Tailored MgSO4 Supplementation to Reduce Complications in Pediatric Heart Surgery

Hypothesis: Modulating patient Mg levels based on ionized Mg will have clinical and functional benefits over using total Mg, due to the increased sensitivity and specificity of the ionized form. The primary goal of this project is to experimentally test the benefit of maintaining ionized normomagnesemia after cardiac surgery in children with regard to renal function and arrhythmia incidence . A secondary goal is to develop a model for predicting AKI after cardiac surgery in children, using a machine learning approach to understand interrelationships between magnesium-dependent physiological processes (Figure 1B). Successful completion of this project will define the utility and positionality of ionized Mg as an actor in pediatric post-surgical AKI, and its synergy with established clinical and physiological outcomes.

Aim 1: Investigating use of ionized Mg for Mg repletion therapy

In this aim, patients will be randomized to one of two strategies for Mg repletion therapy, one utilizing ionized Mg, the other using total Mg. The effects of these two strategies on clinical and physiological outcomes will be measured, as will the durability of the different Mg repletion strategies in preventing or correcting hypomagnesemia. 96 participants will be enrolled in this study. Because arrhythmia risk and AKI risk are dramatically stratified by age, subjects will be age-matched into the following groups: 0-1 month, 2 months to 2 years, 3- 9 years, 9 years -18 years. Children will be randomly assigned to one of two Mg repletion strategies. Randomization will occur after consenting and reaffirmation that the child/family/guardian still continue to agree to participate in the study. For each age group there will be 24 sealed envelopes that identify which treatment strategy for magnesium repletion they will be assigned (Total or ionized). This envelope will be opened at SBAR prior to the induction of anesthesia. Magnesium levels will be drawn and sent as per standard protocol. All patients will have ionized magnesium levels obtained with every blood gas, but only those in the ionized group will the physicians see and treat the magnesium based upon that value. Patients with hypomagnesemia ( value less than or equal to 1.8 Mg/dl in the total Magnesium group will be given MgSO4 at a standard dose of 50 mg/kg over 1 hour beginning at the intraoperative stage and at every subsequent timepoint where an individual's lab values show hypomagnesemia (Table 1). Those patients in the ionized magnesium group will be dosed according to Table 1 beginning at the intraoperative stage and at every subsequent timepoint where an individual's lab values show hypomagnesemia (Table 1). Study participants will be blinded to treatment group. Researchers will not be blinded at the time of MgSO4 administration due to logistical pharmacy requirements. All data analysis including ECG analysis will be performed by blinded researchers. In one arm, Mg repletion will be titrated using ionized Mg as a measure, maintaining an ionized Mg level of 0.98-1.46 mg/dl. In the other, Mg repletion will be titrated using total Mg as a measure. Due to reagents used by WVU labs, the reference range for total Mg is 1.9-3.1 mg/dL; patients in the total Mg arm will be maintained in this range. To ensure proper electrolyte balance, Ca2+, K+, and Na+ will be maintained within appropriate ranges using standard methodology.

Mg level will be measured on all arterial blood gases. Mg will be measured at least: pre-incision, at the completion of the procedure, and twice a day for 48 hours after surgery. In order to assess differences in post-treatment Mg maintenance after cessation of therapy, ionized and total Mg levels will also be measured 4 hours after Mg supplementation.

Urinary NGAL and Creatinine will be measured pre-bypass, 2 hours after bypass and 24 hours after bypass to assess for renal injury.

Clinical outcomes to be measured include:

1. Urine output, measured hourly for 48 hours after surgery.
2. Blood lactate, measured at least daily (standard of care).
3. Time to extubation.
4. Occurrence of non-sinus cardiac rhythms, with special attention given to accelerated junctional rhythms.

Magnesium dosing Total Mg (mg/dL) Less than or equal to 1.8 MgSO4 dose 50 mg/kg Ionized Mg Observed Mg(Mg/dL) MgSO4 dose 1.3 10 mg/kg - 1 hr 1.2 20 mg/kg - 1 hr 1.0 30 mg/kg - 1 hr 0.9 40 mg/kg - 1 hr 0.8 50 mg/kg - 1hr