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Cardiovascular Toxicology

, Volume 19, Issue 1, pp 62–71 | Cite as

Electrocardiographic Findings in Mortalities Due to Pure Methadone Toxicity

  • Mehdi Sheibani
  • Nasim Zamani
  • Hossein Hassanian-MoghaddamEmail author
Article
  • 60 Downloads

Abstract

We aimed to evaluate electrocardiographic (ECG) abnormalities in mortalities due to pure methadone toxicity in ICU patients since methadone-related mortality may be due to cardiac complications even in acute toxicities. In a retrospective single-center study, files of all patients who had died with confirmed diagnosis of pure methadone toxicity between 2011 and 2016 were evaluated. Autopsy was performed in all cases. A cardiologist measured all ECG quantitative and qualitative indices. Fifty-one deaths were recorded. Forty-two dead patients were males. Median [IQR] age of the patients was 44 [30, 60] years. Of them, 38 (69%) were methadone-dependent and were significantly older than methadone-naïve patients (p = 0.008 and p = 0.001, respectively). ECG abnormalities were detected in all cases. ST-T abnormalities were found in 33 (64.7%) patients. Except longer PR interval in dependent patients (p = 0.017) and specific ST elevation in naïve cases (p = 0.008), other ECG indices were similar in two groups. No correlation was found between ST-T abnormalities and coronary disease in autopsy. ECG abnormalities irrelevant to coronary artery diseases are common in methadone-related mortalities. Methadone toxicity may affect myocardium and play a role in death. Further prospective studies to evaluate other cardiac indices in methadone-poisoned patients are recommended.

Keywords

Methadone Poisoning Coronary artery disease Electrocardiography 

Notes

Acknowledgements

This study was supported by Social Determinants of Health Research Center, Shahid Beheshti University of Medical sciences, Tehran, Iran and approved by our local ethics committee (IR.SBMU.RETECH.REC.1397.31).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no competing interests.

References

  1. 1.
    Rudd, R. A., Seth, P., David, F., & Scholl, L. (2016). Increases in drug and opioid-involved overdose deaths—United States, 2010–2015. MMWR. Morbidity and Mortality Weekly Report, 65, 1445–1452.CrossRefGoogle Scholar
  2. 2.
    Hassanian-Moghaddam, H., & Zamani, N. (2016). An overview on methadone-intoxicated patients. In Neuropathology of drug addictions and substance misuse volume 3: General processes and mechanisms, prescription medications, caffeine and areca, polydrug misuse, emerging addictions and non-drug addictions (pp. 525–531). Amsterdam: Elsevier.CrossRefGoogle Scholar
  3. 3.
    Khosravi, N., Zamani, N., Hassanian-Moghaddam, H., Ostadi, A., Rahimi, M., & Kabir, A. (2017). Comparison of two naloxone regimens in addicted methadone-overdosed patients, a clinical trial study. Current Clinical Pharmacology, 12(4), 259–265.CrossRefGoogle Scholar
  4. 4.
    Aghabiklooei, A., Shadnia, S., Hassanian-Moghaddam, H., & Zamani, N. (2013). Acute respiratory distress syndrome caused by methadone syrup. Archives of Industrial Hygiene and Toxicology, 64, 439–443.CrossRefGoogle Scholar
  5. 5.
    Alinejad, S., Kazemi, T., Zamani, N., Hoffman, R. S., & Mehrpour, O. (2015). A systematic review of the cardiotoxicity of methadone. EXCLI Journal, 14, 577–600.Google Scholar
  6. 6.
    Akhgari, M., Amini-Shirazi, N., & Iravani, F. S. (2017). Forensic toxicology perspectives of methadone-associated deaths in Tehran, Iran, a 7-year overview. Basic & Clinical Pharmacology & Toxicology, 122(4), 436–441.CrossRefGoogle Scholar
  7. 7.
    Hassanian-Moghaddam, H., Hakiminejhad, M., Farnaghi, F., Mirafzal, A., Zamani, N., & Kabir, A. (2017). Eleven years of children methadone poisoning in a referral center: A review of 453 cases. Journal of Opioid Management, 13, 27–36.CrossRefGoogle Scholar
  8. 8.
    Soltaninejad, K., Hassanian-Moghaddam, H., & Shadnia, S. (2014). Methadone related poisoning on the rise in Tehran, Iran. Asia Pacific Journal of Medical Toxicology, 3, 104–109.Google Scholar
  9. 9.
    Shadnia, S., Rahimi, M., Hassanian-Moghaddam, H., Soltaninejad, K., & Noroozi, A. (2013). Methadone toxicity: Comparing tablet and syrup formulation during a decade in an academic poison center of Iran. Clinical Toxicology, 51, 777–782.CrossRefGoogle Scholar
  10. 10.
    Gharehdaghi, J., Takaloo-Bakhtiari, A., Hassanian-Moghaddam, H., Zamani, N., & Hedayatshode, M. J. (2017). Suspected methadone toxicity; from hospital to autopsy bed. Basic & Clinical Pharmacology & Toxicology, 121, 531–539.CrossRefGoogle Scholar
  11. 11.
    Hassanian-Moghaddam, H., Zamani, N., Rahimi, M., Shadnia, S., Pajoumand, A., & Sarjami, S. (2014). Acute adult and adolescent poisoning in Tehran, Iran; the epidemiologic trend between 2006 and 2011. Archives of Iranian Medicine, 17, 534–538.Google Scholar
  12. 12.
    Hassanian-Moghaddam, H. (2013). An educational and research opportunity for the largest university hospital poison control centers; Tehran and Cairo. Egyptian Journal of Forensic Sciences, 3, 64–65.CrossRefGoogle Scholar
  13. 13.
    Leonard, S., & Lilly, M. D. (Eds.). (2015). Braunwald’s heart disease review and assessment. Toronto: Elsevier.Google Scholar
  14. 14.
    de Jong, J. (2017). ECG pedia. Available form: http://en.ecgpedia.org/index.php?title=Main_Page Accessed on 25 Dec 2017.
  15. 15.
    Athanasos, P., Farquharson, A. L., Compton, P., Psaltis, P., & Hay, J. (2008). Electrocardiogram characteristics of methadone and buprenorphine maintained subjects. Journal of Addictive Diseases, 2, 31–35.CrossRefGoogle Scholar
  16. 16.
    Decerf, J. A., Gressens, B., Brohet, C., Liolios, A., & Hanston, P. (2004). Can methadone prolong the QT interval? Intensive Care Medicine, 30, 1690–1691.CrossRefGoogle Scholar
  17. 17.
    Pimentel, L., & Mayo, D. (2008). Chronic methadone therapy complicated by torsades de pointes: A case report. The Journal of Emergency Medicine, 34, 287–290.CrossRefGoogle Scholar
  18. 18.
    Routhier, D. D., Katz, K. D., & Brooks, D. E. (2007). QTc prolongation and torsades de pointes associated with methadone therapy. The Journal of Emergency Medicine, 32, 275–278.CrossRefGoogle Scholar
  19. 19.
    Aghabiklooei, A., Edalatparvar, M., Zamani, N., & Mostafazadeh, B. (2014). Prognostic factors in acute methadone toxicity: A 5-year study. Journal of Toxicology, 2014, 12.CrossRefGoogle Scholar
  20. 20.
    Hassanian-Moghaddam, H., Soltaninejad, K., Shadnia, S., Kabir, A., Movahedi, M., & Mirafzal, A. (2016). Risk factors for mortality and endotracheal intubation after methadone intoxication. Basic & Clinical Pharmacology & Toxicology, 118, 231–237.Google Scholar
  21. 21.
    Farsi, D., Mirafzal, A., Hassanian-Moghaddam, H., Azizi, Z., Jamshidnejad, N., & Zehtabchi, S. (2014). The correlation between prolonged corrected QT interval with the frequency of respiratory arrest, endotracheal intubation, and mortality in acute methadone overdose. Cardiovascular Toxicology, 14, 358–367.CrossRefGoogle Scholar
  22. 22.
    Ghane, T., Zamani, N., Hassanian-Moghaddam, H., Beyrami, A., & Noroozi, A. (2018). Lead poisoning outbreak among opium users in the Islamic Republic of Iran, 2016–2017. Bulletin of the World Health Organization, 96(3), 165.CrossRefGoogle Scholar
  23. 23.
    Gao, L., Dimitropoulou, P., Robertson, J. R., McTaggart, S., Bennie, M., & Bird, S. M. (2016). Risk-factors for methadone-specific deaths in Scotland’s methadone-prescription clients between 2009 and 2013. Drug and Alcohol Dependence, 167, 214–223.CrossRefGoogle Scholar
  24. 24.
    Ashwath, M. L., Ajjan, M., & Culclasure, T. (2005). Methadone-induced bradycardia. The Journal of emergency medicine, 29, 73–75.CrossRefGoogle Scholar
  25. 25.
    Rad, M. A., Firoozi, A., Akbarirad, F., et al. (2017). Relationship between corrected-QT intervals and other ECG characteristics with methadone dose in methadone maintenance treatment (MMT) patients and healthy subjects: A case-control study. Razavi International Journal of Medicine, 5, 2.Google Scholar
  26. 26.
    Hassanian-Moghaddam, H., Amiri, H., Zamani, N., Rahimi, M., Shadnia, S., & Taherkhani, M. (2014). QT dispersion and prognostication of the outcome in acute cardiotoxicities: A comparison with SAPS II and APACHE II scoring systems. Cardiovascular Toxicology, 14, 129–133.CrossRefGoogle Scholar
  27. 27.
    Alizadeh, A. M., Hassanian-Moghaddam, H., Shadnia, S., Zamani, N., & Mehrpour, O. (2014). Simplified acute physiology score II and acute physiology and chronic health evaluation II and prediction of the mortality and later development of complications in poisoned patients admitted to intensive care unit. Basic & Clinical Pharmacology & Toxicology, 115, 297–300.CrossRefGoogle Scholar
  28. 28.
    Srivatsa, U., Hoppe, B., Lu, J., & Feld, G. K. (2005). Sequential appearance of both Brugada and long QT patterns on EKG in a single patient receiving methadone. Heart Rhythm, 2, S50.CrossRefGoogle Scholar
  29. 29.
    Deamer, R. L., Wilson, D. R., Clark, D. S., & Prichard, J. K. (2001). Torsades de pointes associated with high dose levomethadyl acetate (Orlaam®). Journal of Addictive Diseases, 20, 7–15.CrossRefGoogle Scholar
  30. 30.
    Kuryshev, Y. A., Kirsch, G. E., & Brown, A. M. (2010). Increased cardiac risk in concomitant methadone and diazepam treatment: Pharmacodynamic interactions in cardiac ion channels. Biophysical Journal, 98, 339a.CrossRefGoogle Scholar
  31. 31.
    Stoetzer, C., Kistner, K., Stüber, T., Wirths, M., Schulze, V., Doll, T., et al. (2015). Methadone is a local anaesthetic-like inhibitor of neuronal Na + channels and blocks excitability of mouse peripheral nerves. British Journal of Anaesthesia, 114, 110–120.CrossRefGoogle Scholar
  32. 32.
    Agahi, M., Shakoori, V., & Marashi, S. M. (2016). Electrocardiogram abnormality associated with methadone overdose. Sultan Qaboos University Medical Journal, 16, e113–e114.CrossRefGoogle Scholar
  33. 33.
    John, J., Amley, X., Bombino, G., Gitelis, C., Topi, B., Hollander, G., & Ghosh, J. (2010). Torsade de pointes due to methadone use in a patient with HIV and hepatitis C coinfection. Cardiology Research and Practice, 2010, 524764.CrossRefGoogle Scholar
  34. 34.
    Price, L. C., Wobeter, B., Delate, T., Kurz, D., & Shanahan, R. (2014). Methadone for pain and the risk of adverse cardiac outcomes. Journal of pain and Symptom Management, 48, 333–342.CrossRefGoogle Scholar
  35. 35.
    Huh, B., & Park, C. H. (2010). Retrospective analysis of low-dose methadone and QTc prolongation in chronic pain patients. Korean Journal of Anesthesiology, 58, 338–343.CrossRefGoogle Scholar
  36. 36.
    Chou, R., Cruciani, R. A., Fiellin, D. A., Compton, P., Farrar, J. T., Haigney, M. C., Inturrisi, C., Knight, J. R., Otis-Green, S., Marcus, S. M., Mehta, D., Meyer, M. C., Portenoy, R., Savage, S., Strain, E., Walsh, S., & Zeltzer, L., American Pain Society, Heart Rhythm Society (2014). Methadone safety: A clinical practice guideline from the American pain society and college on problems of drug dependence, in collaboration with the heart rhythm society. The Journal of Pain, 15, 321–337.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Cardiovascular Research CenterShahid Beheshti University of Medical SciencesTehranIslamic Republic of Iran
  2. 2.Department of Clinical Toxicology, School of MedicineShahid Beheshti University of Medical SciencesTehranIslamic Republic of Iran
  3. 3.Department of Clinical ToxicologyLoghman-Hakim HospitalTehranIslamic Republic of Iran

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