Electrical storm due to amiodarone induced thyrotoxicosis in a young adult with dilated cardiomyopathy: thyroidectomy as the treatment of choice

For a patient with idiopathic dilated cardiomyopathy, an implantable defibrillator, and amiodarone induced thyrotoxicosis associated with ventricular fibrillation storm. Medical therapy was ineffective. Thyroidectomy resulted in immediate control of the arrhythmia and permitted reinitiation of amiodarone. At 18-month follow-up, the patient remained euthyroid on amiodarone and ventricular arrhythmia free.     

Thyrotoxic Periodic Paralysis: A Case Report and Literature Review

Thyrotoxic periodic paralysis (TPP) is a rare presentation of thyrotoxicosis most commonly associated with Graves’ disease. It is rare in Caucasians, but it affects approximately 2% of Asians (occurring in those of Chinese, Japanese, Vietnamese, Filipino, and Korean descent) with thyrotoxicosis of any cause. Typical thyrotoxic features may be absent despite biochemical thyrotoxicosis. Hypokalemia and muscle paralysis are the result of an acute intracellular shift of potassium and not due to total body potassium deficiency. TPP is a self-limiting condition that is easily corrected by treatment of the thyrotoxicosis. We present a case of a Filipino man, aged 47 years, who presented to the emergency department with acute bilateral lower extremity weakness and hypokalemia who was subsequently diagnosed with TPP due to Graves’ disease.     

Bilateral upper extremity thrombophlebitis related to intravenous amiodarone: a case report

A 47-year-old male had bilateral upper extremity thrombophlebitis after use of intravenous amiodarone for sustained ventricular tachycardia complicating myocardial infarction. Intravenous amiodarone has been widely used since it was introduced 20 years ago for severe intractable arrhythmias. Superficial thrombophlebitis was frequently noted in the early case reports when high-dose intravenous amiodarone was used. Superficial thrombophlebitis could extend hospitalization and become a significant source of distress to our patients. Some authors recommend insertion of a central line to administer intravenous amiodarone especially with expected extended use of therapy. The treating physician should be vigilant and switch from intravenous therapy to oral therapy as soon as the patient's condition stabilizes and oral therapy can be started.     

Amiodarone-induced thyrotoxicosis: not a benign condition

Amiodarone is a heavily iodinated drug effective in the control of various tachyarrhythmias. Despite its undoubted benefit, treatment with amiodarone is not without risk, because a number of potentially serious side-effects may develop during therapy. Thyrotoxicosis is most commonly recognised but its potential consequences tend to be underestimated, and its treatment can be challenging and difficult. We report several cases of amiodarone-induced thyrotoxicosis which serve to highlight the potential severity of the condition.     

Prise en charge en réanimation du coma myxoedémateux et des formes graves de thyrotoxicose

Hypothyroidism and hyperthyroidism, generally benign conditions, may result in severe features leading to patient admission to the intensive care unit (ICU). Myxedema coma, generally related to the non-compliance with replacement therapy in a patient with chronic hypothyroidism, is characterized by coma associated with hypothermia, bradycardia, and respiratory failure. Thyroid hormone measurement allows the diagnosis. Protocols with rapid intravenous administration of high doses of thyroid hormones, together with warming and mechanical ventilation, have improved the prognosis which remains severe with 50% mortality rate. Nowadays, severe forms of thyrotoxicosis admitted to the ICU are more frequently amiodaroneassociated thyrotoxicosis (whose severity is related to the presence of underlying cardiac diseases) than classic thyroid storms. Treatment of thyroid storm with antithyroid drugs, corticoids, and beta-blockers is generally effective and allows avoiding the need for plasma exchange or emergency thyroidectomy. Prognosis of thyroid storm has improved but remains severe with 20% mortality rate. Diagnosis of the mechanism of amiodarone-induced thyrotoxicosis (type 1 versus type 2) is crucial for treatment. In type 1 (latent preexisting hyperthyroidism worsened by iodine excess), treatment is similar to the one proposed for thyroid storm; in type 2 (thyrotoxicosis related to amiodarone-induced destructive thyroditis), antithyroid drugs are ineffective and treatment relies on corticoids at high doses. However, in these cases, interruption of amiodarone may not be mandatory.     

Thyrotoxic periodic paralysis in a Chinese population

We retrospectively evaluated the characteristics of adult patients admitted with thyrotoxic hypokalaemic periodic paralysis in Hong Kong. From 1984 to 1993, 45 Chinese adult patients were admitted with acute limb weakness, plasma potassium ⩽3.5 mmol/l and thyrotoxicosis confirmed by laboratory investigations. All but one were male. Seventy-five percent of attacks occurred between 9pm and 9am. Half of the attacks occurred between July and October (49.1%), most commonly in August (20%). Mean (+SEM) plasma potassium on admission was 2.17 ± 0.08 mmol/l (range 1.1-3.5). In 15 episodes (27.3%), plasma potassium on recovery exceeded 5.0 mmol/l, while in three episodes (5.5%), potassium exceeded 6.0 mmol/l. No patient had a positive family history of thyrotoxic periodic paralysis. Only 28.9% had a known history of thyrotoxicosis before their first presentation with periodic paralysis. Twenty-seven (60%) had clinical evidence of thyrotoxicosis. Although all were biochemically thyrotoxic, 11.4% had only a mild degree of thyrotoxicosis (suppressed thyroid-stimulating hormone, high free thyroxine, but normal free triiodothyronine). One quarter of the patients had a normal erythrocyte zinc concentration, indicating either a short history of thyrotoxicosis or transient thyrotoxicosis. The diagnosis of thyrotoxic hypokalaemic paralysis should always be considered in Chinese patients with acute muscle weakness, especially in young males. Absence of clinical thyrotoxicosis does not exclude the diagnosis. Plasma potassium should be monitored carefully during treatment to prevent rebound hyperkalaemia.      

胺碘酮致间质性肺疾病误诊为社区获得性肺炎

目的探讨胺碘酮肺毒性的临床特点及误诊原因,并提出防范措施。方法回顾性分析1例胺碘酮致间质性肺疾病误诊为社区获得性肺炎的临床资料。结果患者因咳嗽伴气喘10 d就诊,门诊X线胸片提示右肺感染,入院诊断为社区获得性肺炎。行经验性抗感染治疗,3 d后患者出现发热。查体肺部可闻及较明显Velcro啰音。胸部CT检查示:右肺各叶均有不规则片状毛玻璃影,上叶前段有肺泡渗出影。考虑肺部病变涉及多个肺叶,调整抗生素,患者体温降至正常,但出现呼吸衰竭。经复习原住院病案并追询病史,了解到患者长期口服胺碘酮。肺功能检查提示限制性通气功能障碍。诊断考虑胺碘酮肺毒性致间质性肺疾病,加用糖皮质激素等治疗,症状改善,肺部病变明显吸收,病情好转出院。结论应用胺碘酮者出现间质性肺炎时应警惕胺碘酮肺毒性,双侧肺间质病变不对称为其特点,仔细了解用药史是确立诊断依据,高分辨率CT检查有助于诊断。     

Hyperthyroidism and heart

This review discusses the clinically relevant effects of thyroid hormone excess on the heart. Tachycardia and atrial fibrillation are usually reversible after euthyroidism is restored. Atrial fibrillation may, however, take several months to return to sinus rhythm. The increase in contractility leads to an increase of cardiac output. The development of a relative myocardial hypertrophy following long-term high-dose therapy with thyroid hormones is controversial. Cardiac failure at stress in spite of an increased cardiac output at rest is a phenomenon typical for thyrotoxicosis. Reports of dilated cardiomyopathy associated with Graves' disease and evidence for TSH-receptors in the human myocardium suggest a relationship between these two diseases. Endomyocardial biopsy studies have, however, failed to prove this hypothesis. Mitral valve prolapse is more frequent in hyperthyroid patients than in normals. Thyroid hormone excess as well as the autoimmune origin of the disease are suggested as etiology for this phenomenon. The frequently observed angina pectoris seems to be a consequence of the increase in consumption of oxygen in the presence of an unchanged oxygen supply rather than of obstruction of coronary circulation. Well documented cases of myocardial infarction patients with thyroid hormone excess and normal coronary arteries in angiography substantiate this theory. Finally diagnostic and therapeutic options of the two forms of thyrotoxicosis induced by the antiarrhythmic drug amiodarone are presented.     

Reversibility of blue-gray cutaneous discoloration from amiodarone

A 45-year-old man had severe blue-gray cutaneous discoloration during amiodarone therapy for atrial fibrillation. Therefore, this drug regimen was discontinued, and long-term anticoagulation and digoxin therapy were used. The patient was advised to avoid exposure of his skin to sunlight, and a bleaching agent was prescribed. After 18 months of follow-up, the blue-gray hyperpigmentation had diminished. Although photosensitivity reactions from amiodarone occur in more than 50% of patients, blue-gray cutaneous discoloration occurs in less than 10% of patients on prolonged therapy with amiodarone. The presence of high concentrations of iodine, detected by electron probe analysis, suggests that the cutaneous deposits are amiodarone itself or a metabolite. The slow rate of elimination of amiodarone and a high uptake by fat-associated tissues may explain the delayed disappearance of cutaneous photosensitivity and late resolution of the blue-gray discoloration. Our current case supports the reversibility of these adverse effects on long-term follow-up.     

Amiodarone Attenuates Fluoride-induced Hyperkalemia in Vitro

Poisoning by hydrofluoric acid or fluoride salts results in hypocalcemia, hypomagnesemia, and hyperkalemia with subsequent cardiac dysrhythmias. In previous studies, quinidine attenuated fluoride-induced hyperkalemia in vitro, and enhanced survival in animals. Like quinidine, amiodarone is a potassium channel blocker, although amiodarone is more familiar to clinicians due to its recent inclusion in advanced cardiac life support (ACLS) protocols. OBJECTIVES: This in-vitro study of human erythrocytes was designed to determine whether amiodarone could attenuate fluoride-induced hyperkalemia. METHODS: Six healthy volunteers each donated 60 mL of blood on three occasions. Each specimen was divided into 12 tubes, incubated at 37 degrees C, and oxygenated with room air. An aqueous sodium fluoride (F(-)) solution was added to tubes 1-9. Incremental amounts of quinidine were added to tubes 1-4 (Q(1)-Q(4)) to attain calculated concentrations of 0.73 microg/mL, 1.45 microg/mL, 2.9 microg/mL, and 5.8 microg/mL, respectively. Incremental amounts of amiodarone were added to tubes 5-8 (A(1)-A(4)) to attain calculated concentrations of 0.38 microg/mL, 0.75 microg/mL, 1.5 microg/mL, and 3.0 microg/mL, respectively. Tubes 9-12 were controls for each of F(-), amiodarone, quinidine alone, and no additive, respectively. Extracellular potassium concentration ([K(+)]) was followed, and an objective endpoint was defined as the rise in potassium concentration at 6 hours. RESULTS: Fluoride produced a significant change in [K(+)] by 6 hours in all samples. Quinidine produced a J-shaped curve in its ability to attenuate the rise in [K(+)], with only one concentration, Q(3), demonstrating significance versus tube 9 (control). Amiodarone also demonstrated a J-shaped dose-response effect, with statistical significance at A(1), A(2), and A(3) versus tube 9 (control). There was no significant difference among the effective concentrations (Q(3), A(1), A(2), and A(3)) of both drugs. CONCLUSIONS: In this in-vitro model using human blood, amiodarone and quinidine both attenuated F(-)-induced hyperkalemia. Further study is indicated to determine whether amiodarone enhances survival in F(-)-poisoned animals.     

Pulmonary hypertension and predominant right heart failure in thyrotoxicosis

In this report we discuss a patient with predominant right heart failure and pulmonary hypertension, caused by thyrotoxicosis due to Graves disease, which deteriorated to asystole, due to amiodarone administration for rapid atrial fibrillation.     

Serial electrophysiological studies in a young patient with recurrent ventricular fibrillation

A 28-year-old male with recurrent episodes of ventricular fibrillation, which were initiated by very early ventricular premature depolarizations with a normal QT interval, was subjected to three consecutive electrophysiological studies. During the first study, which was carried out to test the efficacy of amiodarone treatment, no ventricular arrhythmias could be induced. While on amiodarone therapy, the patient experienced another syncopal episode and therefore a second electrophysiological study was done. In that study, ventricular fibrillation was induced by ventricular stimulation. During the third study, which was carried out in order to evaluate the effect of the addition of quinidine to the ongoing amiodarone therapy, no more than three repetitive ventricular responses could be induced. The patient has been asymptomatic since the third study (fifteen months) with combined therapy of amiodarone and quinidine. The significance of the ability to induce ventricular fibrillation during an electrophysiological study is discussed as well as the value of such studies in determining the long-term efficacy of antiarrhythmic drug therapy.     

门冬氨酸钾镁联合胺碘酮对慢性心力衰竭并室性心律失常患者心功能的影响

目的探讨门冬氨酸钾镁联合胺碘酮对慢性心力衰竭并室性心律失常患者心功能的影响。方法选择232例慢性心力衰竭并室性心律失常患者,用随机数字法分为观察组和对照组,每组116例。对照组采用胺碘酮治疗,观察组在胺碘酮基础上加用门冬氨酸钾镁。治疗前后,检测两组患者的血压、心率、P-R与Q-T间期、左室舒张末期内径(LVD)、左室射血分数(LVEF)、室后壁厚度(LVWP),并统计治疗效果和不良反应发生率。结果治疗后,两组心率均明显降低,P-R与Q-T间期明显增加(P0.05),观察组心率、P-R间期和Q-T间期较对照组,均P0.05;治疗后,两组LVD、LVEF、LVWP均明显改善(P0.05),且观察组LVD、LVEF和LVWP改善效果显著优于对照组(P0.05);治疗后,观察组总有效率为83.6%,显著高于对照组的72.4%(χ2=4.247,P0.05)。结论门冬氨酸钾镁联合胺碘酮可有效缓解慢性心力衰竭并室性心律失常患者的心脏收缩和舒张功能,减慢心率,恢复正常射血,改善患者临床症状。     

Optic Neuropathy Following Amiodarone Therapy

Ocular changes during treatment with amiodarone are almost universal but are rarely serious. In this article we describe three patients from a single electrophysiology practice in whom optic neuropathy developed during treatment with amiodarone. All three patients were more than 65 years of age. The doses of amiodarone ranged from 100 to 400 mg/day, and the time intervals between the initiation of the amiodarone therapy and the appearance of first symptoms of optic neuropathy were 5 to 19 months. Two patients had bilateral involvement, and one had only unilateral involvement. Whether this result was due solely to amiodarone therapy, to the underlying poor health of these patients, or to the combination of these two factors is uncertain. These findings prompt us to recommend that all patients who receive amiodarone undergo complete ophthalmologic examinations, including careful evaluation of the ocular fundus regularly during such therapy. No randomized study had been undertaken to determine the true incidence of complications associated with this medication.     

Amiodarone and/or lidocaine for cardiac arrest: A Bayesian network meta-analysis

IntroductionAlthough available studies have not demonstrated that antiarrhythmic drugs could increase long-term survival or survival with favorable neurological outcome, some studies have shown that the rate of hospital admission is higher with amiodarone or lidocaine than with placebo. To study the effects of antiarrhythmic drugs during cardiac arrest, a meta-analysis was conducted to assess the efficacy of amiodarone and/or lidocaine.MethodsWe searched studies from inception until Jan 21, 2020. The primary endpoint was survival to hospital discharge in cardiac arrest, and the secondary endpoints were survival to hospital admission/24 h and favorable neurological outcome.ResultsA total of 9 studies were included. In head-to-head studies, amiodarone (odds ratio [OR] 2.96, 95% credible interval [CrI] 1.02–8.53) and lidocaine (OR 3.12, 95% CrI 1.08–9.98) had superior effects on survival to hospital admission/24 h compared to the combination of the two drugs. In terms of survival to hospital discharge, amiodarone (OR 1.18, 95% CrI 1.03–1.35) and lidocaine (OR 1.22, 95% CrI 1.06–1.41) were more effective than placebo. Amiodarone (OR 1.20, 95% CrI 1.02–1.41) was significantly better than placebo in favorable neurological outcome. However, there was no significant difference in other pairwise comparisons. The surface under cumulative ranking curve (SUCRA) revealed that lidocaine was the most effective therapy for survival to hospital admission (84.1%) and discharge (88.4%), while amiodarone was associated with a more favorable neurological outcome (88.2%).ConclusionsLidocaine had the best effect on both survival to hospital admission and discharge, while amiodarone was associated with a more favorable neurological outcome.Trial registration: This study is registered with PROSPERO, number CRD42020171049.     

Prophylactic Amidarone Treatment for Atrial Fibrillation After Coronary Artery Bypass Surgery

In this study we performed a retrospective chart review to evaluate the efficacy of short-term postoperative oral amiodarone therapy on postoperative atrial fibrillation (POAF) after coronary artery bypass surgery. The incidence of POAF in 372 patients (60.6%) without prophylactic amiodarone therapy was compared with that in 240 patients (39.4%) receiving the medication immediately after the surgery. Patients who received prophylactic amiodarone developed significantly less POAF than those without prophylactic treatment (17.0% versus 25.9%, P = .01), with relative and absolute risk reductions of 0.7% and 8.9%, respectively. Postoperative oral amiodarone therapy is simple to administer and may be a valuable adjunct therapy for patients after coronary artery bypass surgery.     

State of the renin-angiotensin-aldosterone system in thyroid pathology based on the results of radioimmunoassay

The activity of plasma renin, concentration of serum aldosterone and plasma corticotropin were determined by a radioimmunoassay in 78 patients with diffuse toxic goiter with thyrotoxicosis of various degrees of gravity, im 21 patients with primary hypothyroidism and 25 controls in euthyroid condition. In the patients with thyrotoxicosis such investigations were conducted before and after a course of drug therapy. In thyrotoxicosis the activity of the renin-angiotensin-aldosterone system was raised, in hypothyroidism it was lowered, a degree of expression of appropriate changes being associated with the gravity of disease. In the patients with marked thyrotoxicosis after a course of drug therapy the indices of plasma renin activity and serum aldosterone concentration did not return to normal. Hypophyseal corticotropic function was raised in marked thyrotoxicosis, mild hypothyroidism and corresponded to the normal level in the patients with hypothyroidism of average gravity. Plasma ACTH concentration in the patients with marked thyrotoxicosis returned to normal after a course of drug therapy.     

Clinical and electromyographic examination of tremor in patients with thyrotoxicosis

Tremor is a well-known symptom of thyrotoxicosis, yet no detailed clinical and electromyographic (EMG) examination of it has been published. The aim of this investigation was to establish the clinical and EMG pattern of tremor in patients with thyrotoxicosis and to compare it with the well-known pattern of enhanced physiological tremor caused by anxiety. Twenty-six patients with thyrotoxicosis and tremor and 30 patients with tremor and generalised anxiety disorder were investigated. Tremor was scored clinically in all possible limb positions. EMG examination of tremor activity from antagonist hand muscles was performed. A postural and kinetic tremor with characteristics of an enhanced physiological tremor was found in patients with thyrotoxicosis and generalised anxiety disorder. Tremor involved only the upper limbs in all patients. In conclusion, tremor in thyrotoxicosis and generalised anxiety disorder is an enhanced physiological tremor which cannot be separated clinically or by EMG measurement. Both types of tremor have similar mechanisms and can be distinguished only by the circumstances responsible for their occurrence. Despite only a moderate correlation between tremor intensity and thyroid hormone levels, successful treatment of thyrotoxicosis results in a dramatic improvement of tremor.