J Korean Med Assoc.  2014 Jun;57(6):537-544. 10.5124/jkma.2014.57.6.537.

Lipid emulsion treatment of systemic toxicity induced by local anesthetics or other drugs

• Shin IW
• Sohn JT

• KMID: 1958092
• DOI: http://doi.org/10.5124/jkma.2014.57.6.537

Abstract

Although intravenous lipid emulsion (LE) is used mainly for parenteral nutrition, recently it has been used to treat patients with cardiopulmonary resuscitation (CPR)-resistant cardiovascular collapse induced by a toxic dose of local anesthetics or other drugs. Intravenous LE resolves symptoms of local anesthetic systemic toxicity, including convulsion, myoclonus, loss of consciousness, cardiac arrest, supraventricular tachycardia, and ventricular fibrillation. The main underlying mechanisms suggested to be responsible for LE-induced reversal of cardiac arrest due to drug toxicity are the lipid sink effect and the metabolic effect. The lipid sink theory posits that LE extracts a lipid-soluble toxic drug from the tissue. When a patient with cardiovascular collapse induced by a local anesthetic or another lipid-soluble drug is unresponsive to supportive treatments, including CPR and vasopressor therapy, LE administration can be considered. The suggested dosing regimen is as follows: 1) an initial intravenous bolus administration of 20% LE (1.5 mL/kg) is followed by a continuous infusion of 20% LE (0.25 mL/kg/min); and 2) when hemodynamic functions are unstable after the initial LE infusion, an intravenous administration of 20% LE (1.5 mL/kg) is repeated and followed by an increased continuous infusion of 20% LE (0.5 mL/kg/min). Further research is warranted regarding other possible mechanisms of LE's effect, the timing of LE administration, and the effect of various fatty acids on the LE-mediated reversal of cardiac arrest. This article reviews case reports and experimental evidence concerning the LE-mediated reversal of intractable cardiac arrest induced by drug toxicity, the underlying mechanism, and the dosing regimen.

Keyword

Lipid emulsion; Toxicity; Local anesthetics; Heart arrest

MeSH Terms

Administration, Intravenous
Anesthetics, Local*
Cardiopulmonary Resuscitation
Drug-Related Side Effects and Adverse Reactions
Fatty Acids
Heart Arrest
Hemodynamics
Humans
Myoclonus
Parenteral Nutrition
Seizures
Tachycardia, Supraventricular
Unconsciousness
Ventricular Fibrillation
Anesthetics, Local
Fatty Acids

Reference

1. Neal JM, Bernards CM, Butterworth JF 4th, Di Gregorio G, Drasner K, Hejtmanek MR, Mulroy MF, Rosenquist RW, Weinberg GL. ASRA practice advisory on local anesthetic systemic toxicity. Reg Anesth Pain Med. 2010; 35:152–161.

2. Mulroy MF. Systemic toxicity and cardiotoxicity from local anesthetics: incidence and preventive measures. Reg Anesth Pain Med. 2002; 27:556–561.

3. Weinberg G. Lipid rescue resuscitation from local anaesthetic cardiac toxicity. Toxicol Rev. 2006; 25:139–145.

4. Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology. 1998; 88:1071–1075.

5. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006; 105:217–218.

6. Ozcan MS, Weinberg G. Update on the use of lipid emulsions in local anesthetic systemic toxicity: a focus on differential efficacy and lipid emulsion as part of advanced cardiac life support. Int Anesthesiol Clin. 2011; 49:91–103.

7. Sirianni AJ, Osterhoudt KC, Calello DP, Muller AA, Waterhouse MR, Goodkin MB, Weinberg GL, Henretig FM. Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after overdose of bupropion and lamotrigine. Ann Emerg Med. 2008; 51:412–415.

8. Gil HW, Park JS, Park SH, Hong SY. Effect of intravenous lipid emulsion in patients with acute glyphosate intoxication. Clin Toxicol (Phila). 2013; 51:767–771.

9. Cho BN, Ryu S, Yoo IS, Ahn HJ, Kim GD, Kim H. Effect of intravenous fat emulsion on glyphosate surfactant herbicide-induced shock in a rat model: a preliminary study. J Korean Soc Emerg Med. 2013; 24:750–756.

10. Ozcan MS, Weinberg G. Intravenous lipid emulsion for the treatment of drug toxicity. J Intensive Care Med. 2014; 29:59–70.

11. Waring WS. Intravenous lipid administration for drug-induced toxicity: a critical review of the existing data. Expert Rev Clin Pharmacol. 2012; 5:437–444.

12. Mazoit JX, Le Guen R, Beloeil H, Benhamou D. Binding of long-lasting local anesthetics to lipid emulsions. Anesthesiology. 2009; 110:380–386.

13. Ruan W, French D, Wong A, Drasner K, Wu AH. A mixed (long- and medium-chain) triglyceride lipid emulsion extracts local anesthetic from human serum in vitro more effectively than a long-chain emulsion. Anesthesiology. 2012; 116:334–339.

14. Li Z, Xia Y, Dong X, Chen H, Xia F, Wang X, Dong H, Jin Z, Ding X, Papadimos TJ, Xu X. Lipid resuscitation of bupivacaine toxicity: long-chain triglyceride emulsion provides benefits over long- and medium-chain triglyceride emulsion. Anesthesiology. 2011; 115:1219–1228.

15. Ok SH, Park CS, Kim HJ, Lee SH, Choi BH, Eun SY, Kim KN, Yang SM, Shin IW, Choi MJ, Sohn JT. Effect of two lipid emulsions on reversing high-dose levobupivacaine-induced reduced vasoconstriction in the rat aortas. Cardiovasc Toxicol. 2013; 13:370–380.

16. Weinberg GL. Lipid emulsion infusion: resuscitation for local anesthetic and other drug overdose. Anesthesiology. 2012; 117:180–187.

17. Ok SH, Sohn JT, Baik JS, Kim JG, Park SS, Sung HJ, Shin MK, Kwon YH, Park CS, Shin IW, Lee HK, Chung YK. Lipid emulsion reverses Levobupivacaine-induced responses in isolated rat aortic vessels. Anesthesiology. 2011; 114:293–301.

18. Heavner JE. Local anesthetics. Curr Opin Anaesthesiol. 2007; 20:336–342.

19. Ok SH, Han JY, Lee SH, Shin IW, Lee HK, Chung YK, Choi MJ, Sohn JT. Lipid emulsion-mediated reversal of toxic-dose aminoamide local anesthetic-induced vasodilation in isolated rat aorta. Korean J Anesthesiol. 2013; 64:353–359.

20. Zausig YA, Zink W, Keil M, Sinner B, Barwing J, Wiese CH, Graf BM. Lipid emulsion improves recovery from bupivacaine-induced cardiac arrest, but not from ropivacaine- or mepivacaine-induced cardiac arrest. Anesth Analg. 2009; 109:1323–1326.

21. Pang DC, Sperelakis N. Uptake of calcium antagonistic drugs into muscles as related to their lipid solubilities. Biochem Pharmacol. 1984; 33:821–826.

22. Fettiplace MR, Ripper R, Lis K, Lin B, Lang J, Zider B, Wang J, Rubinstein I, Weinberg G. Rapid cardiotonic effects of lipid emulsion infusion. Crit Care Med. 2013; 41:e156–e162.

23. Weinberg GL, Palmer JW, VadeBoncouer TR, Zuechner MB, Edelman G, Hoppel CL. Bupivacaine inhibits acylcarnitine exchange in cardiac mitochondria. Anesthesiology. 2000; 92:523–528.

24. Partownavid P, Umar S, Li J, Rahman S, Eghbali M. Fatty-acid oxidation and calcium homeostasis are involved in the rescue of bupivacaine-induced cardiotoxicity by lipid emulsion in rats. Crit Care Med. 2012; 40:2431–2437.

25. Mottram AR, Valdivia CR, Makielski JC. Fatty acids antagonize bupivacaine-induced I(Na) blockade. Clin Toxicol (Phila). 2011; 49:729–733.

26. Weinberg GL. Treatment of local anesthetic systemic toxicity (LAST). Reg Anesth Pain Med. 2010; 35:188–193.

27. Hicks SD, Salcido DD, Logue ES, Suffoletto BP, Empey PE, Poloyac SM, Miller DR, Callaway CW, Menegazzi JJ. Lipid emulsion combined with epinephrine and vasopressin does not improve survival in a swine model of bupivacaine-induced cardiac arrest. Anesthesiology. 2009; 111:138–146.

28. Hiller DB, Gregorio GD, Ripper R, Kelly K, Massad M, Edelman L, Edelman G, Feinstein DL, Weinberg GL. Epinephrine impairs lipid resuscitation from bupivacaine overdose: a threshold effect. Anesthesiology. 2009; 111:498–505.

29. Leskiw U, Weinberg GL. Lipid resuscitation for local anesthetic toxicity: is it really lifesaving? Curr Opin Anaesthesiol. 2009; 22:667–671.

30. Marwick PC, Levin AI, Coetzee AR. Recurrence of cardiotoxicity after lipid rescue from bupivacaine-induced cardiac arrest. Anesth Analg. 2009; 108:1344–1346.