Tri-iodothyronine treatment in children after cardiac surgery: a double-blind, randomised, placebo-controlled study

Summary

Background

Serum thyroid hormone concentrations decline transiently during critical illness and after surgical procedures. We investigated prospectively the endocrine and haemodynamic effects of tri-iodothyronine treatment after cardiopulmonary bypass operations in children with congenital cardiac malformations.

Methods

We did a randomised, double-blind, placebo-controlled trial, in which 40 children (median age 0·6 years; range 2 days to 10·4 years) were randomly assigned placebo (saline) or one daily infusion of tri-iodothyronine (2 μg/kg bodyweight on day 1 after surgery and 1 μg/kg bodyweight on subsequent postoperative days up to 12 days after surgery. Before and 2 h, 24 h, and 72 h after the first infusion, plasma concentrations of thyroid hormones were measured by RIA, and systolic cardiac function was evaluated by echocardiography. During the postoperative course intensive-care measures were assessed by use of the therapeutic intervention scoring system.

Findings

In all patients, postoperative plasma concentrations of thyrotropin, thyroxine, free thyroxine, tri-iodothyronine were abnormally low and plasma concentrations of reverse tri-iodothyronine were raised. After start of treatment, tri-iodothyronine was significantly higher in patients given tri-iodothyronine than in those receiving placebo, whereas thyrotropin, thyroxine, free thyroxine, and reverse tri-iodothyronine remained similar in the two groups. At discharge, thyroid hormones of all patients were within the normal range, but thyrotropin secretion increased to plasma concentrations higher than those seen before treatment. The mean change of cardiac index was significantly higher in children given tri-iodothyronine (20·4% [SD 19·6] vs 10·0% [15·2]; p=0·004). Systolic cardiac function improved most in patients given tri-iodothyronine after longer cardiopulmonary bypass operations. Overall, patients given tri-iodothyronine had significantly lower mean treatment scores.

Interpretation

Treatment of children with tri-iodothyronine after cardiopulmonary bypass operations raises tri-iodothyronine plasma concentrations and improves myocardial function especially in patients with low postoperative cardiac output without adverse events, and without delaying postoperative recovery of thyroid function. Furthermore, tri-iodothyronine reduces the need for postoperative intensive care.

Introduction

Thyroid-hormone secretion is greatly suppressed in children and adults with critical illness and after surgical procedures.1, 2, 3, 4 These transient abnormalities in thyroid function resemble thyroid-hormone alterations associated with secondary hypothyroidism.⁵ The clinical importance of low plasma iodothyronine concentrations for metabolic thyroid status of patients remains unclear.6, 7 The so-called euthyroid sick syndrome, which is interpreted as an adaptive response of the organism to keep to a minimum metabolic demands during stress of critical illness, has been suggested to be a dangerous dogma in medicine, and has also been referred to as the non-thyroidal illness syndrome.6, 8 This designation does not presume the metabolic status of patients, but implies that transient hypothyroidism could be present in some patients, and that thyroid hormone replacement should be considered.

Sequelae of the postoperative intensive care course of children with congenital cardiac malformations recovering from cardiac surgery, such as low cardiac output, left-ventricular dysfunction, increased vascular resistance, and impaired ventilatory drives, resemble symptoms associated with hypothyroidism.⁹ Poor cardiac performance affects the outlook in children after open-heart surgery. Transient hypothyroidism after cardiac surgery in children could compromise the immediate postoperative course, and might endanger future development of the central nervous system. Therefore, perioperative management of these patients needs further assessment to improve overall outcome. Experimental and clinical evidence in adults, as well as a report in a subgroup of paediatric patients, indicates that tri-iodothyronine has beneficial inotropic effects after cardiopulmonary bypass operations and prevents low cardiac output.10, 11 We did a randomised, double-blind, placebo-controlled trial to assess prospectively the safety and efficacy of tri-iodothyronine treatment after cardiac surgery in children with congenital heart defects.