Effects of fentanyl administration in mechanically ventilated patients in the intensive care unit: a systematic review and meta-analysis

Background: Fentanyl is selected to manage pain in critical care patients on mechanical ventilation in the intensive care unit (ICU). However, the usefulness of fentanyl compared with other opioids is unknown. This study examined the evidence for using fentanyl to improve the clinical outcomes of ICU patients, using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Methods: We searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases in June 2021. Two independent assessors reviewed studies to identify randomized, controlled trials (RCTs) that compared the intravenous administration of fentanyl and other opioids in mechanically ventilated patients in the ICU. The study quality was assessed using the GRADE system and Cochrane methodology. The primary outcome was mortality. The secondary outcomes were the duration of mechanical ventilation, duration of the ICU stay, incidence of severe adverse events, and incidence of delirium. We integrated outcome data using a random-effects model and showed absolute values and certainty of evidence in the GRADE evidence profile. Results: Seven RCTs met the study inclusion criteria with 534 patients (251 were treated with fentanyl and 283 with other opioids, including 242 with remifentanil and 41 with morphine). Among 191 participants from 2 RCTs, fentanyl was not associated with mortality (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.24 to 2.60; low-quality evidence). Regarding the secondary outcomes, fentanyl did not shorten the duration of mechanical ventilation (mean difference, 0.49 h; 95% CI, - 0.90 to 1.88; moderate-quality evidence) or the duration of the ICU stay (mean difference, 7.04 h; 95% CI, - 3.27 to 17.35; moderate-quality evidence) compared with other opioids. Fentanyl did not increase the incidence of severe adverse events (RR, 0.98; 95% CI, 0.50 to 1.90; low-quality evidence) or delirium (RR, 1.27; 95% CI, 0.79 to 2.04; low-quality evidence). Conclusions: Although fentanyl is a frequently administered opioid in the ICU, patients' outcomes are not different between fentanyl use and use of other opioids. However, the GRADE evaluation provides little certainty to support the results of this systematic review. Therefore, further large RCTs are required to confirm our conclusions.