AbstractThe opioid crisis has emphasized identification of opioid‐sparing analgesics. This study was designed as a prospective trial with retrospective control group to determine feasibility for implementing a high‐dose prolonged magnesium sulfate infusion for adjuvant analgesia in the pediatric intensive care unit. Approval was granted for study of children receiving total pancreatectomy with islet cell autotransplantation and liver transplantation ages 3–18 years. Study exclusions were pregnancy, neuromuscular disease, hypersensitivity, preoperative creatinine >1.5 times upper limit normal, arrhythmia or pacemaker presence, and clinician concern. Eleven patients were enrolled between January 2020 and December 2022. Magnesium sulfate bolus (50 mg/kg) followed by intravenous infusion (15 mg/kg/h) was initiated in the operating room and extended postoperatively (maximum 48 h). Serum magnesium levels were monitored serially. To prioritize safety, infusion dose was decreased by 5 mg/kg/h for levels greater than 3.5 mg/dL. Clinical team otherwise followed standard multimodal pain practice. Primary outcome was oral morphine equivalent per kg per day during intensive care course (maximum 7 days). Secondary outcomes focused primarily on magnesium safety, including hemodynamic variables, electrolyte variables, respiratory support, and opioid‐related side effects. There were no serious adverse events. Treatment group trended toward slightly higher intravenous fluid requirement (~1 bolus), however no increase in blood product. Treatment and control groups were otherwise comparable in targeted outcomes and overall adverse event profile. Use of a high‐dose magnesium sulfate infusion protocol for analgesic postoperative use in select transplant recipients appears feasible for continued optimization of study in the PICU.