Use of Intrathecal Neostigmine as an Adjunct to Other Spinal Medications in Perioperative and Peripartum Analgesia: A Meta-analysis

Abstract

Intrathecal neostigmine has been used as an adjunct to intrathecal local anaesthetic or opioid to prolong regional analgesia and improve haemodynamic stability, with variable results. This meta-analysis aims to evaluate the effectiveness and side-effects of intrathecal neostigmine in the perioperative and peripartum settings. The literature search was based on Cochrane Controlled Trials Register, EMBASE and MEDLINE (from 1966 to 14 November 2003) databases. Volunteer and animal studies were excluded. We identified 26 studies and 19 were considered suitable for detailed data extraction. Intrathecal neostigmine increased the incidence of nausea and vomiting (OR 5.0, 95% CI: 3.4 to 7.3; P<0.00001), bradycardia requiring intravenous atropine (OR 2.7, 95% CI: 1.4 to 5.4; P=0.005), and anxiety, agitation, or restlessness (OR 10.3, 95% CI: 3.7 to 28.9; P=0.00001). It improved the overall 24 hour VAS score (–1.4 VAS pain score, 95% CI: -1.7 to -1.2, P<0.00001), delayed the time of first request for rescue analgesia (168 min, 95% CI: 125 to 211; P<0.00001), and reduced the total number of rescue injections of nonsteroidal anti-inflammatory drug within the first 24 hours (-0.8, 95% CI: -1.1 to -0.4; P=0.00001). It did not affect the duration of motor blockade (3.5 min, 95% CI: -1.5 to 8.6; P=0.17) or the total amount of ephedrine required (-0.4 mg, 95% CI: -1.5 to 0.7; P=0.5). Adding intrathecal neostigmine to other spinal medications improves perioperative and peripartum analgesia marginally when compared with placebo. It is associated with significant side-effects and the disadvantages outweigh the minor improvement in analgesia achieved.