Triiodothyronine Supplementation for Children Undergoing Cardiopulmonary Bypass: A Meta-Analysis

Introduction: Specific pediatric populations have exhibited disparate responses to triiodothyronine (T3) repletion during and after cardiopulmonary bypass (CPB). Objective: To determine if T3 supplementation improves outcomes in children undergoing CPB. Methods and Materials: We searched randomized controlled trials (RCT) evaluating T3 supplementation in children ages 0–3 years undergoing CPB between 1/1/2000 and 1/31/2022. We calculated Hazard ratios (HR) for time to extubation (TTE), ICU length of stay (LOS) and hospital LOS. Results 5 RCTs met inclusion criteria with available patient-level data. Three were performed in United States (US) and 2 in Indonesia with 767 total subjects (range 29–220). Median (IQR) age 4.1 (1.6, 8.0) months; female 43%; RACHS-1 scores: 1–1%; 2–55%; 3–27%; 4–13%; 5-0.1%; 6-3.9%; 54% of subjects in US vs 46% in Indonesia. Baseline TSH and T3 were lower in Indonesia (p < 0.001). No significant difference occurred in TTE between treatment groups overall [HR 1.09 (CI, 0.94–1.26)]. TTE numerically favored T3-treated patients ages 1–5 months [HR 1.24 (CI, 0.97–1.60)]. TTE HR for the Indonesian T3 group was 1.31 (CI, 1.04–1.65) vs. 0.95 (CI, 0.78–1.15) in US. The ICU LOS HR for the Indonesian T3 group was 1.19 vs. 0.89 in US (p = 0.046). There was a significant T3 effect on hospital LOS [HR 1.30 (CI, 1.01–1.67)] in Indonesia but not in US [HR 0.99 (CI, 0.78–1.23)]. Conclusions T3 supplementation in children undergoing CPB is simple, inexpensive and safe, showing benefit in resource-limited settings. Differences in effects between settings likely relate to depression in baseline thyroid function often associated with malnutrition.