Authors: Amy Babb, MD AND Amanpreet Kalsi, MBBS, FRCA - Monroe Carell Jr. Children's Hospital at Vanderbilt - Vanderbilt University Medical Center
A 5-day-old term neonate with VSD and interrupted aortic arch presents to the operating room for repair. Triiodothyronine (T3) supplementation is given upon separation from cardiopulmonary bypass. In neonates undergoing surgery with cardiopulmonary bypass, T3 administration is MOST associated with which outcome?
EXPLANATION
Cardiopulmonary bypass (CPB) in neonates and infants causes a predictable decline in circulating levels of thyroid hormones (T3 and T4), which is related to many factors, including hemodilution, hypothermia, and suppression of the hypothalamic-pituitary-thyroid axis.1,2 T3 is known to have positive effects on myocardial function as well as systemic vascular resistance.2 This has led to the question of whether supplementation with T3 could improve cardiac function and outcomes after CPB.
The large multicenter TRICC trial by Portman et al in 20103 assessed T3 supplementation versus placebo in infants and children requiring cardiac surgery with CPB. The authors hypothesized T3 would improve post operative outcomes with time to extubation as the primary endpoint. The study noted an improvement in time-to-extubation, a reduction in inotrope requirement and improved cardiac function when T3 supplementation was given to patients less than 5 months of age. However, patients older than 5 months did not demonstrate the same reduction in time-to-extubation and therefore appeared to benefit less from T3. T3 was noted to be safe, with no difference in adverse events or arrhythmias between groups.
A follow up study by Portman et al in 20234, specifically evaluating infants less than 5 months old receiving T3 repletion after CPB, found no effect on time-to-extubation as the primary endpoint. Secondary endpoints, including vasoactive score, ICU length of stay, presence of low cardiac output, need for mechanical support, and death, were not different between the T3 and placebo group. The authors concluded T3 repletion did not increase adverse events but did not provide overall benefit.
Subsequent studies done in Indonesia demonstrate a reduced time-to-extubation, low cardiac output syndrome (LCOS) and ICU length of stay in patients less than 5 months old, suggesting a benefit in settings where thyroid dysfunction and malnutrition may be more prevalent.5-7
Across multiple trials, T3 administration has demonstrated a neutral safety profile, with no increase in arrhythmias or adverse events but has not consistently shown improvement in clinically relevant end points across all pediatric patients in all settings. Potential benefits include decreased time-to-extubation, reduced LCOS and ICU length of stay.3-7
Dosing regimens from various studies:
TRICC trial3: Triostat Intravenous - 0.4 mcg/kg bolus immediately before CPB, 0.4 mcg/kg bolus on release of aortic cross clamp, 0.2 mcg/kg bolus at intervals 3, 6, 9 hrs after cross clamp release
TRICC 2 trial4: T3 Intravenous - 0.4 mcg/kg bolus after cross clamp release followed by an infusion of drug totaling approximately 3 mcg/kg infused as 0.06 mcg/kg/hr until extubation or at 48 hours (if not extubated)
Marwali studies5,6: T3 oral – 1 mcg/kg given by nasogastric tube every 6 hours starting from anesthesia induction until 60 hours after initial administration (11 doses)
REFERENCES
1. Bettendorf M, Schmidt KG, Tiefenbacher U, Grulich-Henn J, Heinrich UE, Schönberg DK. Transient secondary hypothyroidism in children after cardiac surgery. Pediatr Res. 1997 Mar;41(3):375-9. doi: 10.1203/00006450-199703000-00012. PMID: 9078538.
2. Klemperer JD, Klein I, Gomez M, et al. Thyroid hormone treatment after coronary-artery bypass surgery. N Engl J Med. 1995;333(23):1522-1527. doi:10.1056/NEJM199512073332302
3. Portman MA, Slee A, Olson AK, et al. Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC): a multicenter placebo-controlled randomized trial: age analysis. Circulation. 2010;122(11 Suppl):S224-S233. doi:10.1161/CIRCULATIONAHA.109.926394
4. Portman MA, Slee AE, Roth SJ, et al. Triiodothyronine Supplementation in Infants Undergoing Cardiopulmonary Bypass: A Randomized Controlled Trial. Semin Thorac Cardiovasc Surg. 2023;35(1):105-112. doi:10.1053/j.semtcvs.2022.01.005
5. Marwali EM, Lopolisa A, Sani AA, et al. Indonesian Study: Triiodothyronine for Infants Less than 5 Months Undergoing Cardiopulmonary Bypass. Pediatr Cardiol. 2022;43(4):726-734. doi:10.1007/s00246-021-02779-8
6. Marwali EM, Caesa P, Darmaputri S, et al. Oral Triiodothyronine Supplementation Decreases Low Cardiac Output Syndrome After Pediatric Cardiac Surgery. Pediatr Cardiol. 2019;40(6):1238-1246. doi:10.1007/s00246-019-02143-x
7. Radman MR, Slee AE, Marwali EM, Portman MA. Triiodothyronine Supplementation for Children Undergoing Cardiopulmonary Bypass: A Meta-Analysis. Pediatr Cardiol. 2024;45(5):1100-1109. doi:10.1007/s00246-024-03465-1