Lipid resuscitation for local anesthetic toxicity: is it ......Although pulmonary edema may occur after resus- citation from cardiac arrest treated with standard ACLS protocols, the
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C
Lipid resuscitation for local ane
sthetic toxicity: is it
really lifesaving?Ulana Leskiwa and Guy L. Weinberga,b
aUniversity of Illinois at Chicago College of Medicineand bJesse Brown VA Medical Center, Chicago, Illinois,USA
Correspondence to Ulana Leskiw, MD, University ofIllinois at Chicago College of Medicine, 1740 WestTaylor, Suite 3200W, M/C 515, Chicago, IL 60612,USATel: +1 312 996 4020; fax: +1 312 996 4019;e-mail: [email protected]
Current Opinion in Anaesthesiology 2009,22:667–671
Purpose of review
Laboratory studies and clinical reports have led to the acceptance of lipid emulsion
as an effective treatment of local anesthetic-induced cardiac arrest. This review
discusses subsequent clinical reports, relevant laboratory studies and topics for further
research.
Recent findings
Case reports have confirmed the efficacy of lipid resuscitation for local anesthetic
systemic toxicity. Furthermore, lipid emulsion has been used with apparent success
early in the spectrum of local anesthetic systemic toxicity to preempt cardiac arrest. The
role of lipid emulsion has expanded to treatment of cardiac toxicity due to other lipophilic
drugs. This appears to have an acceptable safety profile, although elevated amylase has
been reported. Laboratory investigations in animals suggest that concomitant
hypoxemia hinders resuscitation attempts, and that epinephrine and vasopressin are
more likely to be associated with poor outcomes than lipid.
Summary
Lipid emulsion infusion appears to be an effective treatment for cardiac toxicity induced
by lipophilic medications. Given the difficulties of performing clinical trials, further
laboratory investigation and clinical correlation are needed to better define its role in
resuscitation.
Keywords
lipid emulsion, local anesthetics, resuscitation, toxicity
Curr Opin Anaesthesiol 22:667–671� 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins0952-7907
IntroductionLocal anesthetic systemic toxicity (LAST) is a rare but
potentially catastrophic complication of regional anesthe-
sia [1]. Laboratory findings made over the last decade and
recent case reports suggest that lipid emulsion is a poten-
tial antidotal treatment and might reduce the morbidity
of this complication. Weinberg et al. [2] first reported in
1998 that lipid emulsion infused during resuscitation
increased the median lethal dose (LD50) of bupivacaine
in rats by 50%. In a subsequent study [3] of bupivacaine-
induced cardiac arrest in dogs, treatment with lipid
improved hemodynamics and survival compared with
isotonic saline-treated controls. This review will summar-
ize clinical experience with lipid emulsion, highlight
relevant laboratory studies and address the current status
of this therapy with respect to timing, dose, potential
adverse effects and its overall role in resuscitation.
Clinical experienceIn 2006, Rosenblatt et al. [4] and Litz et al. [5] reported
successful clinical use of lipid emulsion to reverse local
MechanismInsights into the mechanism of action of lipid emulsion
will aid in optimizing its use. At present, the most likely
theory appears to be that of the lipid ‘sink’ binding the
lipophilic drugs and thereby reducing tissue content of
the toxin. Plasma levels are difficult to obtain during
resuscitation, however, and results so far are inconsistent.
An in-vitro study did indeed demonstrate high solubility
of local anesthetics in lipid emulsions and high binding
capacity of these emulsions; interestingly, Intralipid
appeared about 2.5 times more efficacious than Media-
lipid and binding was reduced at lower pH [28�].
ConclusionLipid emulsion has an apparently acceptable safety pro-
file in currently recommended doses and appears to be
effective in the treatment of cardiac arrest resulting
from lipophilic toxins. Clinicians report successful, early
administration of lipid emulsion to preempt cardiac
arrest. Continued diligent observation and reporting by
clinicians as well as appropriate laboratory investigation
will lead to better information and understanding of the
precise role of lipid emulsion in resuscitation.
AcknowledgementsDr Weinberg has Veterans’ Affairs Merit Funding. Dr Weinberg wasawarded U.S. patent 7 261 903 B1 ‘Lipid emulsion in the treatment ofsystemic poisoning’. He does not have equity interest or agreementswith any company or commercial entity related to this method. He hasnever received salary or support from any company. He does notintend to prohibit or restrict the practice of this method on any patientrequiring this treatment. Dr Weinberg also created and maintainswww.lipidrescue.org, an educational, noncommercial website provid-ing information and a forum for discussing the use of lipid emulsion intreating cardiac toxicity. He derives no salary or support related tothis website.
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. 696).
1 Albright G. Cardiac arrest following regional anesthesia with etidocaine orbupivacaine. Anesthesiology 1979; 51:285–287.
2 Weinberg G, VadeBoncouer T, Ramaraju G, et al. Pretreatment or resuscita-tion with a lipid infusion shifts the dose-response to bupivacaine-inducedasystole in rats. Anesthesiology 1998; 88:1071–1075.
4 Rosenblatt MA, Abel M, Fischer GW, et al. Successful use of a 20% lipidemulsion to resuscitate a patient after a presumed bupivacaine-relatedcardiac arrest. Anesthesiology 2006; 105:217–218.
5 Litz RJ, Popp M, Stehr SN, Koch T. Successful resuscitation of a patient withropivacaine-induced asystole after axillary plexus block using lipid infusion.Anaesthesia 2006; 61:800–801.
6 Foxall G, McMahon R, Lamb J, et al. Levobupivacaine-induced seizures andcardiovascular collapse treated with Intralipid. Anaesthesia 2007; 62:516–518.
�McCutchen T, Gerancher JC. Early Intralipid therapy may have preventedbupivacaine-associated cardiac arrest. Reg Anesth Pain Med 2008; 33:178–180.
This study describes use of lipid emulsion to successfully treat CNS signs andventricular tachycardia with a pulse in a patient after nerve block.
8
�Ludot H, Tharin JY, Belouadah M, et al. Successful resuscitation afterropivacaine and lidocaine-induced ventricular arrhythmia following posteriorlumbar plexus block in a child. Anesth Analg 2008; 106:1572–1574.
This study describes the successful use of Medialipid to treat a 13-year-old girlwho developed ventricular tachycardia after lumbar plexus block with ropivacaine.
9
�Litz RJ, Roessel T, Heller AR, Stehr S. Reversal of central nervous system andcardiac toxicity after local anesthetic intoxication by lipid emulsion injection.Anesth Analg 2008; 106:1575–1577.
This study describes the successful use of lipid emulsion to reverse CNS signs andtreat ventricular ectopy in a patient who received brachial plexus block.
10
�Warren J, Thoma RB, Georgescu A, Saurin S. Intravenous lipid infusion in thesuccessful resuscitation of local anesthetic-induced cardiovascular collapseafter supraclavicular brachial plexus block. Anesth Analg 2008; 106:1578–1580.
This study describes the successful use of Liposyn III to treat cardiac arrest afterbrachial plexus block.
11 Tebbutt S, Harvey M, Nicholson T, Cave G. Intralipid prolongs survival in a ratmodel of verapamil toxicity. Acad Emerg Med 2006; 13:134–139.
12 Bania TC. Hemodynamic effects of intravenous fat emulsion in an animalmodel of severe verapamil toxicity resuscitated with atropine, calcium andnormal saline. Acad Emerg Med 2007; 14:105–111.
13 Harvey M, Cave G. Intralipid outperforms sodium bicarbonate in a rabbitmodel of clomipramine toxicity. Ann Emerg Med 2007; 49:178–185.
14 Harvey MG, Cave GR. Intralipid infusion ameliorates propranolol-inducedhypotension in rabbits. J Med Toxicol 2008; 4:71–76.
15
��Sirianni AJ, Osterhoudt KC, Callelo DP, et al. Use of lipid emulsion in theresuscitation of a patient with prolonged cardiovascular collapse afteroverdose of bupropion and lamotrigine. Ann Emerg Med 2008; 51:412–415.
This study describes the first clinical use of lipid emulsion to treat a patient withtoxicity due to lipophilic medications other than local anesthetics.
16
�Finn SDH, Uncles DR, Willers J, Sable N. Early treatment of quetiapine andsertraline overdose with Intralipid. Anaesthesia 2009; 64:191–194.
This study describes the use of lipid emulsion to reverse coma in a patient withdrug overdose.
�Perez E, Bania TC, Medlej K, Chu J. Determining the optimal dose ofintravenous fat emulsion for the treatment of severe verapamil toxicity in arodent model. Acad Emerg Med 2008; 15:1284–1289.
In this animal study of treatment of verapamil toxicity, the optimal dose of lipid wasapproximately 18 ml/kg.
20 Spence A. Lipid reversal of central nervous system symptoms of bupivacainetoxicity (letter). Anesthesiology 2007; 107:516–517.
21
��Marwick PC, Levin AI, Coetzee AR. Recurrence of bupivacaine toxicity afterlipid rescue from bupivacaine-induced cardiac arrest. Anesth Analg 2009;108:1344–1346.
This study describes a patient who developed recurrence of ventricular ectopy40 min after successful resuscitation from cardiac arrest with lipid. Amylase waselevated postoperatively, but no signs of pancreatitis were noted.
22
��Weinberg G, DiGregorio G, Ripper R, et al. Resuscitation with lipid versusepinephrine in a rat model of bupivacaine overdose. Anesthesiology 2008;108:907–913.
This study of bupivacaine-induced cardiac arrest in a rat model found that lipid wassuperior to epinephrine with respect to resuscitation rates and metabolic parameters.
23
��Di Gregorio G, Schwartz D, Ripper R, et al. Lipid emulsion is superior tovasopressin in a rodent model of resuscitation from toxin-induced cardiacarrest. Crit Care Med 2009; 37:993–999.
This study in a rat model found that lipid was superior to vasopressin andvasopressin/epinephrine for resuscitation of bupivacaine-induced cardiac arrest.
24
��Hiller D, Di Gregorio G, Ripper R, et al. Epinephrine impairs lipid resuscitationfrom bupivacaine overdose: a threshold effect. Anesthesiology (in press).
In this study of bupivacaine-induced cardiac arrest in a rat model, epinephrine morethan 10 mg/kg hindered resuscitation.
25
��Mayr VD, Mitterschiftthaler L, Neurater A, et al. Comparison of the combinationof epinephrine and vasopressin with lipid emulsion in a porcine model ofasphyxial cardiac arrest after intravenous injection of bupivacaine. AnesthAnalg 2008; 106:1566–1571.
In this study of bupivacaine toxicity in a porcine asphyxial model, vasopressin/epinephrine resulted in a better short-term survival than lipid emulsion.
26
��Harvey M, Cave G, Kazemi A. Intralipid infusion diminishes return of sponta-neous circulation after hypoxic cardiac arrest in rabbits. Anesth Analg 2009;108:1163–1168.
In this study, in a rabbit asphyxial model of cardiac arrest without lipophilic toxins,ACLS alone resulted in better return of spontaneous circulation than ACLS/lipidemulsion.
27
�Gueugniaud PY, David JS, Chanzy E, et al. Vasopressin and epinephrine vs.epinephrine alone in cardiopulmonary resuscitation. N Engl J Med 2008;359:21–30.
In this large study of epinephrine/vasopressin versus epinephrine alone for out-of-hospital cardiac arrest, there were no significant differences between groups insurvival to hospital admission (approximately 21%) or survival to hospital discharge(approximately 2%).
28
�Mazoit JX, Le Guen R, Beloeil H, Benhamou D. Binding of long-lasting localanesthetics to lipid emulsions. Anesthesiology 2008; 106:1333–1336.
This in-vitro study demonstrated high solubility of local anesthetics in lipid emulsionand high binding capacity of lipid emulsions.
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