Clinical Reasoning: Heart to swallow

SECTION 1

A 55-year-old woman was admitted to our intensive care department after intoxication with lithium. Her medical history was relevant for bipolar disorder for which she received medical treatment with lithium, haloperidol, and citalopram. In the week before admission, she had developed a clinical picture of gastroenteritis with diarrhea and vomiting, which resulted in dehydration and a marked deterioration in kidney function. During the last days before admission, she had become progressively lethargic and had developed dysarthria as well as postural tremors of the extremities. The tremors were coarse and irregular, most clearly present in the hands with a frequency of approximately 8 Hz. At admission, she opened her eyes spontaneously, localized pain, and showed normal verbal responses (E4M5V5). Physical examination showed severe dysarthria, ataxia, and no focal neurologic deficits. Reflexes were normal. Laboratory investigation revealed a de novo elevated creatinine level (220 μmol/L, normal 49–90) corresponding to an estimated glomerular filtration rate of 22 mL/min/1.73 m² (normal >60) and a lithium level that was 5.8 mmol/L (target value 0.6–0.8 mmol/L). ECG at admission was normal except for a prolonged QTc interval of 533 milliseconds (normal <450).

SECTION 2

Potential explanations for altered consciousness and tremors include intoxications (lithium, serotonergic, or antiepileptic drugs) and alcohol withdrawal. The tremor described here has the typical characteristics of a lithium tremor.¹ These symptoms, in combination with elevated lithium levels led to a diagnosis of severe lithium neurotoxicity due to hypovolemia-induced renal failure. Since the excretion of lithium is almost uniformly renal, acute lithium toxicity may be initiated by a loss of renal function. Patients with lithium intoxication often develop gastrointestinal symptoms, e.g., nausea and vomiting. If these symptoms are severe, dehydration and decreased renal function may develop. This impairs the ability to excrete lithium and exacerbates lithium toxicity. Therapeutic intervention should focus on rehydration and the removal of lithium from the body. Restoration of electrolyte and water balance by rehydration in hypovolemic patients with lithium toxicity is mandatory to maintain or restore kidney function and maximize lithium clearance. Removal of lithium should be achieved by discontinuation of the drug as well as extracorporeal removal by means of hemodialysis or continuous veno-venous hemofiltration (CVVH). Lithium is readily dialyzable since it is nonprotein bound and has a low molecular weight and a small volume of distribution. Usually one session of hemodialysis or 24 hours of CVVH is sufficient, although some experts advise to continue dialysis after normal (<1 mmol/L) levels of lithium have been achieved to prevent a rebound effect.²

In our patient, treatment was initiated with rehydration as well as CVVH and the patient was admitted to our intensive care unit (ICU). CVVH was continued for 24 hours, which resulted in a decrease of lithium levels toward therapeutic levels. However, severe lethargy as well as neurologic sequelae persisted for 14 days despite normalization of lithium levels.

SECTION 3

Neurologic complications of lithium intoxication usually develop later in the clinical course because of the relatively slow absorption in the CNS. Furthermore, they may persist despite removal of lithium by hemodialysis of hemofiltration. This “syndrome of irreversible lithium effectuated neurotoxicity” (SILENT) is characterized by prolonged neurologic and neuropsychiatric sequelae, which may persist for months. Demyelination at multiple sites in the CNS has been suggested to be the cause and can sometimes be observed on MRIs as focal white matter abnormalities.^3,4 In our patient, in addition to her neurologic symptoms, episodic symptomatic bradycardias and atrioventricular (AV) blocks associated with hypotension were observed during her stay at the ICU. Upon careful analysis, we observed a close relationship of bradycardias with swallowing. The patient denied ever having symptomatic bradycardias or presyncopal complaints when swallowing before the current episode of lithium intoxication. A representative ECG after swallowing is shown in the figure; also see the video on the Neurology® Web site at Neurology.org (which was recorded relatively late in the clinical course). These bradycardias persisted during the first week of admission but eventually diminished and disappeared. After 2 weeks of admission, her neurologic symptoms slowly improved as well and she was discharged toward a psychiatric care facility for rehabilitation, reinstitution, and optimization of medical therapy for her bipolar disorder.

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Figure Bradycardia and atrioventricular block during swallowing

A real-time ECG recording during swallowing is shown. Initial normal sinus rhythm changes after swallowing, and bradycardia as well as high-degree atrioventricular block are observed.

SECTION 4

Our patient had episodes of swallow-induced transient bradycardia. As bradycardia was not severe enough to cause loss of consciousness, these episodes do not fulfill the criteria for syncope. Nonetheless, episodes of swallow-induced bradycardia are characteristic for “swallow syncope,” a rare syndrome that belongs to the reflex syncope syndromes.⁵ The pathophysiology of swallow syncope is incompletely understood but likely involves a vagal reflex that is initiated by activation of the glossopharyngeal nerve during swallowing.^5,–,7 Efferent impulses lead to the sinoatrial node (right vagus nerve) or the AV node (left vagus nerve) and may lead to various types of paroxysmal bradycardias and reduction of cardiac output. The importance of vagal pathways in this reflex is stressed by studies in which pretreatment with atropine or other anticholinergic drugs is effective in preventing swallow-induced bradycardia. A recent review of all 80 published cases of swallow syncope showed that the majority of cases (62%) had underlying cardiac or gastrointestinal disease, although a substantial minority of patients did not have any underlying pathology.⁵ Treatment of the syndrome may involve implantation of a permanent pacemaker. In patients in whom quality of life is severely affected by recurrent syncopal events, this treatment is usually effective.