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

BackgroundVariable 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.MethodsDatabases 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.ResultsEleven 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; I²=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; I²=100%). The risk of pruritus increased by 13% (95% CI 5 to 21%; P=0.001; I²=81%). Pooled data suggest that the incidence of nausea and vomiting, and neonatal outcomes did not significantly differ.ConclusionsIn 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.