Intrathecal bupivacaine versus bupivacaine plus fentanyl for anaesthesia for Caesarean delivery: a randomised double-blind noninferiority trial

BACKGROUND: Fentanyl is commonly mixed with bupivacaine for spinal anaesthesia for Caesarean delivery. However, fentanyl has potential disadvantages. We hypothesised that simply increasing the bupivacaine dose would be at least as effective as adding fentanyl. METHODS: We performed a randomised, double-blinded trial in 626 women having elective Caesarean delivery under combined spinal-epidural anaesthesia to determine whether intrathecal hyperbaric bupivacaine 10.75 mg is noninferior to bupivacaine 9.0 mg plus fentanyl 15 μg for the primary outcome of effective anaesthesia, defined as T5 sensory block within 10 min and no intraoperative pain requiring treatment within the first 45 min. The chosen noninferiority margin was an absolute difference of 5%. Secondary outcomes included the incidences of intraoperative pain, nausea and vomiting, hypotension, and pruritus. RESULTS: Effective anaesthesia was achieved in 94.4% (95% confidence interval [CI], 91.1-96.7%) of patients with bupivacaine vs 92.5% (95% CI, 88.9-95.2%) with bupivacaine plus fentanyl. The absolute difference between groups was 1.9% (95% CI, -2.0% to 5.9%); because the lower confidence limit is greater than the noninferiority margin, noninferiority of bupivacaine was demonstrated (P=0.003). The incidence of pruritus was greater with bupivacaine plus fentanyl (7.2%) vs bupivacaine alone (0.7%) (P<0.001). There was no difference between groups for other secondary outcomes. CONCLUSIONS: Under the condition of this study, use of a higher dose of intrathecal bupivacaine was noninferior to bupivacaine plus fentanyl for providing effective anaesthesia for Caesarean delivery. Use of bupivacaine alone for spinal anaesthesia for Caesarean delivery can be considered when adding fentanyl is not desired or not feasible. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2400080830).