Use of Intrathecal Midazolam to Improve Perioperative Analgesia: A Meta-Analysis

Abstract

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; I 2 =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; I 2 =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, I 2 =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.

Midazolam Activates the Intrinsic Pathway of Apoptosis Independent of Benzodiazepine and Death Receptor Signaling

“…6,7 Although no neurotoxicity was observed in any of these clinical studies and its use has been advocated recently, large randomized controlled studies with prolonged follow-up are required to confirm the clinical safety of intrathecal midazolam. 1 The aim of this study was to elucidate the mechanism of midazolam-induced toxicity. Results of animal studies are controversial; most studies could demonstrate a neurotoxic effect when midazolam was applied as a bolus or as a continuous infusion in different animal models.…”

“…4,5 Used as an adjuvant for spinal anesthesia, midazolam could reduce postoperative nausea and vomiting, delay the first administration of rescue pain medication, and increase cardiovascular stability. 1,6,7 Although clinical studies suggested safety in more than 500 patients, there is still considerable concern based on the potential neurotoxicity of intrathecal midazolam. 8,9 Animal studies have been contradictory.…”

Intrathecal Midazolam as an Adjuvant in Pregnancy-Induced Hypertensive Patients Undergoing an Elective Caesarean Section: A Clinical Comparative Study

“…As a result, various studies have shown that the analgesic effect of intrathecal bupivacaine is enhanced by intrathecal midazolam without producing significant side effects (9, 10). Various researchers have evaluated the effectiveness of intrathecal midazolam in postoperative analgesia in normal caesarean patients (11, 12). However, the effect of intrathecal midazolam has not been evaluated in PIH patients.…”

The Influence of Adjuvants Used in Regional Anesthesia on Lidocaine-Induced Neurotoxicity In Vitro

“…52 Regarding possible neurotoxicity of midazolam, data are contradictory. 53,54 On the one hand, in hundreds of patients, the incidence of observed neurologic symptoms was uncommon (1.8%) and not different from placebo, 52 whereas on the other hand, severe neurotoxicity has been described in most animal models of spinal anesthesia. 46,55Y57 As with lidocaine before, we demonstrated that midazolam induces apoptosis via activation of the intrinsic pathway.…”