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

backgroundIntrathecal morphine is recommended for post-caesarean analgesia, but its implementation remains inconsistent in resource-constrained obstetric services, where short-acting intrathecal fentanyl is often favoured instead because of familiarity and perceived simplicity of use. We compared two low doses of intrathecal morphine with intrathecal fentanyl in women undergoing caesarean delivery under spinal anaesthesia in a South African public-sector hospital.

methodsThis was a single-centre, participant- and outcome-assessor-blinded, parallel-group pragmatic randomised trial. Women undergoing caesarean delivery under single-shot spinal anaesthesia were allocated to hyperbaric bupivacaine 0.5% 1.8 ml mixed with intrathecal morphine 100 µg (M100), intrathecal morphine 50 µg (M50), or intrathecal fentanyl 25 µg (F25). All participants received postoperative intravenous (IV) morphine patient-controlled analgesia (PCA) and rectal indomethacin. The primary outcome was cumulative 24-hour IV PCA morphine consumption. Secondary outcomes were morphine consumption for 0-12 h and 12-24 h, pain numerical rating scale (NRS) scores at rest and with cough at 12 and 24 h, perceived pain relief over 24 h, and whether participants wanted more analgesic treatment. The prespecified primary analysis was per protocol, with a supportive intention-to-treat analysis.

resultsOne hundred women were randomised. Ninety-three comprised the per-protocol efficacy cohort (M100 n = 32, M50 n = 29, F25 n = 32). Median 24-hour IV PCA morphine consumption differed significantly between groups: 12.5 mg (Q1, Q3: 6.0, 20.25) in M100, 15.0 mg (9.0, 25.0) in M50, and 26.0 mg (16.5, 38.5) in F25 (p < 0.001). After Holm adjustment for the three pairwise comparisons at the primary endpoint, the morphine groups required less rescue opioid than F25 (M100 vs. F25 adjusted p = 0.00081; M50 vs. F25 adjusted p = 0.019), whereas M100 and M50 did not differ (adjusted p = 0.326). Hodges-Lehmann estimates of the median difference in 24-hour morphine consumption were - 13.0 mg (95% CI -20.0 to -7.0) for M100 vs. F25 and - 10.5 mg (95% CI -18.0 to -3.0) for M50 vs. F25, and - 3.0 mg (95% CI -8.0 to 3.0) for M100 vs. M50. The same directional pattern was present for 0-12 h and 12-24 h. Pain scores at rest and with cough did not differ significantly between groups at either postoperative assessment. Perceived pain relief over 24 h was similar across groups, and the proportion of women who wanted more analgesic treatment did not differ significantly. The intention-to-treat analysis was concordant with the per-protocol analysis.

conclusionsIn this single-centre pragmatic trial conducted in a South African public-sector hospital, low-dose intrathecal morphine at both 50 µg and 100 µg reduced 24-hour postoperative opioid requirements after caesarean delivery compared with intrathecal fentanyl 25 µg. These findings additionally support 50 µg intrathecal morphine as an effective and implementable option for post-caesarean analgesia in resource-constrained obstetric settings.

trial registrationClinicalTrials.gov NCT02577809 (retrospectively registered 10 October 2015).