Maternal and neonatal outcomes with the addition of intrathecal midazolam as an adjuvant to spinal anesthesia in cesarean delivery: A systematic review and meta-analysis of randomized controlled trials

Abstract

Study objectiveTo determine the efficacy and safety, in terms of maternal and neonatal outcomes, of adding intrathecal midazolam to spinal anesthesia for cesarean delivery in healthy pregnant women. DesignA meta-analysis of randomized controlled trials was conducted. PubMed, Cochrane Library, Embase, and Web of Science were searched manually, and citation screening was completed on May 20, 2021. SettingMost of the included data were collected in the operating room and postoperative recovery area. PatientsA total of 1382 healthy parturients undergoing cesarean delivery with single-shot spinal anesthesia were recruited in 19 eligible randomized controlled trials. InterventionsSingle intrathecal midazolam adjuvant was compared to a control, with the local anesthetic dose in spinal anesthesia identical between the intervention and control groups. MeasurementsThe primary outcomes were time to first analgesic use, maternal adverse effects, and neonatal Apgar scores at 1 and 5 min. The secondary outcomes were the onset and duration of the sensory and motor blocks. Main resultsAdjuvant intrathecal midazolam prolonged the time to the first analgesic (mean difference [MD]: 59.96 min, 95% confidence interval [CI]: [23.12, 96.79]) and decreased perioperative maternal nausea and/or vomiting (odds ratio [OR], 0.28; 95% CI: [0.17, 0.45]). However, more sedation events were observed with midazolam (OR, 3.93; 95% CI: [1.12, 13.78]). There was no significant difference in the neonatal Apgar scores at 1 or 5 min (MD: -0.29, 95% CI: [−0.61, 0.03]; MD: -0.00, 95% CI: [−0.11, 0.1], respectively). Intrathecal midazolam also shortened sensory and motor block onset by less than 1 min and prolonged sensory block duration but had no significant effect on motor block duration. ConclusionsCurrent evidence indicates that intrathecal midazolam, as an adjuvant to spinal anesthesia, provides modest analgesic and significant antiemetic effects at the cost of more sedation events in cesarean delivery patients. The neonatal Apgar score was not affected by intrathecal midazolam administration. However, more objective, sensitive, and long-term measurements of neonatal safety and maternal neurological effects should be performed in the future.