High‐dose IV magnesium in mesothelioma patients receiving surgery with hyperthermic intraoperative cisplatin: Pilot studies and design of a phase II randomized clinical trial

Abstract

AbstractIntroductionHyperthermic intraoperative cisplatin (HIOC) is associated with acute kidney injury (AKI). Administration of high‐dose magnesium attenuates cisplatin‐induced AKI (CP‐AKI) in animal models but has not been rigorously examined in humans.MethodsWe tested the feasibility and safety of different doses of magnesium in mesothelioma patients receiving HIOC. In Pilot Study 1, we administered a 36‐h continuous infusion of magnesium at 0.5 g/h, targeting serum magnesium levels between 3 and 4.8 mg/dL. In Pilot Study 2A, we administered a 6 g bolus followed by an infusion starting at 2 g/h, titrated to achieve levels between 4 and 6 mg/dL. We eliminated the bolus in Pilot Study 2B.ResultsIn Pilot Study 1, all five patients enrolled completed the study; however, median postoperative Mg levels were only 2.4 mg/dL. In Pilot Study 2A, two of four patients (50%) were withdrawn due to bradycardia during the bolus. In Pilot Study 2B, two patients completed the study whereas two developed postoperative bradycardia attributed to the magnesium.ConclusionsA 0.5 g/h infusion for 36 h did not achieve therapeutic magnesium levels, while an infusion at 2 g/h was associated with bradycardia. These studies informed the design of a randomized clinical trial testing whether intravenously Mg attenuates HIOC‐associated AKI.