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J Thorac Cardiovasc Surg 2001;122:1023-1025
© 2001 The American Association for Thoracic Surgery
Brief Communications |
From the Departments of Medicine and Pediatrics, Divisions of Pediatric Cardiology, Endocrinology and Biostatistics, North Shore-Long Island Jewish Health System, Manhasset, NY.
This study was supported by National Institutes of Health Grants HL-58849 (to I.K.), HL-56804 and HL-03775 (to K.O.) and the Hutzler Fund.
Received for publication Dec 11, 2000. Accepted for publication March 28, 2001. Address for reprints: Irwin Klein, MD, Division of Endocrinology, North Shore University Hospital, 300 Community Dr, Manhasset, NY 11030 (E-mail: iklein{at}nshs.edu).
Infants and children undergoing operations for complex congenital heart disease form a group of extremely sick patients who require specialized care in the postoperative period.
1-4 Treatment strategies to minimize morbidity and increase survival aim to improve cardiac function and optimize postoperative hemodynamic parameters. Changes in thyroid hormone metabolism have been documented in patients undergoing pediatric cardiac surgery, as well as in adult patients. 1-6 A recent study in children undergoing cardiac surgery who received a single daily bolus dose of triiodothyronine (T3) in the postoperative period showed significant improvement in cardiac function and decreased postoperative therapeutic intervention, especially in those patients undergoing more complex surgical procedures. 6 The present report is the first prospective randomized study to use a continuous infusion protocol to achieve normal steady-state serum T3 levels in children for up to 7 days after cardiac surgery and to assess clinical outcomes.
Methods
We evaluated 75 consecutive patients of either sex undergoing cardiac surgery between the ages of birth and 18 years. The protocol was approved by the institution's committee on human rights in research. Parents or guardians gave informed consent before the operation, and patients older than 7 years of age gave assent.
Serum thyroid hormone levels were measured preoperatively, immediately postoperatively, and then once a day. Criteria for assignment to the treatment arm of the study included a serum total T3 level of less than 40 ng/dL (or <60 ng/dL for newborns) on postoperative days 0, 1, or 2 and a requirement for mechanical ventilation. Patients randomized to the T3 treatment group received continuous T3 infusion at 0.05 to 0.15 µg/kg of body weight per hour to maintain serum levels within the normal range (80-200 ng/dL). 4 Serum thyrotropin levels were analyzed to ensure that the treatment dose did not render the patient chemically hyperthyroid.
The degree of inotropic support required was calculated as previously described by Wernovsky and colleagues. 7 Cardiac rhythm was continuously monitored with bedside monitors and telemetry. The overall degree of postoperative care was analyzed by calculating the Therapeutic Interventional Scoring System (TISS) score. Scores were given for 76 different therapeutic and monitoring procedures and reflected the invasiveness, intensity, and complexity of care rendered to the patient. 4,6
All demographic, baseline, and outcome variables were compared by the Mann-Whitney test. Categoric variables were compared by the Fisher exact test. Results are expressed as means ± standard deviation. A 2-factor repeated-measures analysis of variance with group and day as the main effects and including the interaction effect (group x day) in the model was initially carried out for the serum T3 level. Bonferroni-adjusted pairwise comparisons between days were carried out.
Results
Twenty-eight of 75 patients were eligible for the study, with 14 patients randomized to T3 treatment. Figure 1 shows serum total T3 levels preoperatively and postoperatively in all study patients. Serum T3 levels fell in all patients after operations with the lowest values consistently measured after 24 and 48 hours. Patients receiving continuous T3 infusion achieved serum T3 values equivalent to the mean preoperative levels within 24 hours of initiation of treatment. Of the 28 study patients, serum T3 levels were equivalent at the time of randomization. T3 treatment did not alter outcome measures in the randomized groups when all 28 patients were considered (Table 1). No differences were found for TISS score, inotropic score, or dose requirements for milrinone and furosemide. Similarly, no significant differences were measured between the 2 groups for days of mechanical ventilation or length of hospital stay.
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). No significant differences between the T3-treated and untreated newborns were found with respect to the number of patients requiring cardiopulmonary bypass, the total bypass time, duration of crossclamping, and duration of hypothermic cardiac arrest. Twenty-four hours after initiation of T3 treatment, the serum total T3 level was restored to normal at 130 ± 38 ng/dL, which was significantly higher than the level of 34 ± 7 ng/dL found in the untreated group.
The TISS score was not different on day 0 of randomization, but on randomization days 1, 2, and 3, scores were significantly lower (P = .037) in the T3-treated group (40 ± 7 ng/dL) compared with the untreated group (49 ± 3 ng/dL), indicating lower postoperative management requirements(Table 1). T3 treatment significantly decreased the need for inotropic support, as documented by a lower mean daily inotropic score of 5 ± 3 compared with 23 ± 26 (P = .037) in the untreated group(Table 1). Mixed venous oxygen saturation (MVO2) values were obtained in 8 newborns. The mean MVO2 values at the time of randomization were similar at 53% ± 13% and 42% ± 10% for the T3-treated and untreated patient groups, respectively. After 18 to 24 hours, the mean MVO2 increased to 70% ± 12% in the T3-treated group and remained unchanged at 44% ± 18% in the untreated group. These differences, however, did not reach statistical significance because of the small sample size. Although the length of hospital stay and days of mechanical ventilation were not significantly different between the 2 groups, the mean values showed a trend toward shorter times in the T3-treated group(Table 1).
Discussion
Previous studies in adult 5 and pediatric heart surgery patients 1-4,6,8 have reported alterations in thyroid hormone metabolism, leading to significant decreases in postoperative serum total T3 levels and normal or reduced serum thyrotropin and thyroxine levels. A recent study showed that the half-life of serum T3 in children after heart surgery was markedly decreased. 9 Bettendorf and colleagues 1,6 reported that a low serum T3 level in children after cardiac surgery was a predictor of adverse outcome and that T3 treatment significantly improved cardiac function. Because we and others have shown that thyroid hormones have both inotropic and vasoactive effects, 10 we undertook a study to determine whether T3 replacement by continuous infusion of pediatric patients after cardiac surgery would improve clinical outcome. Evaluation of 75 patients showed that serum total T3 levels fell predictably within 72 hours of the operation to a mean nadir value of 42 ± 13 ng/dL. The present data are in agreement with the results reported by Mainwaring, 2 Bettendorf, 1,6 and their colleagues, who showed that the fall in serum T3 was greater in patients undergoing complex cardiac surgical procedures. In the present study T3 treatment was accomplished safely with no untoward changes in blood pressure, heart rate, or cardiac rhythm. T3 treatment of the overall study group did not significantly alter postoperative outcome measures, including the TISS, days of mechanical ventilation, or overall length of hospital stay. In contrast, newborn patients showed the tendency for a positive therapeutic response to T3 treatment, as indicated by a significantly lower TISS score and lower inotropic requirements that persisted throughout the randomization period. As a measure of cardiac output and peripheral perfusion, the MVO2 measurements in the newborns showed a 17% increase after T3 treatment compared with a 2% increase in the untreated group.
This positive postoperative outcome can be explained in part by the known molecular effects of thyroid hormone to increase cardiac contractility and to lower systemic vascular resistance in cardiac disease, 10 after cardiac surgery, 4-6 and in the low-T3 syndrome. 10 In conclusion, the present data suggest a therapeutic benefit of T3 in the postoperative period by using a continuous infusion protocol to normalize serum T3 levels in newborn patients undergoing operations for complex congenital heart disease. A prospective randomized study of greater statistical power will be required to confirm these results.
References
This article has been cited by other articles:
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  I. Klein and S. Danzi Thyroid Hormone Treatment to Mend a Broken Heart J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1172 - 1174. [Full Text] [PDF]
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 A. Kenessey and K. Ojamaa Thyroid Hormone Stimulates Protein Synthesis in the Cardiomyocyte by Activating the Akt-mTOR and p70S6K Pathways J. Biol. Chem., July 28, 2006; 281(30): 20666 - 20672. [Abstract] [Full Text] [PDF]
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 A. S. Mackie, K. L. Booth, J. W. Newburger, K. Gauvreau, S. A. Huang, P. C. Laussen, J. A. DiNardo, P. J. del Nido, J. E. Mayer Jr, R. A. Jonas, et al. A randomized, double-blind, placebo-controlled pilot trial of triiodothyronine in neonatal heart surgery J. Thorac. Cardiovasc. Surg., September 1, 2005; 130(3): 810 - 816. [Abstract] [Full Text] [PDF]
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 S. Danzi, K. Ojamaa, and I. Klein Triiodothyronine-mediated myosin heavy chain gene transcription in the heart Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H2255 - H2262. [Abstract] [Full Text] [PDF]
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 G. Iervasi, A. Pingitore, P. Landi, M. Raciti, A. Ripoli, M. Scarlattini, A. L'Abbate, and L. Donato Low-T3 Syndrome: A Strong Prognostic Predictor of Death in Patients With Heart Disease Circulation, February 11, 2003; 107(5): 708 - 713. [Abstract] [Full Text] [PDF]
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