The management of hypothyroid patients before coronary artery bypass graft (CABG) surgery is controversial. Preoperative thyroid hormone therapy may precipitate angina in patients with ischemic heart disease and may contribute to myocardial infarction, although this seems to be an infrequent event (1–3). Conversely, limited data suggest a more frequent incidence of heart failure in hypothyroid patients undergoing cardiac surgery (4). Other evidence indicates that untreated hypothyroid patients tolerate cardiac surgery with few significant perioperative complications, rendering aggressive preoperative thyroid hormone replacement unnecessary (1,2,5,6). We describe a previously unreported case of a patient with undiagnosed hypothyroidism who developed severe myxedema during cardiac surgery that dramatically impaired intraoperative cardiopulmonary function.
The patient was a 49-yr-old man with a history of diabetes mellitus, hypertension, hypercholesterolemia, peripheral vascular disease, heavy tobacco use, and chronic renal insufficiency scheduled for an urgent CABG. His preoperative medications included NPH insulin, isosorbide, atorvastatin, amlodipine, metoprolol, and aspirin. Laboratory values were normal except for a creatinine of 1.6 mEq/dL and calcium of 9.8 mEq/dL. Physical examination outside the operating room revealed tense and tight skin of his chest and extremities, but no edema or swelling was evident. After placement of femoral and pulmonary artery catheters, anesthesia was induced with midazolam and fentanyl and a transesophageal echocardiography (TEE) probe placed. The operative course was uneventful and a four-vessel CABG performed after cooling to 34°C. Cardiopulmonary bypass (CPB) and aortic clamp times were 156 and 112 min, respectively. Dopamine (1.5 μg · kg−1 · min−1) and insulin (2–4 U/h) infusions were maintained throughout the procedure. Separation from CPB was uncomplicated, and protamine was administered without adverse response. Dopamine was subsequently discontinued.
Approximately 20 min after the completion of CPB, but before the chest was closed, airway pressures increased from 28 to 40 cm H2O and arterial oxygen saturation decreased from 100% to 92% with an Fio2 of 1.0. Although auscultation revealed no wheezing, albuterol and IV methylprednisolone were administered because of the history of heavy tobacco use and the possibility of anaphylaxis. No improvement in airway pressures was noted and examination revealed a tense, distended abdomen as well as a massively edematous face and head, with a swollen and protruding tongue. The TEE probe was removed, and the stomach emptied with an orogastric tube. Bilateral chest tubes were inserted, but no fluid or air was retrieved. Bronchoscopy revealed no secretions or obstruction of the endotracheal tube. Because of the tense abdomen, a small incision was made into the peritoneum from the chest cavity, but no ascitic fluid was found. During these interventions, hypotension ensued and the cardiac index was noted to be 1.5 L · min−1 · m−2 with central venous and pulmonary artery pressures of 25 and 35/21 mm Hg, respectively. Dobutamine (5 μg · kg−1 · min−1) was then started and the TEE probe reinserted after removal of the orogastric tube. Subsequent TEE examination revealed small, underfilled and hyperkinetic ventricles and crystalloids were rapidly administered to increase intracardiac filling volumes. In addition, an epinephrine infusion was started because of the possibility of anaphylaxis and to restore perfusion pressure.
After chest closure and further hemodynamic stabilization, he was transferred to the intensive care unit where physical examination revealed severe, diffuse soft tissue edema with especially prominent swelling of his face and extremities. The lower extremities were so tense that consideration was given to measuring calf pressures to exclude an acute compartment syndrome. When evaluated 1 h later by an endocrinologist for management of diabetes, the diagnosis of severe myxedema was strongly considered and confirmed later that day with the following thyroid function tests: thyroxine (T4) 1.3 μg/dL (normal, 4.5–10.7), free thyroxine index 2.2 (normal, 5–10.6), and thyroid stimulating hormone (TSH) 79.2 μIU/mL (normal, 0.38–6.15). Levothyroxine 0.4 mg IV was immediately given followed by 0.1 mg IV every day thereafter. The soft tissue edema and hemodynamic status improved over the next 24 h and tracheal extubation was successfully performed on postoperative day 3. A follow-up TSH level on postoperative day 6 was 30.0 μIU/mL. He continued to have mild, diffuse edema for the next 7 days, but was eventually discharged in stable condition.
This case highlights the probable adverse influence of CPB on preexisting thyroid dysfunction and the impact of severe tissue and chest wall edema on systemic hemodynamics. This detrimental interaction only became apparent after separation from CPB as the observed anasarca severely impaired thoracic compliance, thus impairing ventilation, increasing intrathoracic and central venous pressures, and profoundly reducing venous return and cardiac output. After therapy with volume expansion, vasoconstrictors, IV thyroxine and several days of mechanical ventilation, the patient’s symptoms improved and he tolerated extubation.
The syndrome of severe and profound hypothyroidism is termed myxedema coma and, although not precisely applicable to our patient, may present with a constellation of findings including depressed mental status, bradycardia, hypothermia, hypoventilation (especially in response to sedatives or opioids), ileus, pericardial effusion without tamponade, and hypotension (7). The acute management of severe hypothyroidism includes the administration of IV thyroxine, slow correction of hypothermia, assisted ventilation if necessary, judicious administration of IV fluids, and stress doses of corticosteroids (autoimmune adrenal insufficiency may also be associated with hypothyroidism) (7). Initial thyroid hormone replacement is typically with 200–500 μg T4 IV, followed by 100 μg daily thereafter. T4 is generally preferred as initial therapy over T3 because of its long history of clinical efficacy, ability to prevent relapse, longer half-life, and the avoidance of supranormal levels of T3 that have been associated with malignant arrhythmias and early mortality after treatment with IV T3(7,8).
Clinical myxedema during the perioperative period is uncommon, despite mild degrees of hypothyroidism demonstrated by thyroid function tests. Several reports suggest that patients with mild-to-severe hypothyroidism can undergo cardiac surgery without significant morbidity or mortality compared with euthyroid patients (1,3,4–6,9–11). Drucker and Burrow (11) reported 10 hypothyroid patients undergoing cardiac surgery with a mean TSH level of 39 μU/mL (normal, <10 μU/mL) who developed no significant postoperative complications compared with control patients. One patient was grossly myxedematous with an undetectable preoperative serum thyroxine level, but had an uncomplicated recovery. Although Ladenson et al. (4) documented a more frequent prevalence of heart failure and minor gastrointestinal complications in a small group of mild-to-moderately hypothyroid patients undergoing cardiac surgery, serious complications did not occur, and other investigators have confirmed the absence of significant complications in similar patients (5,9,11). Nonetheless, surgery in myxedematous patients can be complicated by an increased risk of infection, cardiovascular instability, respiratory insufficiency, paralytic ileus, and friable tissues (12). The severe anasarca and profound hypothyroidism that we observed has not been previously reported. Whether more careful preoperative evaluation would have suggested the possibility of underlying thyroid dysfunction is unknown, although the urgent nature of the procedure precluded a detailed history of symptoms pertinent to the diagnosis of hypothyroidism.
Evaluation of the impact of cardiac surgery and CPB on thyroid hormone levels has yielded conflicting results. Several authors have documented decreases in total triiodothyronine (T3), free T3, T4, and increases in TSH levels after completion of CPB and during the first 24–48 hours after surgery (13–20), whereas others have found no change in TSH and increased free T3 and T4 levels (21,22). The impact of these changes on cardiac performance is conflicting; some reports suggest an improvement in myocardial function with T3 administration after CPB (23), whereas more recent, prospective trials have found no benefit with IV T3 administration after CPB (19,20). Data also show diminished responsiveness of the pituitary gland to thyrotropin-releasing hormone during CPB in normal patients (21,24). This may produce secondary hypothyroidism, as well as a diminished compensatory response to CPB-induced reductions in T3 levels. This scenario seems unlikely in our case, because the TSH level was markedly increased.
The potential causes of decreased thyroid hormone levels during and after CPB are varied and include hypothermia, reduced peripheral conversion of T4 to T3, hemodilution, nonpulsatile blood flow, the suppressive effect of cytokines and tumor necrosis factor on thyroid function, iodine skin preparations, and cortisol-induced effects on TSH secretion (24). Hemodilution is an unlikely explanation, however, because several reports have demonstrated persistently low thyroid hormone levels despite correction for hemodilution (20,21). Studies also indicate a variable effect of dopamine infusions on thyroid hormone levels, with both reduced (24) and increased (15) TSH levels reported in patients receiving dopamine infusions. It is likely that the severity of the underlying disease state requiring dopamine use has a more substantial effect on thyroid homeostasis than dopamine itself. The small-dose infusion we used and the stable hemodynamics encountered probably had an ill-defined but minor impact on thyroid function.
The precise etiology of decreased thyroid hormone levels during CPB remains unknown and the clinical significance unclear. In contrast to previous reports of uncomplicated perioperative recovery, our patient sustained dramatic alterations in tissue integrity with marked peripheral edema. Severe long-standing hypothyroidism produces glycosaminoglycan accumulation in soft tissues (25) and the large volume of hydrated glycosaminoglycan molecules in subcutaneous areas causes edema of the overlying skin. Facial fullness, periorbital edema, tongue swelling, and edema of the hands and feet are prominent clinical manifestations of generalized myxedema (25). In addition, absent compensatory increases in lymph flow in hypothyroid patients leads to generalized lymphedema (25). It is unclear why our patient developed such severe and diffuse edema, although alterations in free water excretion from both the hypothyroid state and renal insufficiency, and further CPB-related reductions of thyroid hormone levels in an untreated patient with long-standing severe hypothyroidism, may have precipitated his dramatic clinical appearance. Although generalized edema from anaphylaxis cannot be excluded, there was no initial hypotension, bronchospasm, or rash to suggest an allergic reaction.
In conclusion, this case demonstrates a potential danger of withholding thyroid hormone replacement before cardiac surgery in known hypothyroid patients undergoing CPB and also alerts the clinician to severe hypothyroidism as a diagnostic possibility in any patient developing generalized edema after CPB. Although one case cannot refute current recommendations regarding the preoperative management of known hypothyroid patients undergoing CABG, this report should raise awareness of the possible consequences of untreated hypothyroidism and the potential impact of CPB on thyroid homeostasis.
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