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Replacement of Fentanyl Infusion by Enteral Methadone Decreases the Weaning Time from Mechanical Ventilation: A Randomized Controlled Trial
Study Question: Can a regimen of enteral methadone decrease mechanical ventilation (MV) weaning time in adult critically patients?
Study Description: This article described a randomized, double-blind, multi-centered trial conducted in adult ICUs in Brazil. Adult, MV patients (n = 68) who received five or more consecutive days of fentanyl and met defined MV weaning criteria were randomized to receive either enteral methadone (10 mg every 6 h) or matching placebo. After 24 hours of enrollment, patients in the methadone group were taken off fentanyl and given an IV infusion of saline in its place while the placebo group was maintained on a fentanyl infusion. In both groups, the infusions were reduced by 20% every 24 hours to prevent withdrawal syndrome. Daily interruptions of sedation, sedation scales, and delirium diagnoses were not standardized. Patients were assessed for spontaneous breathing trial eligibility daily and were followed until death or hospital discharge. Outcomes included weaning time, duration of MV, and ICU and hospital lengths of stay (LOSs).
Results: Fourteen patients died before ventilation weaning could take place. Among the survivors, weaning time was significantly lower in the methadone group (p < 0.004), with a median time of 4 days vs. 7 days in the placebo group. However, there was no significant difference in total MV duration or ICU or hospital LOSs. In the methadone group, 10 patients experienced signs of opioid withdrawal intolerance compared to 12 in the placebo group (p = 0.30).
Conclusion(s): The study’s authors conclude that results show that introducing enteral methadone during MV weaning may shorten weaning time. Larger trials needed to confirm these results and apply to clinical practice setting.
Perspective: MV patients often require prolonged or high dose opioids that may contribute to a withdrawal syndrome and difficulty in weaning. Patients in either group who experienced symptoms of opioid withdrawal were allowed intermittent doses of fentanyl and dose of methadone was increased by 50%. This trial suggests that methadone may be one possible adjunctive therapy in the weaning of fentanyl by continuous infusion. However, there are several alternative strategies that may be employed (intermittent opioids doses, switching to short acting analgesia/sedative regimens, etc.) to achieve the same goals.