Abstract
Objectives: Magnesium (Mg) is the fourth most common cation in the body and has numerous physiological activities and anti-nociceptive effects. The anti-nociceptive effects are primarily mediated by regulation of calcium influx into the cell and antagonism of the N-Methyl-D-aspartate glutamate receptors. Opioids are widely used as analgesics to minimize postoperative pain, but their use is associated with various side effects as well as the potential for addiction and tolerance. Systemic Mg has been proposed as an adjunct to minimize postoperative pain in numerous clinical studies. This meta-analysis aims to critically examine the ability of perioperative intravenous (IV) Mg to reduce opioid use and its’ side effects. Methods: A comprehensive literature search of Pub Med, Cochrane Central Registry of Controlled Trials, and Google Scholar (1966-2016) was performed to identify all randomized control trials (RCTs) assessing the use of perioperative IV Mg in the reduction of postoperative opioid consumption. Keywords searched included combinations of “magnesium”, “pain”, “postoperative”, “preoperative”, “analgesia” and “opioid”. Inclusion criteria included RCTs comparing the use of perioperative IV Mg with a control group in adult patients (>18 yrs) undergoing elective surgery. Cumulative opioid consumption within the first 24 hours (hrs) postoperative period and the incidence of nausea and vomiting were analyzed. Results: 14 RCTs involving 910 patients were identified (455 patients received Mg and 455 patients received placebo or no therapy). Opioid consumption was significantly decreased in the systemic Mg group (standard mean difference [SMD]: 1.39, 95% CI 1.83 to -0.96; p < 0.001) at 24 hrs postoperatively. Subgroup analysis revealed a significant reduction in the morphine consumption (SMD: -1.37, 95% CI: -1.79 to -0.95; p < 0.001) with the use of IV Mg. There was a decrease in tramadol consumption; however, this did not reach statistical significance (SMD: -1.74, 95% CI: -4.62 to 1.13; p = 0.234). Systemic Mg adjunct had no significant effect on postoperative nausea and vomiting (RR = 0.63; 95% CI 0.38 to 1.04; p = 0.07). Conclusion: Perioperative IV Mg administration reduces opioid use in the first 24 hours postoperatively without any serious adverse events. The decreased need for postoperative opioids in the Mg group was not associated with a decrease in opioid-related side effects such as nausea and vomiting. Mg is an efficacious adjunct for postoperative analgesia and should be considered in multimodal analgesic treatment plans. Additional studies are required to optimize the Mg dose and timing, and to address whether specific opioids display unique benefit or resistance to adjunct Mg therapy.
Highlights
Pain is an “unpleasant sensory and emotional experience associated with actual or potential tissue damage.” [1]
Mg is an efficacious adjunct for postoperative analgesia and should be considered in multimodal analgesic treatment plans
Meta-analysis showed a significant decrease in cumulative opioid consumption with the use of Mg compared to the control group (SMD: −1.45, 95% confidence interval (95% CI) −1.86 to −1.05; p < 0.001 and Mean difference (MD): −8.90 mg, 95% CI −11.18 to −6.62; p < 0.001) (Figure 2)
Summary
Pain is an “unpleasant sensory and emotional experience associated with actual or potential tissue damage.” [1]. Inadequate postoperative pain management leads to worse outcomes in the immediate postoperative period which include patient discomfort and increased risk of wound infection, and cardiovascular, respiratory and gastrointestinal complications [1]-[3]. Chronic post-surgical pain (CPSP) is an additional serious complication of major surgery and is defined as pain that develops after a surgical procedure, of at least 2 months duration, and is not the result of other causes or a pre-existing pain [5]. While most surgical patients heal within months and return to their baseline functional status, certain surgical procedures and surgical candidates are at increased risk of developing CPSP and using opioid medications in the long-term [6] [7]. Procedures associated with a high incidence of post-surgical pain include limb amputation (30% - 50%), breast cancer surgery (20% - 30%), thoracotomy (30% - 60%) and heart bypass surgery (30% - 50%) [8]
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