Adverse side effects and route of administration of opioids in combined spinal-epidural analgesia for labour: a meta-analysis of randomised trials

Background: Studies report an increased risk of maternal and fetal adverse side effects when combined spinal-epidural, rather than standard epidural, analgesia is provided for labour and delivery. Intrathecal opioids used with local anaesthetic in combined spinal-epidural analgesia may be a cause. It is not known whether this is due to the addition of opioid to local anaesthetic in the intrathecal space only or due to concomitant administration into the intrathecal and epidural spaces. Methods: We searched for randomised trials comparing maternal, obstetrical and neonatal outcomes in parturients having combined spinal-epidural or standard epidural analgesia, and compared subgroups of patients according to the route of administration of opioids in combined spinal-epidural techniques. Studies were evaluated for eligibility and quality. Fixed and random-effects models were used for pooled data analysis and outcomes were compared using relative risk (RR) or mean difference with 95% confidence intervals (CI). Results: We identified 1658 reports and 41 fully published randomised controlled trials. In patients who received combined spinal epidural techniques, an increased risk of nausea/vomiting (RR 1.31, CI 1.0 to 1.72), pruritus (RR 4.26, CI 2.59 to 7.0) and fetal bradycardia (RR 2.38, CI 1.57 to 3.62) was observed regardless of the route of administration. In contrast, hypotension occurred more frequently after combined intrathecal and epidural opioid (RR 1.54, 1.22 to 1.93; P-value 0.02 for subgroup difference). Conclusion: For combined spinal-epidural techniques, the administration of opioids in combination with local anaesthetic, particularly when used in both the intrathecal and epidural space, should be carefully considered. (C) 2019 Elsevier Ltd. All rights reserved.