Evaluation of Safety Outcomes for Methadone Induction and Rapid Titration in Critically Ill Patients

Introduction: Initiating methadone therapy for opioid use disorder (OUD) in the intensive care unit (ICU) presents unique challenges due to altered pharmacokinetics, drug interactions, and heightened risks of adverse events. The American Society of Addiction Medicine recommends initial methadone doses of 10 to 30 mg, with titrations not exceeding 10 mg every 5 days. We define rapid titration as increasing methadone dose more frequently than every 3 days. While rapid induction protocols are increasingly used in hospitalized patients, literature addressing rapid induction practices within the critically ill is limited.


Methods: This study is a retrospective review of adult patients who had an addiction medicine consult initiated on methadone in the medical or surgical intensive care unit for management of OUD between January 2022 and 2025 at a level 1 trauma center and urban safety net hospital. The primary outcome was incidence of adverse effects related to methadone initiation defined as: naloxone administration and/or methadone regimen reduction or discontinuation. Secondary outcomes include incidence of QTc prolongation, in-hospital mortality, treatment program enrollment at discharge, and 90-day re-hospitalization for suspected overdose.


Results: A total of 89 critically ill patients initiated on methadone during the study period met inclusion criteria. The mean daily dose of methadone on days 1-7 was 32 mg, 40 mg, 44 mg, 50 mg, 55 mg, 57 mg, and 59 mg, respectively. In the first 7 days there were 23 (25.8%) patients who required a dose to be held or reduced. There were 29 patients who experienced QTc prolongation, 2 patients who experienced in-hospital mortality, 3 patients were re-hospitalized for suspected overdose, and 84 patients were enrolled in a treatment program at discharge. Dose reduction was more common in patients who underwent guideline recommended titration (34.8%) compared to rapid titration (22.4%).


Conclusions: Rapid titration of methadone was well tolerated in critically ill patients compared to standard titration, with over 80% of patients continuing methadone treatment at time of discharge. This data contributes safety outcomes of methadone induction in the critically ill patient population.