Comparative efficacy of remifentanil and fentanyl in mechanically ventilated ICU patients: a systematic review and meta-analysis on ventilation duration and delirium incidence

Abstract

Background: The ultrashort-acting properties and organ-independent metabolism of remifentanil may be advantageous in mechanical ventilation management. Unlike fentanyl, which accumulates over time and may prolong sedation, remifentanil enables more predictable titration and rapid weaning. This study aimed to determine the effect of remifentanil on shortening the duration of mechanical ventilation in comparison with fentanyl in adult intensive care unit (ICU) patients.

Methods: A systematic review and meta-analysis was conducted, including randomised controlled trials (RCTs) and observational studies from MEDLINE, Cochrane, EMBASE, ICTRP, and ClinicalTrials.gov, from inception to July 2024. Studies comparing remifentanil with fentanyl in mechanically ventilated ICU patients were included, whereas those that used only remifentanil or fentanyl intraoperatively were excluded. The primary outcome was ventilation duration, with a minimal important difference (MID) of 90 min. A random-effects meta-analysis was performed and the certainty of evidence was assessed using the GRADE approach. The risk of bias was evaluated using RoB 2.0 and ROBINS-I tools.

Results: We included 18 studies (14 RCTs and 4 observational studies). Ten studies (8 RCTs and 2 observational studies; 901 patients) were analysed. Remifentanil may reduce ventilation duration compared to fentanyl (8 RCTs: MD -6.70 h, 95% CI -14.36 to 0.97; low certainty; 2 observational studies: MD -21.26 h, 95% CI -37.29 to -5.24; low certainty).

Conclusions: Remifentanil may reduce the duration of mechanical ventilation, potentially improving patient outcomes. However, owing to the low certainty of the evidence and study heterogeneity, further high-quality RCTs are required to validate these findings.

Trial registration: PROSPERO 2024 and CRD42024557414.

Keywords: Critical care; Fentanyl; Mechanical ventilation; Meta-analysis; Remifentanil; Systematic review.

Fig. 1

PRISMA flow diagram of study selection. Eighteen studies were identified through a database search. After removing duplicates and screening based on eligibility criteria, X studies were included in the final meta-analysis

Fig. 2

Forest plot comparing duration of mechanical ventilation between remifentanil and fentanyl. The mean difference (MD) with 95% confidence intervals (CI) is displayed for each study. The pooled effect estimate (black diamonds) suggests that remifentanil may reduce the duration of mechanical ventilation compared to fentanyl, although the statistical significance varies across subgroups. In randomised controlled trials (RCTs) (MD: −6.70 h, 95% CI: −14.36 to 0.97, P = 0.02), the reduction was not significant, while it was significant in non-randomised studies (MD: −21.26 h, 95% CI: −37.29 to −5.24, P = 0.009)

Fig. 3

Forest plot comparing incidence of delirium between remifentanil and fentanyl in randomized controlled trials (RCTs). The risk ratios (RR) with 95% confidence intervals (CI) for each study are shown The pooled effect estimate (black diamond) suggests that remifentanil may reduce the risk of the outcome compared to fentanyl (RR: 0.73, 95% CI: 0.51–1.04, P = 0.08), although the result is not significant. The heterogeneity among the studies was low (I² = 0%), indicating consistency across the included trials