CLINICAL TRIAL Effect of magnesium supplementation on lactate clearance in critically ill patients with severe sepsis: a randomized clinical trial Afsaneh Noormandi 1 & Hossein Khalili 1 & Mostafa Mohammadi 2 & Alireza Abdollahi 3 Received: 22 March 2019 /Accepted: 25 October 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Objectives In this study, changes in lactate clearance following magnesium supplementation were evaluated in critically ill patients with severe sepsis. Methods Fifty-eight patients with severe sepsis were randomly assigned to receive either magnesium (n = 30) or placebo (n = 28). Patients in the magnesium group received intravenous magnesium sulfate to maintain serum magnesium level around 3 mg/ dL for 3 days. The placebo group received the same volume of normal saline. Change in lactate clearance was considered primary outcome of the study. Results Mean increase in the lactate clearance in the magnesium group was significantly higher than the placebo group on day 2 (27.53% vs. 23.79% respectively, p < 0.001) and day 3 (49.83% vs. 37.02% respectively, p < 0.001). Time to lactate clearance was also significantly shorter in the magnesium group than the placebo group (47.28 ± 20.59 vs. 61.20 ± 24.31 h respectively, p = 0.03). Sepsis-related mortality was not significantly different but median length of ICU stay was significantly shorter in the magnesium group than the placebo group (8 vs. 15 days respectively, p < 0.01). Conclusions Magnesium supplementation increased lactate clearance in critically ill patients with severe sepsis. Optimizing serum magnesium level near the upper limit of the normal range may improve severe sepsis outcomes. Keywords Magnesium . Lactate clearance . Sepsis . Lactate . Severe sepsis Introduction Hypomagnesemia is a common electrolyte disturbance in crit- ically ill patients. It was reported in 90% and 65% of the critically ill surgical and medical patients respectively [1–8]. Magnesium (Mg) as a forgotten electrolyte is involved in var- ious physiological processes including storage and transfer of energy, protein and nucleic acid synthesis, inflammation, oth- er electrolyte balances, and hemostasis [1, 2, 6, 7]. By regulating function of the immune system, Mg may ameliorate endotoxin-induced cellular injury [7]. It also affects respiratory and cardiovascular function. Mg may prevent muscle weakness, respiratory failure, arrhythmia, release of proinflammatory cytokines, insulin resistance, and poor gly- cemic control in septic patients [4, 9–13]. Serum lactate is defined as an indicator of tissue hypoper- fusion that may predict sepsis outcome. Serum lactate levels more than 36 mg/dl associated with hospital mortality [11, 14, 15]. Various interventions including fluid resuscitation, anti- biotic therapy, and vasopressor administration significantly affect the lactate clearance in sepsis [14]. Also, Mg may de- crease lactate production through attenuation of the anaerobic * Hossein Khalili khalilih@tums.ac.ir Afsaneh Noormandi yalda.nor@gmail.com Mostafa Mohammadi mohammady_mm@tums.ac.ir Alireza Abdollahi dr_p_abdollahi@yahoo.com 1 Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O.Box: 14155/6451, Tehran 1417614411, Iran 2 Department of Intensive Care Unit, Imam Khomeini Hospital, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran 3 Department of Pathology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran European Journal of Clinical Pharmacology https://doi.org/10.1007/s00228-019-02788-w