Pharmacological Efficacy of Intravenous Magnesium in Attenuating Remifentanil-Induced Postoperative Hyperalgesia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background/Objectives: Remifentanil-based anesthesia is linked to opioid-induced hyperalgesia (OIH), increasing postoperative pain and analgesic requirements. Magnesium, an N-methyl-D-aspartate (NMDA) receptor antagonist, might alleviate OIH. We aimed to assess whether intravenous magnesium reduces postoperative pain, analgesic requirements, and hyperalgesia in adults receiving remifentanil-based anesthesia. Methods: We searched PubMed, Embase, the Cochrane Library, and Web of Science (1 December 2024) for randomized controlled trials (RCTs) comparing intravenous magnesium vs. placebo. Risk of bias was evaluated with the Cochrane RoB 2 tool, and random-effects meta-analyses were conducted. GRADE was used to assess evidence quality. Primary outcomes were postoperative analgesic requirements and pain scores; secondary outcomes included intraoperative remifentanil consumption, shivering, postoperative nausea/vomiting (PONV), extubation time, hypotension, and bradycardia. PROSPERO registration: CRD42024609911. Results: Twenty-two RCTs (n = 1362) met eligibility. Magnesium significantly decreased 24 h analgesic requirements (standardized mean difference [SMD] −1.51; 95% confidence interval [CI] −2.15 to −0.87; p < 0.0001) and pain scores (SMD −0.61; 95% CI −0.90 to −0.32; p < 0.0001), with benefits persisting up to 48 h. It also reduced intraoperative remifentanil use (SMD −0.52), shivering (odds ratio [OR] 0.25), and PONV (OR 0.66), without prolonging extubation or increasing hypotension/bradycardia risk. High heterogeneity, potential publication bias, and moderate-to-very-low evidence certainty warrant caution. Conclusions: Intravenous magnesium appears beneficial in remifentanil-based anesthesia, but further large-scale, methodologically robust trials are needed to confirm optimal and clarify safety profiles across diverse surgical populations.