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Randomized Controlled Trial
. 2025 Jul 1;53(7):e1470-e1480.
doi: 10.1097/CCM.0000000000006721. Epub 2025 May 21.

Methylprednisolone for Infant Heart Surgery: Subpopulation Analyses of a Randomized Controlled Trial

Sudeep D Sunthankar  1 , Kevin D Hill  2 , Jeffrey P Jacobs  3 , H Scott Baldwin  1 , Marshall L Jacobs  4 , Jennifer S Li  2 , Eric M Graham  5 , Brian Blasiole  6 , S Adil Husain  7 , Mark S Bleiweis  3 , Bret Mettler  4 , Alexis Benscoter  8 , Eric Wald  9 , Tara Karamlou  10 , Andrew H Van Bergen  11 , Pirooz Eghtesady  12 , John P Scott  13 , Brett R Anderson  14 , George Alfieris  15 , David F Vener  16 , Prince J Kannankeril  1
Affiliations
Randomized Controlled Trial

Methylprednisolone for Infant Heart Surgery: Subpopulation Analyses of a Randomized Controlled Trial

Sudeep D Sunthankar et al. Crit Care Med. .

Abstract

Objectives: Evaluate benefits and harms of prophylactic intraoperative methylprednisolone in subpopulations undergoing infant heart surgery.

Design: Subpopulation analyses of The Steroids to Reduce Systemic Inflammation after Infant Heart Surgery (STRESS) trial, a double-blind randomized placebo-controlled trial.

Setting: Twenty-four congenital heart centers.

Patients: Infants (< 1 yr old) undergoing heart surgery with cardiopulmonary bypass. Patients stratified by Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery (STAT) mortality category, age, gestational age, and presence of chromosomal or syndromic diagnosis (CSD).

Interventions: Methylprednisolone (30 mg/kg) vs. placebo administered into cardiopulmonary bypass pump-priming fluid.

Measurements and main results: Six postoperative outcomes: steroid use, acute kidney injury (AKI), thrombosis, infections, prolonged mechanical ventilation, peak blood glucose levels, and insulin exposure. One thousand two hundred patients received methylprednisolone or placebo. Beneficial effects associated with methylprednisolone included reduced use of postoperative hydrocortisone in neonates (odds ratio [OR], 0.39 [0.25-0.60]), both STAT category groups (1-3: OR, 0.64 [0.46-0.89]; 4-5: OR, 0.57 [0.34-0.97]), term infants (OR, 0.63 [0.47-0.83]), and those without CSD (OR, 0.63 [0.46-0.86]). Methylprednisolone was associated with lower thrombosis occurrence among neonates (OR, 0.37 [0.16-0.87]) and term infants (OR, 0.38 [0.19-0.75]). Adverse associations included increased thrombosis among premature infants ( p = 0.005), increased AKI among neonates (OR, 1.55 [1.02-2.37]) and those following STAT category 1-3 operations (OR, 1.34 [1.02-1.75]), and increased peak blood glucose levels and insulin exposure (all subgroups; p < 0.001). No increase in overall infection or reduction in prolonged mechanical ventilation with methylprednisolone.

Conclusions: Both beneficial and adverse associations were observed with prophylactic methylprednisolone. Reduction in postoperative hydrocortisone administration and absence of increased infection rates are arguments favoring prophylactic methylprednisolone use. Methylprednisolone was associated with increased peak blood glucose levels and a neutral to harmful association with odds of AKI. These data suggest certain subpopulations may benefit from prophylactic intraoperative methylprednisolone without significant harm.

Keywords: cardiac surgery; congenital heart disease; critical care; methylprednisolone.

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Conflict of interest statement

Drs. Sunthankar, Hill, J. P. Jacobs, Li, Graham, Benscoter, Van Bergen, Scott, Anderson, and Kannankeril received support for article research from the National Institutes of Health (NIH). Dr. Hill’s institution received funding from the National Center for Advancing Translational Sciences (NCATS); he received funding from Bristol Myers Squibb and Johnson & Johnson. Dr. M. L. Jacobs’ institution received funding from the NCATS (U01TR001803). Drs. Van Bergen’s, Anderson’s, and Kannakeril’s institutions received funding from the NIH. Dr. Anderson’s institution received funding from the National Heart, Lung, and Blood Institute (R01HL140055; UM1 4833193) and Autus. Dr. Anderson was a consultant for Autus Valve Technologies. Dr. J. P. Jacobs was a consultant for SpecialtyCare. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Figures

Figure 1:
Figure 1:. Outcomes for STAT Mortality Categories
Univariate unadjusted odds ratio for the postoperative event listed on y-axis for respective subgroup. Odds ratio > 1 reflects an increase in event given prophylactic intraoperative methylprednisolone. **Indicates statistical significance (P<0.05). MV, mechanical ventilation.
Figure 2:
Figure 2:. Outcomes for Age Categories
Univariate unadjusted odds ratio for the postoperative event listed on y-axis for respective subgroup. Odds ratio > 1 reflects an increase in event given prophylactic intraoperative methylprednisolone. **Indicates statistical significance (P<0.05). MV, mechanical ventilation.
Figure 3:
Figure 3:. Outcomes for Birth Gestational Age Categories
Univariate unadjusted odds ratio for the postoperative event listed on y-axis for respective subgroup. Odds ratio > 1 reflects an increase in event given prophylactic intraoperative methylprednisolone. The odds ratio for thrombosis in premature gestational age infants could not be calculated as there were no events in the placebo group. **Indicates statistical significance (P<0.05). MV, mechanical ventilation.
Figure 4:
Figure 4:. Outcomes for Presence and Absence of a Chromosomal or Syndromic Diagnosis
Univariate unadjusted odds ratio for the postoperative event listed on y-axis for respective subgroup. Odds ratio > 1 reflects an increase in event given prophylactic intraoperative methylprednisolone. **Indicates statistical significance (P<0.05). MV, mechanical ventilation.
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References

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