Introduction: Verapamil is a drug that is used often due to its wide spectrum of action. Many authors consider it to be the most dangerous of the calcium channel blockers due to its negative chronotropic and inotropic effect on the heart, leading to severe cardiodepression. Overdose is difficult to treat and is associated with high mortality despite existing treatment options.
Over the last 15 years, lipid emulsions (LEs) have been increasingly used for resuscitation after overdosing with lipophilic drugs such as verapamil. Despite the convincing results and the improved patient status, the association of the administration of LE with the recovery of patients may be questioned since LE was given in addition to standard therapy.
Aim: The aim of this article is to conduct an evaluation of the self-cardioprotective effect of LE in acute verapamil overdose (15 mg/kg) in rats by measurement of the heart rate and survival at the recommended LE dose of 1.5 mL/kg and 7 times the recommended LE dose (10 mL/kg).
Material and Methods: The experiment was performed on 30 male Wistar rats, provided by the Medical University of Varna. Instrumental methods included monitoring the heart rate of rats using an electrocardiographic monitor. The statistical analysis was performed using the statistical functions in Excel 2016 and Statistica 7.0.
Results: A survival rate of 100% was observed in rats pretreated and treated with low and high LE dose. The high LE dose (10 mL/kg) showed a faster improvement in cardiac function as the highest mean heart rates were established.
Conclusion: Pretreatment and resuscitation with low or high LE dose reduce toxicity and prevent dose-dependent asystole induced by verapamil. The administration of a high LE dose (10 mL/kg) proved to be more effective in terms of heart rate in rats.
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(4):1071-5. doi: 10.1097/00000542-199804000-00028.
Weinberg GL. Treatment of local anesthetic systemic toxicity (LAST). Reg Anesth Pain Med. 2010;35(2):188-93. doi: 10.1097/AAP.0b013e3181d246c3.
Perez E, Bania TC, Medlej K, Chu J. Determining the optimal dose of intravenous fat emulsion for the treatment of severe verapamil toxicity in a rodent model. Acad Emerg Med. 2008;15(12):1284-9. doi: 10.1111/j.1553-2712.2008.00259.x.
Olson KR. What is the best treatment for acute calcium channel blocker overdose? Ann Emerg Med. 2013 Sep;62(3):259-61. doi: 10.1016/j.annemergmed.2013.03.026. Epub 2013 Apr 6. PMID: 23567061.
Walter E, McKinlay J, Corbett J, Kirk-Bayley J. Review of management in cardiotoxic overdose and efficacy of delayed intralipid use. J Intensive Care Soc. 2017;19(1):50-5. doi: 10.1177/1751143717705802.
Hasnain M, Vieweg WV. QTc interval prolongation and torsade de pointes associated with second-generation antipsychotics and antidepressants: a comprehensive review. CNS Drugs. 2014;28(10):887-920. doi: 10.1007/s40263-014-0196-9.
Oh SW, Kim J, Myung SK, Hwang SS, Yoon DH. Antidepressant use and risk of coronary heart disease: meta-analysis of observational studies. Br J Clin Pharmacol. 2014;78(4):727–37. doi:10.1111/bcp.12383.
Gul F, Duman NC, Arslantas MK, Haliloglu M, Cinel I, Gören MZ. The effect of low dose sildenafil on verapamil - induced cardiovascular toxicity in rats. Intensive Care Med Exp. 2015;3(Suppl 1):A500. doi: 10.1186/2197-425X-3-S1-A500.
Heizmann P, Eckert M, Ziegler WH. Pharmacokinetics and bioavailability of midazolam in man. Br J Clin Pharmacol. 1983;16 Suppl 1(Suppl 1):43S-9S. doi: 10.1111/j.1365-2125.1983.tb02270.x.
Neal JM, Mulroy MF, Weinberg GL; American Society of Regional Anesthesia and Pain Medicine. American Society of Regional Anesthesia and Pain Medicine checklist for managing local anesthetic systemic toxicity: 2012 version. Reg Anesth Pain Med. 2012;37(1):16-8. doi: 10.1097/AAP.0b013e31822e0d8a.
Rothschild L, Bern S, Oswald S, Weinberg G. Intravenous lipid emulsion in clinical toxicology. Scand J Trauma Resusc Emerg Med. 2010;18(1):51. doi: 10.1186/1757-7241-18-51.
Weinberg G, Ripper R, Feinstein DL, Hoffman W. Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med. 2003;28(3):198-202. doi: 10.1053/rapm.2003.50041.
Moshiri M, Mohammadpour AH, Vahabzadeh M, Etemad L, Memar B, Hosseinzadeh H. Evaluating the effects and safety of intravenous lipid emulsion on haloperidol-induced neurotoxicity in rabbit. Biomed Res Int. 2014;2014:949262. doi: 10.1155/2014/949262.
Harvey MG, Cave GR. Intralipid infusion ameliorates propranolol-induced hypotension in rabbits. J Med Toxicol. 2008;4(2):71-6. doi: 10.1007/BF03160958.
Nishimura T, Maruguchi H, Nakao A, Nakayama S. Unusual complications from amitriptyline intoxication. BMJ Case Rep. 2017;2017:bcr2017219257. doi: 10.1136/bcr-2017-219257 .
Cave G, Harvey MG, Castle CD. The role of fat emulsion therapy in a rodent model of propranolol toxicity: a preliminary study. J Med Toxicol. 2006;2(1):4-7. doi: 10.1007/BF03161005.