A Phase II Cluster-Crossover Randomized Trial of Fentanyl vs. Morphine for Analgosedation in Mechanically Ventilated Patients.

Abstract

The continuous infusion of fentanyl or morphine is often prescribed to assist with analgesia and sedation (analgosedation) during mechanical ventilation. To compare the effect of fentanyl vs. morphine on patient-centered outcomes in ventilated patients. We conducted a cluster-randomized, cluster-crossover trial between July 2019 and August 2020 in two adult Intensive Care Units. We compared two continuous infusion regimens (fentanyl vs. morphine). One Intensive Care Unit was randomized to the fentanyl-morphine sequence and the other to the morphine-fentanyl sequence. The primary outcome was the number of ventilator free days at day 28. Secondary outcomes included, among others, duration of mechanical ventilation in survivors and Intensive Care Unit free days at day 28. Via cluster allocation, we randomized 737 patients. Of these, 56 were excluded due to the opt-out consent process, leaving 681 (344 to fentanyl and 337 to morphine) for primary analysis (median [IQR] age, 59 [44-69] years). Median ventilator free days at day 28 were 26.1 (20.7-27.3) in the fentanyl vs 25.3 (19.1-27.2) in the morphine group (median difference, 0.79 [95% CI, 0.31 to 1.28], p=0.001). Intensive Care Unit-free days were greater (P<0.001) and Intensive Care Unit length of stay in survivors shorter (P<0.001) in the fentanyl group. All other secondary outcomes were not statistically different by treatment group. Among adult patients requiring mechanical ventilation, compared with morphine, fentanyl infusion significantly increased the median number of ventilator free days at day 28. The choice of opioid infusion agent may affect clinical outcomes and requires further investigation. Clinical trial registration available at https://www.anzctr.org.au/, ID: ACTRN12619000939190.