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Place des émulsions lipidiques intraveineuses en toxicologie

Lipid resuscitation in acute poisonning

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Médecine Intensive Réanimation

Résumé

Un intérêt croissant est porté à l’utilisation des émulsions lipidiques intraveineuses (ELI) en toxicologie clinique depuis une dizaine d’années. Leur administration est à ce jour recommandée uniquement en cas d’arrêt cardiorespiratoire secondaire à une intoxication à la bupivacaïne et en cas d’échec des mesures de réanimation standards pour tout autre toxique cardiotrope et lipophile. Plusieurs mécanismes d’action sont proposés : le piège-siphon lipidique, la modulation du métabolisme myocardique et une action propre hémodynamique; mais le mécanisme d’action réel reste à déterminer. Le schéma d’administration est empirique et de multiples questions restent en suspens. Cette revue refait le point sur le passé, le présent et le futur de l’utilisation thérapeutique des ELI, au vu des dernières publications et recommandations d’experts. Elle apporte des éléments de réflexion quant à l’utilisation pratique des ELI au quotidien. Le niveau de preuve reste très faible. Les ELI ne doivent pas être substituées aux autres moyens de réanimation mais sont une option thérapeutique complémentaire de sauvetage.

Abstract

There has been a growing interest in using intravenous lipid emulsions therapy (ELIs) in acute poisonings for the past decade. Present evidence supports use of ILEs only in local anesthetics-related systemic toxicity especially bupivacaïne and in lipophilic cardiotoxin intoxication when an immediate threat to life exists and other therapies have proven ineffective. Recent works have expanded our understanding of the mechanisms of action including both a dynamic scavenging component and a direct cardiotonic effect; however, its actual mechanism remains to be determined. The dosing regimen is arbitrary and many questions remain unsolved. Here, we discuss the past, present, and future of lipid resuscitation therapy with a focus on our understanding of the mechanisms and latest evidence-based recommendations. This review provides advices about the practical use of ELIs. Consistently, the level of evidence remains very low. ELIs should not be substituted to any other effective resuscitative treatment but be considered as additional rescue therapy.

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Références

  1. Hoegberg LC, Bania TC, Lavergne V, Bailey B, Turgeon AF, Thomas SH, Morris M, Miller-Nesbitt A, Mégarbane B, Magder S, Gosselin S, Lipid Emulsion Workgroup, (2016) Systematic review of the effect of intravenous lipid emulsion therapy for local anesthetic toxicity. Clin Toxicol 54: 167–193

    Article  CAS  Google Scholar 

  2. Gosselin S, Hoegberg LC, Hoffman RS, Graudins A, Stork CM, Thomas SH, Stellpflug SJ, Hayes BD, Levine M, Morris M, Nesbitt-Miller A, Turgeon AF, Bailey B, Calello DP, Chuang R, Bania TC, Mégarbane B, Bhalla A, Lavergne V, (2016) Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning. Clin Toxicol 54: 899–923

    Article  CAS  Google Scholar 

  3. Mowry JB, Spyker DA, Brooks DE, Zimmerman A, Schauben JL, (2016) 2015 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 33rd Annual Report. Clin Toxicol 54: 924–1109

    Article  CAS  Google Scholar 

  4. Russel RL, Westfall BA (1962) Alleviation of barbiturate depression. Anesth Analg 41: 582–585

    Google Scholar 

  5. Shinaberger JH, Shear L, Clayton LE, Barry KG, Knowlton M, (1965) Dialysis for intoxication with lipid soluble drugs: enhancement of glutethimide extrcation with lipid dialysate. Trans Am Soc Artif Intern Organs 11: 173–177

    Article  CAS  PubMed  Google Scholar 

  6. Krieglstein J, Meffert A, Niemeyer DH, (1974) Influence of emulsified fat on chlorpromazine availability in rabbit blood. Experientia 30: 924–926

    Article  CAS  PubMed  Google Scholar 

  7. Clarke L (1974) Dialysis of drugs in vitro. Br J Clin Pharmacol 1: 442–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  10. Sirianni AJ, Osterhoudt KC, Calello DP, Muller AA, Waterhouse MR, Goodkin MB, Weinberg GL, Henretig FM, (2008) Use of Lipid Emulsion in the Resuscitation of a Patient With Prolonged Cardiovascular Collapse After Overdose of Bupropion and Lamotrigine. Ann Emerg Med 51: 412–415.e1

    Article  PubMed  Google Scholar 

  11. Cave G, Harvey MG, (2014) Should we consider the infusion of lipid emulsion in the resuscitation of poisoned patients? Crit Care 18: 457

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  13. Harvey M, Cave G, (2014) Lipid rescue: does the sink hold water? And other controversies. Br J Anaesth 112: 622–625

    Article  CAS  PubMed  Google Scholar 

  14. Weinberg GL, (2012) Lipid Emulsion Infusion. Anesthesiology 117: 180–187

    Article  PubMed  PubMed Central  Google Scholar 

  15. Leroux JC, (2007) Injectable nanocarriers for biodetoxification. Nat Nanotechnol 2: 679–684

    Article  CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  17. Laine J, Lokajová J, Parshintsev J, Holopainen JM, Wiedmer SK, (2010) Interaction of a commercial lipid dispersion and local anesthetics in human plasma: implications for drug trap** by “lipid-sinks”. Anal Bioanal Chem 396: 2599–2607

    Article  CAS  PubMed  Google Scholar 

  18. Weinberg G, Lin B, Zheng S, Di Gregorio G, Hiller D, Ripper R, Edelman L, Kelly K, Feinstein D, (2010) Partitioning effect in lipid resuscitation: further evidence for the lipid sink. Crit Care Med 38: 2268–2269

    Article  PubMed  Google Scholar 

  19. Weinberg GL, Ripper R, Murphy P, Edelman LB, Hoffman W, Strichartz G, Feinstein DL, (2006) Lipid infusion accelerates removal of bupivacaine and recovery from bupivacaine toxicity in the isolated rat heart. Reg Anesth Pain Med 31: 296–303

    Article  CAS  PubMed  Google Scholar 

  20. Niiya T, Litonius E, Petäjä L, Neuvonen PJ, Rosenberg PH, (2010) Intravenous lipid emulsion sequesters amiodarone in plasma and eliminates its hypotensive action in pigs. Ann Emerg Med 56: 402–408.e2

    Article  PubMed  Google Scholar 

  21. Heinonen JA, Litonius E, Backman JT, Neuvonen PJ, Rosenberg PH, (2013) Intravenous Lipid Emulsion Entraps Amitriptyline into Plasma and Can Lower its Brain Concentration-An Experimental Intoxication Study in Pigs. Basic Clin Pharmacol Toxicol 113: 193–200

    Article  CAS  PubMed  Google Scholar 

  22. French D, Smollin C, Ruan W, Wong A, Drasner K, Wu AH, (2011) Partition constant and volume of distribution as predictors of clinical efficacy of lipid rescue for toxicological emergencies. Clin Toxicol 49: 801–809

    Article  CAS  Google Scholar 

  23. Kuo I, Akpa BS, (2013) Validity of the Lipid Sink as a Mechanism for the Reversal of Local Anesthetic Systemic Toxicity. Anesthesiology 118: 1350–1361

    Article  CAS  PubMed  Google Scholar 

  24. Fettiplace MR, Lis K, Ripper R, Kowal K, Pichurko A, Vitello D, Rubinstein I, Schwartz D, Akpa BS, Weinberg G, (2015) Multimodal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion. J Control Release 198: 62–70

    Article  CAS  PubMed  Google Scholar 

  25. Heinonen JA, Litonius E, Backman JT, Neuvonen PJ, Rosenberg PH, (2013) Intravenous lipid emulsion entraps amitriptyline into plasma and can lower its brain concentration—an experimental intoxication study in pigs. Basic Clin Pharmacol Toxicol 113: 193–200

    Article  CAS  PubMed  Google Scholar 

  26. French D, Armenian P, Ruan W, Wong A, Drasner K, Olson KR, Wu AH, (2011) Serum verapamil concentrations before and after Intralipid® therapy during treatment of an overdose. Clin Toxicol 49: 340–344

    Article  CAS  Google Scholar 

  27. Harvey M, Cave G, (2012) Case report: successful lipid resuscitation in multi-drug overdose with predominant tricyclic antidepressant toxidrome. Int J Emerg Med 5: 8

    Article  PubMed  PubMed Central  Google Scholar 

  28. Shi K, **a Y, Wang Q, Wu Y, Dong X, Chen C, Tang W, Zhang Y, Luo M, Wang X, Papadimos TJ, Xu X, (2013) The effect of lipid emulsion on pharmacokinetics and tissue distribution of bupivacaine in rats. Anesth Analg 116: 804–809

    Article  CAS  PubMed  Google Scholar 

  29. Perichon D, Turfus S, Gerostamoulos D, Graudins A, (2013) An assessment of the in vivo effects of intravenous lipid emulsion on blood drug concentration and haemodynamics following orogastric amitriptyline overdose. Clin Toxicol 51: 208–215

    Article  CAS  Google Scholar 

  30. Harvey M, Cave G, Shaw T, (2013) Effect of intravenous lipid emulsion and octreotide on enteric thiopentone absorption; a pilot study. Clin Toxicol 51: 117–118

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  32. Stehr SN, Ziegeler JC, Pexa A, Oertel R, Deussen A, Koch T, Hübler M, (2007) The effects of lipid infusion on myocardial function and bioenergetics in l-bupivacaine toxicity in the isolated rat heart. Anesth Analg 104: 186–192

    Article  CAS  PubMed  Google Scholar 

  33. Li J, Fettiplace M, Chen SJ, Steinhorn B, Shao Z, Zhu X, Li C, Harty S,Weinberg G, Van den Hoek TL, (2014) Lipid emulsion rapidly restores contractility in stunned mouse cardiomyocytes: a comparison with therapeutic hypothermia. Crit Care Med 42: e734–40

    Article  CAS  Google Scholar 

  34. Lou PH, Lucchinetti E, Zhang L, Affolter A, Schaub MC, Gandhi M, Hersberger M, Warren BE, Lemieux H, Sobhi HF, Clanachan AS, Zaugg M, (2014) The mechanism of Intralipid®-mediated cardioprotection complex IV inhibition by the active metabolite, palmitoylcarnitine, generates reactive oxygen species and activates reperfusion injury salvage kinases. PLoS One 9: e87205

    Article  Google Scholar 

  35. Fettiplace MR, Akpa BS, Ripper R, Zider B, Lang J, Rubinstein I, Weinberg G, (2014) Resuscitation with lipid emulsion: dosedependent recovery from cardiac pharmacotoxicity requires a cardiotonic effect. Anesthesiology 120: 915–925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Fettiplace MR, Ripper R, Lis K, Lin B, Lang J, Zider B, Wang J, Rubinstein I, Weinberg G, (2013) Rapid cardiotonic effects of lipid emulsion infusion. Crit Care Med 41: e156–62

    Article  PubMed  Google Scholar 

  37. Wagner M, Zausig YA, Ruf S, Rudakova E, Gruber M, Graf BM, Volk T, (2014) Lipid rescue reverses the bupivacaine-induced block of the fast Na+ current (INa) in cardiomyocytes of the rat left ventricle. Anesthesiology 120: 724–736

    Article  CAS  PubMed  Google Scholar 

  38. Gueret G, Pennec JP, Arvieux CC, (2007) Hemodynamic effects of intralipid after verapamil intoxication may be due to a direct effect of fatty acids on myocardial calcium channels. Acad Emerg Med 14: 761

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  40. Hoegberg LC, Bania TC, Lavergne V, Bailey B, Turgeon AF, Thomas SH, Morris M, Miller-Nesbitt A, Mégarbane B, Magder S, Gosselin S; Lipid Emulsion Workgroup, (2016) Systematic review of the effect of intravenous lipid emulsion therapy for local anesthetic toxicity. Clin Toxicol 54: 167–193

    Article  CAS  Google Scholar 

  41. Levine M, Hoffman RS, Lavergne V, Stork CM, Graudins A, Chuang R, Stellpflug SJ, Morris M, Miller-Nesbitt A, Gosselin S; Lipid Emulsion Workgroup, (2016) Systematic review of the effect of intravenous lipid emulsion therapy for non-local anesthetics toxicity. Clin Toxicol 54: 194–221

    Article  CAS  Google Scholar 

  42. Gosselin S, Morris M, Miller-Nesbitt A, Hoffman RS, Hayes BD, Turgeon AF, Gilfix BM, Grunbaum AM, Bania TC, Thomas SH, Morais JA, Graudins A, Bailey B, Mégarbane B, Calello DP, Levine M, Stellpflug SJ, Hoegberg LC, Chuang R, Stork C, Bhalla A, Rollins CJ, Lavergne V; AACT Lipid Emulsion Therapy workgroup, (2015) Methodology for AACT evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning. Clin Toxicol 53: 557–564

    Article  CAS  Google Scholar 

  43. Taftachi F, Sanaei-Zadeh H, Sepehrian B, Zamani N, (2012) Lipid emulsion improves Glasgow coma scale and decreases blood glucose level in the setting of acute non-local anesthetic drug poisoning—a randomized controlled trial. Eur Rev Med Pharmacol Sci 16 Suppl 1: 38–42

    PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  45. Ludot H, Tharin JY, Belouadah M, Mazoit JX, Malinovsky JM, (2008) Successful Resuscitation After Ropivacaine and Lidocaine-Induced Ventricular Arrhythmia Following Posterior Lumbar Plexus Block in a Child. Anesth Analg 106: 1572–1574

    Article  CAS  PubMed  Google Scholar 

  46. Mazoit JX, Le Guen R, Beloeil H, Benhamou D, (2009) Binding of Long-lasting Local Anesthetics to Lipid Emulsions. Anesthesiology 110: 380–386

    PubMed  Google Scholar 

  47. Fettiplace MR, Akpa BS, Rubinstein I, Weinberg G, (2015) Confusion About Infusion: Rational Volume Limits for Intravenous Lipid Emulsion During Treatment of Oral Overdoses. Ann Emerg Med 66: 185–188

    Article  PubMed  Google Scholar 

  48. Perez E, Bania TC, Medlej K, Chu J, (2008) Determining the optimal dose of intravenous fat emulsion for the treatment of severe verapamil toxicity in a rodent model. Acad Emerg Med 15: 1284–1289

    Article  PubMed  Google Scholar 

  49. Gosselin S, Hoegberg LC, Hoffman RS, Graudins A, Stork CM, Thomas SH, Stellpflug SJ, Hayes BD, Levine M, Morris M, Nesbitt-Miller A, Turgeon AF, Bailey B, Calello DP, Chuang R, Bania TC, Mégarbane B, Bhalla A, Lavergne V, (2016) Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning. Clin Toxicol 54: 899–923

    Article  CAS  Google Scholar 

  50. American College of Medical Toxicology, (2017) ACMT Position Statement: Guidance for the Use of Intravenous Lipid Emulsion. J Med Toxico l13: 124–125

    Article  Google Scholar 

  51. Salmela L, Washington C, (2014) A continuous flow method for estimation of drug release rates from emulsion formulations. Int J Pharm 472: 276–281

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  53. Benhamou D, Mazoit JX, Zetlaoui P, (2010) [Early administration of lipid rescue after initial signs of local anesthetic-induced systemic toxicity]. Ann Fr Anesth Reanim 29: 826

    Article  CAS  PubMed  Google Scholar 

  54. Hayes BD, Gosselin S, Calello DP, Nacca N, Rollins CJ, Abourbih D, Morris M, Nesbitt-Miller A, Morais JA, Lavergne V; Lipid Emulsion Workgroup, (2016) Systematic review of clinical adverse events reported after acute intravenous lipid emulsion administration. Clin Toxicol 54: 365–404

    Article  CAS  Google Scholar 

  55. Grunbaum AM, Gilfix BM, Hoffman RS, Lavergne V, Morris M, Miller-Nesbitt A, Gosselin S, (2016) Review of the effect of intravenous lipid emulsion on laboratory analyses. Clin Toxicol 54: 92–102

    Article  CAS  Google Scholar 

  56. Forster V, Leroux JC, (2015) Nano-antidotes for drug overdose and poisoning. Sci Transl Med 7: 290ps14

    Article  PubMed  Google Scholar 

  57. Muhammad F, Nguyen TD, Raza A, Akhtar B, Aryal S, (2017) A review on nanoparticle-based technologies for biodetoxification. Drug Chem Toxicol 40: 489–497

    Article  CAS  PubMed  Google Scholar 

  58. Rahman YE, Rosenthal MW, Cerny EA, (1973) Intracellular plutonium: removal by liposome-encapsulated chelating agent. Science 180: 300–302

    Article  CAS  PubMed  Google Scholar 

  59. Allen TM, Cullis PR, (2013) Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 65: 36–48

    Article  CAS  PubMed  Google Scholar 

  60. Forster V, Luciani P, Leroux JC, (2012) Treatment of calcium channel blocker-induced cardiovascular toxicity with drug scavenging liposomes. Biomaterials 33: 3578–3585

    Article  CAS  PubMed  Google Scholar 

  61. Forster V, Signorell RD, Roveri M, Leroux JC, (2014) Liposomesupported peritoneal dialysis for detoxification of drugs and endogenous metabolites. Sci Transl Med 6: 258ra141

    Article  Google Scholar 

  62. Szilasi M, Budai M, Budai L, Petrikovics I, (2012) Nanoencapsulated and microencapsulated enzymes in drug antidotal therapy. Toxicol Ind Health 28: 522–531

    Article  CAS  PubMed  Google Scholar 

  63. Buys M, Scheepers PA, Levin AI, (2015) Lipid emulsion therapy: non-nutritive uses of lipid emulsions in anaesthesia and intensive care. South Afr J Anaesth Analg 21: 124–130

    Google Scholar 

  64. Corriol O, (2007) Nutrition parentérale: produits. In: Traité de nutrition artificielle de l’adulte. Springer, Paris, p. 625–634

    Google Scholar 

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  1. Réanimation médicale et toxicologique, hôpital Lariboisière, INSERM UMRS1144, université Paris-Diderot, 2 rue Ambroise Paré, F-75475, Paris, France

    K. Jaffal, L. Chevillard & B. Megarbane

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  1. K. Jaffal
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  2. L. Chevillard
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  3. B. Megarbane
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Correspondence to B. Megarbane.

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Jaffal, K., Chevillard, L. & Megarbane, B. Place des émulsions lipidiques intraveineuses en toxicologie. Méd. Intensive Réa 26, 373–382 (2017). https://doi.org/10.1007/s13546-017-1299-3

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