Abstracts

Rationale: Severe peri-ictal respiratory depression is likely linked to SUDEP risk but its determinants remain largely unknown. Central CO₂ chemo-responsiveness (hypercapnic ventilatory response, HCVR) plays a critical role in control of ventilation. Inter-individual differences in HCVR may identify patients who are at increased risk for severe peri-ictal hypoventilation. We measured inter-ictal HCVR and examined its relationship to post-ictal hypercapnia after generalized tonic-clonic seizures (GTCS) in an epilepsy monitoring unit (EMU). Methods: Patients age > 18 years with epilepsy who were admitted to an EMU underwent inter-ictal HCVR testing using a modified rebreathing technique, with mixture of 6% CO₂, 50% O₂, and balance N₂. Minute ventilation (V_E), tidal volume, respiratory rate, end tidal (ET) CO₂, and ETO₂ were recorded continuously. The HCVR slope (?V_E/?ETCO₂), for each subject was determined by linear regression. A subset of subjects also underwent HCVR measurement in the post-ictal period.All subjects underwent continuous video EEG monitoring along with additional cardio-respiratory monitoring: chest and abdominal respiratory inductance plethysmography (RIP), nasal pressure, oronasal thermistor, EKG, pulse oximeter, and transcutaneous CO₂.All recorded GTCS with artifact-free transcutaneous CO₂ data were subjected to univariate analysis to explore the relationship between inter-ictal HCVR slope and clinical variables as well as (a) duration and (b) magnitude of post-ictal CO₂ elevation.Postictal HCVR slope was compared to inter-ictal HCVR slope when available. Results: Sixty-five subjects had only inter-ictal HCVR measurements and three subjects had both inter-ictal and postictal HCVR measurements. A total of 13 GTCS in 11 subjects had artifact-free CO₂ recordings.Inter-ictal HCVR slope was inversely correlated with both the duration of peri-ictal CO₂ elevation and the magnitude of CO₂ rise expressed as ?CO₂ (peak post-ictal CO₂ minus pre-ictal CO₂, see Table 1 and Figure 1).Two of three subjects had additional postictal HCVR measurements 61 and 68 minutes after a focal seizure with impaired awareness, and one in 4 hours and 53 minutes after a generalized convulsive seizure.  All three showed attenuation of post-ictal HCVR slope by 23% to 68% of their corresponding inter-ictal measurements. Conclusions: Inter-ictal HCVR may predict the severity of postictal hypercapnia, which may in turn be due to attenuated HCVR in the post-ictal state.  Measurement of HCVR thus may be a useful tool for screening SUDEP risk. Funding: This study was supported by the National Institute of Neurologic Disorders and Stroke:  U01 NS090414 (Center for SUDEP Research), Citizen united for research in epilepsy (CURE) - SUDEP award, and National Institute of Health CTSA program grant U54TR001356.