Is intravenous magnesium sulphate a suitable adjuvant in postoperative pain management? - A critical and systematic review of methodology in randomized controlled trials

A growing worldwide focus on opioid-free anaesthesia entails multimodal analgesic strategies involving non-opioids such as magnesium sulphate (MgSO4). Several systematic reviews have concluded there is beneficial analgesic effect of MgSO4 administration but do not take considerable heterogeneity among the studies into consideration. Medical literature published until June 2021 was searched in PubMed/Medline, Embase, Central and Web of Science: The final search yielded a total of 5,672 articles. We included only randomised controlled trials assessing the effect of intravenous MgSO4 on opioid consumption and acute postoperative pain when compared to either placebo or standardized analgesic treatment. The primary aim was to compare the homogeneity of essential variables and confounders. A post-hoc meta-analysis demonstrated a reduction in both postoperative morphine consumption (-6.12 mg) and pain score (-12.32 VAS points) in favour of the MgSO4-groups. Data for meta-analysis was missing from 19 studies (45%) on morphine consumption and 29 studies (69%) for pain score, the majority of which reports no effect for either morphine consumption or pain score. The calculated heterogeneity among the included studies was considerable for both outcomes; I 2=91% for morphine consumption and I 2=96% for pain score. Although we found a per se reduction in opioid consumption and pain score, methodological heterogeneity and clinical shortcomings of pre-, intra-, and post anaesthetic data precludes conclusions on clinical importance of intraoperative intravenous MgSO4. In addition, the reduction is likely less than what can be gained from using standardized analgesic treatment.