Low-dose intrathecal morphine versus intrathecal fentanyl for post-caesarean analgesia in a resource-constrained setting: a pragmatic randomised trial

Citation:

Chetty S, Paruk F, Kamerman P. Low-dose intrathecal morphine versus intrathecal fentanyl for post-caesarean analgesia in a resource-constrained setting: a pragmatic randomised trial. BMC Anesthesiol. 2026. doi:10.1186/s12871-026-04034-0

This trial asked whether low-dose intrathecal morphine reduces rescue morphine use compared with intrathecal fentanyl after caesarean delivery. Intrathecal morphine probably reduced 24-hour rescue morphine use compared with fentanyl. The trial was single-centre, retrospectively registered, and mainly analysed per protocol.

Study at a glance

- Design and setting: Single-centre, participant- and outcome-assessor-blinded, parallel-group pragmatic randomised trial at Rahima Moosa Mother and Child Hospital, a tertiary public-sector maternity hospital in Johannesburg, South Africa, between July and September 2015. Randomisation was blocked in a 1:1:1 ratio with adequate allocation concealment; the attending anaesthetist preparing and administering the intrathecal solution was aware of allocation.

- Population: 105 women were screened, 100 were randomised, and 93 were analysed: M100 32, M50 29, and F25 32. Eligible participants were women aged 18 years or older undergoing elective or emergency caesarean delivery under single-shot spinal anaesthesia; sex female was 100%. Age, mean (range), was 31 (21–40) years in M100, 30 (23–39) years in M50, and 30 (21–41) years in F25.

- Interventions: M100 received hyperbaric bupivacaine 0.5% 1.8 ml plus preservative-free intrathecal morphine 100 μg; M50 received hyperbaric bupivacaine 0.5% 1.8 ml plus preservative-free intrathecal morphine 50 μg; F25 received hyperbaric bupivacaine 0.5% 1.8 ml plus intrathecal fentanyl 25 μg. Total intrathecal volume was standardised to 2.3 ml during single-shot spinal anaesthesia. Postoperative analgesia included intravenous morphine patient-controlled analgesia solution 1 mg.ml-1, 1 mg bolus, 5-minute lockout, maximum 10 mg.h-1, no background infusion, plus rectal indomethacin.

- Primary outcome: Cumulative 24-hour intravenous patient-controlled analgesia morphine consumption probably was lower with intrathecal morphine versus fentanyl (moderate certainty): medians were M100 12.5 mg (interquartile range 6 to 20.25), M50 15 mg (interquartile range 9 to 25), and F25 26 mg (interquartile range 16.5 to 38.5); overall p=0.00078. Hodges-Lehmann estimates were M100 vs F25 -13 mg (95% CI -20 to -7; p=0.00081), M50 vs F25 -10.5 mg (95% CI -18 to -3; p=0.019), and M100 vs M50 -3 mg (95% CI -8 to 3; p=0.326).

- Key secondary outcome: Intravenous patient-controlled analgesia morphine consumption during 0–12 h may have been lower with morphine: M100 8 mg (interquartile range 2.75 to 12), M50 8 mg (interquartile range 4 to 17), and F25 16 mg (interquartile range 11 to 25.5); overall p=0.0021. Pairwise point estimates and 95% confidence intervals were not reported (low certainty).

- Safety: Respiratory depression, defined as respiratory rate < 8 breaths/min, occurred in 0/32 M100, 0/29 M50, and 0/32 F25. Any nausea or vomiting occurred in 9/32, 9/29, and 9/32; severe nausea or vomiting in 5/32, 0/29, and 5/32; any pruritus in 12/32, 14/29, and 9/32; severe pruritus in 1/32, 1/29, and 1/32; and any sedation in 7/32, 7/29, and 10/32, respectively. Serious adverse events and withdrawals due to adverse events: Not reported; harms were descriptive and the study was powered for analgesic efficacy rather than uncommon adverse events.

- Risk of bias and certainty: RoB 2 overall judgement was Some concerns. Low risk was judged for randomization process and measurement of outcome; Some concerns were judged for deviations from intended interventions, missing outcome data, and selection of reported result, including unblinded attending anaesthetist, per-protocol primary contrasts after post-randomisation exclusions, outcome data available for 93/100 randomised participants, and retrospective registration. Overall GRADE certainty was Moderate for the primary outcome and Low for secondary outcomes.