The analgesic efficacy and safety of neuraxial magnesium sulphate: a quantitative review

Abstract

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.

Potential strategies for preventing chronic postoperative pain: a practical approach: Continuing Professional Development

“…For many years, animal studies suggested that intrathecal magnesium was able to block acute pain and hyperalgesia after surgery. Recent reviews of the literature in humans showed that intrathecal magnesium does allow for an interesting decrease in postoperative acute pain, 50 but intravenous magnesium was less potent. 51 The fact that intravenous magnesium was less convincing to decrease acute postoperative pain might be explained by one clinical trial from Mercieri et al 52 In their study, the authors reported that intravenous magnesium did not properly cross the blood-brain barrier and, thus, could hardly be expected to decrease acute postoperative pain if this effect relied on its activity at the CNS level.…”

Comparative Study of Intrathecal Dexmedetomidine vs Fentanyl as an Adjuvant to Hyperbaric Bupivacaine

“…Nevertheless, IT magnesium has been used in significant number of humans and there have been no documented neurological complications. [16] Onset of analgesia at T6 was delayed with intrathecal magnesium sulphate compared to intravenous magnesium and placebo. Time to 2 segment regression of sensory block, duration of spinal anaesthesia as well as duration of effective analgesia were significantly prolonged in intrathecal as well as intravenous magnesium as compared to placebo.…”

“…[12][13][14][15] However, IT magnesium has been used in significant number of humans and there were no documented neurological complications. [16] Histopathological and ultra-structural human spinal cord studies may sound interesting but are practically next to impossible. In such circumstances off label use of magnesium intrathecally is supposed to thrive because of its advantages.…”

A Prospective, Double Blind Randomized Controlled Study Comparing the Effects of Magnesium Sulphate Versus Clonidine as an Adjunct to Bupivicaine in Sub Umbilical Surgeries

“…The frequency of rescue analgesic was also significantly less on addition of magnesium sulphate (p<0.01) Albrecht et al 15 in their review found that the time for first analgesic request increased by 11.1% after intrathecal magnesium administration and by 72.2 % after epidural administration with doses between 50 and 100mgs.…”