Use of intrathecal midazolam to improve perioperative analgesia: a meta-analysis

Intrathecal midazolam binds with gamma aminobutyric acid-A receptors in the spinal cord leading to an analgesic effect. Clinical studies suggested that intrathecal midazolam may also reduce nausea and vomiting when used as an adjunct to other spinal medications. However, the potential neurotoxic effect of intrathecal midazolam remains a concern. This meta-analysis aims to evaluate the effectiveness and side-effects of intrathecal midazolam in the perioperative and peripartum settings. Thirteen randomised controlled studies from MEDLINE (from 1966 to July 1, 2007), EMBASE and Cochrane Controlled Trials Register databases, involving a total of 672 patients, were considered. Volunteer, animal and chronic pain studies were excluded. Adding intrathecal midazolam to other spinal medications reduced the incidence of nausea and vomiting (odds ratio 0.50, 95% confidence interval [CI] 0.27 to 0.90, P=0.02; I2=4%) and delayed the time to request for rescue analgesia (weighted-mean-difference=98.7 min, 95% CI: 76.1 to 121.4, P<0.00001; I2=98.5%). Intrathecal midazolam did not affect the duration of motor blockade (weighted-mean-difference =25.1 min, 95% CI -7.6 to 57.8, P=0.13, I2=94.8%). The incidence of neurological symptoms after intrathecal midazolam was uncommon (1.8%) and did not differ from placebo (odds ratio 1.20, 95% CI 0.22 to 6.68, P=0.84). Based on the limited data available, intrathecal midazolam appears to improve perioperative analgesia and reduce nausea and vomiting during caesarean delivery. A multicentre registry or large randomised controlled study with a prolonged follow-up period would be useful to confirm the clinical safety of intrathecal midazolam.