Preoperative oral thyroid hormones to prevent euthyroid sick syndrome and attenuate myocardial ischemia-reperfusion injury after cardiac surgery with cardiopulmonary bypass in children

Abstract

Background:Both euthyroid sick syndrome and myocardial ischemia-reperfusion injury are common and have been significantly associated with morbidity and mortality after pediatric cardiac surgery with cardiopulmonary bypass. This single-center, prospective, double-blind, randomized placebo-controlled clinical pilot trial was designed to assess if preoperative oral thyroid hormone therapy could prevent the occurrence of euthyroid sick syndrome (ESS) and attenuate myocardial ischemia-reperfusion injury (IRI) after cardiac surgery with cardiopulmonary bypass (CPB) in children.Methods:Forty children aged 3 to 12 year, scheduled for elective congenital heart disease repair surgery with CPB, were randomized into 2 groups of equal size to receive the following treatments in a double-blind manner: placebo (control group) and thyroid tablet 0.4 mg/kg (trial group) taken orally once a day for 4 days before surgery. The perioperative serum thyroid hormone levels and hemodynamic variables were determined. The extubation time, duration of intensive care unit (ICU) stay, and use of inotropic drugs in the ICU were recorded. The myocardial expressions of heat shock protein 70 (HSP70), myosin heavy chain (MHC) mRNA, and thyroid hormone receptor (TR) mRNA were detected. The serum creatine kinase-MB (CK-MB) activity and troponin I (TnI) positive ratio at 24 hour after surgery were assessed.Results:There were no significant differences in hemodynamic variables at all observed points, extubation time, and duration of ICU stay between groups. As compared with baselines on administration, serum triiodothyronine (T3) and free T3 (FT3) levels on the first, second, and fourth postoperative day, and serum thyrotropic-stimulating hormone (TSH), tetraiodothyronine (T4), and free T4 (FT4) levels on the first postoperative day were significantly decreased in the 2 groups. Serum T3, FT3, and T4 levels on the first and second postoperative day, and serum FT4 level on the first postoperative day were significantly higher in the trial group than in control group. As compared with the control group, the number of patients requiring inotropic drugs in the ICU, serum CK-MB activity, serum positive TnI ratio, and myocardial expression of MHCβ mRNA were significantly decreased, and myocardial expressions of both HSP70 and MHCα mRNA were significantly increased in the trial group.Conclusions:In children undergoing cardiac surgery with CPB, preoperative oral small-dose thyroid hormone therapy reduces severity of postoperative ESS and provides a protection against myocardial IRI by increasing HSP70 and MHCα expression.

Thyroid Hormones Predict ICU Mortality After Cardiopulmonary Bypass in Congenital Heart Disease Patients Under 3 Months Old

“…Thyroid hormones have important effects on the cardiovascular system, such as increasing cardiac output and decreasing systemic vascular resistance, which are predictive of good outcomes 24,25 . However, several studies have veri ed that cardiac surgery with CPB induces a marked depression of thyroid hormones 14,26,27 .…”

Euthyroid sick syndrome in paediatric and adult patients requiring extracorporeal circulatory support and the role of thyroid hormone supplementation: a review

“…The studies of Marwali et al and the Triiodothyronine supplementation in infants and children undergoing CPB (TRICC) trial found that T3 administration provides clinical advantages and reduces time to extubation (TTE) in patients younger than 5 months undergoing congenital heart disease surgery and no advantage for those older than 5 months. 29,31 The study of Zhang et al 42 found that thyroid hormone significantly decreased the requirement of inotropic drugs in the ICU and provided protection against myocardial IR injury in paediatric patients undergoing simple cardiac surgery with CPB. The study of Talwar et al 40 showed that oral T4 improved the cardiac index, reduced inotropic requirements, the duration of mechanical ventilation, ICU stay, and TISS in infants after surgery for complex congenital heart defects.…”

The impact of thyroid hormone dysfunction on ischemic heart disease

“…In isolated dogs hearts, a bolus of T3 (0.2 µg/kg) after reperfusion increased coronary blood flow by decreasing coronary arterial resistance (123). The results of a double-blind, randomized placebo-controlled clinical trial suggested that 0.4 mg/kg taken orally once a day for 4 days before surgery may provide protection against myocardial IRI during cardiac surgery in children by increasing HSP70 and MHC-α expression, inducing pharmacological ischemic preconditioning (128). A study in humans that aimed to evaluate the effects of TH replacement therapy on systolic and diastolic function in SCH patients showed a statistically significantly increase in ejection fraction after five months of levothyroxine therapy (129).…”