SummaryEighteen published trials have examined the use of neuraxial magnesium as a peri-operative adjunctive analgesic since 2002, with encouraging results. However, concurrent animal studies have reported clinical and histological evidence of neurological complications with similar weight-adjusted doses. The objectives of this quantitative systematic review were to assess both the analgesic efficacy and the safety of neuraxial magnesium. Eighteen trials comparing magnesium with placebo were identified. The time to first analgesic request increased by 11.1% after intrathecal magnesium administration (mean difference: 39.6 min; 95% CI 16.3-63.0 min; p = 0.0009), and by 72.2% after epidural administration (mean difference: 109.5 min; 95% CI 19.6-199.3 min; p = 0.02) with doses of between 50 and 100 mg. Four trials monitored for neurological complications: of the 140 patients included, only a 4-day persistent headache was recorded. Despite promising peri-operative analgesic effect, the risk of neurological complications resulting from neuraxial magnesium has not yet been adequately defined. Magnesium has analgesic properties, primarily related to the regulation of calcium influx into cells [1] and antagonism of N-methyl-D-aspartate (NMDA) receptors in the central nervous system [2,3]. This analgesic effect was first demonstrated in humans in 1996 when magnesium was administered intravenously in the peri-operative period [4]. Since then, a number of additional trials investigating the analgesic efficacy of peri-operative intravenous magnesium have been published, with conflicting results [5][6][7]. One possible explanation for the reported variability in analgesic efficacy of magnesium administered intravenously may be limited passage of this molecule across the blood-brain barrier, which has been demonstrated even in the presence of induced systemic hypermagnesaemia [8][9][10]. Consequently, it has been suggested that an intrathecal injection would allow more effective magnesium activity at spinal cord NMDA receptors. Indeed, rat models reveal that direct intrathecal administration of magnesium enhances the antinociceptive effect of opioids for acute incisional pain [11], and suppresses nociceptive responses in neuropathic pain models [12]. The earliest clinical trials investigating intrathecal and epidural magnesium reported an increase in the median duration of analgesia [13] and decrease in opioid consumption by 25% [14], respectively.