Society of Cardiovascular Anesthesiologists

Effects of triiodothyronine supplementation following modified Fontan procedure

Reviewer: Denise Joffe, M.D.

Children's Hospital of Pittsburgh

Pittsburgh, PA

Mainwaring RD, Lamberti JJ, Nelson JC et al. Cardiol Young 1997;7:194-200

Abstract: The use of triiodothyronine (T₃) supplementation is not a recent addition to the pharmacological management of patients undergoing cardiac surgery. However, it is still considered to be an unconventional drug to use in their management. It is usually reserved as a last ditch effort in the care of the critically ill. It has occasionally been credited with dramatic improvements in the condition of some patients¹. This paper documents the use of triiodothyronine supplementation following modified Fontan procedures in the pediatric population.

Methods: Ten patients were studied between November 1993 and April 1994 who were undergoing modified Fontan procedures for a variety of congenital heart disease lesions. The average age was 30 +/- 5 months and their average weight was 13 +/- 2 kg. The surgical technique was all the same except that only 4 patients had a fenestration placed in their baffle. Patients received intravenous triiodothyronine 0.4mg/kg. Half was given over 20 minutes in the operating room and the second half was administered in the ICU within 1 hour of arrival. Venous samples measuring total triiodothyronine, free triiodothyronine, total thyroxine, free thyroxine, TSH and thyroglobulin were obtained the day prior to surgery, 10 minutes after bypass and at 1 and 24 hours and 5 and 8 days post surgery. A control group consisted of 8 patients undergoing the Fontan procedure immediately prior to this study who had their thyroid hormone profiles studied at similar intervals and who had not received triiodothyronine supplementation. Statistical analysis was performed separately for the two groups of patients. For each group the preoperative patient serum values served as baseline. The intraoperative and postoperative patient samples were compared to preoperative values using Wilcoxen paired analysis. A comparison of the group receiving triiodothyronine to the group which did not receive supplementation was performed using repeated measured of analysis of variance. A p< 0.05 was considered significant.

Results: The data demonstrated that the duration of mechanical ventilation (17 hours, range 2-48 hours), duration of ICU stay (3.5 days, range 2-6 days), and total length of hospitalization (9 days, range 6-14 days) was longer in the patients who did not receive triiodo-thyronine. Patients who did not receive triiodothyronine demonstrated decreases in serum free triiodothyronine upon institution of bypass. On the fifth post-op day the level of free triiodothyronine was only 28% of the preoperative value. Patients who received triiodothyronine had higher free triiodothyronine and total triiodothyronine levels at 1 hour post op but by 24 hours the 2 groups were similar. By the 5th and 8th post op days, free triiodothyronine and total triiodothyronine levels were higher in the triiodothyronine supplemented group. Free thyroxine levels increased in both groups but returned to baseline by 24 hours. Thereafter, there was a decrease in free thyroxine in the group not receiving triiodothyronine. Total thyroxine levels decreased in both groups upon institution of bypass and was markedly decreased at 1 and 24 hours. The group that received triiodothyronine then showed an increase to preoperative levels. TSH decreased in both groups upon institution of bypass and at 1 and 24 hours post op. By the fifth day, TSH increased in both groups. By the eighth day patients who had received triiodothyronine had supranormal TSH levels.

Discussion: This study supports the conclusions of previous studies showing that patients undergoing cardiopulmonary bypass demonstrate decreased levels of thyroid hormones². This study demonstrated that patients receiving triiodothyronine had a more rapid recovery of their endocrinologic profiles. In addition, patients receiving triiodothyronine had significantly shorter hours of ventilation, length of ICU stay and length of hospitalization.

The mechanism of action of triiodo-thyronine is purported to be improving cardiac output via direct cardiac effects (increased heart rate, contractility and improved diastolic relaxation). Because the patients have congenital heart disease, technical reasons precluded the determination of thermodilution cardiac outputs. However, no attempt was made to use other techniques to assess cardiac output such as venous saturations³. It is really conjectural to conclude that the decreased duration of ventilation, and ICU stay was due to an improvement in cardiac output secondary to triiodothyronine when outputs were not measured! Furthermore, none of the patients had clinical evidence of low cardiac output states. What clinical factors might have been improved by triiodothyronine therapy is speculative. Several studies have failed to show improvements in the hemodynamic status of adult patients despite triiodothyronine supplementation^4,5. At this point, the only valid conclusion from this study about triiodo-thyronine therapy was that it was associated with more normal endocrinologic profiles of thyroid function. Why and if this is associated with better outcomes after cardiac surgery is still not clear.

Bibliography

1. Novitsky D, Cooper DK, Swanepoel A. 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 1989;3(2):140-145

2. Bettendorf M, Schmidt KG, Tiefenbacher U, et al. Transient secondary hypothyroidism in children after cardiac surgery. Pediatr Res 1997;41:375-379

3. Rossi AF, Sommer RJ, Lotvin A, et al. Usefulness of intermittent monitoring of mixed venous oxygen saturation after stage 1 palliation for hypoplastic left heart syndrome. Am J Cardiol 1994;73:1118-1123

4. Bennett-Guerrero E, Jimenez JL, White WD, et al. Cardiovascular effects of intravenous triiodothyronine in patients undergoing coronary artery bypass graft surgery. A randomized, double-blind, placebo-controlled trial. Duke T3 study group. JAMA 1996;275(9):687-692

5. Teiger E, Menasche P, Mansier P, et al. Triiodothyronine therapy in open-heart surgery: from hope to disappointment. Eur Heart J 1993;14(5):629-633

In elective coronary artery bypass grafting, preoperative troponin t level predicts the risk of myocardial infarction

Reviewer: Jane C.K. Fitch, M.D.

Yale University School of Medicine

New Haven, CT

M Carrier, LC Pelletier, R Martineau, M Pellerin, and BC Solymoss. J Thorac Cardiovasc Surg 1998;115:1328-34

Summary: This study investigated the prognostic value of preoperative levels of cardiac troponin T. The population under study included 468 elective CABG patients. Preoperative and postoperative levels of troponin T, creatine kinase MB, ECG, and clinical data were collected. Sampling intervals were as follows: baseline, 1, 3, 6, 12, 24, and 48 hours after chest closure. Preoperatively, there were no acute ischemic ECG changes and CK-MB were all within normal limits. The normal range for troponin T used in this study was 0 - 0.02 mcg/L. 97 (21%) patients had serum troponin T levels above the limit of 0.02 mcg/L preoperatively (group 1). The remaining 371 (79%) had levels equal to or below 0.02 mcg/L (group 2). Findings were that patients with a troponin T level greater than 0.02 mcg/L preoperatively were older and more likely to have unstable or severe angina, congestive heart failure or a lower left ventricular ejection fraction. Preoperative serum CK-MB levels were not significantly different between the two groups. Patients with elevated troponin T levels preoperatively had longer CPB times and a greater need for pharmacological and mechanical support when weaning from CPB. Although there was no difference in hospital mortality between the two groups, the morbidity was higher in the group with elevated troponin T preoperatively. Specifically, perioperative MI (9% vs 3%) or CHF (10% vs 2%) were more likely in patients with elevated troponin T preoperatively. In addition, intensive care unit and hospital length of stay were longer in patients with elevated troponin T preoperatively. The variable most strongly associated with postoperative MI or CHF was elevated preoperative troponin T level.

Comments: The diagnosis of perioperative MI (PMI) remains difficult. More PMIs are non-Q-wave, thus making detection by ECG or echocardiography more difficult. In addition, creatine kinase (CK) activity may be of limited value perioperatively due to skeletal muscle trauma and cardiac surgical damage. CK-MB is more sensitive and specific for PMI, but even in the isoenzyme form it is not 100% cardioselective, as skeletal muscle may contain 1 to 3 % CK-MB. Cardiac-specific troponins are highly sensitive markers for myocardial necrosis. Troponins are located in the thin filaments of the myocardial contractile apparatus. Both troponin T and I have been isolated as cardiac isoforms. In previous investigations, troponin T has been evaluated and found not to be 100% cardiospecific, being expressed by skeletal muscle during development and in regenerating muscle. Troponin T is also expressed in chronic renal disease. To the contrary, troponin I has been found to be unique to cardiac muscle. The time course of troponin I is such that there is a slow rise reaching a plateau at 24 hours postoperatively. Thus the sampling frequency is significantly less with troponin I than with CK-MB. In fact, a single troponin I sample taken at 20 - 24 hours postoperatively would be sufficient to meet the criteria for diagnosing a PMI. Thus in the current study, one has to question whether the predictive value of troponin testing would have been improved using the I rather than the T isoform. That issue aside, the authors are to be applauded for their attempt at surgical risk stratification, as a major issue for specialty societies, the government and third-party payers, has been the prediction of clinical outcomes after cardiac surgery. No one would argue that PMIs have a negative effect on long-term outcome. The morbidities predicted by this study (MI and CHF), reflect the overall decision-making process from surgical indication to coronary anatomy to grafting techniques to conduits to myocardial preservation to postoperative care.

Newsletter