Intravenous Magnesium Sulfate for Prevention of Vancomycin Plus Piperacillin-tazobactam Induced Acute Kidney Injury in Critically Ill Patients: An Open-label, Placebo-controlled, Randomized Clinical Trial

Background: Recent studies have shown an increased risk of acute kidney injury (AKI) induced by vancomycin + piperacillin-tazobactam (VPT) combination. In this study, the efficacy of intravenous magnesium sulfate in prevention of VPT induced AKI in critically ill patients admitted to the ICU has been evaluated.

Methods: In an open-label, placebo-controlled, randomized clinical trial, 72 adults (≥ 18 years old) who had indications to receive VPT as empiric therapy were assigned to the magnesium or control group in 1:1 ratio. Concomitant with VPT, intravenous infusion of magnesium sulfate was started for patients in the magnesium group. The target serum level of magnesium was defined 3 mg/dl. Patients in the control group received normal saline as placebo. The target serum level of magnesium was defined 1.9 mg/dl in this group. The study's primary outcome was incidence of AKI during and up to 48 h after the treatment course. Escalation and de-escalation of VPT regimen, duration of hospitalization, length of ICU stay and 28-day mortality were secondary outcomes.

Results: Thirty patients in each group completed the examination. Five patients in the magnesium group and 11 patients in the control group experienced AKI (p = 0.072). De-escalation of VPT regimen was done approximately in 60% of patients. Duration of hospitalization and length of ICU stay were not statistically different between the groups. Finally, 28-day mortality was 23.33% in each group. Although the incidence of AKI was not statistically different between the groups in unadjusted logistic regression model, it became significant after adjusting for confounding factors [unadjusted model (OR = 0.34; 95% CI: 0.10-1.16, p = 0.084), adjusted model: (OR = 0.26; 95% CI: 0.07-0.96, p = 0.04)].

Conclusions: Administration of magnesium sulfate with the target serum levels around 3 mg/dL reduced the incidence of AKI in critically ill patients who were receiving VPT as empric therapy.