Fentanyl as an induction agent for tracheal intubation in critically ill patients: a systematic review and...

Tracheal intubation in critically ill adults is frequently complicated by severe physiological adverse events, particularly cardiovascular instability. Although fentanyl is commonly used for induction, observational data suggest that its use may increase the risk of post-intubation hypotension. However, the overall randomized evidence remains unclear. In this systematic review and meta-analysis of randomized controlled trials (RCTs), we hypothesized that induction regimens including fentanyl or its analogs would increase the risk of peri-intubation cardiovascular instability in critically ill patients.

We comprehensively searched PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and the WHO ICTRP from inception through October 31, 2025. Eligible studies were RCTs comparing an induction regimen including fentanyl or its analogs with one without them in critically ill adults undergoing tracheal intubation. The primary outcome was peri-intubation cardiovascular instability. Secondary outcomes included peri-intubation hypoxemia, successful intubation on the first attempt, duration of mechanical ventilation, ICU length of stay, and mortality. Random-effects meta-analyses were performed for all outcomes. Trial sequential analysis (TSA) was conducted for the primary outcome. Certainty of evidence was assessed using the GRADE approach.

We included five RCTs and 515 participants. Two studies were judged to be low risk of bias, two raised some concerns, and one was at high risk of bias. Comparators included various induction agents and placebo. Definitions of peri-intubation cardiovascular instability also varied. The evidence was very uncertain regarding the effect of fentanyl on the risk of peri-intubation cardiovascular instability (risk ratio, 1.41; 95% confidence interval, 0.83-2.40; risk difference, 9.2% more; 95% confidence interval, 3.8% fewer to 31.3% more; very low certainty). In TSA, the required information size (n = 5586) was not reached, indicating the lack of statistical power. The certainty of evidence for pooled secondary outcomes was generally low or very low.

The effect of fentanyl on peri-intubation cardiovascular instability remains highly uncertain, with pooled estimates compatible with substantial harm, substantial benefit, or no effect. Current randomized evidence is insufficient to guide routine clinical practice, given their very low or low certainty and susceptibility to random error.

PROSPERO (registration number: CRD420251241214).