An unusual case of nonsustained ventricular tachycardia

Abstract

A 54-year-old woman with advanced cirrhosis secondary to hepatitis C, end-stage kidney failure on hemodialysis, and nonischemic cardiomyopathy was admitted to the medical intensive care unit for treatment of a superior vena cava (SVC) thrombus involving a recently implanted cardioverter–defibrillator (ICD). During her hospitalization, the patient abruptly developed frequent ventricular ectopy with up to 20 beat runs of hemodynamically significant nonsustained ventricular tachycardia. Because ventricular ectopy was not previously seen in the patient, the sudden onset prompted a thorough evaluation. After other causes were excluded, a recently placed scopolamine patch was removed; the ventricular ectopy completely resolved within 24 hours and did not recur for the remainder of the patient’s extended hospitalization. While anticholinergic syndrome is associated with a vagally mediated sinus tachycardia, ventricular arrhythmias have not previously been reported with scopolamine, to the best of the authors’ knowledge. The observed cardiac side effects of scopolamine rarely occur at therapeutic doses. Scopolamine is metabolized primarily in the liver and excreted by the kidneys, so renal and hepatic impairment should be considered when initiating and dosing this medication. Because anticholinergic medications including scopolamine are commonly used in various clinical settings, we believe that clinicians should be aware of this significant but completely reversible adverse effect.

Presentation

A 54-year-old woman with end-stage cirrhosis secondary to hepatitis C, end-stage kidney failure on hemodialysis, and nonischemic cardiomyopathy with most recent ejection fraction of 30% was admitted to the medical intensive care unit (ICU) for treatment of a superior vena cava (SVC) thrombus involving a recent implanted cardioverter–defibrillator (ICD) implantation. During a prolonged hospital course, the patient suddenly and inexplicably developed frequent ventricular ectopy with up to 20 beat runs of hemodynamically significant nonsustained ventricular tachycardia (Figure 1a). This problem had not occurred before in this patient, despite her multiorgan dysfunction. The cardiology service was consulted to assist in management.

Figure 1.

(a) Representative samples demonstrating the patient’s ventricular ectopy and correlated decrease in arterial pressure. (b) 12-lead surface electrocardiogram of the ventricular ectopy.

Assessment

At the time of initial evaluation, all history was obtained via patient records due to the patient’s obtunded mentation. Weeks prior to admission, the patient had undergone ICD implantation for primary prevention of lethal arrhythmias secondary to nonischemic cardiomyopathy. Subsequently, a SVC thrombus developed, the ICD was explanted and the SVC was stented open. Several days later, the patient suddenly developed a high burden of ventricular ectopy. A 12-lead electrocardiogram (ECG) was performed (Figure 1b).

Initial clinical evaluation revealed an obtunded, thin female with pulse ranging from 100 to 120 beats per minute and blood pressure averaging 110/50 mmHg. Overall her blood pressure was marginal, but with continuous invasive monitoring, the blood pressure could be seen to diminish during successive ectopic contractions. She was not febrile or hypoxic. Physical exam revealed decreased breath sounds in the right lung base but was otherwise unremarkable. Review of pertinent labs revealed leukocytosis (white blood cell count of 15.8 × 10³ cells/mm³), stable chronic anemia (hemoglobin 7.4 g/dl and hematocrit 24.3%) and mild hyponatremia (sodium 133 mm/l) with otherwise normal electrolytes. Morning cortisol at 8 a.m. was mildly elevated (31 µg/dl) felt to be secondary to normal stress response. Thyroid-stimulating hormone (TSH) was mildly elevated (7.58 mIU/l) while free T4 was within normal limits (1.13 ng/dl), which were attributed to the recovery phase of nonthyroidal illness. Troponin T was mildly elevated (0.09 ng/ml), but stable in the setting of renal failure and normal creatinine kinase (33 U/l) and myocardial band (3.4 ng/ml). Microbiology tests including blood, urine, and sputum cultures were negative and lactate was within normal limits. A bedside transthoracic echocardiogram revealed moderate to severe left ventricular systolic dysfunction without valvular abnormalities or pericardial effusion, consistent with prior imaging. Single view chest X-ray revealed a large cardiopericardial silhouette, right pleural effusion, bilateral interstitial lung disease and right-lower lobe opacity. The previously placed SVC stent was in unchanged and acceptable position. There were no invasive lines or tubes in place. Medications included low-dose aspirin, unfractionated heparin infusion, darbopoeitin and transdermal scopolamine.

Diagnosis

Premature ventricular contractions (PVCs) are common with prevalence in the range of 1–4% in the general population. Usually asymptomatic, some patients present with symptoms such as palpitations, shortness of breath, syncope, or near syncope. If the PVCs become frequent, cardiac output can be affected and cardiomyopathy can potentially be induced. The evaluation of PVCs should include assessments for structural abnormalities, myocardial ischemia, electrolyte derangements, infections, endocrinopathies and drugs/toxins [Yong-Mei et al. 2012].

In this case, each of these potential causes were evaluated and systematically ruled out and the medication list was reviewed. All medications had been stable until the onset of the noted ventricular ectopy, with the exception of a transdermal scopolamine patch which was initiated for excessive airway secretions, approximately 48 hours prior. Without any other evident culprit, the scopolamine patch was removed. The patient’s ventricular ectopy resolved within 24 hours (Figure 2) and did not return. The patient remained in the hospital for another 10 days without recurrence of arrhythmia; she was discharged to a long-term acute care facility outside our university health system.

Figure 2.

This figure demonstrates resolution of ventricular ectopy in the patient less than 24 hours following removal of the scopolamine patch.

Discussion

The approach to the management of PVCs depends on determining the clinical significance of the ectopy, and identifying and reversing the underlying cause. Asymptomatic and hemodynamically stable patients generally do not require any therapy, but should be monitored for the development of cardiomyopathy if the burden of ectopy is high [Adams et al. 2012]. The most common arrhythmias in the ICU setting are atrial fibrillation and ventricular tachycardia, and arrhythmias in general are associated with higher mortality [Reinelt et al. 2001]. In symptomatic patients or those with documented PVC mediated cardiomyopathy, therapy should then be directed at suppression of further ventricular ectopy. Usual first-line therapy includes either beta-blockers or nondihydropyridine calcium channel blockers. A minority of patients fail to respond to first-line therapy and require a class IC or III antiarrhythmic agent. In those with refractory symptoms or those who cannot tolerate medical therapy, catheter ablation remains an option [Adams et al. 2012]. In the case presented here, an underlying cause was identified as an unusual presentation of an anticholinergic side effect. After removal of the scopolamine patch, further ectopy ceased.

Tachycardia is a common finding associated with anticholinergic syndrome; however, supraventricular tachycardia is the typical rhythm disturbance encountered [Renner et al. 2005]. In this case, the anticholinergic in question is scopolamine, a transdermal medication occasionally used in the critical care setting to decrease nausea and oropharyngeal secretions. It is a nonselective muscarinic antagonist producing both peripheral and central effects [Renner et al. 2005]. Despite years of clinical use, its metabolism and excretion, even in healthy individuals, is incompletely understood. Scopolamine has complex, dose-dependent, variable effects on the cardiovascular system. Low doses are associated with slowing of heart rate while higher doses, through inhibition of vagal stimulation of the sinoatrial node, cause dose-dependent increases in heart rate [Renner et al. 2005]. The drug is excreted in urine over a period of hours and undergoes oxidative demethylation during incubation with CPY3A. In this case, the patient had both end-stage liver and kidney disease requiring hemodialysis, possibly altering the metabolism and excretion of scopolamine and resulting in the observed ventricular ectopy.

While adverse events of scopolamine are common, at therapeutic doses arrhythmias are not common. One systematic review of 23 trials with a total of 1963 patients comparing transdermal scopolamine versus placebo for prevention of postoperative nausea and vomiting found that 29% of patients receiving scopolamine experienced at least one adverse effect, none of which were arrhythmias [Kranke et al. 2002]. For patients who do experience toxicity, the recovery is usually prompt, as described by Repéssé and colleagues [Repéssé et al. 2007].

Scopolamine has been studied for cardioprotective effects in heart failure and myocardial infarction (MI)/ischemia. The ATRAMI study provided prospective data that heart rate variability (HRV) and baroreceptor sensitivity (BRS) carry significant and independent prognostic value in the postmyocardial infarction setting [La Rovere et al. 1998]. Pedretti and colleagues then showed in a prospective study of 28 post-MI patients that transdermal scopolamine administration led to significant increases in cardiac vagal activity, as reflected by HRV and BRS [Pedretti et al. 1993]. Despite the observed effect on vagal tone, other studies have failed to document any improvement in clinical outcomes. A study evaluating the effect of scopolamine in mongrel dogs with previous anterior MI subjected to exercise and ischemia found that scopolamine had only minimal antifibrillatory effects [Hull et al. 1995]. Another study designed to address the effects of transdermal scopolamine on HRV, BRS and exercise performance in stable congestive heart failure patients found that low-dose scopolamine increased cardiac vagal activity without affecting the incidence or severity of ventricular arrhythmias [Casedei et al. 1996].

The exact mechanism of anticholinergic related effects on cardiac dysrhythmias is poorly understood. While multiple postulates exist, the true mechanism is probably multifactorial and dependent on the patient’s underlying physiology including drug metabolism and excretion. Conditions that negatively alter these processes potentially lead to supratherapeutic drug levels increasing the likelihood of potential adverse events. In the clinical setting, one must pay close and special attention to these factors. Interactions with other drugs that modulate autonomic tone could also play a role. If side effects such as cardiac dysrhythmias are noted, the offending agent should be discontinued.