Skip to main content

Advertisement

Log in

Effects of opioid receptor agonist and antagonist medications on electrocardiogram changes and presentation of cardiac arrhythmia: review article

  • Reviews
  • Published:
Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

Abstract

Background/Purpose

Mortality associated with prescription opioids has significantly increased over the past few decades and is considered a global pandemic. Prescribed opioids can cause cardiac arrhythmias, leading to fatal outcomes and unexpected death, even in the absence of structural cardiac disease. Despite the extent of cardiac toxicity and death associated with these medications, there is limited data to suggest their influences on cardiac electrophysiology and arrhythmias, with the exception of methadone. The goal of our review is to describe the possible mechanisms and to review the different ECG changes and arrhythmias that have been reported.

Methods

A literature search was performed using Google Scholar, PubMed, Springer, Ovid, and Science Direct to identify studies that demonstrated the use of prescription opioids leading to electrocardiogram (ECG) changes and cardiac arrhythmias.

Results

Many of the commonly prescribed opioid medications can uniquely effect the ECG, and can lead to the development of various cardiac arrhythmias. One of the most significant side effects of these drugs is QTc interval prolongation, especially when administered to patients with a baseline risk for QTc prolongation. A prolonged QTc interval can cause lethal torsades de pointes and ventricular fibrillation. Obtaining an ECG at baseline, following a dosage increase, or after switching an opioid medication, is appropriate in patients taking certain prescribed opioids. Opioids are often used first line for the treatment of acute and chronic pain, procedural sedation, medication opioid use disorders, and maintenance therapy.

Conclusions

To reduce the risk of cardiac arrhythmias and to improve patient outcomes, consideration of accurate patient selection, concomitant medications, electrolyte monitoring, and vigilant ECG monitoring should be considered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Data Overview | CDC’s response to the opioid overdose epidemic | CDC. Available from: https://www.cdc.gov/opioids/data/index.html.

  2. Opioid Overdose Crisis | National Institute on Drug Abuse (NIDA). Available from: https://www.drugabuse.gov/drug-topics/opioids/opioid-overdose-crisis.

  3. Krantz MJ, Palmer RB, Haigney MCP. Cardiovascular complications of opioid use: JACC State-of-the-Art Review. J Am Coll Cardiol. 2021;77(2):205–23.

    Article  CAS  PubMed  Google Scholar 

  4. Behzadi M, Joukar S, Beik A. Opioids and cardiac arrhythmia: a literature review. Med Princ Pract. 2018;27(5):401–14.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Chugh SS, Socoteanu C, Reinier K, Waltz J, Jui J, Gunson K. A community-based evaluation of sudden death associated with therapeutic levels of methadone. Am J Med. 2008;121(1):66–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. O’Connell CW, Schricker AA, Schneir AB, Metushi IG, Birgersdotter-Green U, Minns AB. High-dose loperamide abuse–associated ventricular arrhythmias. Hear Case Rep. 2016;2(3):232.

    Google Scholar 

  7. Etaee F, Rezvani-Kamran A, Taheri M, Omidi G, Hasanein P, Komaki A. Comparing the antinociceptive effects of methamphetamine, buprenorphine, or both after chronic treatment and withdrawal in male rats. Basic and clinical neuroscience. 2019 Jul;10(4):313.

  8. Marraffa JM, Holland MG, Sullivan RW, Morgan BW, Oakes JA, Wiegand TJ, et al. Cardiac conduction disturbance after loperamide abuse. Clin Toxicol. 2014;52(9):952–7.

    Article  CAS  Google Scholar 

  9. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004;350(10):1013–22.

    Article  CAS  PubMed  Google Scholar 

  10. Hanon S, Seewald RM, Yang F, Schweitzer P, Rosman J. Ventricular arrhythmias in patients treated with methadone for opioid dependence. J Interv Card Electrophysiol. 2010;28(1):19–22.

    Article  PubMed  Google Scholar 

  11. Harris SC, Morganroth J, Ripa SR, Thorn MD, Colucci S. Effects of buprenorphine on QT intervals in healthy subjects: results of 2 randomized positive-and placebo-controlled trials. Postgrad Med. 2017;129(1):69–80.

    Article  PubMed  Google Scholar 

  12. Shuster JP. Buprenorphine-induced hypertension and tachycardia: rare but serious. Hosp Pharm. 1996;31(1):41–2.

    Google Scholar 

  13. Wolstein J, Gastpar M, Finkbeiner T, Heinrich C, Heitkamp R, Poehlke T, et al. A randomized, open-label trial comparing methadone and levo-alpha-acetylmethadol (LAAM) in maintenance treatment of opioid addiction. Pharmacopsychiatry. 2009;42(01):1–8.

    Article  CAS  PubMed  Google Scholar 

  14. Anglin MD, Conner BT, Annon J, Longshore D. Levo-alpha-acetylmethadol (LAAM) versus methadone maintenance: 1-year treatment retention, outcomes and status. Addiction. 2007;102(9):1432–42.

    Article  PubMed  Google Scholar 

  15. Wieneke H, Conrads H, Wolstein J, Breuckmann F, Gastpar M, Erbel R, et al. Levo-α-acetylmethadol (LAAM) induced QTc-prolongation-results from a controlled clinical trial. Eur J Med Res. 2009;14(1):7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Deamer RL, Wilson DR, Clark DS, Prichard JG. Torsades de pointes associated with high dose levomethadyl acetate (Orlaam®). J Addict Dis. 2001;20(4):7–15.

    Article  CAS  PubMed  Google Scholar 

  17. Ojo A, Nag T, Iwai S, Jacobson J, Cohen M, Frenkel D. Life threatening arrhythmia induced by a common over-the-counter drug. J Am Coll Cardiol. 2018;71(11 Supplement):A2561.

    Article  Google Scholar 

  18. Salama A, Levin Y, Jha P, Alweis R. Ventricular fibrillation due to overdose of loperamide, the “poor man’s methadone.” J Community Hosp Intern Med Perspect. 2017;7(4):222–6.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Vakkalanka JP, Charlton NP, Holstege CP. Epidemiologic trends in loperamide abuse and misuse. Ann Emerg Med. 2017;69(1):73–8.

    Article  PubMed  Google Scholar 

  20. Enakpene EO, Bin Riaz I, Shirazi FM, Raz Y, Indik JH. The long QT teaser: loperamide abuse. Am J Med. 2015;128(10):1083–6.

    Article  PubMed  Google Scholar 

  21. Rasla S, PharmDC ASA, Garas MK, Amr El Meligy MD, Taro Minami MD. Unexpected serious cardiac arrhythmias in the setting of loperamide abuse. R I Med J. 2017;100(4):33.

    Google Scholar 

  22. Wu PE, Juurlink DN. Clinical review: loperamide toxicity. Ann Emerg Med. 2017;70(2):245–52.

    Article  PubMed  Google Scholar 

  23. De Vera J, Ben Kim H, Sakr AE. A case report of loperamide-induced ventricular storm. J Investig Med High Impact Case Rep. 2021;9:2324709621990768.

    PubMed  PubMed Central  Google Scholar 

  24. Leung G, Altshuler D, Goldenberg R, Fridman D, Yuriditsky E. Conduction disturbances and ventricular arrhythmias associated with high-dose loperamide. J Clin Toxicol. 2016;6(3):495–2161.

    Article  Google Scholar 

  25. Vaughn P, Solik MMK, Bagga S, Padanilam BJ. Electrocardiographic abnormalities, malignant ventricular arrhythmias, and cardiomyopathy associated with loperamide abuse. J Cardiovasc Electrophysiol. 2016;27(10):1230–3.

    Article  PubMed  Google Scholar 

  26. Eggleston W. Notes from the field: cardiac dysrhythmias after loperamide abuse—New York, 2008–2016. MMWR. Morbidity and mortality weekly report. 2016;65.

  27. Minhas AS, Schulman SP. Syncope with unusual wide complex arrhythmia in a young woman. Circulation. 2018;138(20):2289–92.

    Article  PubMed  Google Scholar 

  28. Rojas SF, Bonilla HG, Oglat A, Jeroudi O, Schurmann PA. Loperamide induced brugada pattern. J Am Coll Cardiol. 2018;71(11 Supplement):A2598.

    Article  Google Scholar 

  29. Whittaker G, Newman J. Loperamide: an emerging drug of abuse and cause of prolonged QTc. Clin Med (Lond). 2021;21(2):150.

    Article  Google Scholar 

  30. Spinner HL, Lonardo NW, Mulamalla R, Stehlik J. Ventricular tachycardia associated with high-dose chronic loperamide use. Pharmacother J Hum Pharmacol Drug Ther. 2015;35(2):234–8.

    Article  CAS  Google Scholar 

  31. Van Tuyl JS, Brock G, Campbell KB, Al-Khatib SM. Torsades de pointes secondary to excessive loperamide use. J Pharm Pharmacol. 2016;4:322–7.

    Google Scholar 

  32. Kapaganti S, Ansari SA, Saba R, Elkhouly A, Hassib M. A Rare Case of Loperamide-Induced Cardiac Arrest. Cureus. 2020 Jul;12(7).

  33. Kozak PM, Harris AE, McPherson JA, Roden DM. Torsades de pointes with high-dose loperamide. J Electrocardiol. 2017;50(3):355–7.

    Article  PubMed  Google Scholar 

  34. Stefek B, Wolfe LT, Cohen M. Brugada syndrome associated with adolescent loperamide abuse. Pediatrics. 2018;142(4):e20181423.

    Article  PubMed  Google Scholar 

  35. Akel T, Bekheit S. Loperamide cardiotoxicity:“a brief review.” Ann Noninvasive Electrocardiol. 2018;23(2):e12505.

    Article  PubMed  Google Scholar 

  36. Zaman MO, Ali MU, Finkel J. A case of loperamide induced cardiac syncope. J Am Coll Cardiol. 2018;71(11 Supplement):A2550.

    Article  Google Scholar 

  37. Hughes A, Hendrickson RG, Chen BC, Valento M. Severe loperamide toxicity associated with the use of cimetidine to potentiate the “high”. The American journal of emergency medicine. 2018 Aug 1;36(8):1527-e3.

  38. Larsen TR, McMunn J, Ahmad H, AlMahameed ST. Ventricular tachycardia triggered by loperamide and famotidine abuse. Drug Saf Case Rep. 2018;5(1):11.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Krantz MJ. Heterogeneous impact of methadone on the QTc interval: what are the practical implications? J Addict Dis. 2008;27(4):5–9.

    Article  PubMed  Google Scholar 

  40. Alinejad S, Kazemi T, Zamani N, Hoffman RS, Mehrpour O. A systematic review of the cardiotoxicity of methadone. EXCLI J. 2015;14:577.

    PubMed  PubMed Central  Google Scholar 

  41. Chou R, Weimer MB, Dana T. Methadone overdose and cardiac arrhythmia potential: findings from a review of the evidence for an American Pain Society and College on Problems of Drug Dependence clinical practice guideline. J Pain. 2014;15(4):338–65.

    Article  CAS  PubMed  Google Scholar 

  42. Ray WA, Chung CP, Murray KT, Cooper WO, Hall K, Stein CM. Out-of-hospital mortality among patients receiving methadone for noncancer pain. JAMA Intern Med. 2015;175(3):420–7.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Nash D, Okrzesik S, Scarpace Lucas S, Patel A. Methadone Use in Children: Assessment of Cardiotoxicity. Circulation. 2017 Nov 14;136(suppl_1):A17078-.

  44. Ramalho D, Freitas J. Drug-induced life-threatening arrhythmias and sudden cardiac death: A clinical perspective of long QT, short QT and Brugada syndromes. Revista Portuguesa de Cardiologia. 2018 May 1;37(5):435-46.

  45. Krantz MJ, Lowery CM, Martell BA, Gourevitch MN, Arnsten JH. Effects of methadone on QT-interval dispersion. Pharmacother J Hum Pharmacol Drug Ther. 2005;25(11):1523–9.

    Article  CAS  Google Scholar 

  46. Kornick CA, Kilborn MJ, Santiago-Palma J, Schulman G, Thaler HT, Keefe DL, et al. QTc interval prolongation associated with intravenous methadone. Pain. 2003;105(3):499–506.

    Article  CAS  PubMed  Google Scholar 

  47. Fanoe S, Hvidt C, Ege P, Jensen GB. Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen. Heart. 2007;93(9):1051–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Chang K, Huang C, Liang H, Chang S, Wang Y, Liang W, et al. Gender-specific differences in susceptibility to low-dose methadone-associated QTc prolongation in patients with heroin dependence. J Cardiovasc Electrophysiol. 2012;23(5):527–33.

    Article  PubMed  Google Scholar 

  49. Fanoe S, Jensen GB, Sjøgren P, Korsgaard MPG, Grunnet M. Oxycodone is associated with dose-dependent QTc prolongation in patients and low-affinity inhibiting of hERG activity in vitro. Br J Clin Pharmacol. 2009;67(2):172–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Anchersen K, Clausen T, Gossop M, Hansteen V, Waal H. Prevalence and clinical relevance of corrected QT interval prolongation during methadone and buprenorphine treatment: a mortality assessment study. Addiction. 2009;104(6):993–9.

    Article  PubMed  Google Scholar 

  51. Peles E, Bodner G, Kreek MJ, Rados V, Adelson M. Corrected-QT intervals as related to methadone dose and serum level in methadone maintenance treatment (MMT) patients—a cross-sectional study. Addiction. 2007;102(2):289–300.

    Article  PubMed  Google Scholar 

  52. Chowdhury M, Wong J, Cheng A, Khilkin M, Palma E. Methadone therapy in underserved urban community: QT c prolongation and life-threatening ventricular arrhythmias. Cardiovasc Ther. 2015;33(3):127–33.

    Article  CAS  PubMed  Google Scholar 

  53. Ehret GB, Voide C, Gex-Fabry M, Chabert J, Shah D, Broers B, et al. Drug-induced long QT syndrome in injection drug users receiving methadone: high frequency in hospitalized patients and risk factors. Arch Intern Med. 2006;166(12):1280–7.

    Article  CAS  PubMed  Google Scholar 

  54. Hassamal S, Fernandez A, Rekabdarkolaee HM, Pandurangi A. QTc prolongation in veterans with heroin dependence on methadone maintenance treatment. International journal of high risk behaviors & addiction. 2015 Jun;4(2).

  55. Krantz MJ, Rowan SB, Mehler PS. Cocaine-related torsade de pointes in a methadone maintenance patient. J Addict Dis. 2005;24(1):53–60.

    Article  PubMed  Google Scholar 

  56. Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, Robertson AD, Mehler PS. Torsade de pointes associated with very-high-dose methadone. Ann Intern Med. 2002;137(6):501–4.

    Article  CAS  PubMed  Google Scholar 

  57. Justo D, Gal-Oz A, Paran Y, Goldin Y, Zeltser D. Methadone-associated torsades de pointes (polymorphic ventricular tachycardia) in opioid-dependent patients. Addiction. 2006;101(9):1333–8.

    Article  PubMed  Google Scholar 

  58. Cruciani RA, Sekine R, Homel P, Lussier D, Yap Y, Suzuki Y, et al. Measurement of QTc in patients receiving chronic methadone therapy. J Pain Symptom Manage. 2005;29(4):385–91.

    Article  CAS  PubMed  Google Scholar 

  59. Hussain T, Ewer AK. Maternal methadone may cause arrhythmias in neonates. Acta Paediatr. 2007;96(5):768–9.

    Article  PubMed  Google Scholar 

  60. Butler B, Rubin G, Lawrance A, Batey R, Bell J. Estimating the risk of fatal arrhythmia in patients in methadone maintenance treatment for heroin addiction. Drug Alcohol Rev. 2011;30(2):173–80.

    Article  PubMed  Google Scholar 

  61. Grodofsky S, Edson E, Huang S, Speck RM, Hatchimonji J, Lacy K, et al. The QTc effect of low-dose methadone for chronic pain: a prospective pilot study. Pain Med. 2015;16(6):1112–21.

    Article  PubMed  Google Scholar 

  62. Mercadante S, Prestia G, Adile C, Casuccio A. Changes of QTc interval after opioid switching to oral methadone. Support Care Cancer. 2013;21(12):3421–4.

    Article  PubMed  Google Scholar 

  63. Fredheim OMS, Borchgrevink PC, Hegrenæs L, Kaasa S, Dale O, Klepstad P. Opioid switching from morphine to methadone causes a minor but not clinically significant increase in QTc time: a prospective 9-month follow-up study. J Pain Symptom Manage. 2006;32(2):180–5.

    Article  CAS  PubMed  Google Scholar 

  64. Krantz MJ, Garcia JA, Mehler PS. Effects of buprenorphine on cardiac repolarization in a patient with methadone-related torsade de pointes. Pharmacother J Hum Pharmacol Drug Ther. 2005;25(4):611–4.

    Article  Google Scholar 

  65. Walton G, Nolan S, Sutherland C, Ahamad K. Case Report: Sustained release oral morphine as an alternative to methadone for the treatment of opioid-use disorder post Torsades de Pointes cardiac arrest. BMJ Case Reports. 2015;2015.

  66. Wedam EF, Bigelow GE, Johnson RE, Nuzzo PA, Haigney MCP. QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial. Arch Intern Med. 2007;167(22):2469–75.

    Article  CAS  PubMed  Google Scholar 

  67. Stallvik M, Nordstrand B, Kristensen Ø, Bathen J, Skogvoll E, Spigset O. Corrected QT interval during treatment with methadone and buprenorphine—relation to doses and serum concentrations. Drug Alcohol Depend. 2013;129(1–2):88–93.

    Article  CAS  PubMed  Google Scholar 

  68. Athanasos P, Farquharson AL, Compton P, Psaltis P, Hay J. Electrocardiogram characteristics of methadone and buprenorphine maintained subjects. J Addict Dis. 2008;27(3):31–5.

    Article  PubMed  Google Scholar 

  69. Kao DP, Haigney MCP, Mehler PS, Krantz MJ. Arrhythmia associated with buprenorphine and methadone reported to the Food and Drug Administration. Addiction. 2015;110(9):1468–75.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Sessler NE, Walker E, Chickballapur H, Kacholakalayil J, Coplan PM. Disproportionality analysis of buprenorphine transdermal system and cardiac arrhythmia using FDA and WHO postmarketing reporting system data. Postgrad Med. 2017;129(1):62–8.

    Article  PubMed  Google Scholar 

  71. Bohn LM, Gainetdinov RR, Lin F-T, Lefkowitz RJ, Caron MG. μ-Opioid receptor desensitization by β-arrestin-2 determines morphine tolerance but not dependence. Nature. 2000;408(6813):720.

    Article  CAS  PubMed  Google Scholar 

  72. Chen S, Xiong J, Zhan Y, Liu W, Wang X. Role of different concentrations of morphine after coronary perfusion for myocardial protection. WIMJ Open. 2014;1(3):107–10.

    Article  Google Scholar 

  73. Skrabalova J, Neckar J, Hejnova L, Bartonova I, Kolar F, Novotny J. Antiarrhythmic effect of prolonged morphine exposure is accompanied by altered myocardial adenylyl cyclase signaling in rats. Pharmacol Rep. 2012;64(2):351–9.

    Article  CAS  PubMed  Google Scholar 

  74. Lee CW, Muo CH, Liang JA, Lin MC, Kao CH. Atrial fibrillation is associated with morphine treatment in female breast cancer patients: a retrospective population-based time-dependent cohort study. Medicine. 2016 Mar;95(11).

  75. Vincenzo Z, Alphonse S, Matteo P, Lorenzo S, Riccardo C, Pietro G, et al. Morphine-induced supraventricular tachycardia in near-term fetus. Ital J Pediatr. 2018;44(1):111.

    Article  PubMed Central  Google Scholar 

  76. Skulec R, Callerova J, Knor J, Ostadal P, Kmonicek P, Cerny V. Case of morphine-induced ventricular fibrillation. World J Emerg Med. 2017;8(4):310.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Bonin M, Mewton N, Roubille F, Morel O, Cayla G, Angoulvant D, et al. Effect and safety of morphine use in acute anterior ST-segment elevation myocardial infarction. J Am Heart Assoc. 2018;7(4):e006833.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Baranchuk A, Simpson CS, Methot M, Gibson K, Strum D. Corrected QT interval prolongation after an overdose of escitalopram, morphine, oxycodone, zopiclone and benzodiazepines. Can J Cardiol. 2008;24(7):S38-40.

    Article  Google Scholar 

  79. Beheshti A, Lucas L, Dunz T, Haydash M, Chiodi H, Edmiston B, et al. An evaluation of naloxone use for opioid overdoses in West Virginia: a literature review. Am Med J. 2015;6(1):9.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Deshpande G, Gill A. Cardiac arrest following naloxone in an extremely preterm neonate. Eur J Pediatr. 2009;168(1):115.

    Article  PubMed  Google Scholar 

  81. Sarne Y, Hochman I, Eshed M, Oppenheimer E. Antiarrhythmic action of naloxone: direct, non-opiate effect on the rat heart. Life Sci. 1988;43(10):859–64.

    Article  CAS  PubMed  Google Scholar 

  82. Lameijer H, Azizi N, Ligtenberg JJM, Ter Maaten JC. Ventricular tachycardia after naloxone administration: a drug related complication? Case report and literature review. Drug Saf Case Rep. 2014;1(1):2.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Alho H, Sinclair D, Vuori E, Holopainen A. Abuse liability of buprenorphine–naloxone tablets in untreated IV drug users. Drug Alcohol Depend. 2007;88(1):75–8.

    Article  CAS  PubMed  Google Scholar 

  84. Kazbour H, Harrison J, Brown S, Yanowitz F, Snow G, McDonald A, et al. Does buprenorphine/naloxone therapy prolong ventricular repolarization during sleep? Chest. 2014;146(4):955A.

    Article  Google Scholar 

  85. Orman JS, Keating GM. Buprenorphine/naloxone. Drugs. 2009;69(5):577–607.

    Article  CAS  PubMed  Google Scholar 

  86. Baker JR, Best AIM, Pade PA, McCance-Katz EF. Effect of buprenorphine and antiretroviral agents on the QT interval in opioid-dependent patients. Ann Pharmacother. 2006;40(3):392–6.

    Article  CAS  PubMed  Google Scholar 

  87. Poole SA, Pecoraro A, Subramaniam G, Woody G, Vetter VL. The presence or absence of QTc prolongation in buprenorphine-naloxone among youth with opioid dependence. J Addict Med. 2016;10(1):26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Dadpour B, Gholoobi A, Tajoddini S, Habibi A. Acute myocardial infarction following naltrexone consumption; a case report. Emergency. 2017;5(1).

  89. Herman BH, Asleson GS, Powell A, Borghese IF, Ruckman R, Fitzgerald C. Cardiovascular and other physical effects of acute administration of naltrexone in autistic children. J Child Adolesc Psychopharmacol. 1993;3(3):157–68.

    Article  CAS  PubMed  Google Scholar 

  90. Biancofiore G. Oxycodone controlled release in cancer pain management. Ther Clin Risk Manag. 2006;2(3):229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Meents JE, Juhasz K, Stölzle‐Feix S, Peuckmann‐Post V, Rolke R, Lampert A. The opioid oxycodone use‐dependently inhibits the cardiac sodium channel NaV1. 5. British journal of pharmacology. 2018 Jul;175(14):3007-20.

  92. Davis MP, Varga J, Dickerson D, Walsh D, LeGrand SB, Lagman R. Normal-release and controlled-release oxycodone: pharmacokinetics, pharmacodynamics, and controversy. Support Care Cancer. 2003;11(2):84–92.

    Article  PubMed  Google Scholar 

  93. Syed IA, Kuzel AR, Lodhi MU, Chowdhury W, Rahim U, Rahim M. Persistent Bradycardia with the Long-term Use of Phenytoin and Oxycodone: First Case Report. Cureus. 2018 Feb;10(2).

  94. Berling I, Whyte IM, Isbister GK. Oxycodone overdose causes naloxone responsive coma and QT prolongation. QJM An Int J Med. 2012;106(1):35–41.

    Article  Google Scholar 

  95. Daniell HW. Torsades-de-pointes associated with Taku-Tsubo cardiomyopathy following greatly reduced oxycodone use in an elderly woman. J Opioid Manag. 2011;7(2):155–9.

    Article  PubMed  Google Scholar 

  96. Song MK, Bae EJ, Baek JS, Kwon BS, Kim GB, Il Noh C, et al. QT prolongation and life threatening ventricular tachycardia in a patient injected with intravenous meperidine (Demerol®). Korean Circ J. 2011;41(6):342–5.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Keller GA, Villa Etchegoyen MC, Fernandez N, Olivera NM, Quiroga PN, Diez RA. Meperidine-induced QTc-interval prolongation: prevalence, risk factors, and correlation to plasma drug and metabolite concentrations. Int J Clin Pharmacol Ther. 2017;55:275–85.

    Article  PubMed  Google Scholar 

  98. Chakravarthy M, Reddy K, Kavarganahalli D, Rajathadri S, Devanahalli A. Complete heart block after administration of intravenous pethidine. Karnataka Anaesth J. 2015;1(1):31.

    Article  Google Scholar 

  99. Cole JB, Sattiraju S, Bilden EF, Asinger RW, Bertog SC. Isolated tramadol overdose associated with Brugada ECG pattern. Pacing Clin Electrophysiol. 2012;35(8):e219–21.

    Article  PubMed  Google Scholar 

  100. Mehrpour O, Sharifi M, Zamani N. Tramadol poisoning. Toxicology Studies: Cells, Drugs and Environment. 2015 Jul 8;101.

  101. Keller GA, Etchegoyen MCV, Fernandez N, Olivera NM, Quiroga PN, Belloso WH, et al. Tramadol induced QTc-interval prolongation: prevalence, clinical factors and correlation to plasma concentrations. Curr Drug Saf. 2016;11(3):206–14.

    Article  CAS  PubMed  Google Scholar 

  102. Emamhadi M, Sanaei-Zadeh H, Nikniya M, Zamani N, Dart RC. Electrocardiographic manifestations of tramadol toxicity with special reference to their ability for prediction of seizures. Am J Emerg Med. 2012;30(8):1481–5.

    Article  PubMed  Google Scholar 

  103. Samanta S, Samanta S, Chatterjee D, Soni KD. Cardiac arrest after tramadol injection in a polytrauma patient. J Anaesthesiol Clin Pharmacol. 2016;32(4):539.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Ghamsari AA, Dadpour B, Najari F. Frequency of electrocardiographic abnormalities in tramadol poisoned patients; a brief report. Emergency. 2016;4(3):151.

    Google Scholar 

  105. Massarella J, Ariyawansa J, Natarajan J, Francke S, Murtaugh T, DeLemos B, Vaughan S, Fonseca S. Tramadol hydrochloride at steady state lacks clinically relevant QTc interval increases in healthy adults. Clinical pharmacology in drug development. 2019 Jan;8(1):95-106.

  106. Sahutoglu C, Kocabas S, Askar FZ. Tramadol use in a patient with Brugada syndrome and morphine allergy: a case report. J Pain Res. 2018;11:191.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Moghadam PH, Zarei N, Farsi D, Abbasi S, Mofidi M, Rezai M, et al. Electrocardiographic changes in patients with tramadol-induced idiosyncratic seizures. Turk J Emerg Med. 2016;16(4):151–4.

    Article  Google Scholar 

  108. Chen A, Ashburn MA. Cardiac effects of opioid therapy. Pain Med. 2015;16(suppl_1):S27-31.

    Article  PubMed  Google Scholar 

  109. Chang DJ, Kweon TD, Nam SB, Lee JS, Shin CS, Park CH, et al. Effects of fentanyl pretreatment on the QTc interval during propofol induction. Anaesthesia. 2008;63(10):1056–60.

    Article  CAS  PubMed  Google Scholar 

  110. Hancı V, Yurtlu S, Karabağ T, Okyay D, Hakimoğlu S, Kayhan G, et al. Effects of esmolol, lidocaine and fentanyl on P wave dispersion, QT, QTc intervals and hemodynamic responses to endotracheal intubation during propofol induction: a comparative study. Braz J Anesthesiol. 2013;63(3):235–44.

    Article  PubMed  Google Scholar 

  111. Wilton NCT, Hantler CB. Congenital long QT syndrome: changes in QT interval during anesthesia with thiopental, vecuronium, fentanyl, and isoflurane. Anesth Analg. 1987;66(4):357–60.

    Article  CAS  PubMed  Google Scholar 

  112. Lischke V, Wilke H, Probst S, Behne M, Kessler P. Prolongation of the QT–interval during induction of anesthesia in patients with coronary artery disease. Acta Anaesthesiol Scand. 1994;38(2):144–8.

    Article  CAS  PubMed  Google Scholar 

  113. Cho JS, Kim SH, Shin S, Pak H-N, Yang SJ, Oh YJ. Effects of dexmedetomidine on changes in heart rate variability and hemodynamics during tracheal intubation. Am J Ther. 2016;23(2):e369–76.

    Article  PubMed  Google Scholar 

  114. Fareed A, Vayalapalli S, Scheinberg K, Gale R, Casarella J, Drexler K. QTc interval prolongation for patients in methadone maintenance treatment: a five years follow-up study. Am J Drug Alcohol Abuse. 2013;39:235–40.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Claude S. Elayi.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethical approval

Not applicable.

Informed consent

Not applicable.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Etaee, F., Tobin, M., Vuppala, S. et al. Effects of opioid receptor agonist and antagonist medications on electrocardiogram changes and presentation of cardiac arrhythmia: review article. J Interv Card Electrophysiol 63, 471–500 (2022). https://doi.org/10.1007/s10840-021-01072-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10840-021-01072-1

Keywords

Navigation