Lack of evidence for fentanyl as the optimal opioid for critically ill patients on mechanical ventilation: a systematic review and meta-analysis

Abstract

Abstract Background: Fentanyl is selected to manage pain in critical care patients in the intensive care unit (ICU). However, the usefulness of fentanyl has not been established. This study examined the evidence for the use of fentanyl to improve the clinical outcomes in 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 that compared the intravenous administration of fentanyl and other opioids in mechanically ventilated patients. The study quality was assessed using the GRADE system and Cochrane methodology. The primary outcome was mortality. 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: Eleven Randomized Controlled Trials met the study inclusion criteria with 1312 patients (643 were treated with fentanyl and 669 with other opioids, including 628 with remifentanil and 41 with morphine). Among 816 participants from 4 RCTs, fentanyl was not associated with mortality (risk ratio [RR], 0.74; 95% confidence interval [CI], 0.28 to 2.00; low-quality evidence). Regarding the secondary outcomes, fentanyl did not shorten the duration of mechanical ventilation (mean difference [MD], −1.71 h; 95% CI, −3.79 to 0.37; moderate-quality evidence) or the duration of the ICU stay (MD, −1.89 h; 95% CI, −5.00 to 1.22; moderate-quality evidence) compared with other opioids. Fentanyl also did not increase the incidence of severe adverse events (RR, 0.80; 95% CI, 0.56 to 1.15; moderate-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 ICUs worldwide, the current analysis found no evidence to support its clinical use. However, the GRADE evaluation provides little certainty to support the results of this systematic review, and further large RCTs are therefore needed to confirm the conclusions.Trial registration: PROSPERO, CRD42019130648https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=130648