Document Type : Original Article

Authors

1 Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran

2 Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran

Abstract

Lidocaine toxicity is caused by unintended intravascular injection or overdose. Lidocaine is metabolized in the liver by the CYP3A4 isoenzyme. The objective was to investigate if the administration of rifampin could accelerate animal recovery and reduce the symptoms of lidocaine toxicity by induction of the CYP3A4. Thirty-six male rats were divided into control and treatment groups, each containing three subgroups. The treatment group received oral rifampin suspension daily for 1 week. In all rats, 2.00% lidocaine was injected intravenously. The first subgroup was monitored for neurological symptoms. In the second subgroup, data were recorded after the electrode was placed in the right hippocampus. Electrocardiograms were taken from the third subgroup. CYP3A4 was measured using an ELISA kit. Neurological recovery was seen after 22 and 15 min in the control and treatment groups, respectively. Rifampin also caused a significant reduction in amplitude and number of field action potentials compared to the control group. Numerous cardiac arrhythmias were observed in the control group. The mean level of CYP3A4 in the treatment group was significantly higher than in the control group. In conclusion, oral rifampin could increase the synthesis of CYP3A4, therefore, the animal recovery from lidocaine toxicity was accelerated.

Keywords

Main Subjects

  1. Rahimi M, Elmi M, Hassanian-Moghaddam H, et al. Acute lidocaine toxicity; a case series. Emerg (Tehran) 2018; 6(1): e38. PMCID: PMC6036540.
  2. Imani H, Vesal N, Mohammadi-Samani S. Evaluation of intravenous lidocaine overdose in chickens (Gallus domesticus). Iran J Vet Surg 2013; 8(1): 9-16.
  3. Menif K, Khaldi A, Bouziri A, et al. Lidocaine toxicity secondary to local anesthesia administered in the community for elective circumcision. Fetal Pediatr Pathol 2011; 30(6): 359-362.
  4. El-Boghdadly K, Chin KJ. Local anesthetic systemic toxicity: continuing professional development. Can J Anaesth 2016; 63(3): 330-349.
  5. Ok SH, Hong JM, Lee SH, et al. Lipid emulsion for treating local anesthetic systemic toxicity. Int J Med Sci 2018; 15(7): 713-722.
  6. Beaussier M, Delbos A, Maurice-Szamburski A, et al. Perioperative use of intravenous lidocaine. Drugs 2018; 78(12): 1229-1246.
  7. Bill TJ, Clayman MA, Morgan RF, et al. Lidocaine metabolism pathophysiology, drug interactions, and surgical implications. Aesthet Surg 2004; 24(4): 307-311.
  8. Botts S, Ennulat D, Francke-Carroll S, et al. Introduction to hepatic drug metabolizing enzyme induction in drug safety evaluation studies. Toxicol Pathol 2010; 38(5): 796-798.
  9. Wang Z, Lin YS, Dickmann LJ, et al. Enhancement of hepatic 4‐hydroxylation of 25‐hydroxyvitamin D3 through CYP3A4 induction in vitro and in vivo: implications for drug‐induced osteomalacia. J Bone Miner Res 2013; 28(5): 1101-1116.
  10. Boeree MJ, Diacon AH, Dawson R, et al. A dose-ranging trial to optimize the dose of rifampin in the treatment of tuberculosis. Am J Respir Crit Care Med 2015; 191(9): 1058-1065.
  11. Yuan X, Lu H, Zhao A, et al. Transcriptional regulation of CYP3A4 by nuclear receptors in human hepatocytes under hypoxia. Drug Metab Rev 2020; 52(2): 225-234.
  12. Yamashita F, Sasa Y, Yoshida S, et al. Modeling of rifampicin-induced CYP3A4 activation dynamics for the prediction of clinical drug-drug interactions from in vitro data. PloS One 2013; 8(9): e70330. doi: 10.1371/journal.pone.0070330.
  13. Imaoka T, Mikkaichi T, Abe K, et al. Integrated approach of in vivo and in vitro evaluation of the involvement of hepatic uptake organic anion transporters in the drug disposition in rats using rifampicin as an inhibitor. Drug Metab Dispos 2013; 41(7): 1442-1449.
  14. Nair G, Kim M, Nagaoka T, et al. Effects of common anesthetics on eye movement and electroretinogram. Doc Ophthalmol 2011; 122(3): 163-176.
  15. Panahi Y. Effect of ketamine on pentylenetrazole-induced experimental epileptiform activity in male rat [Persian]. Vet Res Biol Prod 2020; 33(1): 101-107.
  16. Rashan S, Panahi Y, Khalilzadeh E. Stimulatory and inhibitory effects of morphine on pentylenetetrazol-induced epileptic activity in rat. Int J Neurosci 2021; 131(9): 885-893.
  17. Aygun H, Basol N, Gul SS. Cardioprotective effect of paricalcitol on amitriptyline-induced cardiotoxicity in rats: comparison of [99m Tc] PYP cardiac scintigraphy with electrocardiographic and biochemical findings. Cardiovasc Toxicol 2020; 20(4): 427-436.
  18. Gomes LMRS, Czeczko NG, Araújo RLTM, et al. Effect of intra-articular dexmedetomidine on experimental osteoarthritis in rats. Plos One 2021; 16(1): e0245194. doi: 10.1371/journal.pone.0245194.
  19. Karasu D, Yılmaz C, Özgünay ŞE, et al. Knowledge of the research assistants regarding local anaesthetics and toxicity. Turk J Anaesthesiol Reanim 2016; 44(4): 201-205.
  20. Tierney KJ, Murano T, Natal B. Lidocaine-induced cardiac arrest in the emergency department: effectiveness of lipid therapy. J Emerg Med 2016; 50(1): 47-50.
  21. Ciechanowicz SJ, Patil VK. Intravenous lipid emulsion - rescued at LAST. Br Dent J 2012; 212(5): 237-241.
  22. Mehra P, Caiazzo A, Maloney P. Lidocaine toxicity. Anesth Prog 1998; 45(1): 38-41.
  23. Aburawi EH, Souid AK. Inhibition of murine cardiomyocyte respiration by amine local anesthetics. Eur J Drug Metab Pharmacokinet 2014; 39(4): 293-299.
  24. Abdullah S, Tokiran MF, Ahmad AA, et al. Safety of lidocaine during wide-awake local anesthesia no tourniquet for distal radius plating. J Hand Surg Glob Online 2023; 5(2): 196-200.
  25. Cheung HM, Lee SM, MacLeod BA, et al. A comparison of the systemic toxicity of lidocaine versus its quaternary derivative QX-314 in mice. Can J Anaesth 2011; 58(5): 443-450.
  26. Luo G, Cunningham M, Kim S, et al. CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug Metab Dispos 2002; 30(7): 795-804.
  27. Jha SC. To achieve target international normalized ratio with concurrent warfarin and rifampicin therapy is a challenge: A case report and review of literature. Int J Res Dermatol 2015; 1(1): 17-19.
  28. Lu C, Li AP. Species comparison in P450 induction: effects of dexamethasone, omeprazole, and rifampin on P450 isoforms 1A and 3A in primary cultured hepatocytes from man, Sprague–Dawley rat, minipig, and beagle dog. Chem Biol Interact 2001; 134(3): 271-281.
  29. Howard P, Twycross R, Grove G, et al. Rifampin (INN rifampicin). J Pain Symptom Manage 2015; 50(6): 891-895.