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.

Abstract

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. In an open-label, placebo-controlled, randomized clinical trial, 72 adults (≥ 18years 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 3mg/dl. Patients in the control group received normal saline as placebo. The target serum level of magnesium was defined 1.9mg/dl in this group. The study's primary outcome was incidence of AKI during and up to 48h 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. 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)]. Administration of magnesium sulfate with the target serum levels around 3mg/dL reduced the incidence of AKI in critically ill patients who were receiving VPT as empric therapy.