Replacement of fentanyl infusion by enteral methadone decreases the weaning time from mechanical ventilation: a randomized controlled trial

Abstract

IntroductionPatients undergoing mechanical ventilation (MV) are frequently administered prolonged and/or high doses of opioids which when removed can cause a withdrawal syndrome and difficulty in weaning from MV. We tested the hypothesis that the introduction of enteral methadone during weaning from sedation and analgesia in critically ill adult patients on MV would decrease the weaning time from MV.MethodsA double-blind randomized controlled trial was conducted in the adult intensive care units (ICUs) of four general hospitals in Brazil. The 75 patients, who met the criteria for weaning from MV and had been using fentanyl for more than five consecutive days, were randomized to the methadone (MG) or control group (CG). Within the first 24 hours after study enrollment, both groups received 80% of the original dose of fentanyl, the MG received enteral methadone and the CG received an enteral placebo. After the first 24 hours, the MG received an intravenous (IV) saline solution (placebo), while the CG received IV fentanyl. For both groups, the IV solution was reduced by 20% every 24 hours. The groups were compared by evaluating the MV weaning time and the duration of MV, as well as the ICU stay and the hospital stay.ResultsOf the 75 patients randomized, seven were excluded and 68 were analyzed: 37 from the MG and 31 from the CG. There was a higher probability of early extubation in the MG, but the difference was not significant (hazard ratio: 1.52 (95% confidence interval (CI) 0.87 to 2.64; P = 0.11). The probability of successful weaning by the fifth day was significantly higher in the MG (hazard ratio: 2.64 (95% CI: 1.22 to 5.69; P < 0.02). Among the 54 patients who were successfully weaned (29 from the MG and 25 from the CG), the MV weaning time was significantly lower in the MG (hazard ratio: 2.06; 95% CI 1.17 to 3.63; P < 0.004).ConclusionsThe introduction of enteral methadone during weaning from sedation and analgesia in mechanically ventilated patients resulted in a decrease in the weaning time from MV.

Sedation, Analgesia, and Paralysis in COVID-19 Patients in the Setting of Drug Shortages

“…28 A multicenter, double-blind randomized control trial evaluated the use of enteral methadone in mechanically ventilated critically ill patients who received fentanyl continuous infusion for at least 5 days. 44 In this study, after patients were started on enteral methadone 10 mg every 6 hours, fentanyl infusion rates were reduced by 20% every 24 hours. The methadone dose was increased by 50% if patients exhibited opioid withdrawal intolerance.…”

Enteral versus intravenous approach for the sedation of critically ill patients: a randomized and controlled trial

“…Analgesic [21] and sedative [22] drugs are rarely administered enterally (EN) because of their slower onset of effect and unpredictable pharmacokinetics, even when intestinal absorption is adequate from ICU admission [23]. Our “EN sedation” protocol [24] uses hydroxyzine (a first-generation antihistaminic drug, with antiemetic and gastric antisecretory properties) and allows the addition of low doses of lorazepam (a medium-half-life benzodiazepine) if necessary.…”

The use of methadone to facilitate opioid weaning in pediatric critical care patients: a systematic review of the literature and meta‐analysis

“…In adult intensive care, methadone has been used successfully to facilitate narcotic weaning, reducing the duration of opioid infusion and the length of exposure to mechanical ventilation in specific populations . Transitioning to a long‐acting opioid such as methadone is a generally accepted approach to narcotic weaning in pediatric patients .…”