Letter: Vagus nerve stimulation and cardiac asystole

Abstract

To the Editors: This month’s issue of Epilepsia highlights important issues regarding refractory epilepsy, cardiac dysfunction, and vagus nerve stimulation (VNS). In a Brief Communication (Iriarte et al., 2009), a patient with refractory epilepsy and VNS developed heart block during status epilepticus 9 years after asymptomatic function. In a Letter from the same issue, Schuurman & Beukers, 2009 report asystole during intraoperative lead testing. Asystole has been known to occur intraoperatively (Tatum et al., 1999), with a prior case described extraoperatively (Amark et al., 2007). While underreporting could exist, there are nearly 50,000 implants worldwide, with reported cases still approximating an incidence of <0.1% (Data on file, Cyberonics, 2009). Fortunately, excessive death in patients with VNS has not been encountered (Annegers et al., 2000). However, in contrast sudden unexpected death in epilepsy (SUDEP) occurs at a rate of 1 per 150 person-years with uncontrolled seizures (Thompson et al., 2005), and is more prevalent and a significant risk. Delayed arrhythmia reported by Iriarte et al. (2004) bears several points worth noting. First, the patient had a VNS model 101 functioning with a current intensity of 1.75 mA, which after 9 years of use could have manifest erratic function representing end-of-service and resulting in status. Earlier models had limited predictability of generator battery failure (Tatum et al., 2004). Secondly, status epilepticus can produce a chronic alteration in cardiac sympathovagal balance (Metcalf et al., 2009) and could have predisposed to arrhythmia (Ali et al., 2004). Lastly, intravenous and γ-aminobutyric acid (GABA)ergic antiepileptic drugs (AEDs) may have provided an added “inhibitory” response, further taxing an already compromised cardiac reserve. Therefore, it seems plausible that asystole reflect factors unique to the operating room (OR) setting at implant, although may include multiple factors postimplant. In >250 implants, we have encountered two cases of asystole. Both occurred in the OR, with the first patient reported in 1999, and a second that occurred in 2008 during battery replacement. A 19-year-old woman had a single 15-s asystole that occurred in the OR in 2008 during the second cycle of stimulation. Despite initial deactivation, this patient was subsequently successfully reactivated postoperatively in the intensive care unit without recurrent arrhythmia thereafter. These reports emphasize the importance of continued vigilance for the patients with refractory epilepsy and VNS. Given the at-risk population, postmarketing surveillance should exist for all treatments. General suggestions for clinicians using VNS include ensuring patients are nonsurgical candidates, maintaining a heightened awareness during initial lead testing, and minimizing polypharmacy. Specific recommendations include careful observation for a change in seizure semiology, frequency, or intensity to suggest an alternate diagnosis or end of service, identifying concomitant heart disease, and early treatment of comorbidities that could predispose to arrhythmia. We also minimize inhalant neuro-anesthesia during surgery, repeat the lead test if bradycardia or asystole occurs, and deactivate the VNS prior to elective surgery. Despite isolated cases of arrhythmia, the overall effectiveness of VNS has “survived” for more than 10 years. We agree with Schuurman and Beukers that “it would be unfortunate…if VNS surgery was aborted (or deferred) as a result of these data.” With all treatments, the balance between risk and benefit must be weighted. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Conflict of interest: Dr. Tatum has received honoraria from Cyberonics Inc.