Extracorporeal Membrane Oxygenation Rescues Thyrotoxicosis-Related Circulatory Collapse

Introduction

H eart failure is one of the most well-known complications of thyrotoxicosis. About 6% of thyrotoxic individuals develop symptoms of heart failure, but less than 1% develop dilated cardiomyopathy with impaired left ventricular systolic function (1). Symptoms of congestive heart failure (CHF) will subside, and left ventricle ejection fraction (LVEF) will increase when patients become euthyroid. However, serious complications such as heart failure and hypotension resulting in cardiovascular collapse and death may occur even in previously well and young patients. If unrecognized or left untreated, the disease may result in cardiovascular collapse and death (2).

Circulatory collapse often requires mechanical support bridging until recovery. Mechanical support with extracorporeal membrane oxygenation (ECMO) can stabilize patients with acute hemodynamic compromise (3), permitting further evaluation and treatment. Here, we report four patients who developed severe heart failure during thyroid storm and were rescued by ECMO. The clinical data are summarized in Table 1.

Patient

Patient 1, a 47-year-old man, was seemingly healthy but, approximately 1 month before his presentation, he developed exertional dyspnea and intermittent palpitations. He was seen at the local hospital initially where he was diagnosed with CHF and was treated with digoxin and diuretics. His symptoms did not improve, however, and he presented to our emergency department complaining of chest tightness and severe dyspnea. Under the impression of acute coronary syndrome, he received coronary angiography. The coronary angiography showed patent coronary arteries, LVEF of 32%, global hypokinesia, and severe mitral valve regurgitation. He was then admitted to intensive care unit (ICU) with the impression of CHF. During the initial part of his ICU stay, atrial fibrillation (AF) with rapid ventricular response despite treatment with digoxin and verapamil as medications and electrical cardioversion. The body temperature was above 38.5°C during the admission period. Chest X-ray showed pulmonary edema. Intubation was, therefore, performed and the fever persisted. Thyroid function tests were performed showing a suppressed serum thyrotropin (TSH) (<0.004 μIU/mL, normal range, 0.25–4.0 μIU/mL) and elevated free thyroxine (FT4) (4.26 ng/dL, normal range, 0.89–1.79 ng/dL). Antithyroid drugs, as propylthiouracil (PTU) 300 mg four times daily, and glucocorticoids, as hydrocortisone 100 mg thrice daily, were administered for a diagnosis of thyrotoxicosis. At that time, the hemodymamic profile showed a mean arterial blood pressure (MAP) 70 mmHg under Dopamine 8 μg/(kg · min) and metabolic acidosis with a base deficiency of 8 mEq/L. Asystole occurred on the fourth day in ICU, and cardiopulmonary resuscitation was started and venous-artery mode ECMO (V-A mode ECMO) and intra- arterial balloon pump (IABP) were set up. However, he was refractory to inotropic agents and mechanical circulation support and expired on the fifth ICU day.

Patient 2, a 43-year-old man, had a two year history of hyperthyroidism but he was not taking his PTU and β-blocker on a regular basis. He presented to the emergency department for worsened dyspnea with a body temperature of 38°C. He had a sudden collapse, and the electrocardiography (EKG) showed pulseless electrical activity. Cardiopulmonary resuscitation (CPR) was performed and his pulse returned in 10 minutes. The echocardiogram showed dilated four chambers and severe left ventricular systolic dysfunction. Thyroid function tests showed a suppressed serum TSH level (<0.03 μIU/mL) and elevated serum FT4 (2.42 ng/dL), serum triiodothyronine (237 ng/dL, normal range, 60–190 ng/dL). The course and studies were consistent with thyrotoxicosis with circulatory collapse. The patient was started on PTU 300 mg four times and hydrocortisone 100 mg thrice a day. In addition, V-A mode ECMO and IABP were inserted immediately for hemodynamic support. Two days later, the serum triiodothyronine level declined to 110 ng/dL, and the heart rate returned from 120 beat per minute (bpm) to 90 bpm. The MAP was around 85 mmHg, and normal lactic acid level (<2 mmol/L) was noted under low-dose Dopamine used (3 μg/[kg · min]). The ECMO was removed 5 days later, and the IABP was removed 6 days later. Two weeks later, the echocardiogram showed improvement in LV function (LVEF: 20%–64%). The patient was discharged from ICU 20 days later.

Patient 3, a 37-year-old woman who was not taking antithyroid medications or receiving regular medical care, had a history of hyperthyroidism due to Graves' disease. She was brought to emergency department due to loss of consciousness. Initially, hypoglycemia was noted. After glucose injection, her consciousness was recovered but AF with rapid ventricular response occurred and she then developed circulatory collapse. The EKG showed pulseless electrical activity. CPR was performed. Five minutes later, consciousness recovered and the MAP was 40 mmHg under a high dosage of inotropic agents. An echocardiogram showed four chamber dilatation with poor left ventricular contractility. Thyroid function tests showed suppressed serum TSH level (<0.035 μIU/mL) and elevated FT4 (7.5 ng/dL). A diagnosis of thyroitoxicosis with severe cardiogenic shock was made, and she was treated with 300 mg PTU four times daily and 100 mg hydrocortisone thrice daily. In addition, V-A mode ECMO was started. The FT4 level returned to 1.5 ng/dL, and MAP increased to 75 mmHg with decreasing dosage of inotropic agents. Normal circulating lactic acid level was achieved, and she was weaned from the ECMO 5 days later. An echocardiogram, performed 20 days after ECMO was started, showed improvement in LV function (LVEF increased from 32% to 60%).

Patient 4 was a 42-year-old man in whom Graves' disease was diagnosed about 22 years earlier. He took PTU but did not take it regularly. He developed severe dyspnea and delirium and was sent to our emergency department. Thyroid function tests showed a high serum FT4 level (4.5 ng/dL) and a suppressed serum TSH level (0.018 μIU/mL). The MAP was about 50 mmHg, and heart rate was 110 bpm. Fever (38.5°C) and metabolic acidosis with elevated lactic acid (5.6 mmol/L) were also found. The echocardiogram revealed poor LV contractility (EF: 29%). A diagnosis of severe thyrotoxicosis with decompensated heart failure was made. He was intubated and started on PTU, 300 mg four times daily, and hydrocortisone, 100 mg thrice daily. Profound shock with an MAP of 40–50 mmHg persisted despite the use of high doses of inotropic agents (Dopamine 15 μg/[kg · min] and norepinephrine 5 μg/[kg · min]). He was started on V-A mode ECMO on the second day of hospitalization. The FT4 level decreased to1.42 ng/dL, and the MAP improved to 75 mmHg with the use of low-dose Dopamine. His cardiac function improved (LVEF increased from 29% to 45%). He was weaned off ECMO 5 days later.

Discussion

Thyrotoxicosis is a clinical syndrome with various perturbations including hypermetabolism; it is due to inappropriately elevated serum thyroid hormone concentrations. Thyrotoxicosis has an important impact on the cardiovascular system. Mild signs and symptoms related to this are palpitations (e.g., sinus tachycardia, AF) and hypertension that mimic those of increased beta-adrenergic activity. More severe complications are exertional dyspnea or exercise intolerance caused from high output heart failure that, in some patients, can induce circulatory collapse, which, if not successfully treated, leads to death (4). Thyroid storm is a poorly understood syndrome that occurs in a small number of patients with thyrotoxicosis (5). Beyond the appearance of severe thyrotoxicosis, fever and mental disturbances are hallmarks of thyroid storm. The mortality rate of thyroid storm varies from 20% to 30% (5). Death, when it occurs, is typically accompanied by lethal arrhythmias and shock. One of the patients presented here had fever, perhaps indicative of thyroid storm. Regardless of whether they met the universally accepted definition of thyroid storm, all four patients had life-threatening cardiovascular complications of severe thyrotoxicosis and one succumbed to these complications.

Through a variety of direct and indirect mechanisms, excess thyroid hormone alters cardiovascular physiology (6 –10). In addition to its effect on peripheral vasodilation, excess thyroid hormone increases heart rate, cardiac contractility, cardiac mass, and blood volume. The result of the combination of these effects is an increase in the cardiac output and myocardial hypertrophy (11), thus allowing the heart to cope better with this hemodynamic burden. However, if left untreated, thyrotoxicosis can cause dilated cardiomyopathy (9,12,13). About 6% of thyrotoxic individuals develop symptoms of heart failure, but less than 1% of them develop dilated cardiomyopathy with impaired left ventricular systolic function (2).

Patients with the full syndrome of thyroid storm or with severe cardiovascular complications of thyrotoxicosis are critically ill and require intensive care to monitor their fluid status and hemodynamic parameters. β-adrenergic blockade has the most dramatic effect on the cardiovascular manifestations of thyroid storm. In patients who have contraindications to β-adrenergic blockade, alternative therapy with reserpine can be used. However, neither of these agents should be used in the presence of cardiovascular collapse or shock (5,14,15).

All of our patients had decompensated heart failure with dilated chambers on echocardiography. As shown in Table 1, three of these patients experienced sudden cardiovascular collapse. Therefore, patients who have thyrotoxicosis-induced severe heart failure should be admitted to ICU for close hemodynamic monitoring.

Lactic acidosis, as was noted in all of our patients, is likely to be due to a combination of acute cardiomyopathy with reduction in cardiac output and increase in cellular demands of oxygen in their hypermetabolic state (16). Measurement of blood lactate in critically ill patients has shown prognostic value in several situations (eg., trauma, shock, and other severe diseases in adults, children, and also in preterm newborns) (17). Smith et al. concluded that lactate can be used for the prognosis of outcome in ICU (18). In our series, three patients survived under the V-A mode ECMO support and one patient expired. Pre-ECMO blood lactate levels in the patient who expired were higher than those in the three patients who survived. The outcome in our patients, therefore, is consistent with the observations of Smith et al. (18) with regard to blood lactate levels.

Dilated cardiomyopathy with low-cardiac output may be reversible. A previous report indicated that conventional treatment of hyperthyroidism usually results in rapid resolution of the clinical manifestations of heart failure, in partial or complete reversal of the associated cardiomyopathy, and in marked improvement of left ventricular systolic function (9). In our series, the three patients who survived had improved cardiovascular function after 5 days of ECMO support. These results are consistent with the results of ECMO when used successfully in patients with acute hemodynamic compromise (even under CPR) related to other conditions such as fulminant myocarditis and pheochromocytoma (3,19).

We conclude that severe heart failure and dilated cardiomyopathy in thyrotoxicosis is potentially reversible with antithyroid treatment but that these patients should be admitted to the ICU for close hemodynamic monitoring. Mechanical circulatory support such as ECMO should be immediately provided for circulatory collapse or severe hypotension.