**4. The non-thyroidal illness syndrome**

266 Perioperative Considerations in Cardiac Surgery

administration increases sensitivity to catecholamines15, 16. TH also acts upon the expression of calcium handling proteins within the myocyte including the sarcoplasmic reticulum calcium ATPase (SERCA) and its negative regulator phospholamban (PLB). Administration of T3 increases the level of SERCA mRNA and protein and also lowers phospholamban levels and increases its phosphorylation state, which enhances the activity of SERCA17-22. The combined effect of these changes is an increase in the force of

Hypothyroid patients may have symptoms or signs associated with heart failure including dyspnoea, oedema, cardiomegaly and effusions. Low cardiac output in these patients is due to decreased heart rate, reduced ventricular filling and decreased myocardial contractility. Hypothyroidism is a risk factor for coronary artery disease23, the incidence of angina and myocardial infarction is however lower and this may relate to a reduction in metabolic requirements of the myocardium. Hypothyroidism is associated with hypertension, secondary to alterations in peripheral vascular resistance. Prolongation of the cardiac action potential and QT interval are also noted 24 and this leads to an increased risk of ventricular arrhythmias in this group. Supplementation with TH can lead to a reversal of some of these cardiovascular manifestations25. However, in the setting of cardiac surgery post-operative reductions in circulating THs have been demonstrated to be associated with an increase in the occurrence of atrial fibrillation26, 27. The vast majority of patients who are hypothyroid are receiving hormone replacement therapy and are therefore euthyroid at the time of surgery. However, in theory, in the untreated hypothyroid patient acute TH replacement could worsen myocardial ischaemia if myocardial oxygen consumption were increased in the face of fixed oxygen delivery28. Surgery in the hypothyroid patient may be performed without increased risk. In patients with untreated mild to moderate hypothyroidism undergoing cardiac surgery, Drucker reported no adverse effects29 and Syed et al. reported no increase in complications in patients with known hypothyroidism on treatment who were biochemically hypothyroid over those that were biochemically euthyroid without utilising additional TH replacement therapy30. O'Connor et al31 in undiagnosed patients with hypothyroidism have reported the occurrence of severe myxoedema post cardiac surgery leading to significant haemodynamic compromise which recovered with

Hyperthyroid patients commonly have a resting tachycardia. The most common rhythm disturbances are supraventricular arrhythmias including atrial fibrillation which predispose to thromboembolic diseases. Cardiac output may be supranormal (between 50-300% higher than in normal subjects). This is secondary to increases in heart rate, left ventricular contractility, blood volume and a reduction in SVR8. Improvements in LV systolic and diastolic function are believed to be modulated by changes in the expression of contractile and calcium regulating proteins (SERCA and PLB). Even though cardiac output is high it may be suboptimal at times of exertion32, due to an inability to further augment heart rate or lower systemic vascular resistance. Long-term follow-up of patients with hyperthyroidism reveals an increased cardiovascular and cerebrovascular mortality. This may partially be related to the increased rate of supraventricular dysrhythmias33,34. In the setting of overt clinical and biochemical hyperthyroidism surgery should be deferred if possible, until the

patient can be rendered euthyroid in order to avoid thyroid storm.

contraction and speed of diastolic relaxation.

replacement TH therapy.

**3. The consequences of the hypo-and hyperthyroid states** 

In response to severe physiological stress including cardiac surgery, changes in circulating concentrations of T3, T4 and TSH occur. The term non-thyroidal illness syndrome (NTIS) has been used to describe this phenomenon as it makes no presumption regarding the metabolic state of the patient. Whether hormone supplementation to correct these abnormalities is beneficial or not is unproven and much debated35. There are a variety of mechanisms that could potentially explain the biochemical profile observed in the NTIS including modifications of the hypothalamic-pituitary-thyroid axis, altered binding of TH to circulating proteins, modified entry of TH into tissues, changes in TH metabolism due to modification of the iodothyronines deiodinases as well as changes in TH receptor expression or function36. Circulating levels of T3 decrease within two hours of severe physiological stress and this is thought to reflect a reduction in the peripheral conversion of T4 to T337, 38. The most common abnormality observed in severely ill hospitalised patients is a low T3 syndrome, which occurs in up to 70% of patients39. Reduction in concentrations of free T3 (fT3) in hospitalised patients have been demonstrated to be predictive of mortality40. Deficiencies in TH metabolism have also been demonstrated to occur at a tissue level with a positive correlation between circulating and tissue TH levels41. As T3 levels fall reverse T3 (rT3, an inactive metabolite) increases. With increasing severity of illness, T4 levels also begin to fall (low T3-low T4 syndrome). Whether these observed responses are energy conserving to reduce metabolic rate or pathological requiring TH supplementation still remains a matter of debate.
