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:
Urine output, measured hourly for 48 hours after surgery.
Blood lactate, measured at least daily (standard of care).
Time to extubation.
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