T,. Caldwell,JE. Feiner JR, Liu, L, Ward, T, B,. Wright PMC. Relationship between Normalized Adductor PollicisTrain-of-four Ratio and Manifestations of Residual
Neuromuscular Block A Study Using Acceleromyography during Near Steady–stateConcentrations of Mivacurium Anesthesiology 2010 : 113 ;2010.825-83
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Number of individuals who lost muscle functions TOF ratio of 0.85– 0.95 (block level 1), TOF ratio of 0.65– 0.75
(block level 2), and TOF ratio of 0.45– 0.55 (block level 3).
TOFR 0.85-0.95 TOFR 0.65-0.75 TOFR ratio of 0.45–0.55
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Anesthesiology. 2003 Jun;98(6):1333-7.Accelerometry of adductor pollicis muscle predicts recovery of
respiratory function from neuromuscular blockade.Eikermann M, Groeben H, Hüsing J, Peters J.
Source Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Germany. [email protected] Abstract BACKGROUND: Residual paralysis increases the risk of pulmonary complications but is difficult to detect. To test the hypothesis that accelerometry predicts
effects of residual paralysis on pulmonary and upper airway function, the authors related tests of pulmonary and pharyngeal function to accelerometry of adductor pollicis muscle in 12 partially paralyzed volunteers.
METHODS: Rocuronium (0.01 mg/kg + 2-10 microg x kg-1 x min-1) was administered to maintain train-of-four (TOF) ratios (assessed every 15 s) of
approximately 0.5 and 0.8 over a period of more than 5 min. The authors evaluated pharyngeal and facial muscle functions during steady state relaxation and performed spirometric measurements every 5 min until recovery. Upper airway obstruction was defined as a mean ratio of expiratory and inspiratory flow at 50% of vital capacity of greater than 1. The TOF ratio associated with "acceptable" pulmonary recovery (forced vital capacity and forced inspiratory volume in 1 s of > or =90% of baseline) was calculated using a linear regression model.
RESULTS: At peak blockade (TOF ratio 0.5 +/- 0.16), forced inspiratory flow was impaired (53 +/- 19%) to a greater degree than forced expiratory flow
(75 +/- 20%) with a mean ratio of expiratory and inspiratory flow at 50% of vital capacity of 1.18 +/- 0.6. Upper airway obstruction, observed in 8 of 12 volunteers, paralleled an impaired ability to swallow reported by 10 of 12 volunteers. In contrast, all volunteers except one could sustain a head lift for more than 5 s. The authors calculated that a mean TOF ratio of 0.56 (95% confidence interval, 0.22-0.71) predicts "acceptable" recovery of forced vital capacity, whereas forced inspiratory volume in 1 s was impaired until a TOF ratio of 0.95 (0.82-1.18) was reached. A 100% recovery of TOF ratio predicts an acceptable recovery of forced vital capacity, forced inspiratory volume in 1 s, and mean ratio of expiratory and inspiratory flow at 50% of vital capacity in 93%, 73%, and 88% of measurements (calculated negative predictive values), respectively.
CONCLUSION: Impaired inspiratory flow and upper airway obstruction frequently occur during minimal neuromuscular blockade (TOF ratio 0.8), and
extubation may put the patient at risk. Although a TOF ratio of unity predicts a high probability of adequate recovery from neuromuscular blockade, respiratory function can still be impaired.
Comment in Residual neuromuscular blockade: importance of upper airway integrity. [Anesthesiology. 2004
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Anesthesiology. 2003 Jun;98(6):1333-7.Accelerometry of adductor pollicis muscle predicts
recovery of respiratory function from neuromuscular blockade.
Eikermann M, Groeben H, Hüsing J, Peters J.
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Muscle function and tofr in 12 partially paralyzed volunteersAnesthesiology. 2003 Jun;98(6):1333-7.
Accelerometry of adductor pollicis muscle predicts recovery of respiratory function from neuromuscular blockade. Eikermann M, Groeben H, Hüsing J, Peters J.
inabili
ty to
susta
in h
ead lift
>5 sec
iabili
ty to
seal m
outhpie
ce
inabili
ty to
sw
allow
norm
ally
fade o
f contra
ction v
isib
le
upper airw
ay obstru
ction
0
2
4
6
8
10
12
tof 0.5tof 0.8tof 1
Num
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Eikermann M, Vogt FM, Herbstreit F, Vahid-Dastgerdi M,Zenge MO, Ochterbeck C, de Greiff A, Peters J. The predisposition to inspiratory upper airway collapse during partialneuromuscular blockade. Am J
Respir Crit Care Med 2007;175:9–15
Partial neuromuscular blockade (train-of-four [TOF] ratio: 0.5 and 0.8) was associated with the following:
(1) a decrease of inspiratory retropalatal and retroglossal upper airway volume to 66 ( 22) and 82 (12)% of baseline, whichwas significantly more intense in the retropalatal area;
(2) an attenuation of the normal increase in anteroposterior upper airway diameter during forced inspiration to 74 (18)% of baseline;
(3) a decrease in genioglossus activity during maximum voluntary tongue protrusion to 39 (19)% (TOF, 0.5) and 73 (29)% (TOF, 0.8) of Baseline
(4) no effects on upper airway size during expiration, lung volume, and respiratory timing.
Conclusions: Thus, impaired neuromuscular transmission, even to a degree insufficient to evoke respiratory symptoms, markedly impairs upper airway dimensions and function. This may be explained by an impairment of the balance between upper airway dilating forces and negative intraluminal pressure generated during inspiration by respiratory “pump” muscles.
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T1-weighted spin echo magnetic
resonance midsagittal image of a
subject before neuromuscular
blockade (baseline
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End-inspiratory and end-expiratory upper airway volume before neuromuscular blockade (baseline) at a steady-state train-of-four (TOF) ratio of 0.5 and 0.8, after
recovery of the TOF ratio to 1.0, and15 min later (same TOF ratio)
.Before neuromuscular blockade and with
recovery fromneuromuscular blockade, end-
inspiratory volume was significantly
greater than end-expiratory volume. End-inspiratory
volume decreasedsignificantly during
partial neuromuscular
blockade, and was even lower
than end-expiratory
upper airway volume at a TOF ratio
of 0.5.
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Upper airway volume at end inspiration (quiet breathing) before neuromuscular blockade, at a steady-state TOF ratio of 0.5 and 0.8, after recovery of the TOF ratio to 1.0, and 15 min later. Upperpanel:
retroglossal area; lower panel: retropalatal area. 15 min.
During partial
neuromuscular blockade, upper airway volume
decreased significantlyboth in the
retroglossal and
retropalatal part of
the upper airway, butwas no longer
significantly different from baseline values
with recoveryof the TOF ratio to 1.0.
However, 4 of 10 volunteers still showed a
marked impairment of retropalatal airway
volume despite recovery of
the TOF ratio to unity, which disappeared
within 15 min.
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Changes in upper airway volume at end inspiration (quiet breathing) from baseline during steady-state neuromuscular blockade.The percentage decrease of retroglossal and retropalatal upper airway volume.
At a TOF ratio of 0.5, upper airway volume decrease wassignificantly greater in the retropalatal area compared with the retroglossal
area.
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Minimum cross-sectional area at end inspiration of the retroglossaland retropalatal part of the upper airway. Measurements during
quiet breathing before neuromuscular blockade (baseline) at a steadystateTOF ratio of 0.5 and 0.8, after recovery of the TOF ratio to 1.0,
and 15 min later.
During neuromuscular
blockade, airway crosssectionalarea decreased significantly in
both regions of the upper airway
and recovered to baseline values with a TOF ratio of unity. The
smallestcross-sectional area of
the retropalatal area was significantly less than
the smallest cross-sectional area of the
retroglossal area of the upperairway.
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Genioglossus function
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Impaired upper airway integrity by residual neuromuscular blockade: increased airway collapsibility and blunted genioglossus muscle activity in response to negative pharyngeal pressure.
Herbstreit F, Peters J, Eikermann M. Anesthesiology. 2009 Jun;110(6):1253-60
Epiglottic and nasal mask pressures, genioglossus electromyogram, respiratory timing, and changes in lung volume were measured in awake healthy volunteers (n 15) before, during (TOF 0.5 and 0.8 [steady state]), and after recovery of TOF to unity from rocuronium-induced partial neuromuscular blockade.
Passive upper airway closing pressure (negative pressure drops, random order, range 2 to –30 cm H2O) and pressure threshold for flow limitation were determined.
Results: Upper airway closing pressure increased (was less negative) significantly from baseline by 54 (4.4)% ,37 (4.2)%, and 16 ( 4.1) % at TOF ratios of 0.5, 0.8, and 1.0.,respectively (P < 0.01 vs. baseline for any level).
Phasic genioglossus activity almost quadrupled in response to negative (–20 cm H2O) pharyngeal pressure at baseline, and this increase was significantly impaired by
57 ( 44)% and 32 (6)% at TOF ratios of 0.5 and 0.8, respectively (P < 0.01 vs. baseline). End-expiratory lung volume, respiratory rate, and tidal volume did not change. Conclusion: Minimal neuromuscular blockade markedly increases upper airway closing
pressure, partly by impairing the genioglossus muscle compensatory response. Increased airway collapsibility despite unaffected values for resting ventilation may predispose patients to postoperative respiratory complications, particularly during airway challenges.
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. Representative recording of main variables from an awake healthy volunteer before partial neuromuscular blockade, duringimpaired neuromuscular transmission with a target train-of-four (TOF) ratio of 0.5 and 0.8 and with the TOF ratio recovered to unity.(A) Mask pressure at 2 cm H2O. Phasic
(respiratory) genioglossus activity is very low while breathing near atmospheric pressure.Inspiratory time was longer during impaired neuromuscular transmission, but no flow limitation was observed at this maskpressure. (B) Same volunteer during a negative pressure challenge (–20 cm H2O).
Before partial neuromuscular blockade, phasicgenioglossus activity is markedly increased compared to breathing near atmospheric pressure, but no flow limitation is observed,despite such negative pharyngeal pressure. During partial neuromuscular blockade, phasic genioglossus activity is markedlyincreased compared with breathing at atmospheric pressure. However, the magnitude of the compensatory increase in genioglossus
activity to negative pharyngeal pressure is impaired and flow limitation is observed. EMG electromyogram.
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Upper airway closing pressure (black bars) significantl increased during partial neuromuscular blockade and was still abnormal, even with recovery of the TOF ratio to
unity. With neuromuscular transmission intact at baseline, evidenceof flow limitation (gray bars) was first observed at anaverage pressure of –12 cm H2O. With partial neuromuscular blockade at a TOF ratio of 0.5 and
0.8, flow limitation occurred at significantly less negative values of mask pressure, i.e.,airwayintegrity is impaired
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.Genioglossus activity increases markedly and significantly as negativepressure is applied. However, the magnitude of this effect
is significantly attenuated with partial neuromuscular blockade
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Herbstreit F, Peters J, Eikermann M. Anesthesiology. 2009;110(6):1253-60
Minimal neuromuscular blockade (TOF ratio 0.5–1) markedly increased upper airway collapsibility and impaired the genioglossus response to negative pharyngeal pressure challenges.
Thus, our data suggest that minimal neuromuscular blockade evokes increased upper airway collapsibility by blunting upper airway dilator compensatory responses to negative pharyngeal pressure.
Imaging studies during complete or partialEikermann M, Vogt FM, Herbstreit F, Vahid-Dastgerdi M, Zenge
MO, Ochterbeck C, de Greiff A, Peters J: The predisposition to inspiratory upper airway collapse during partial neuromuscular blockade. Am J Respir Crit Care
Med 2007; 175:9–15 neuromuscular blockade and in patients with obstructive sleep apnea suggest that the soft palate plays an important role in mediating airway narrowing during airway muscle paralysis and sleep.
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Eur J Anaesthesiol. 201128(12):842-8.The influence of residual neuromuscular block on the incidence of critical respiratory events. A randomised, prospective, placebo-
controlled trial.Sauer M, Stahn A, Soltesz S, Noeldge-Schomburg G, Mencke T.
Department of Anaesthesiology and Intensive Care Medicine, University of Rostock, Rostock, Germany.
incidence of critical respiratory events, such as hypoxaemia, in patients with minimal residual neuromuscular blockade and compared these data with those from patients with full recovery of blockade.
Randomised, prospective, placebo-controlled trial. 132 adult patients, 18-80ASA I-III ,orthopaedic surgery ,GA with rocuronium randomised to one of two groups: neostigmine group (neostigmine 20 μg kg-1) or
placebo group (saline). In the patients in the neostigmine group, the tracheal tube was removed at a
train-of-four (TOF) ratio of 1.0; in the patients in the placebo group, the trachea was extubated at a TOF ratio less than 1.0, but without fade in TOF and double-burst stimulation (DBS).
Neuromuscular monitoring was assessed simultaneously with qualitative TOF/DBS monitoring, and with quantitative calibrated acceleromyography.
Critical respiratory events, such as hypoxaemia, were assessed in the post-anaesthesia care unit.
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The influence of residual neuromuscular block on the incidence of critical respiratory events. A randomised,
prospective, placebo-controlled trial
45 pts (39.5%) became hypoxaemic (SaO2 < 93%); there was a significant difference between the groups (29
patients in the placebo group versus 16 in the neostigmine group; P = 0.021).
In the neostigmine group, all patients were extubated at a TOF ratio of 1.0. In the placebo group, the median TOF ratio was 0.7 (range: 0.46-0.9; P < 0.001). The median time for spontaneous recovery in the placebo group was 16 min (range 3-49 min). Neostigmine 20 μg kg was effective in antagonising rocuronium-induced blockade without fade in TOF and DBS.
In this randomised, prospective, placebo-controlled trial, minimal residual block was associated with hypoxaemia in the post-anaesthesia care unit. Neostigmine 20 μg kg was effective in antagonising rocuronium-induced (minimal) blockade
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Bissinger U,Schimek,F,Lenz,G.Postoperative residual paralys and respiratory status:a comparative study of
pancuronium and vecuronium.Physiol Rev. 2000:49;455-462.
83 patients,balanced or inhalation maintenance
Panc for op>2hrs,vecu for op>1 hr PORP defined as tofr<70,hypoxemia as
SaO” > 5% lower than basal or postop SaO2<93%,hypercapnia as paCO2>46 mmHg.
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Bissinger U,Schimek,F,Lenz,G.Postoperative residual paralys and respiratory status:a comparative study of
pancuronium and vecuronium.Physiol Rev. 2000:49;455-462.
panc vecu
PORP 20% 7%
hypoxemia 60% 10%
hypercapnia 30% 8%
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.Bissinger U,Schimek,F,Lenz,G.Postoperative residual paralys and respiratory status:a comparative study of
pancuronium and vecuronium.Physiol Rev. 2000:49;455-462.
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MA CHE CI IMPORTA DEL TOFR 0.90?
Viby Mogensen et al,AAS 1997
• 693 paz.randomizzati,cieco
• chir elettiva
• monitoraggio periop con Myotest e Tof
• confronto fra 1-5-2 ED95 diatrac,vecu,panc.
• Antagonismo se necessario;
• estubaz a tof eguale, tattile e resp adeguata.
Paralisi residua e % di tof<0.40 in RR,subito dopo
trasferimento
0
5
10
15
20
25
30
35
40
45
Tof <0.70 tof<0.40
pancatracvecu
Andamento temporale del tof <0.80 nella RR
05
101520253035404550
0 5 10 15 20 30 40 50
min
% t
of<
0.8
0
pancatracvecu
Postoperative pulmonary complications
0
5
10
15
20
%
popc popc conbloccoresiduo
popc senzabloccoresiduo
pancvecu
atrac
pancvecuatrac
Popc secondo il tipo di chirurgia
0
2
4
6
8
10
12
14
16
%
popc
addomortopginecol
Fattori di rischio per POPC nello studio AAS1997
Tipo di chirurgia;freq * 2-10(addominale) età:ogni 10 anni * 1.68 durata di anestesia(> o < 200 min)*3.3 panc e tof<0.70:*5
What is the validity and correlation between the
different PORP diagnostic tests ? Clinical tests have shown the following values of sensitivity,
specificity, positive and negative predictive values19(D): Capacity to keep the head up for 5 seconds: 0.19; 0.88; 0.51; 0.64; • Capacity to hold up the arm or the leg for 5 seconds: 0.25; 0.84; 0.50; 0.64; • Protrusion or capacity to remove the tongue: 0.22; 0.88; 0.52; 0.64; • Maintenance of hand grip strength: 0.18; 0.89; 0.51; 0.63. None of the available clinical trials showed a positive correlation with the T4/T1 >
0.9, or ruled out the possibility of PORP7,8,19(B)21(C).
Br J Anaesth. 2010 Sep;105(3):304-9. Postoperative residual curarization from intermediate-acting neuromuscular blocking
agents delays recovery room discharge.Butterly A, Bittner EA, George E, Sandberg WS, Eikermann M, Schmidt U.
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Postoperative residual curarization (PORC) [train-of-four ratio (T4/T1) <0.9] is associated with increased morbidity and may delay postoperative recovery room (PACU) discharge. We tested the hypothesis that postoperative T4/T1 <0.9 increases PACU length of stay.
At admission to the PACU, neuromuscular transmission was assessed by acceleromyography (stimulation current: 30 mA) in 246 consecutive patients. The potential consequences of PORC-induced increases in PACU length of stay on PACU throughput were estimated by application of a validated queuing model taking into account the rate of PACU admissions and mean length of stay in the joint system of the PACU plus patients recovering in operation theatre waiting for PACU beds.
PACU length of stay was significantly longer in patients with T4/T1 <0.9 (323 min), compared with patients with adequate recovery of neuromuscular transmission (243 min). Age (P=0.021) and diagnosis of T4/T1 <0.9 (P=0.027), but not the type of neuromuscular blocking agent, were independently associated with PACU length of stay. The incidence of T4/T1 <0.9 was higher in patients receiving vecuronium. Delayed discharge significantly increases the chances of patients having to wait to enter the PACU. The presence of PORC is estimated to be associated with significant delays in recovery room admission.
CONCLUSIONS: PORC is associated with a delayed PACU discharge. The magnitude of the effect is clinically significant. In
our system, PORC increases the chances of patients having to wait to enter the PACU.
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Postoperative residual curarization from intermediate-acting neuromuscular blocking agents delays recovery
room discharge.
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Postoperative residual curarization from intermediate-acting neuromuscular blocking agents delays recovery
room discharge.
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DO WE ALWAYS NEED TO REVERSE NMB?
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Anesthesiology. 2005 Feb;102(2):257-68.Impact of anesthesia management characteristics on severe morbidity and mortality.
Arbous MS, Meursing AE, van Kleef JW, de Lange JJ, Spoormans HH, Touw P, Werner FM, Grobbee DE.
A case-control study was performed of all patients undergoing anesthesia (1995-1997): 869,483 patients; 807 cases and 883 controls were analyzed
ONLY coma or death reported during or within 24 h of undergoing anesthesia..
.The incidence of 24-h postoperative death was 8.8 ( 8.2-9.5) per 10,000 anesthetics. The incidence of coma was 0.5 (0.3-0.6).
Anesthesia management factors that associated with a decreased risk : equipment check with protocol and checklist, documentation of the equipment check , a directly available anesthesiologist, no change of anesthesiologist during anesthesia, presence of a full-time working anesthetic nurse two persons present at emergence, reversal of anesthesia (for muscle relaxants and the combination of muscle
relaxants and opiates; postoperative pain medication as opposed to no pain medication, particularly
if administered epid or i.m. as opposed toi.v..Napoli SIA 2013
Neostigmine/glycopyrrolate administered after recovery from neuromuscular block increases upper airway collapsibility by decreasing genioglossus muscle activity in response to negative pharyngeal pressure.
Herbstreit F, Zigrahn D, Ochterbeck C, Peters J, Eikermann M.Anesthesiology. 2010 ;113(6):1280-8. 10 healthy male volunteers
epiglottic and nasal mask pressures, genioglossus electromyogram, air flow, respiratory timing, and changes in lung volume before, during (TOF ratio: 0.5), and after recovery of the TOF ratio to unity, and after administration of neostigmine 0.03 mg/kg IV (with glycopyrrolate 0.0075 mg/kg).
Upper airway critical closing pressure (Pcrit) was calculated from flow-limited breaths during random pharyngeal negative pressure challenges.
Pcrit increased significantly after administration of neostigmine/glycopyrrolate compared with both TOF recovery (mean SD, by 27 21%; P 0.02) and baseline (by 38 17%; P 0.002). In parallel, phasic genioglossus activity evoked by negative pharyngeal pressure decreased (by 37 29%, P 0.005) compared with recovery, almost to a level observed at a TOF ratio of 0.5.
Lung volume, respiratory timing, tidal volume, and minute ventilation remained unchanged after neostigmine/glycopyrrolate injection.
Conclusion: Neostigmine/glycopyrrolate, when administered after recovery from neuromuscular block, increases upper airway collapsibility and impairs genioglossus muscle activation in response to negative pharyngeal pressure. Reversal with acetylcholinesterase inhibitors may be undesirable in the absence of neuromuscular blockade.
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Representative recording of main variables from an awake healthy volunteer before partial neuromuscular blockade
(baseline), during impaired neuromuscular transmission with a target train-of-four (TOF) ratio of 0.5, after spontaneous recoveryof the TOF ratio to unity, and during measurements initiated 2 min
after injection of neostigmine (0.03 mg/kg) and glycopyrrolate(0.0075 mg/kg).
A) Mask pressure at 2 cm H2O. Phasic (respiratory) genioglossus activity is very low while breathing
nearatmospheric pressure. During impaired
neuromuscular transmission, no flow limitation is observed at this mask pressure.
(B) Same volunteer during a negative pressure challenge (20 cm H2O). Before partial
neuromuscular blockade, phasicgenioglossus activity is markedly increased compared with breathing near atmospheric
pressure. During partial neuromuscularblockade, phasic genioglossus activity is markedly increased compared with breathing at atmospheric
pressure. However, themagnitude of the compensatory increase in
genioglossus activity in response to negative pharyngeal pressure is impaired, and
flow limitation is observed. After spontaneous recovery of the TOF ratio to unity, the
compensatory phasic genioglossus activityis restored. Injection of neostigmine/glycopyrrolate attenuates the increase in genioglossus activity,
and the changes observedattain similar values as those seen with partial
neuromuscular blockade with a TOF ratio of 0.5.
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Upper airway closing pressure significantly increased during partial neuromuscular blockade and wasstill abnormal even with recovery of the TOF ratio to unity (i.e.,before injection of
neostigmine/glycopyrrolate) (P 0.01 vs.baseline). However, upper airway closing pressure significantlyincreased after injection of neostigmine/glycopyrrolate.
Upper airway critical closing pressure (Pcrit) in awake healthy volunteers at baseline before neuromuscular blockade, with impaired neuromuscular
transmission and a target train-of-four (TOF) ratio of 0.5, after spontaneous recovery of the TOF ratio to unity, and after injection of
neostigmine/glycopyrrolate
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The genioglossus activity is presente as a percentage of maximal activity (observed when the volunteer pressed his tongue with maximum strength against his teeth with the mouth closed). Genioglossus activity
evoked in response to negative pressure challenges isimpaired with neuromuscular blockade. The compensatorygenioglossus response to a pressure drop is restored after return of the TOF ratio to unity. After administration ofneostigmine/glycopyrrolate, genioglossus activity in response to negative airway pressure
is markedly and significantly decreased.
Genioglossus muscle activity as a function of negative mask pressure with neuromuscular blockade at a target TOFratio of 0.5 (open squares), after spontaneous recovery of the TOF
ratio to unity (solid squares), and after injection of neostigmine/glycopyrrolate
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Neostigmine/glycopyrrolate administered after recovery from neuromuscular block increases upper airway collapsibility by decreasing genioglossus muscle activity in response to negative pharyngeal pressure.
Herbstreit F, Zigrahn D, Ochterbeck C, Peters J, Eikermann M.Anesthesiology. 2010 ;113(6):1280-8.
Administration of neostigmine/glycopyrrolate, when administered after spontaneous recovery of neuromuscular function, in a dose similar to that recommended, and in routine clinical use, led to a significant increase in Pcrit and thus increased airway collapsibility in healthy volunteers. The increase in airway collapsibility was of a magnitude comparable with neuromuscular blockade with a TOF ratio of 0.5.
Furthermore, the normal compensatory activation of the genioglossus muscle in response to airway negative pressure challenges was blunted after administration of neostigmine/ glycopyrrolate (i.e. , neostigmine/glycopyrrolate evoked a significant impairment of upper airway dilator muscle function).
Accordingly, whereas previous studies demonstrated airway compromise with residual neuromuscular blockade and thus a probable clinical need for reversal agents, theresults of this study reveal increased airway collapsibility as a result of neostigmine/glycopyrrolate, if given after recovery from neuromuscular transmission blockade.
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Antagonismo dei miorilassanti
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Presenza dei vapori….
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TOF vs time after neostigmine 40 gr/kg (from T1 25%);control(fent/N2O),isoflurane stopped,isoflurane continued (1.25%)Baurain MJ, d'Hollander AA,Melot C, Dernovoi BS,Barvais L.Effects of residual concentrations of isoflurane on the reversal of vecuronium induced neuromuscular blockade.Anesthesiology 1991:71:474- )
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Valori del tetanic fade (stimolazione a 50 Hz sn,100 Hz dx)dopo 15 min dalla somministrazione di neostigmina 40 microgr/kg Baurain MJ, d'Hollander AA,Melot C, Dernovoi BS,Barvais L.Effects of residual concentrations of isoflurane on the reversal of vecuronium induced neuromuscular blockade.Anesthesiology 1991:71:474- )
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Insomma,continuare la soministraz del vapore ritarda la ripresa nm anche dopo rovesciamento……
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Neo vs edrofonio e profondità del blocco nm.
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Mean first twitch height vs time after administration of various doses of neostigmine and edrophonium starting from T 1 10% following atracurium and vecuronium Smith, CE, Donati F., Bevan DR.Dose‑Response Relationships for Edrophonium and Neostigmine as Antagonists of Atracurium and Vecuronium neuromuscular Blockade.Anesthesiology 1989;71: 37-43.
Inspired enflurane concentration maintained at 0.5-1%
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Dose response relationship of first twitch and TOF assisted recovery 5 and 10 min. following administration of the antagonist as a function of the dose of neostigmine and edrophonium following atracurium and vecuronium. Smith, CE, Donati F., Bevan DR.Dose‑Response Relationships for Edrophonium and Neostigmine as Antagonists of Atracurium and Vecuronium Neuromuscular Blockade.Anesthesiology 1989;71: 37-43.
Inspired enflurane concentration maintained at 0.5-1%
???
?
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Effect on Tof of 2 doses of neostigmine and edrophonium following atracurium and vecuronium Smith, CE, Donati F., Bevan DR.Dose‑Response Relationships for Edrophonium and Neostigmine as Antagonists of Atracurium and Vecuronium Neuromuscular Blockade.Anesthesiology 1989;71: 37-43.
Inspired enflurane concentration maintained at 0.5-1%
Tof si ferma a 0.7!!!
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Conclusione 1
La dose giusta di neostigmina è…………
Meditate gente meditate………………
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Insomma,l’antagonismo dipende da:
Profondità di blocco al momento della somministrazione dell’antagonista
Presenza o meno di potenzianti nmb. Tipo di antagonista somministrato Tipo di miorilassante somministrato Dose dell’antagonista somministrato end point scelto;T1/Tc,Tof,ecc.
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Conclusione 2
E’ meglio somministrare gli antidoti quando la ripresa nm è iniziata
È meglio cessare la somministrazione degli alogenati ( e monitorizzare la % et)…….
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Anesthesiology. 2002 Jan;96(1):45-50. Efficacy of tactile-guided reversal
from cisatracurium-induced neuromuscular block.
Kirkegaard H, Heier T, Caldwell JE. Source Department of Anesthesia and
Perioperative Care, University of California, San Francisco, USA. [email protected]
Abstract BACKGROUND: Because tactile evaluation is the most
common form of clinical neuromuscular monitoring, this study examines the relative efficacy of antagonizing residual block at different levels of recovery of the tactile train-of-four (TOF) response.
METHODS: Anesthesia was induced in 64 adults
with 2-5 microg/kg fentanyl and 1-3 mg/kg propofol and maintained with fentanyl, propofol, and nitrous oxide. The tactile response of the adductor pollicis to TOF stimulation was evaluated at one arm, and the mechanomyographic response was recorded at the other. Patients received 0.15 mg/kg cisatracurium and were randomized to receive 0.07 mg/kg neostigmine on reappearance of the first (group I), second (group II), third (group III), or fourth (group IV) tactile TOF response (16 patients per group). Times from administration of neostigmine until the TOF ratio recovered to 0.7 (R0.7), 0.8 (R0.8), and 0.9 (R0.9) were measured.
RESULTS: Data are presented as median with
range in parentheses. R0.7 was 10.3 (5.9-23.4), 7.6 (3.2-14.1), 5.0 (2.0-18.4), and 4.1 (2.4-11.0) min in groups I, II, III, and IV, respectively (P < 0.05, group I > II, III, and IV, group II > IV). R0.8 was 16.6 (8.9-30.7), 9.8 (5.3-25.0), 8.3 (3.8-27.1), and 7.5 (3.0-74.5) min in groups I, II, III, and IV, respectively (P < 0.05, group I > II, III, and IV, group II > IV). R0.9 was 22.2 (13.9-44.0), 20.2 (6.5-70.5), 17.1 (8.3-46.2), and 16.5 (6.5-143.3) min in groups I, II, III, and IV, respectively (no intergroup differences). Ten minutes after neostigmine, a TOF ratio of 0.7 or greater was achieved in 50, 75, 88, and 93% of patients in groups I, II, III, and IV, respectively (P < 0.05 group I > II, III, and IV). At 30 min, a TOF ratio of 0.9 or less was observed in 21, 13, 13, and 7% of patients in groups I, II, III, and IV respectively (no intergroup differences).
CONCLUSIONS: To achieve rapid (within 10 min) reversal
to a TOF ratio of 0.7 in more than 87% of patients, three or four tactile responses should be present at the time of neostigmine administration. It was not possible within 30 min to achieve a TOF ratio of 0.9 in all patients, regardless of the number of tactile responses present at neostigmine administration
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Kirkegaard H,Heier T,Caldwell JE Efficacy of tactile guided reversal from cisatracurium
induced neuromuscular block.Anesthesiology 2002;96:45-50
Anest with fent/prop/N2O cisatrac 0.15 mg/kg neostigmine 0.07 mg/kg administered at
reappearance of I,II,III,IV of TOF;tactile vs Meccanomyography contralateral.
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Time from neostigmine administration to TOFR
0.70
I twitch II twitch III twitch IV twitch0.00
5.00
10.00
15.00
20.00
25.00
mediana
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Time from neostigmine administration to TOFR 0.80
I twitch II twitch III twitch IV twitch0
10
20
30
40
50
60
70
80
mediana
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Time from neostigmine administration to TOFR 0.90
I twitch II twitch III twitch IV twitch0
10
20
30
40
50
60
70
80
mediana
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MMG magnitude of the first TOF twitch(T1) measured at the reappearance of each of the 4
tactile TOF responses.
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Kirkegaard H,Heier T,Caldwell JE Efficacy of tactile guided reversal from cisatracurium induced
neuromuscular block.Anesthesiology 2002;96:45-50
This study shows that achieving a TOFR of 0.90 in <10 min following neostigmine reversal is not a realistic goal;therefore counting the number of tactile responses to tof stimulation cannot be used as a guide for neostigmine admninistration if the end point of reversal is a TOFR of 0.90 or higher within
10 min;but is a good predictor of TOFR 0.70.
Time to tof 0.9 after neostigmine 0.07 mg/kg + glycopirrolate when tactile tof is 1,2,3,4(groups) Kyo S. Kim,
MD, PhD, Mi A. Cheong, MD, PhD, Hee J. Lee, MD, and Jae M. Lee,.Tactile Assessment for the Reversibility of Rocuronium-Induced Neuromuscular Blockade During Propofol or
Sevoflurane Anesthesia. Anesth Analg 2004;99:1080 –5)
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rocuronium 0.6 mg/kg and maintained with rocuronium
0.1 mg/kg given every time the height of first twitch
(T1) in TOF recovered to approximately 15% of Tcobtained before induction of neuromuscular
blockade.
Conclusione 3
With neostigmine it is impossible to obtain a tof 0.90 within 10 min.
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Effetti collaterali degli anti AchE
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Effetti fisiologici della presenza di Ach
Bradicardia Salivazione Iperperistalsi Secrezioni bronchiali
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Pericoli degli AntiAchE: arresto cardiaco
Bjerke, Richard J., MD; Mangione, Michael P.Asystole after intravenous neostigmine in a heart transplant recipinet.Can.Anaesth.J. 2001;48:305-07.
Purpose: To describe a heart transplant recipient who developed asystole after administration of neostigmine which suggests that surgical dennervation of the heart may not permanently prevent significant responses to anticholinesterases.
Clinical features: A 67-yr-old man, 11 yr post heart transplant underwent left upper lung lobectomy. He developed asystole after intravenous administration of 4 mg neostigmine with 0.8 mg glycopyrrolate for reversal of the muscle relaxant. He had no history of rate or rhythm abnormalities either prior to or subsequent to the event.
Conclusion: When administering anticholinesterase medications to heart transplant patients, despite surgical dennervation, one must be prepared for a possible profound cardiac response.
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Pericoli degli ACHE:FA con rapida risposta ventricolare…..
Kadoya, TSA, Aoyama K, Takenaka I.Development of rapid atrial fibrillation with wide QRS complex after neostigmine in a patient with intermittent WPW stndrome.BJA 1999;83:815-818
1Department of Anaesthesia, Nippon Steel Yawata Memorial Hospital, 1-1-1 Harunomachi,
Yahatahigashi-ku, ABSTRACT: We report the case of a 67-yr-old man with intermittent Wolff-Parkinson-White
(WPW) syndrome in whom neostigmine produced life-threatening tachyarrhythmias. The patient was scheduled for microsurgery for a laryngeal tumour. When he arrived in the operating room, the electrocardiogram showed normal sinus rhythm with a rate of 82 beat min-1 and a narrow QRS complex which remained normal throughout the operative period. On emergence from anaesthesia, the sinus rhythm (87 beat min-1) changed to atrial fibrillation with a rate of 80–120 beat min-1 and a normal QRS complex. We did not treat the atrial fibrillation because the patient was haemodynamically stable. Neostigmine 1 mg without atropine was then administered to antagonize residual neuromuscular block produced by vecuronium. Two minutes later, the narrow QRS complexes changed to a wide QRS complex tachycardia with a rate of 110–180 beat min-1, which was diagnosed as rapid atrial fibrillation. As the patient was hypotensive, two synchronized DC cardioversions of 100 J and 200 J were given, which restored sinus rhythm. No electrophysiological studies of anticholinesterase drugs have been performed in patients with WPW syndrome. We discuss the use of these drugs in this condition.
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Pericoli degli antiAchE:broncocostrizione Shibata O,Tsuda A,Makita T, Iwanaga S,Hara T,Shibata S,Sumikawa K.
Contractile and phosphadytilinositol responses of rat trachea to anticholinesterase drugs.Can.Anaesth.J.1998;45:1190-95Purpose: Some anticholinesterases (anti-ChE) such as neostigmine and pyridostigmine but not edrophonium, stimulate phosphaticlylinositol (PI) response. Although a direct relationship was suggested between the increase in PI response and airway smooth muscle contraction, there are no data regarding the effects of anti-ChE drugs on airway smooth muscle. Thus, we examined the contractile properties and PI responses produced by anti-ChE drugs.
Methods: Contractile response. Rat tracheal ring was suspended between two stainless hooks in Krebs-Henseleit (K-H) solution. (1) Carbachol (CCh), anti-ChE drugs (neostigmine, pyridostigmine, edrophonium) or DMPP (a selective ganglionic nicotinic agonist) were added to induce active contraction. (2) The effects of 4-diphenylacetoxy-N-methyl-piperidine methobromide (4-DAMP), an M3 muscarinic receptor antagonist, on neostigmine- or pyridostigmine-induced contraction of rat tracheal ring were examined. (3) Tetrodotoxin (TTX) was tested on the anti-ChE drugs-induced responses. PI response. The tracheal slices were incubated in K-H solution containing LiCl and 3[H]myo-inositol in the presence of neostigmine or pyridostigmine with or without 4-DAMP, an M3 muscarinic receptor antagonist. 3[H]inositol monophosphate (IP1) formed was counted with a liquid scintillation counter.
Results: Carbachol (0.1 mM), neostigmine. (1 mM), pyridostigmine (10 mM) but not edrophonium or DMPP, caused tracheal ring contraction. 4-DAMP, but not tetrodotoxin, inhibited neostigmine and pyridostigmine-induced contraction. Neostigmine- or pyridostigmine-induced IP1 accumulation was inhibited by 4-DAMP.
Conclusions: The data suggest that anti-ChE drugs activate the M3 receptors at the tracheal effector site.
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Schema delle afferenze parasimpatiche a livello tracheale
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Effetti contrattili di antiACHE,carbacolo e dimetilfenilpiperazinio sugli anelli tracheali di ratto.Shibata O,Tsuda A,Makita T, Iwanaga S,Hara T,Shibata S,Sumikawa K. Contractile and phosphadytilinositol responses of rat trachea to anticholinesterase drugs.Can.Anaesth.J.1998;45:1190-95
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NEOSTIGMINE AND PONV
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Tramèr, M. R. Fuchs-Buder, T..Omitting antagonism of nm block:effect on PONV and risk of residual paralysis.A systematic review.BJA 1999;82:379-386
A systematic search (MEDLINE, EMBASE, Biological Abstracts, Cochrane library, reference lists and hand searching; no language restriction, up to March 1998) was performed for relevant randomized controlled trials. In eight studies (1134 patients), antagonism with neostigmine or edrophonium was compared with spontaneous recovery after general anaesthesia with pancuronium, vecuronium, mivacurium or tubocurarine. On combining neostigmine data, there was no evidence of an antiemetic effect when it was omitted. However, the highest incidence of emesis with neostigmine 1.5 mg was lower than the lowest incidence of emesis with 2.5 mg. These data suggested a clinically relevant emetogenic effect with the higher dose of neostigmine in the immediate postoperative period but not thereafter.
Numbers-needed-to-treat to prevent emesis by omitting neostigmine compared with using it were consistently negative with 1.5 mg, and consistently positive (3–6) with 2.5 mg. There was a lack of evidence for edrophonium. In two studies, three patients with spontaneous recovery after mivacurium or vecuronium needed rescue anticholinesterase drugs because of clinically relevant muscle weakness (number-needed-to-harm, 30). Omitting neostigmine may have a clinically relevant antiemetic effect when high doses are used. Omitting antagonism, however, introduces a non-negligent risk of residual paralysis even with short-acting neuromuscular blocking agents.Napoli SIA 2013
Watcha MF, Safavi FZ, McCulloch DA, et al. Effect of antagonism of mivacurium-induced neuromuscular block on postoperative emesis in children. Anesth Analg 1995;
80:713-7.
**
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Ding Y,Fredman B, White PF.Use of mivacurium during laparoscopic surgery:effect of reversal drungs on postoperaive recovery.Anesth Analg
1994; 78:450–4
outpatient laparoscopic tubal ligation 60 healthy, nonpregnant women. midazolam / fentanyl/tps succ 1 mg/kg (Group I) vs mivacurium 0.2 mg/kg (Groups II
and III) Anesthesia maintained with isoflurane (0.5%-2% +67% N2O Muscle relaxation maintained in all three groups with
intermittent bolus doses of mivacurium, 2–4 mg, IV. In Group III, residual neuromuscular block reversed with
neostigmine 2.5 mg +glycopyrrolate, 0.5 mg,
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Effetti collat dello studio di Ding et al.
*
*
*
*
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Risk of omitting neostigmine….
Residual paralysis!!!
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Comportamento suggerito per l’antagonismo dei miorilassanti a lunga e media durata di azione secondo le risposte al Tof
TOF esaurimento farmaco dose
Twitch visibili
nessuno Posponi antagonismo finchè almeno 1 o 2 contrazioni visibili!!
1-2 ++++ neostigmina 0.07 mg/kg
3-4 +++ neostigmina 0.04 mg/kg
4 ++ edrofonio 0.5 mg/kg
4 +/- edrofonio 0.25
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Time from administration of neostigmine or placebo/spontaneous recovery to recovery of the TOF ratio 0.7, 0.8 or 0.9 in non-sugammadex studies
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tof 0,9 Adamus tof0,9 Barrio tof 0,9 Adamus tof 0,9 Bevan tof 0,8 Della Rocca 0
10
20
30
40
50
60
rocu 0,6+neorocu0,6 spontrocu 0,9+neorocu 0,9 spont
Benefici attesi con Sugammadex
Aumentata sicurezza per I pazienti Aumentata sicurezza in anestesia e
chirurgia Ridotta incidenza(eliminazione) del blocco
nm residuo Aumentata efficienza
» Benefici economici per accelerazione della ripresa,turnover + rapido?
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tactile assessmenttactile assessment
TetanusTetanus
DBSDBS
TOFTOF
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Clinical signsClinical signscorrelation with residual forcecorrelation with residual force
patient cooperation!patient cooperation!
tonguedepressorclenching
tonguedepressorclenching
head lift> 5 sechead lift> 5 sec
arm or leglift> 5 secarm or leglift> 5 sec
sustainedhand gripstrenght
sustainedhand gripstrenght
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clinical signsclinical signsreliable vs not reliablereliable vs not reliable
TV normalTV normal unreliableunreliable
Neg Press < 25 mmHgNeg Press < 25 mmHgunreliableunreliable
Neg press < 50 mmHgNeg press < 50 mmHgreliablereliable
coughcough unreliableunreliable
eye openingeye openingunreliableunreliable
tongue protrusiontongue protrusionunreliableunreliable
before patient cooperationri....before patient cooperationri....
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Drenck NE, Ueda N, Olsen NV, et al. Manual evaluation of residual curarization using double burst stimulation: A comparison with train-of-
four. Anesthesiology 1989; 70:578-81
- Double burst stimulation (DBS. The stimulus consists of two short bursts of 50 Hz tetanic stimulation,
separated by 750 ms 52 healthy patients undergoing surgery were studied. For both stimulation patterns the frequencies of manually detectable
fade in the response to stimulation were determined and compared at various electromechanically measured TOF ratios.
A total of 369 fade evaluations for DBS and TOF were performed.
:
AB
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Probability of being within defined TOFR intervals when different clinical fade evaluations are given
(Drenck NE, Ueda N, Olsen NV, et al. Manual evaluation of residual curarization using double burst stimulation: A comparison with train-of-four.
Anesthesiology 1989; 70:578-81)
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Dbs 3-3 Drenck NE, Ueda N, Olsen NV, et al. Manual evaluation of residual curarization using double burst stimulation: A comparison with train-of-four. Anesthesiology
1989; 70:578-81)
Fade frequencies with DBS more frequent than with TOF
Absence of fade with tof implies a 52% probability than tof>0.60
absence of fade with dbs implies a tof >0.60 in 91% of cases
only tOFR<0.40 can be assessedd manually therefore,evaluation of DBS is relevant only when
there is no fade to tof
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Conclusions:Drenck NE, Ueda N, Olsen NV, et al. Manual evaluation of residual curarization using double burst stimulation: A comparison with train-of-four. Anesthesiology
1989; 70:578-81)
absence of fade to DBS normally excludes severe residual nm blockade(tofr<0.60) BUT DOES NOT NECESSARILY INDICATE ADEQUATE CLINICAL RECOVERY.
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Meccanomiographic vs tactileevaluation
Meccanomiographic vs tactileevaluation
Drenck et al.Anesthesiology 79;578:1989.Drenck et al.Anesthesiology 79;578:1989.
qualitative tofevaluation
qualitative tofevaluation
48% chances ofevaluating a real fade48% chances ofevaluating a real fade
qualitative DBSevaluation
qualitative DBSevaluation
9% chances of nondiscerning a real fade9% chances of nondiscerning a real fade
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Viby-Mogensen J, Jensen NH, Engbæk J, Ørding H, Skovgaard LT, Chæmmer-Jørgensen B. Tactile and visual
evaluation of response to train-of-four nerve stimulation. Anesthesiology 1985; 63:440-3.
Diaz/tps/N2O 66%/haloth 0.75-1.5% IOT with SCC ,then panc simult MMG in one arm & visual/tactile evaluation
in the opposite. Experienced and (inexperienced)
anesthesiologists 6 different TOFR from every patient
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Viby-Mogensen et al Tactile and visual evaluation of response to train-of-four nerve stimulation.
Anesthesiology 1985; 63:440-3.
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Threshold fade by 3 very experienced observers (Viby-Mogensen et al. Tactile and visual evaluation of
response to train-of-four nerve stimulation. Anesthesiology 1985; 63:440-3)
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Threshold fade by 3 very experienced observers (Viby-Mogensen et al. Tactile and visual evaluation of
response to train-of-four nerve stimulation. Anesthesiology 1985; 63:440-3.)
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Which is the TOFR level that can be reliably detected visually by observing tetanic fade of the AP in response to 100-Hz, 5-s tetanus in anesthetized patients.?
RESIDUAL PARALYSIS WITH/OUT MONITORING
TOF MONITORING NO MONIT0
10
20
30
40
50
60
70
80
PEDERSENSHORTEN FRUERGAARD
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FINAL QUESTION 1:
Does qualitative neuromuscular monitoring reduce the risk of residual block?
–NO
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100 Hz visual assessment seems to be highly sensitive in evaluating residual paralysis, as the absence of RF100 Hz visual fading at the AP is compatible
with a TOF ratio >0.85
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Baurain et al.Visual Evaluation of Residual Curarization in Anesthetized Patients Using One Hundred-Hertz, Five-Second
Tetanic Stimulation at the Adductor Pollicis Muscle .Anesth Analg 1998; 87:185–9
Residual block in patients monitored with AMG
Mortensen Gatke Murphy
TOF watch 5.3 34.5No monit 50 17 30
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Final question 2:Does quantitative neuromuscular monitoring reduce the risk of residual block?
It reduces but does not eliminate residual block
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But..... Despite high quality studies demonstrating
a beneficial effect of quantitative monitoring on the incidence of PORC , few clinicians routinely use this type of monitoring.
22.7% USA (Naguib et al , Anesth Analg 2010;1111:110-9)
35% Italy (Della Rocca et al,Minerva Anestesiol. 2012 Jul;78(7):767-73.
Neuromuscular block in Italy: a survey of current management.
Della Rocca G, Iannuccelli F, Pompei L, Pietropaoli P, Reale C, Di Marco P
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Conclusions
Until neuromuscular block during surgery is not routinely monitored with obiective means(MMG,AMG...) residual paralyss would continue and contribute to postoperative complications!
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