To our best knowledge, the present study is the first clinical retrospective analysis of the predictable value of thyroid hormones in patients with CHD undergoing CPB. In our study of 133 consecutive patients, we found that FT3 may be an independent predictor of ICU mortality based on multivariate binary logistic regression and ROC curves. Previous studies 16 have reported that low T3 was an independent predictor of ICU mortality, which is consistent with our finding. However, for CHD patients, especially children, RACHS-1 scores could predict ICU mortality, length of ICU stay and duration of MV 17–20. In our study, compared with survivors, non-survivors had a higher RACHS-1 score. However, in the additional multivariate binary logistic regression, it was not an independent mortality predictor. We suggest that RACHS-1 scores on the basis of CHD subtype should not consider the relationship of year, weight, and levels of thyroid hormone as confounding factors 21. Additionally, the small sample size of children with RACHS-1 scores of 5 or 6 may be another reason for the reduced statistical power. Although the CPB and ACC time were high in non-survivors, no significant difference was found compared with survivors, which demonstrates the improvement of cardiac surgery techniques and perfusion mode of CPB in China.
We found an interesting phenomenon in our study, namely, that all the non-survivors were male. This could be related to the preference for sons over daughters, which is very common in China. Thus, when a child is diagnosed with complex CHD, based on the gender, operative risk and economic status of the parents, girls may not have the opportunity to undergo the operation, especially in rural areas 22, 23. Due to this bias, we removed gender from the multivariate binary logistic regression.
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 verified that cardiac surgery with CPB induces a marked depression of thyroid hormones 14, 26, 27. Researchers have found that low levels of T3 28 or T4 14 were correlated with postoperative morbidity in open heart surgery with CPB. A study was conducted to assess the effects of CPB on thyroid function in infants weighing less than 5 kg, and the results showed that low T3 and T4 were both predictors of high mortality 13. Since postoperative low levels of thyroid hormones could lead to a poor prognosis, a preoperative increase in thyroid hormones may improve the prognosis. A multicenter randomized controlled trial (RCT) of T3 supplementation of patients undergoing heart surgery with CPB (TRICC) showed that T3 supplementation provides clinical advantages in patients younger than 5 months, but not in older patients 29. Talwar et al 30 performed an RCT study of perioperative oral T4 in patients younger than 6 months who underwent open heart surgery with CPB and found that thyroid hormone levels reduced postoperative and that T4 supplementation reduced the duration of MV and ICU and hospital stays. Therefore, the preoperative level of thyroid hormones may predict the prognosis of patients with CHD undergoing CPB. Kumar et al 31 found that low T3 is an important marker of mortality in critically ill patients, while low T4 and TSH did not increase the predictability. In a large-scale prospective, observational study of unselected ICU patients, they found that FT3 was the most powerful and only independent predictor of ICU mortality among the thyroid hormone indicators 16. However, Quispe et al 32 found that the FT3 level was not significantly different between survivors and non-survivors and was not a mortality predictor.
Our study showed that only FT3 is the independent predictor of ICU mortality with a good AUC. Thyroid hormones include T4, which represents the major form of circulating thyroid hormones (> 80%), and T3, which accounts for a small portion (< 20%) of circulating thyroid hormones and has a major biological effect on the heart. Moreover, the levels of TT3 and TT4 can be affected by the concentration of thyroxine-binding globulin (TBG) or the binding ability of TBG, which may be affected by several drugs, including furosemide and heparin 16. In contrast, FT3 and FT4 were not affected in these conditions. Thus, the level of FT3 may be better than other thyroid hormones as a predictor of ICU mortality, which is consistent with our findings.
Some limitations exist in our study. First, this was a retrospective study with a small sample size, which limited the statistical power. Therefore, additional cases need to be enrolled, and a prospective randomized multicenter study should be conducted. Second, patients with RACHS-1 scores of 5 or 6 are rare, which reduced the ability of RACHS-1 to predict ICU mortality in CHD children. Finally, we did not consider the relationship of thyroid hormones with albumin and dopamine, which may provide more robust evidence to assess the predominant predictor.