The causes of hospital mortality in methadone associated poisonings: analysis of the data from the Kyiv toxicological center for 2005–2019

  • Authors: N.V. Kurdil
  • UDC: 615.6+616–091.8:616–099
  • DOI: 10.33273/2663-4570-2021-91-2-54-62
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LI Medved’s Research Centre of Preventive Toxicology, Food and Chemical Safety, Ministry of Health, Ukraine (State Enterprise), Kyiv, Ukraine


ABSTRACT. Scientific interest in poisoning by synthetic opioids, in particular Methadone, is due to a significant increase in their number in Kyiv over the past 15 years and fatal consequences.

The Aim of the Research. Is to identify the causes of fatal poisoning associated with methadone and to determine measures to prevent them.

Materials and Methods. A retrospective analysis of medical data of 1340 patients with Methadone poisoning who were treated at the Toxicology Center in Kyiv in the period 2005–2019; including 38 fatalities cases.

Results. The share of drug poisonings registered at the Kyiv Toxicology Center has increased from 15% to 42% over the past 30 years. The top five drugs and psychotropic substances in 2019 were Benzodiazepines, Methadone, Barbiturates, Amphetamines, and Marijuana. The number of Methadone poisonings in 2005–2014 increased 150 times. The main cause of poisoning is the use of illegal Methadone. There is a direct relationship between the growth of hospital mortality and the appearance of combined poisonings: Methadone-Ethanol (r = 0,79); Methadone-Ethanol-Amphetamines (r = 0,69); Methadone-Ethanol-Benzodiazepines (r = 0,61); Methadone-Ethanol-Cocaine (r = 0,43). According to the results of forensic medical studies of 38 patients who died as a result of Methadone poisoning, the following were identified: toxic hepato-nephropathy – 12 cases (31,57%); long-term soft tissue compression syndrome – 10 (26,31%); acute kidney damage – 4 (10,52%); aspiration of gastric contents – 7 (18,42%); apallic syndrome – 4 (10,52%). The direct effect of polymorbidity on mortality has been confirmed, which justifies the need for a personalized approach to intensive care.

Conclusions. Today in Ukraine, combined illegal methadone poisoning is the most common type of drug poisoning, which has a severe course, high mortality, and requires long and complex treatment.

Key Words: acute poisoning, methadone, combined poisoning, mortality.


1. O’Donnell JK, Gladden RM, Seth P. Trends in Deaths Involving Heroin and Synthetic Opioids Excluding Methadone, and Law Enforcement Drug Product Reports, by Census Region – United States, 2006–2015. MMWR Morb Mortal Wkly Rep. 2017 Sep 1;66(34):897–903. doi:10.15585/mmwr.mm6634a2.

2. Wilson N, Kariisa M, Seth P, Smith H. 4th, Davis NL. Drug and Opioid-Involved Overdose Deaths – United States, 2017–2018. MMWR MorbMortal Wkly Rep. 2020 Mar 20;69(11):290–297. doi:10.15585/mmwr.mm6911a4.

3. Madadi P, Hildebrandt D, Lauwers AE, Koren G. Characteristics of opioid-users whose death was related to opioid-toxicity: a population-based study in Ontario, Canada. PLoS One. 2013;8(4):e60600. doi: 10.1371/journal.pone.0060600.

4. Babakhanian M, Zarghami M, Alipour A, Khosravi A, Hashemi-Nazari SS, Saberi M, et al. An Estimation of Drug-Related Deaths in Iran, Using the Capture-Recapture Method (2014–2016). Addict Health. 2020 Apr; 12(2):87–97. doi:10.22122/ahj.v12i2.266.

5. Kelty E, Hulse G, Joyce D, Preen DB. Impact of Pharmacological Treatments for Opioid Use Disorder on Mortality. CNS Drugs. 2020 Jun; 34(6):629–642. doi:10.1007/s40263-020-00719-3.

6. Ma J, Bao YP, Wang RJ, Su MF, Liu MX, Li JQ, et al. Effects of medication-assisted treatment on mortality among opioids users: a systematic review and meta-analysis. Mol Psychiatry. 2019 Dec; 24(12):1868–1883. doi:10.1038/s41380-018-0094-5.

7. Tori ME, Larochelle MR, Naimi TS. Alcohol or Benzodiazepine Co-involvement With Opioid Overdose Deaths in the United States, 1999–2017. JAMA Network Open. 2020;3(4):e202361. doi:10.1001/jamanetworkopen. 2020.2361.

8. Kleykamp BA, Vandrey RG, Bigelow GE, Strain EC, Mintzer MZ. Effects of methadone plus alcohol on cognitive performance in methadone-maintained volunteers. Am J Drug Alcohol Abuse. 2015 May;41(3):251–256. doi:10.3109/00952990.2014.987348.

9. Strang J, Metrebian N, Lintzeris N, et al. Supervised injectable heroin or injectable methadone versus optimized oral methadone as treatment for chronic heroin addicts in England after persistent failure in orthodox treatment (RIOTT): a randomised trial. Lancet. 2010;375(9729): 1885–1895. doi:10.1016/S0140-6736(10)60349-2.

10. Dobler-Mikola A, Hättenschwiler J, Meili D, Beck T, Böni E, Modestin J. Patterns of heroin, cocaine, and alcohol abuse during long-term methadone maintenance treatment. J Subst Abuse Treat. 2005;29(4):259–265. doi:10.1016/j.jsat. 2005.08.002.

11. Helsinki declaration of the world medical association "Ethical principles of medical research with human participation as an object of study" from 01.06.1964. Electronic resource. URL:

12. Rudd RA, Aleshire N, Zibbell JE, Gladden RM. Increases in Drug and Opioid Overdose Deaths – United States, 2000–2014. CDC. Morbidity and Motrtality Weekly Report (MMWR). January 1 2016;64(50);1378–82.

13. Madden ME, Shapiro SL. The methadone epidemic: methadone-related deaths on the rise in Vermont. Am J Forensic Med Pathol. 2011 Jun;32(2):131–5. doi:10.1097/PAF.0b013e3181e8af3d.

14. PaulozziL J, Logan JE, Hall AJ, McKinstry E, Kaplan JA, Crosby AE. A comparison of drug overdose deaths involving methadone and other opioid analgesics in West Virginia. Addiction. 2009 Sep;104(9):1541-8. doi:10.1111/j.1360-0443.2009.02650.x

15. Schiller EY, Mechanic OJ. Opioid Overdose. National Center for Biotechnology Information. Electronic resource. URL: Last Update: December 27, 2019.

16. Bansal S, Khan R, Tietjen PA. Naloxone-Induced Pulmonary Edema. Chest Journal. 2007;132:692. DOI: 10.1378/chest.132.4_MeetingAbstracts.692.

17. Ravikaran P, Vignesh P, Navjot S, et al. Naloxone-Induced Noncardiogenic Pulmonary Edema. American Journal of Therapeutics. 2020;27:672-3. doi:10.1097/MJT.0000000000001037.

18. Dinis-Oliveira RJ. Metabolomics of methadone: clinical and forensic toxicological implications and variability of dose response. Drug Metabolism Reviews. Published online: 20 Jun 2016. doi:10.1080/03602532.2016.1192642.

19. Ferrari A, Coccia R, Bertolini A, Sternieri E. Methadonemetabolism, pharmacokinetics and interactions. Pharmacol Res. 2004 Dec;50(6):551–9. doi:10.1016/j.phrs.2004.05.002.

20. Volpe DA, Xu Y, Sahajwalla CG, Younis IR, Patel V. Methadone Metabolism and Drug-Drug Interactions: In Vitro and In Vivo Literature Review. J Pharm Sci. 2018 Dec;107(12):2983–2991. doi: 10.1016/j.xphs.2018.08.025.

21. Kumai M, Maeda Y, Miura M, Tsuruga K, Yamada T, Takekuma Y, et al. Serotonin Syndrome. Developing Immediately after the Initiation of Low-Dose Methadone Therapy: A Case Report. Case Rep Oncol. 2020 Mar 24;13(1):281–284. doi:10.1159/000506443.

22. Pullan PT, Watson FE, Seow SS, Rappeport W. Methadoneinduced hypoadrenalism. Lancet. 1983 Mar 26;1(8326 Pt 1): 714. doi:10.1016/s0140-6736(83)92011-1.

23. Makunts T, Atayee RS, Abagyan R. Retrospective analysis reveals significant association of hypoglycemia with tramadol and methadone in contrast to other opioids. Sci Rep. 2019 Aug 28;9(1):12490. doi:10.1038/s41598-019-48955-y.

24. Saad MH, Savonen CL, Rumschlag M, Todi SV, Schmidt CJ, Bannon MJ. Opioid Deaths: Trends, Biomarkers, and Potential Drug Interactions Revealed by Decision Tree Analyses. Front Neurosci. 2018 Oct 23;12:728. doi:10.3389/fnins.2018.00728.

25. Argo A, Spatola GF, Zerbo S, Sortino C, Lanzarone A, Uzzo ML, et al. A possible biomarker for methadone related deaths. J Forensic Leg Med. 2017 Jul;49:8–14. doi:10.1016/j.jflm.2017.05.010.

26. Opdal MS, Arnesen M, Müller LD, et al. Effects of Hemodialysis on Methadone. Pharmacokinetics and QTc. Clin Ther. 2015 Jul;1;37(7):1594–9. doi:10.1016/j.clinthera. 2015.04.009.

27. Arelin V, Schmidt JJ, Kayser N, et al. Removal of methadone by extended dialysis using a high cut-off dialyzer: implications for the treatment of overdose and for pain management in patients undergoing light chain removal. Clin Nephrol. 2016 Jun;85(6):353–7. doi:10.5414/CN108724.


Received 02/18/2021