MAGIC AKI: Magnesium for the Prevention of HIOC-Associated AKI

In this phase 2, open-label randomized, placebo-controlled trial, investigators will test whether prophylactic high-dose IV Mg administration attenuates the risk of HIOC-associated AKI in patients with malignant mesothelioma undergoing surgery with HIOCC. Investigators will randomly assign 130 patients to receive IV Mg versus an equal volume of normal saline (0.9% NS) placebo, of whom it is anticipated 80 will complete the study. Investigators will also collect blood and urine pre- and postoperatively for exploration of secondary outcomes.

Investigators will screen for eligibility at participant's preoperative visit with their thoracic surgeon. Intravenous magnesium will be administered as a continuous infusion, soon after induction and stabilization by anesthesia in the operating room. The magnesium drip will start at 1 g/hour and will be titrated to achieve target levels of 3-5 mg/dl. The total duration of the infusion will be 24 hours.

Inclusion criteria

• • Adult patients (≥18 years old) with malignant mesothelioma undergoing surgery with HIOC with Dr. Raphael Bueno or another BWH thoracic surgeon

Exclusion criteria

• eGFR<45 ml/min/1.73m2 on either screening labs or preoperative labs, or end-stage kidney disease receiving renal replacement therapy. Screening labs refer to those obtained at the preoperative visit with the surgeon or within 90 days prior, whereas preoperative labs are obtained on the day of admission (typically one to three days priors to surgery).
• Serum Mg >3 mg/dl on either screening labs or preoperative labs
• Pregnant/breastfeeding
• Neuromuscular disease (e.g., myasthenia gravis, amyotrophic lateral sclerosis, multiple sclerosis, muscular dystrophy, myositis)
• Coronary artery disease, defined as any of the following in the prior year: a positive stress test; coronary angiogram indicating 1 or more vessels with >70% stenosis; percutaneous coronary intervention with stents; or coronary artery bypass graft surgery
• Sinus bradycardia, defined as a heart rate (HR) <55 beats per minute (bpm) detected on any ECG in the preceding 6 months
• High grade AV block (2nd degree AV block type II or 3rd degree AV block) without a pacemaker
• Positive COVID test in the 10 days prior to surgery
• Prisoner
• Hypersensitivity to Mg sulfate
• Concurrent participation in a study with an alternative experimental therapy that may interact with IV Mg
• Any condition that, in the view of the PI, might place the patient at increased risk or compromise the integrity of the study
• Conflict with other study