Rationale: The continuous infusion of fentanyl or morphine is often prescribed to assist with analgesia and sedation (analgosedation) during mechanical ventilation. Objectives: To compare the effect of fentanyl versus morphine on patient-centered outcomes in ventilated patients. Methods: We conducted a cluster-randomized, cluster-crossover trial between July 2019 and August 2020 in two adult ICUs. We compared two continuous infusion regimens (fentanyl versus morphine). One ICU 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 ICU-free days at Day 28. Measurements and Main Results: Via cluster allocation, we randomized 737 patients. Of these, 56 were excluded because of the opt-out consent process, leaving 681 (344 to fentanyl and 337 to morphine) for primary analysis (median [interquartile range] age, 59 [44-69] years). Median ventilator-free days at Day 28 were 26.1 (20.7-27.3) in the fentanyl versus 25.3 (19.1-27.2) in the morphine group (median difference, 0.79 [95% confidence interval, 0.31 to 1.28], P = 0.001). ICU-free days were greater (P < 0.001) and length of stay in the ICU for survivors shorter (P < 0.001) in the fentanyl group. All other secondary outcomes were not statistically different by treatment group. Conclusions: 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.

中文翻译：

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芬太尼与吗啡用于机械通气患者镇痛镇静的 II 期集群交叉随机试验。

理由：在机械通气期间，经常开出芬太尼或吗啡的连续输注以帮助镇痛和镇静（镇痛镇静）。目的：比较芬太尼与吗啡对通气患者以患者为中心的结局的影响。方法：我们于 2019 年 7 月至 2020 年 8 月在两个成人 ICU 中进行了一项整群随机、整群交叉试验。我们比较了两种连续输注方案（芬太尼与吗啡）。一个 ICU 被随机分配到芬太尼-吗啡序列，另一个被随机分配到吗啡-芬太尼序列。主要结果是第 28 天的无呼吸机天数。次要结果包括幸存者机械通气的持续时间和第 28 天的无 ICU 天数。 测量和主要结果：通过集群分配，我们随机分配了 737 名患者. 其中，56 人因选择退出同意程序而被排除在外，剩下 681 人（344 人为芬太尼，337 人为吗啡）进行初步分析（中位数 [四分位距] 年龄，59 [44-69] 岁）。在第 28 天，芬太尼组的中位无呼吸机天数为 26.1 (20.7-27.3)，而吗啡组为 25.3 (19.1-27.2)（中位数差异，0.79 [95% 置信区间，0.31 至 1.28]，P = 0.001）。芬太尼组的非 ICU 天数更长 (P < 0.001)，幸存者在 ICU 的停留时间更短 (P < 0.001)。所有其他次要结果在治疗组之间没有统计学差异。结论：在需要机械通气的成年患者中，与吗啡相比，芬太尼输注显着增加了第 28 天无呼吸机天数的中位数。