Effect of Cardiopulmonary Bypass Duration on Thyroid Function Tests after Open Heart Surgery in Children
A. Jafari Javid
This study was designed to evaluate the effect of cardiopulmonary bypass duration on thyroid function in children undergoing open heart surgery. One hundred and five children with congenital heart disease in-need of open heart surgery with cardiopulmonary bypass were enrolled during a 12-month period. Patients categorized into two groups: Short-time cardiopulmonary bypass (<90 min) and long-time cardiopulmonary bypass (≥90 min). Serum levels of Triiodothyronine (T3), Thyroxine (T4) and Thyroid Stimulating Hormone (TSH) were measured 2 h before surgery and 2 and 5 days after operation. If needed another laboratory investigation was carried out on week 2 after operation. There were 46 (28 males, 18 females with the mean age of 5.63±3.64 years) and 59 (30 males, 29 females with the mean age of 4.59±3.18 years) children in short-time and long-time cardiopulmonary bypass groups, respectively (p>0.05). The mean serum level of T3, T4 and TSH was not significantly different between the two groups. In each groups, serum TSH and thyroid hormones were decreased until 2 h and 2 days after post-operation, respectively, with gradual increase afterward. Decline of serum thyroid hormones was more longstanding in the long-time cardiopulmonary bypass group. Two weeks after operation, repeating the same laboratory tests in patients with defective results yielded normal consequences. According to our results, there is a transient laboratory abnormality in thyroid function tests in children undergoing cardiopulmonary bypass. This abnormality persists longer in patients with long-time cardiopulmonary bypass.
May 14, 2011; Accepted: August 09, 2011;
Published: September 28, 2011
Different studies have shown that there is a significant compromise in thyroid
function after open heart surgeries in children. This malfunction could be so
extensive that may affect cardiac function (Haas et al.,
2006). However, there is not general agreement about the supplemental use
of thyroid hormones in children undergoing open heart surgery (Mainwaring
and Nelson, 2002). In a study on 20 infants undergoing open heart surgery
with delayed sternal closure it has been shown that exposure to povidone-iodine
increases the risk of transient hypothyroidism (Kovacikova
et al., 2003). In another series, it has been concluded that repetitive
use of iodine-included antiseptics in pediatrics cardiac surgery may influence
the thyroid function tests (Kovacikova et al., 2005).
In a study in turkey on 289 children with congenital heart disease undergoing
open heart surgery, it has been shown that perfusion mode (pulsatile vs. nonpulsatile)
influences the plasma concentration of thyroid hormones. Results of that study
showed that after Cardio Pulmonary Bypass (CPB), plasma levels of thyroid hormones
were reduced but pulsatile perfusion had protective effect on thyroid hormone
homeostasis in comparison to nonpulsatile mode (Akcevin
et al., 2010). The role of chest tube insertion for a long period
has also proposed in other study causing secondary hypothyroidism by Thyroxin
Binding Globulin (TBG) loss after heart operation (Lynch
et al., 2004). There is a strong association between postoperative
decrease in thyroid hormones and atrial fibrillation. However it is not clear
that preoperative replacement therapy can prevent this complication (Kokkonen
et al., 2005; Park et al., 2009).
It has been shown that abnormalities in thyroid hormone levels occure after
cardiac surgery using CPB (Haas et al., 2006).
However, as far as we searched there is not any study covering about the effect
of CPB duration on thyroid dysfunction after open heart surgery in children.
This study aimed at answering this obscurity as well as evaluating other possible
MATERIALS AND METHODS
In an observational study between November 2007 and November 2008, 105 children aged 15 years or younger who were candidates for open heart operation due to congenital abnormalities were recruited in Shahid Madani Hospital, Tabriz, Iran. Patients with proven thyroid disease and abnormal primary thyroid tests were excluded. Open heart surgery was carried out by employment of CPB and intermediate hypothermia (25-28° C) in all patients. Serum Total Triiodothyronine (T3), Total Thyroxine (T4) and Thyroid Stimulating Hormone (TSH) were measured by ELISA method at baseline (before operation) and after that on hour 2 and days 2 and 5. Another thyroid function test was repeated 2 weeks after operation, in all patients with any abnormal result on day 5 post-operation. Based on duration of CPB, patients categorized in two groups; short-time CPB (<90 min) and long-time CPB (90 min≤). Any previous history of thyroid disease and/or taking drugs with potential effect on thyroid function tests was considered as exclusion criteria. Signed informed consent was taken from parents or legal sponsors of the children. This study is approved by the Ethics Committee of Tabriz University of Medical Sciences. Blood samples were taken during routine procedures and no extra sampling was applied.
Statistical analysis: Data were analyzed with the SPSS statistical software package (version 15.0; SPSS Inc, Chicago). Continuous variables were expressed as mean and categorical data were shown as frequency and percent. The contingency table (The Chi square and The Fisher's exact tests where appropriate) and the Independent samples t-test employed for comparisons (univariate studies). Statistically significant variables in a univariate study entered into a logistic regression analysis (multivariate study) for an independent predictive factor. Pearson's r was considered for evaluating correlations. The p-value below 0.05 was considered significant.
According to CPB time, there were 46 (43.8%) children in short-time group and
59 (56.2%) cases in long-time group. In short-time group, there were 28 (60.9%)
males and 18 (39.1%) females with the mean age of 5.63±3.64 years. In
long-time group, there were 30 (50.8%) males and 29 (49.2%) females with the
mean age of 4.59±3.18 years. The two groups were comparable for gender
(p = 0.306) and age (p = 0.225). Dopamine and dobutamine were administered in
8 (17.4%) and 9 (19.6%) cases in short-time group and 32 (54.2%) and 23 (39%)
cases in long-time group, respectively.
||Abnormal values of thyroid function tests on day 5 after operation
The rates of dopamine and dobutamine administrations were significantly higher
in long-time group (p<0.001 and p = 0.032, respectively). There were not
statistically meaningful difference between two groups regarding serum levels
of TSH [before (0.485), 2 h (0.581), 2 days (0.819) and 5 days (0.526) after
operation], T3 [before (0.108), 2 h (0.309), 2 days (0.452) and 5 days (0.318)
after operation] and T4 [before (0.112), 2 h (0.617), 2 days (0.391) and 5 days
(0.317) after operation]. The above mentioned results are summarized in Table
In short-time group, the mean serum TSH level at 2 h after operation was significantly
decreased comparing with the baseline amount (p = 0.020). The mean serum T3
and T4 levels at 2 h and 2 days post-operation were significantly decreased
comparing with the baseline readings (p = 0.001 and p<0.001 for T3, respectively;
p = 0.002 and p = 0.001 for T4, respectively). Other parameters were not significantly
different from the baseline values in this group. In long-time group, the mean
serum TSH levels at 2 h and 2 days post-operation were significantly decreased
comparing with the baseline readings (p = 0.035 and p = 0.003, respectively).
The mean serum levels of T3 and T4 were significantly decreased at
2 h and days 2 and 5 after operation (p = 0.003 for T4 in day 5, p<0.001
for the other values). Abnormal values of thyroid function tests on day 5 after
operation are shown in Fig. 1. As the Fig. 1
shows, on day 5 after operation, 39.5, 39.5 and 14% of children in long-time
group have abnormal levels of TSH, T3 and T4, respectively. These values in
short-time group are 34.3, 22.9 and 8.6%. Accordingly there was no significant
difference between the rates of cases with increased serum TSH (p = 0.633) and
decreased serum T3 (p = 0.116) or T4 (p = 0.504) on day 5 after surgery.
|| Thyroid function test results in two groups with short-time
and long-time cardiopulmonary bypass
Fourteen patients out of 29 primary ones with abnormal thyroid function tests
on day 5 post-operation were connected and followed up to 2 weeks after operation.
Based on these results there was no case with abnormal serum thyroid parameters.
There was a significant reverse weak correlation between serum T4 and duration
of CPB in all patients (r = -0.268, p = 0.018). Other parameters were not significantly
correlated with duration of CPB. In multivariate analysis, age and gender of
patients, duration of CPB and administration of dopamine were not significantly
related with abnormal thyroid test results.
In this study, we showed that although the serum thyroid function test results
were not significantly different between two groups with short-time or long-time
CPB, it seems that longer CPB causes a more delay in return (increase) of serum
T3 and T4 after surgery. Likewise we showed that in open heart operation in
children, there is a decrement of serum TSH by 2 h after operation, with a gradual
elevation afterward. Concomitantly, serum level of T3 and T4 were reduced by
day 2 after operation with a subsequent progressive increase. Ririe
et al. (1998) showed in study on 23 children underwent open heart
operation with assistance of CPB that the serum levels of thyroid hormones and
TSH decreased by the first day after surgery and gradually increased after that
point. Murzi et al. (1995) in another series
on 14 children reported a more longstanding decrease in serum levels of thyroid
hormones (5-7 days after operation). In a study by Belgorosky
et al. (1993), decreased serum levels of thyroid hormones after open
heart surgery was reported. Bettendorf et al. (1997)
emphasized con transitory of these findings. Mainwaring
et al. (1994) reported similar trends in open heart operations in
infants. Dagan et al. (2006) concluded that decreased
levels of serum free T4 (FT4) and TSH was seen by the first day after heart
operation in 20 newborns. Bartkowski et al. (2002)
studied 20 children after heart operation and concluded a reduction of thyroid
hormones and TSH after operation. Keceligil et al.
(1996), on the other hand, did not show a change in FT4 and TSH after operation.
As mentioned, change of thyroid function tests is universal finding in almost
all relevant studies. However, the timing and types of involved parameters are
not fully similar. Different sample sizes and type of thyroid function tests
and their sensitivity may lead to this heterogeneity. There are diverse proposed
mechanisms for changes in thyroid function tests after heart operation. Thyroid
malfunctioning in response to decreased thyroid hormones during CPB is an example.
Change in metabolism of thyroid hormones has been implicated in this regard
(Chu et al., 1991; Holland
et al., 1991; Novitzky et al., 1989).
In some studies, release of inflammatory factors such as IL-6, IL-1 and TNF-1,
as well as elevation of steroids level have been put forward for sick euthyroid
syndrome after heart operation. Haas et al. (2006)
proposed a systemic inflammatory response during CPB as the main underlying
cause of thyroid malfunctioning. Cellular hypoxia is another culprit in this
regard (Peeters et al., 2003). Holzer
et al. (2004) reported a decrease of serum selenium after CPB and
blamed this finding as the underlying etiology of abnormal thyroid function
tests. Trauma of surgery, out-of-body circulation, hypothermia, blood dilution,
anemia, heparin and dopamine use and ultrafiltration have all been proposed
in this regard (Haas et al., 2006; Bartkowski
et al., 2002; Plumpton and Haas, 2005; Dimmick
et al., 2004; Van den Berghe et al., 1994;
Ghorashi et al., 2008). We did not find an independent
predictor of thyroid hormone or TSH abnormality among gender, age, CPB duration
and dopamine administration in the current study. It seems that this condition
is a complex and multifactorial entity. Following up the patients with abnormal
laboratory results on day 5 post-operation 2 weeks after surgery, we did not
find any significant abnormality. This indicates a temporary abnormality of
thyroid or upper controlling systems. In any way, presence of laboratory and
transient hypothyroidism after open heart surgery, its effect on prognosis and
necessity of correction are more important issues than the probable etiologies.
There is not yet a consensus in this regard (Bartkowski
et al., 2002; Klemperer, 2002).
The most important limitation of this study was that we lost some of our patients with abnormal tests on day 5, for evaluation on 2 weeks after operation.
Our results showed that thyroid function abnormalities after open heart surgery in children are aggravated with longer duration of cardio pulmonary bypass. These abnormalities are transient and return to normal status two weeks after surgery.
The authors acknowledge the vice chancellor office of Tabriz University of Medical Sciences and the Cardiovascular Research Institute of shahid madani for financial support of this study (Grant No. 9-365).
Akcevin, A., T. Alkan-Bozkaya, F. Qiu and A. Undar, 2010. Evaluation of perfusion modes on vital organ recovery and thyroid hormone homeostasis in pediatric patients undergoing cardiolopulmonary bypass. Artif. Organs, 34: 879-884.
Bartkowski, R., M. Wojtalik, E. Korman, G. Sharma, J. Henschke and W. Mrowczynski, 2002. Thyroid hormones levels in infants during and after cardiopulmonary bypass with ultrafiltration. Eur. J. Cardiothorac. Surg., 22: 879-884.
Belgorosky, A., G. Weller, E. Chaler, S. Iorcansky and M.A. Rivarola, 1993. Evaluation of serum total thyroxine and triiodothyronine and their serum fractions in nonthyroidal illness secondary to congenital heart disease. Studies before and after surgery. J. Endocrinol. Invest., 16: 499-503.
Bettendorf, M., K.G. Schmidt, U. Tiefenbacher, J. Grulich-Henn, U.E. Heinrich and D.K. Schonberg, 1997. Transient secondary hypothyroidism in children after cardiac surgery. Pediatr. Res., 41: 375-379.
Chu, S.H., T.S. Huang, R.B. Hsu, S.S. Wang and C.J. Wang, 1991. Thyroid hormone changes after cardiovascular surgery and clinical implications. Ann. Thorat. Surg., 52: 791-796.
Dagan, O., B. Vidne, Z. Josefsberg, M. Phillip, D. Strich and E. Erez, 2006. Relationship between changes in thyroid hormone level and severity of the postoperative course in neonates undergoing open-heart surgery. Paediatr. Anaesth., 16: 538-542.
CrossRef | PubMed |
Dimmick, S., N. Badawi and T. Randell, 2004. Thyroid hormone supplementation for the prevention of morbidity and mortality in infants undergoing cardiac surgery. Cochrane Database Syst. Rev., 3: CD004220-CD004220.
Ghorashi, Z., N. Nezami, A.G. Behbahan and S. Ghorashi, 2008. Supplemental food may not prevent iron-deficiency anemia in infants. Indian J. Pediatr., 75: 1121-1124.
Haas, N.A., C.K. Camphausen and D. Kececioglu, 2006. Clinical review: Thyroid hormone replacement in children after cardiac surgery is it worth a try. Crit. Care, 10: 213-219.
Holland, F.W., P.S. Jr. Brown, B.D. Weintraub and R.E. Clark, 1991. Cardiopulmonary bypass and thyroid function: A euthyroid sick syndrome. Ann. Thorac. Surg., 52: 46-50.
Holzer, R., B. Bockenkamp, P. Booker, P. Newland, G. Ciotti and M. Pozzi, 2004. The impact of cardiopulmonary bypass on selenium status, thyroid function and oxidative defense in children. Pediatr. Cardiol., 25: 522-528.
Keceligil, H.T., F. Kolbakir, B. Adam, A. Arikan and M.K. Erk, 1996. Thyroid hormone alterations during and after cardiopulmonary bypass. Cardiovasc. Surg., 4: 617-622.
Klemperer, J.D., 2002. Thyroid hormone and cardiac surgery. Thyroid, 12: 517-521.
Kokkonen L., S. Majahalme, T. Koobi, V. Virtanen and J. Salmi et al., 2005. Atrial fibrillation in e3lderly patients after cardiac surgery: Postoperative hemodynamics and low postoperative serum triiodothyroine. J. Cardiothorac. Vasc. Anesth., 19: 182-187.
Kovacikova, L., P. Kunovsky, M. Lakomy, P. Skrak and Z. Misikova et al., 2003. Thyroid hormone status after cardiac surgery in infants with delayed sternal closure and continued use of cutaneous povidine-iodine. Endocr. Regul., 37: 3-9.
Kovacikova, L., P. Kunovsky, M. Lakomy, P. Skrak, V. Hraska, L. Kostalova and E. Tomeckova, 2005. Thyroid function and ioduria in infants after cardiac surgery: Comparison of patients with primary and delayed sternal closure. Pediatr. Crit. Care Med., 6: 154-159.
Lynch, B.A., D.M. Brown, C. Herrington and E. Braunlin, 2004. Thyroid dysfunction after pediatric cardiac surgery. J. Thorac. Cardiovasc. Surg., 127: 1509-1511.
Mainwaring, R.D. and J.C. Nelson, 2002. Supplementation of thyroid hormone in children undergoing cardiac surgery. Cardiol. Young, 12: 211-217.
Mainwaring, R.D., J.J. Lamberti, G.F. Billman and J.C. Nelson, 1994. Suppression of the pituitary thyroid axis after cardiopulmonary bypass in the neonate. Ann. Thorac. Surg., 58: 1078-1082.
Murzi, B., G. Iervasi, S. Masini, R. Moschetti, V. Vanini, G. Zucchelli and A. Biagini, 1995. Thyroid hormones homeostasis in pediatric patients during and after cardiopulmonary bypass. Ann. Thorac. Surg., 59: 481-485.
Novitzky, D., D.K. Cooper and A. Swanepoel, 1989. Inotropic effect of triiodothyronine (T3) in low cardiac output following cardioplegic arrest and cardiopulmonary bypass: An initial experience in patients undergoing open heart surgery. Eur. J. Cardiothorac. Surg., 3: 140-145.
Park, Y.J., J.W. Yoon, K.I. Kim, Y.J. Lee and K.W. Kim et al., 2009. Subclinical hypothyroidism might increase the risk of transient atrial fibrillation after coronary artery bypass grafting. Ann. Thoracic Surgery, 87: 1846-1852.
Peeters, R.P., P.J. Wouters, E. Kaptein, H. van Toor, T.J. Visser and G. Van den Berghe, 2003. Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients. J. Clin. Endocrinol. Metab., 88: 3202-3211.
Plumpton, K. and N.A. Haas, 2005. Identifying infants at risk of marked thyroid suppression post-cardiopulmonary bypass. Intensive Care Med., 31: 581-587.
CrossRef | PubMed |
Ririe, D.G., J.F. Butterworth, M. Hines, J.W. Jr. Hammon and G.P. Zaloga, 1998. Effects of cardiopulmonary bypass and deep hypothermic circulatory arrest on the thyroid axis during and after repair of congenital heart defects: Preservation by deep hypothermia. Anesth. Analg., 87: 543-548.
Van den Berghe, G., F. de Zegher and P. Lauwers, 1994. Dopamine suppresses pituitary function in infants and children. Crit. Care Med., 22: 1747-1753.