Comparing Two Naloxone Tapering Methods in Management of Methadone Intoxication; a Quasi-experimental Study
Archives of Academic Emergency Medicine,
Vol. 11 No. 1 (2023),
15 November 2022
Introduction: Even though naloxone is the main treatment for methadone poisoning treatment there are controversies about the proper method of its tapering. This study aimed to compare two methods in this regard.
Method: This study was a prospective, single-blind pilot quasi-experimental study on non-addicted adult patients poisoned with methadone. Patients were randomly divided into 2 groups. In one group, after stabilization of respiratory conditions and consciousness, naloxone was tapered using the half-life of methadone and in the other group, naloxone was tapered using the half-life of naloxone. Recurrence of symptoms and changes in venous blood gas parameters were compared between groups as outcome.
Results: 52 patients were included (51.92% female). 31 cases entered Group A (tapering based on methadone’s half-life) and 21 cases entered Group B (tapering based on naloxone’s half-life). The two groups were similar regarding mean age (p = 0.575), gender distribution (p = 0.535), the cause of methadone use (p = 0.599), previous medical history (p = 0.529), previous methadone use (p = 0.654), drug use history (p = 0.444), and vital signs on arrival to emergency department (p = 0.054). The cases of re-decreasing consciousness during tapering (52.38% vs. 25.81%; p = 0.049) and after discontinuation of naloxone (72.73% vs. 37.50%; p = 0.050) were higher in the tapering based on naloxone half-life group. The relative risk reduction (RRR) for naloxone half-life group was -1.03 and for methadone half-life group was 0.51. The absolute risk reduction (ARR) was 0.27 (95% confidence interval (CI) = 0.01-0.53) and the number needed to treat (NNT) was 3.7 (95% CI= 1.87- 150.53). There was not any statistically significant difference between groups regarding pH, HCO3, and PCO2 changes during tapering and after naloxone discontinuation (p > 0.05). However, repeated measures analysis of variance (ANOVA), showed that in the tapering based on methadone’s half-life group, the number of changes and stability in the normal range were better (p < 0.001).
Conclusion: It seems that, by tapering naloxone based on methadone’s half-life, not only blood acid-base disorders are treated, but they also remain stable after discontinuation and the possibility of symptom recurrence is reduced.
- Drug Users
- Drug Tapering
How to Cite
Joseph H, Stancliff S, Langrod J. Methadone maintenance treatment (MMT): a review of historical and clinical issues. Mt Sinai J Med. 2000;67(5-6):347-64.
Clausen T, Anchersen K, Waal H. Mortality prior to, during and after opioid maintenance treatment (OMT): a national prospective cross-registry study. Drug Alcohol Depend. 2008;94(1-3):151-7.
Bell J, Zador D. A risk-benefit analysis of methadone maintenance treatment. Drug Saf. 2000;22(3):179-90.
Marsch LA. The efficacy of methadone maintenance interventions in reducing illicit opiate use, HIV risk behavior and criminality: a meta‐analysis. Addiction. 1998;93(4):515-32.
Glaizal M, Gazin V, Aymard I, Messina-Gourlot C, Richard N, Mallaret M, et al. Suicidal poisonings with methadone in France: Results of a two year national survey by the Toxicovigilance Network. J Clin Toxicol. 2012;50(9):841-6.
Gheshlaghi F, Izadi-Mood N, Mardani A, Piri-Ardekani MR. Dose-dependent effects of methadone on QT interval in patients under methadone maintenance treatment. Asia Pac J Med Toxicol. 2013;2(1):6-9.
Aghabiklooei A, Shadnia S, Hassanian-Moghaddam H, Zamani N. Acute respiratory distress syndrome caused by methadone syrup. Arh Hig Rada Toksikol. 2013;64(3):439-42.
Hoffman RS, Howland MA, Lewin NA, Nelson LS, Goldfrank LR. Goldfrank's Toxicologic Emergencies. 10th ed: McGraw Hill LLC; 2014. p. 329-33.
Walley AY, Doe-Simkins M, Quinn E, Pierce C, Xuan Z, Ozonoff A. Opioid overdose prevention with intranasal naloxone among people who take methadone. J Subst Abuse Treat. 2013;44(2):241-7.
Coffin PO, Sullivan SD. Cost-effectiveness of distributing naloxone to heroin users for lay overdose reversal. Ann Intern Med. 2013;158(1):1-9.
Shaw LV, Moe J, Purssell R, Buxton JA, Godwin J, Doyle-Waters MM, et al. Naloxone interventions in opioid overdoses: a systematic review protocol. Syst Rev. 2019;8(1):1-9.
Nath S, Tripathi M, Pandey C, Rao B. Naloxone-induced pulmonary edema: a potential cause of postoperative morbidity in laparoscopic donor nephrectomy. Indian J Med Sci. 2009;63(2):72.
Kim HK, Nelson LS. Reducing the harm of opioid overdose with the safe use of naloxone: a pharmacologic review. Expert Opin Drug Saf. 2015;14(7):1137-46.
Buajordet I, Næss A-C, Jacobsen D, Brørs O. Adverse events after naloxone treatment of episodes of suspected acute opioid overdose. Eur J Emerg Med. 2004;11(1):19-23.
Sivilotti ML. Flumazenil, naloxone and the ‘coma cocktail’. Br J Clin Pharmacol. 2016;81(3):428-36.
Brown R, Kraus C, Fleming M, Reddy S. Methadone: applied pharmacology and use as adjunctive treatment in chronic pain. Postgrad Med J. 2004;80(949):654-9.
Inturrisi C. Pharmacology of methadone and its isomers. Minerva Anestesiol. 2005;71(7/8):435.
Solhi H, Salehi B, Alimoradian A, Pazouki S, Taghizadeh M, Saleh AM, et al. Beneficial effects of Rosmarinus officinalis for treatment of opium withdrawal syndrome during addiction treatment programs: a clinical trial. Addict Health. 2013;5(3-4):90.
Haghighi-Morad M, Naseri Z, Jamshidi N, Hassanian-Moghaddam H, Zamani N, Ahmad-Molaei L. Methadone-induced encephalopathy: a case series and literature review. BMC Med Imaging. 2020;20(1):1-9.
Salgado R, Jorens P, Baar I, Cras P, Hans G, Parizel P. Methadone-induced toxic leukoencephalopathy: MR imaging and MR proton spectroscopy findings. AJNR Am J Neuroradiol. 2010;31(3):565-6.
Cerase A, Leonini S, Bellini M, Chianese G, Venturi C. Methadone‐Induced Toxic Leukoencephalopathy: Diagnosis and Follow‐up by Magnetic Resonance Imaging Including Diffusion‐Weighted Imaging and Apparent Diffusion Coefficient Maps. JON. 2011;21(3):283-6.
Rando J, Szari S, Kumar G, Lingadevaru H. Methadone overdose causing acute cerebellitis and multi-organ damage. Am J Emerg Med. 2015;34(2):343. e1-3.
Hanna V, Senderovich H. Methadone in pain management: a systematic review. J Pain. 2021;22(3):233-45.
Clarke SF, Dargan PI, Jones AL. Naloxone in opioid poisoning: walking the tightrope. EMJ. 2005;22(9):612-6.
Clarke S, Dargan P. Intravenous bolus or infusion of naloxone in opioid overdose. EMJ. 2002;19(3):249-50.
McDonald R, Lorch U, Woodward J, Bosse B, Dooner H, Mundin G, et al. Pharmacokinetics of concentrated naloxone nasal spray for opioid overdose reversal: Phase I healthy volunteer study. Addiction. 2018;113(3):484-93.
Williams K, Lang ES, Panchal AR, Gasper JJ, Taillac P, Gouda J, et al. Evidence-based guidelines for EMS administration of naloxone. Prehosp Emerg Care. 2019;23(6):749-63.
Clemency BM, Eggleston W, Shaw EW, Cheung M, Pokoj NS, Manka MA, et al. Hospital Observation Upon Reversal (HOUR) with naloxone: a prospective clinical prediction rule validation study. Acad Emerg Med. 2019;26(1):7-15.
Lewter LA, Johnson MC, Treat AC, Kassick AJ, Averick S, Kolber BJ. Slow‐sustained delivery of naloxone reduces typical naloxone‐induced precipitated opioid withdrawal effects in male morphine‐dependent mice. J Neurosci Res. 2022;100(1):339-52.
Rzasa Lynn R, Galinkin J. Naloxone dosage for opioid reversal: current evidence and clinical implications. Ther Adv Drug Saf. 2018;9(1):63-88.
Yazdanbakhsh A, Kazemifar M. Comparison of Effects and Side Effects of Two Naloxone-Based Regimens in Treatment of Methadone Overdose. IJT. 2016;10(1):49-52.
Khosravi N, Zamani N, Hassanian-Moghaddam H, Ostadi A, Rahimi M, Kabir A. Comparison of Two Naloxone Regimens in Opioid-dependent Methadone-overdosed Patients: A Clinical Trial Study. Curr Clin Pharmacol. 2017;12(4):259-65.
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