The effect of two groups of intrathecal fentanyl doses on analgesic outcomes and adverse effects in parturients undergoing cesarean delivery: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.

Background: Variable doses of intrathecal fentanyl (ITF) have been used for peri-operative analgesia during cesarean delivery (CD). We conducted a systematic review and meta-analysis to compare lower doses (LD; ≤12.5 µg) and higher doses (HD; >12.5 µg) of ITF in parturients undergoing CD.

Methods: Databases were searched from inception to December 2020 for randomized controlled trials (RCTs) administering ITF as an additive to local anesthetic. The primary outcome was the use of intra-operative analgesic supplementation. Time to first rescue analgesia, the incidence of peri-operative side effects and neonatal outcomes were secondary outcomes. Additional analysis was performed after stratifying trials using ≤15 µg and >15 µg of ITF. Mean difference (MD) and risk difference (RD) with 95% confidence interval (CI) were calculated.

Results: Eleven RCTs met inclusion criteria. Study groups were 601 patients (LD) and 749 patients (HD). A HD of ITF reduced the risk for supplementation by 6% (95% CI 0 to 13%; P=0.05; I=80%) compared with LD, and increased the time to first rescue analgesia (MD 55.2 min, 95% CI 20.3 to 90.1, P=0.002; I=100%). The risk of pruritus increased by 13% (95% CI 5 to 21%; P=0.001; I=81%). Pooled data suggest that the incidence of nausea and vomiting, and neonatal outcomes did not significantly differ.

Conclusions: In women undergoing CD, doses of ITF >12.5 µg reduced the requirement for intra-operative analgesic supplementation and prolonged the time to first rescue analgesia compared with smaller doses, but increased pruritus. On revising the cut-off to 15 µg, no significant difference was found.