1. Home
  2. JACCOA
  3. From bupivacaine to intralipid leading edge
Submit manuscript...
Journal of
eISSN: 2373-6437

Anesthesia & Critical Care: Open Access

Review Article Volume 4 Issue 6

From Bupivacaine to Intralipid: Leading Edge

Negar Motayagheni

Department of Anesthesiology, Division of Molecular Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine at University of California, USA

Correspondence: Negar Motayagheni, Department of Anesthesiology, Division of Molecular Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine at University of California, Los Angeles, USA, Tel 17164401247

Received: April 13, 2016 | Published: May 2, 2016

Citation: Motayagheni N (2016) From Bupivacaine to Intralipid: Leading Edge. J Anesth Crit Care Open Access 4(6): 00164. DOI: 10.15406/jaccoa.2016.04.00164

Download PDF

Abstract

Recent ILT success stories led to many experiments to find out intralipid mechanism of action. Intralipid as a Lipid-Emulsion not only has been introduced as an effective treatment for LA toxicities but also has shown its effectiveness in reversal of other toxicities as well. Although the story of intralipid started with Bupivacaine but it is going to be a safe treatment option.

Keywords: intralipid, local anesthetic, bupivacaine, cardiotoxicity, resuscitation, cardiac arrest, lipid emulsion

Introduction

Intravenous lipid emulsion therapy was introduced as a treatment for local anesthetic toxicity it has shown couple of reversing and therapeutic efficacies for a number of different drug toxicities. In recent papers many different applications of Intralipid or oil containing products-Lipid Emulsion-have successfully experimented in critical care patients. In 1998 Dr. Weinberg began working on the effects of local anesthetics and discovered that an infusion of lipid emulsion not only protect against but also correct local anesthetic cardiac toxicity. The first case report of successful Lipid Rescue was published in 2006. Reportedly lipid infusion was successful in reversing neurological signs of toxicity from local anesthetics. With appearing more evidences for intralipid different applications there is a hope that many types of drug-induced CNS or cardiac toxicities could be treated by Lipid Rescue effect as a safe treatment option. Since identification of lipid resuscitation therapy in 1998 as a treatment for LA toxicity by Weinberg,1 many studies and experiments have been performed in order to explore more the mechanism of this novel treatment. Intralipid has been used as a source of energy and essential fatty acids for parenteral nutrition. Intralipid is an emulsion of soy bean oil, egg phospholipids and glycerin, and is available in 10%, 20% and 30% concentrations. The 30% concentration has not been approved for direct intravenous infusion. Intralipid and other balanced lipid emulsions provide essential fatty acids. In this review some of the novel applications of Intralipid have introduced.

Local anesthetics /cardioprotection

Intralipid was introduced by Dr. Weinberg as an effective treatment for reversing cardiotoxicity due to local anesthetics.1 Although Lipid Sink theory was the primary theory for mechanism of action but couple of different theories have come to the table to discuss (Figure 1). They showed that Lipid treatment accelerates recovery from Bupivacaine-induced asystole in the isolated rat heart, reduces Bupivacaine content, and increases cardiac Bupivacaine washout.2 Rat and dog studies showed that lipid emulsions could be used in establishing normal sinus rhythm and maintaining oxygenation after Bupivacaine-induced arrest.3 Intralipid was used successfully to treat the refractory hypotension following epidural anaesthesia.4 Lou et al.,5 evaluated the Mechanism of Intralipid-Mediated Cardioprotection and concluded that active metabolite, Palmitoylcarnitine, Generates Reactive Oxygen Species (ROS) and Activates Reperfusion Injury Salvage Kinases. They suggested ROS as active cardioprotective metabolite of Intralipid.5

Figure 1 A hypothetical mechanism of actions for Lipid emulsion. The upper figure shows unknown probable Intracellular effects of Lipid emulsion. The adjacent blood vessel highlights scavenging effect and Lipid Sink theory which removes Bupivacaine/Toxic agents through Lipid emulsion. The lower part of the figure shows accelerated-Shuttel Effect term used by Dr. Weinberg- redistribution and metabolism of Lipid emulsion-Bupivacaine/toxic agent complex to the liver.

Eghbali group demonstrated that post-ischemic treatment with Intralipid prevents the opening of mitochondrial permeability transition pore and protects the heart through glycogen synthase kinase-3 β.6 In another experiment they concluded that ILP not only prevents the development of PAH and RV failure but also rescues preexisting severe PAH.7 They also showed that Intralipid is effective in reducing the infarct size and improving the cardiac functional recovery.8

Toxicities

Interestingly Intralipid has been successful in reversing other toxicities as well.9–12 Herring reported successful treatment of Naproxen overdose in dogs with Lipid emulsion.13 Rodríguez et al.,14 used Lipid emulsion successfully in a 26 year old male who had hypotension and bradycardia because of medication overdose (Amlodipin, Metoprolol, Lisinopril) and was unresponsive to treatment with saline, calcium, glucagon, and vasopressors. In this patient, Intralipid prevented renal replacement therapy correcting both metabolic abnormalities and volume overload.14 Matsumoto et al.,10 reported successful treatment of a commatos 24 year old woman due to overdose of chlorpromazineand mirtazapine with combination of intralipid with adrenalin.10 According to Mc Beth case report severe hemodynamic instability resulting from myocardial irritability in a Female with overdose of Hydroxychloroquinetoxity was treated by intralipid and hemodialysis use.15

In a recent study Weinberg group reported successful treatment of cocaine induced cardiotoxicity. They showed Lipid emulsion can delay progression of cocaine cardiac toxicity both invivo and isolated hearts perfused in langendorff system in rats.16 Intralipid has also been successful in treating pesticides intoxications.17,18 Put together Intralipid or lipid emulsion has shown strong “soap like effect” in removing different toxicities.

Liver

Zheng et al.,19 suggested that Intralipid could decrease hepatic ApoM levels. They showed rats receiving Intralipidhad increased FFAs and decreased glucose infusion rates and ApoM gene expression.19 Xiao group showed Infusion of Intralipid, unlike saline, did not affect plasma glucose concentration or EGP. They concluded there are important interspecies differences between humans and rodents with respect to the gut-brain-liver axis.20 Stephens showed that Lipid infusion reduced whole-body glucose disposal by 20% and the muscle fractional synthetic rate increased during saline infusion, although no change occurred during lipid infusion in this regard. They suggested increased muscle availability may contribute to anabolic resistance in insulin-resistant conditions by damaging translation initiation. In another study during hyper insulinemia without lipid, glucose infusion rate (GIR) was lowest. Lipid infusion reduced GIR in all subjects. But in lipid group, fat oxidation was higher with lipid oversupply. They concluded enhanced mitochondrial performance with exercise is related to better metabolic flexibility and insulin sensitivity when faced with lipid overload.21

Immune system

Sanches evaluated the effects of increasing the energy availability from dextrose and lipid treatments on the pro-inflammatory response to LPS in steers. Their experiment Showed increased circulating non-esterified fatty acids with a lipid emulsion modulates the pro-inflammatory response in steers.22

Anti cancer drugs

In a recent study Intralipid decreased Platinum-Containing Anti-Cancer Nanodrugs (Pt) accumulation in the liver, spleen, and kidney through reducing reticuloendothelial system (RES) uptake and increased the bioavailability of the nanodrug.23

Obstetrics-gynecology

Meng Lili. evaluated effectiveness and potential mechanisms of Intralipid in treating unexplained recurrent spontaneous abortion. They suggested Intralipid as an alternative to IVIG.24

Conclusion

Although fat emulsion have been used in patient care for several decades, as a source of calories, it has shown an important rescuing effect in many toxicities as well as Bupivacaine cardiotoxicity. Several experiments is still necessary to elucidate the underlying mechanism of action and consequent novel applications.

Acknowledgments

Thanks to Sheshanna Phan for her help.

Conflicts of interest

Author declare that there is no conflict of interest.

Funding

None.

References

  1. Weinberg GL, VadeBoncouer T, Ramaraju GA, et al. Pre treatment or resuscitation with a lipid infusion shifts the dose–response to bupivacaine–induced asystole in rats. Anesthesiology. 1998;88(4):1071–1075.
  2. Weinberg G. Lipid Rescue Resuscitation from Local Anaesthetic Cardiac Toxicity. Toxicol Rev. 2006;25(3):139–145.
  3. Corman SL, Skledar SJ. Use of lipid emulsion to reverse local anesthetic–induced toxicity. Ann Pharmacother. 2007;41(11):1873–1877.
  4. Tsui BC, Cheung SS, Ziwenga O, et al. Use of Intralipid® in managing refractory hypotension following epidural blockade. Can J Anaesth. 2014;62(5):548–549.
  5. Lou PH, Lucchinetti E, Zhang L, et al. The mechanism of Intralipid(R)–mediated cardioprotection complex IV inhibition by the active metabolite, palmitoylcarnitine, generates reactive oxygen species and activates reperfusion injury salvage kinases. PLoS One. 2014;9(1):e87205.
  6. Rahman S, Li J, Bopassa JC, Umar S, et al. Phosphorylation of GSK–3ß mediates intralipid–induced cardioprotection against ischemia/reperfusion injury. Anesthesiology. 2011;115(2):242–253.
  7. Umar S, Nadadur RD, Li J, Maltese F, et al. Intralipid prevents and rescues fatal pulmonary arterial hypertension and right ventricular failure in rats. Hypertension. 2011;58(3):512–518.
  8. Li J, Iorga A, Sharma S, Youn JY, et al. Intralipid, a clinically safe compound, protects the heart against ischemia–reperfusion injury more efficiently than cyclosporine–A. Anesthesiology. 2012;117(4):836–846.
  9. Eren Cevik S, Tasyurek T, Guneysel O. Intralipid emulsion treatment as an antidote in lipophilic drug intoxications. Am J Emerg Med. 2014;32(9):1103–1108.
  10. Matsumoto H, Ohnishi M, Takegawa R, et al. Effect of lipid emulsion during resuscitation of a patient with cardiac arrest after overdose of chlorpromazine and mirtazapine. Am J Emerg Med. 2015;33(10):1541.
  11. Muller SH, Diaz JH, Kaye AD. Clinical applications of intravenous lipid emulsion therapy. J Anesth. 2015;29(6):920–926.
  12. Musielak M, McCall J. Lipid Rescue in a Pediatric Burn Patient. J Burn Care Res. 2015.
  13. Herring JM, McMichael MA, Corsi R, et al. Intravenous lipid emulsion therapy in three cases of canine naproxen overdose. J Vet Emerg Crit Care (San Antonio). 2015;25(5):672–678.
  14. Rodriguez B, Wilhelm A, Kokko KE. Lipid emulsion use precluding renal replacement therapy. J Emerg Med. 2014;47(6):635–637.
  15. McBeth PB, Missirlis PI, Brar H, et al. Novel Therapies for Myocardial Irritability following Extreme Hydroxychloroquine Toxicity. Case Rep Emerg Med. 2015;692948.
  16. Fettiplace MR, Pichurko A, Ripper R, et al. Cardiac depression induced by cocaine or cocaethylene is alleviated by lipid emulsion more effectively than by sulfobutylether–β–cyclodextrin. Acad Emerg Med. 2015;22(5):508–517.
  17. Basarslan SK, Alp H, Senol S, et al. Is intralipid fat emulsion a promising therapeutic strategy on neurotoxicity induced by malathion in rats? Eur Rev Med Pharmacol Sci. 2014;18(4):471–476.
  18. Celik MM, Alp A, Dokuyucu R, et al. Protective Effects of Intralipid and Caffeic Acid Phenethyl Ester on Nephrotoxicity Caused by Dichlorvos in Rats. J Anal Methods Chem. 2015;2015:491406.
  19. Zheng L, Feng Y, Shi Y, Zhang J, et al. Intralipid decreases apolipoprotein M levels and insulin sensitivity in rats. PLoS One. 2014;9(8):e105681.
  20. Xiao C, Dash S, Morgantini C, et al. Evaluation of the Effect of Enteral Lipid Sensing on Endogenous Glucose Production in Humans. Diabetes. 2015;64(8):2939–2943.
  21. Stephens FB, Chee C, Wall BT, et al. Lipid–induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men. Diabetes. 2015;64(5):1615–1620.
  22. Sanchez NC, Carroll JA, Donaldson JR, et al. Exogenous administration of lipids to steers alters aspects of the innate immune response to endotoxin challenge. Innate Immun. 2015;21(5):512–522.
  23. Liu L, Ye Q, Lu M, et al. A new approach to reduce toxicities and to improve bioavailabilities of platinum–containing anti–cancer nanodrugs. Sci Rep. 2015;5:10881.
  24. Meng L, Lin J, Chen L, et al. Effectiveness and potential mechanisms of intralipid in treating unexplained recurrent spontaneous abortion. Arch Gynecol Obstet. 2015;2015:1–11.
Creative Commons Attribution License

©2016 Motayagheni. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.

Citations

Journal Menu

Useful Links