Thyroid hormone supplementation for the prevention of morbidity and mortality in infants undergoing cardiac surgery

There is insufficient evidence to advocate the use of triiodothyronine supplementation for the prevention of postoperative morbidity and mortality in infants who undergo cardiopulmonary bypass.Thyroid hormones are integral in cellular metabolism and haemodynamic stability. A transient acquired hypothyroidism occurs after cardiopulmonary bypass and is thought to be associated with low cardiac output, left ventricular dysfunction, increased vascular resistance and impaired ventilatory drives. Thyroid hormone supplementation has been postulated as a possible therapeutic option to improve postoperative outcome measures. This review highlights the lack of evidence concerning the benefits and harms of triiodothyronine supplementation in infants who undergo cardiopulmonary bypass.

Authors' conclusions: 

At present, there is a lack of evidence concerning the effects of triiodothyronine supplementation in infants undergoing cardiac surgery. Further randomised controlled trials which include sufficiently large subject numbers in a variety of different age strata (neonates, infants and older children) need to be undertaken.

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Background: 

Paediatric studies have demonstrated that cardiopulmonary bypass is associated with a decline in thyroid hormone levels. Adult patients who undergo open heart surgery and receive triiodothyronine supplementation have demonstrated a dose-dependent increase in cardiac output which has been associated with an improved clinical outcome. Thyroid hormone supplementation in infants may also reduce postoperative morbidity and mortality.

Objectives: 

To determine if perioperative thyroid hormone supplementation or replacement in infants undergoing cardiac surgery on cardiopulmonary bypass improves postoperative and longer term morbidity and mortality.

Search strategy: 

The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of The Oxford Database of Perinatal Trials, MEDLINE (1966 - October 2007), EMBASE (1980 - October 2007), CINAHL (1982 - October 2007), The Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2007), previous reviews including cross references, abstracts, conferences, symposia proceedings, expert informants and journal handsearching in the English language.

Selection criteria: 

All trials using random allocation to perioperative thyroid hormone therapy (supplementation or replacement) compared to control (placebo or no therapy) in infants (birth to one year of age) undergoing cardiac surgery requiring cardiopulmonary bypass. Thyroid hormone therapy must be triiodothyronine.

Data collection and analysis: 

Primary clinical outcomes included measures of postoperative morbidity and mortality. The standard methods of the Cochrane Neonatal Review Group were used in the assessment of trial quality. Treatment effects were expressed using relative risk (RR) and mean difference (MD).

Main results: 

Three small studies were identified that tested perioperative thyroid hormone supplementation or replacement in infants aged less than one year undergoing cardiac surgery (Mackie 2005; Portman 2000; Chowdhury 2001). In the Chowdhury 2001 study, a subgroup of nine neonates was eligible for this review.

No deaths occurred during the studies. Chowdhury 2001 and Mackie 2005 found no significant effect of perioperative thyroid hormone supplementation in neonates on either length of hospital stay or duration of mechanical ventilation. Portman 2000 found no significant difference in dopamine requirements for the treatment versus control groups for the first 24 hours postoperatively and in Mackie 2005 for up to five days, while in the Chowdhury neonatal subgroup, inotrope requirements were significantly lower in the treatment group. Portman 2000 reported significant differences between the two groups at one and 24 hours postoperatively for free T3 and at one hour postoperatively for total T3 levels. Total T4 levels showed no significant difference between groups, either pre-cardiopulmonary bypass or up to 72 hours postoperatively. In Mackie 2005, total and free T3 levels were significantly higher in the T3 group at 24, 48 and 72 postoperative hours but were similar between groups immediately before and after CPB and at seven postoperative days. The study drug was ceased 33 hours prematurely in one subject in Mackie 2005 due to a seven minute episode of ectopic atrial tachycardia.