Magnesium Infusion for Pain Management in Critically Ill Trauma Patients

This is a single center, double blind, randomized controlled study to demonstrate the effectiveness of continuous, intravenous administration of magnesium sulfate as compared to placebo in decreasing pain in critically injured patients.

Study Hypothesis The primary hypothesis is that continuous infusion magnesium sulfate will significantly decrease opioid requirements and pain scores in critically ill patients.

Background Magnesium is one of the most abundant cations in the human body. The physiologically active form of magnesium, ionized magnesium, is involved in hundreds of enzyme reactions that are important for homeostasis, action potentials, and membrane stability, among others.[Seo, et al] Hypomagnesemia is one of the most common electrolyte disturbances in the hospitalized patient, especially in the critically ill population. Studies have established that low magnesium levels increase mortality and morbidity in the critically ill patient,[Upala, et al] and thus magnesium is often repleted with intermittent infusion. Outside of its role in enzyme reactions, magnesium was discovered to have analgesic effects approximately twenty years ago.[Albrecht, et al] It appears to potentiate morphine analgesia, attenuate morphine tolerance, and suppress neuropathic pain.[Albrecht, et al] At a mechanistic level, these effects are thought to be secondary to magnesium regulating calcium influx into cells and antagonizing NMDA receptors in the central nervous system.

Magnesium has long been utilized in prevention and management of preeclampsia and eclampsia. A typical dosing regimen in this setting involves a 4 g loading dose of magnesium sulfate, followed by a magnesium infusion of 1-2 g/hr. When compared to eclampsia regimens, studies investigating the role of magnesium sulfate in multimodal surgical pain management consistently use lower doses. Even with this dosing, multiple trials have shown reduced postoperative pain and analgesic requirements.[Albrecht, et al, Sousa, et al, Hwang, et al, Shariat, et al] In one example, Shariat Moharari and others used a regimen of 40 mg/kg magnesium bolus followed by 10 mg/kg/hr infusion in perioperative gastrointestinal surgery patients, without adverse effects.[Shariat, et al]

Normal reference range for serum magnesium has been defined as approximately 0.7-1 mmol/L (1.5-2 mEq/L or 1.7-2.4 mg/dL).[Williamson, et al] Tramer et al. reported that a 3 g bolus dose of magnesium sulfate followed with 0.5 g/hr infusion for 20 hours resulted in an increase from baseline serum magnesium of approximately 0.6 mmol/L. Despite the higher post-treatment serum magnesium levels in the treatment group, no difference in safety outcomes was noted in comparison to the control group receiving 0.9% sodium chloride.[Tramer,et al] Similarly, Ozcan et al. found that 30 mg/kg bolus dose of magnesium sulfate followed by infusion of 10 mg/Kg/hr for 48 hours resulted in an increased serum magnesium level from baseline by approximately 0.7 mmol/L. The noted increase in serum magnesium level in this study also did not translate into any difference in safety endpoints between the intervention group and control group receiving 0.9% sodium chloride.[Ozcan, et al] Initial signs of magnesium toxicity following administration of magnesium sulfate have been reported to occur at serum magnesium levels greater than 3.5-5 mmol/L.[Lu, et al, Jahnen-Dechent, et al]