Enteral methadone for iatrogenic opioid withdrawal in patients with COVID-19 acute respiratory distress syndrome: A case series

Rationale: Patients with severe acute respiratory distress syndrome (ARDS) often require deep sedation for extended periods of time to facilitate mechanical ventilation. The emergence of COVID-19 resulted in high volume of patients admitted to our tertiary care center with severe ARDS. Many developed withdrawal symptoms upon tapering of continuous sedation and were unable to be safely extubated despite improved ventilator requirements. A protocol using enteral methadone was developed to facilitate tapering of continuous sedation and mitigate the severity of iatrogenic withdrawal. Methods: Data was collected through retrospective chart review of patients treated with protocolized methadone for IWS during 04/2020-08/2020. Inclusion criteria were FiO2 ≤ 60%, PEEP ≤ 12cmH220, ≥ 5 days of continuous fentanyl or hydromorphone (≥100 mcg/hr or 1.5 mg/hr respectively), and approval by the toxicology and addiction medicine service. Those receiving high dose vasopressors, paralytics, or QTc ≥500ms were excluded. Descriptive statistics after initiation of methadone are presented in the following case series. Results: There were 32 patients treated with methadone for IWS during the study period. Of these participants, 90% were male (N=29) with median age of 59 (IQR 52-63.5). Opioid infusions were successfully weaned in 75% of patients (N=24) treated with methadone. Median time to wean continuous opioids after starting methadone was 2.5 days (mean 4.08, IQR 1-5). At the end of the study period, 40% (N=13) of patients died from complications of COVID-19. Of the patients who survived, 7 required tracheostomy placement and 16 were successfully extubated. One patient developed prolonged QT with ectopy and was switched to IV Buprenorphine. She was subsequently weaned off continuous sedation after 5 days. Another patient developed prolonged QT but was able to resume after holding for 48 hours. Conclusion: IWS is a barrier to de-escalation of care in patients with COVID-19 ARDS. IWS is associated with longer ICU stay and duration of mechanical ventilation. Protocolized methadone use can be an effective tool for mitigating IWS as suggested by the findings in this study. This study is limited by the lack of a control group. Future directions include comparison to a matched cohort of patients not treated with methadone. Continued investigation with prospective studies in the context of changing practice guidelines for COVID-19 are also warranted. If methadone is found to be safe and effective in future studies, widespread use could help reduce the strain on ICU resources by COVID-19.