Hypercapnic ventilatory response in epilepsy patients treated with VNS: A case‐control study

Abstract

Objective Central CO2 chemoreception (CCR), a major chemical drive for breathing, can be quantified with a CO2 re‐breathing test to measure the hypercapnic ventilatory response (HCVR). An attenuated HCVR correlates with the severity of respiratory dysfunction after generalized convulsive seizures and is a potential biomarker for sudden unexpected death in epilepsy (SUDEP) risk. Vagus nerve stimulation (VNS) may reduce SUDEP risk, but for unclear reasons the risk remains higher during the first 2 years after implantation. The vagus nerve has widespread connections in the brainstem, including key areas related to CCR. Here we examined whether chronic electrical stimulation of the vagus nerve induces changes in CCR. Methods We compared the HCVR in epilepsy patients with or without an active VNS in a sex‐ and age‐matched case‐control study. Eligible subjects were selected from a cohort of patients who previously underwent HCVR testing. The HCVR slope, change in minute ventilation (VE) with respect to change in end tidal (ET) CO2 (∆ VE/ ∆ ETCO2) during the test was calculated for each subject. Key variables were compared between the two groups. Univariate and multivariate analyses were carried out for HCVR slope as dependent variable. Results A total of 86 subjects were in the study. HCVR slope was significantly lower in the cases compared to the controls. Cases had longer duration of epilepsy and higher number of anti‐epileptic drugs (AEDs) tried during lifetime. Having active VNS and ETCO2 were associated with a low HCVR slope while high BMI was associated with high HCVR slope in both univariate and multivariate analyses. Discussion We found having an active VNS was associated with relatively attenuated HCVR slope. Although duration of epilepsy and number of AEDs tried during lifetime was significantly different between the groups, they were not predictors of HCVR slope in subsequent analysis. Conclusion Chronic electrical stimulation of VNS nerve by VNS may be associated with an attenuated CCR. A larger prospective study may help to establish the time course of this effect in relation to the time of VNS implantation, whether there is a causal relationship, and determine how it affects SUDEP risk.

Hypoxia modeling techniques: A review

“…(a) Hypoxic hypercapnic hypoxia. It is achieved by creating a variable microspace in the containment system by saturating the exhaled air [ [87] , [88] , [89] , [90] ]. There is no external adjustment of the oxygen concentration.…”

Interictal respiratory variability predicts severity of hypoxemia after generalized convulsive seizures

“…This is a retrospective study of previously collected data of patients monitored in the EMU at the University of Iowa Hospitals and Clinics from June 2015 to April 2019 as part of a multicenter study for the National Institute of Neurological Disorders and Stroke Center for SUDEP Research (CSR). Some data from these participants have been previously published 23–26 . All participants provided written consent prior to enrolling in the study.…”

Sudden unexpected death in epilepsy

“…Duration and regularity of the QT interval may also be emerging as a risk indicator for SUDEP [34 ]. In addition, indicators of respiratory function are also emerging, including incidence of ictal and postictal apnoea [36][37][38], and reduction of the sensitivity of the hypercapnic ventilatory response [39,40] In MORTEMUS, all nine patients for which peri-ictal cardiac and respiratory activity could be discerned experienced terminal apnoea prior to terminal asystole [48]. How seizures affect breathing has been a subject of intense study recently [20 & ,49].…”

“…Duration and regularity of the QT interval may also be emerging as a risk indicator for SUDEP [34 ▪ ], and may be a useful tool for assessing risk at the initial visit [35 ▪ ]. In addition, indicators of respiratory function are also emerging, including incidence of ictal and postictal apnoea [36–38], and reduction of the sensitivity of the hypercapnic ventilatory response [39,40]. It is clear from studies such as the multicentre retrospective Mortality in Epilepsy Monitoring Units Study (MORTEMUS), that multifactorial monitoring will be important to continue to understand and stratify SUDEP risk in patients with epilepsy.…”