Abstracts

Rationale: SUDEP is a major cause of premature mortality in patients with epilepsy. Severe postictal respiratory dysfunction has been proposed as a potential biomarker of SUDEP risk. We have previously shown in patients with epilepsy that the interictal ventilatory response to CO2, or HCVR (hypercapnic ventilatory response), correlates with the severity of respiratory dysfunction after generalized convulsive seizures. We hypothesize that HCVR is attenuated by some seizures, which may contribute to postictal respiratory dysfunction. Hence, we measured HCVR in patients admitted to an epilepsy monitoring unit (EMU) during interictal and postictal periods.  Methods: We enrolled patients age >18 with epilepsy who were admitted to the EMU at the University of Iowa Hospitals and Clinics for video EEG study. HCVR was measured by a modified rebreathing technique. Baseline ventilatory parameters were measured in room air for 2-3 minutes: tidal volume (VT), minute ventilation (VE), respiratory rate (RR), end tidal (ET) CO2, and ETO2. Subjects were then switched to a closed rebreathing system consisting of two 5-liter bags pre-filled with 50% O2, 6% CO2, and balance N2. Ventilatory parameters were then measured on a breath-by-breath basis as ETCO2 levels increased. The test was aborted for: 1) ETCO2 > 55 mm Hg, 2) VE > 100 L/min, 3) PaO2 < 60 mm Hg, or 4) patient intolerance. The HCVR slope (ΔVE/ΔETCO2) for each subject was determined by linear regression (Fig. 1A). HCVR measurements were performed during an interictal period, and as soon after a seizure as feasible.Subjects underwent standard video EEG along with comprehensive cardiorespiratory monitoring with ECG, transcutaneous CO2, pulse oximetry, respiratory inductance plethysmography using chest and abdominal belts, and oro-nasal air flow and thermistry.  Results: A total of 7 subjects had both interictal and postictal measurements of HCVR (9 seizures: 3 right temporal, 2 left temporal, 2 left frontal,1 left fronto-temporal and 1 non localized/non lateralized). Two subjects had postictal measurements after two separate seizures. Of 9 postictal HCVR measurements, 4 occurred after focal to bilateral tonic-clonic seizures (FBTCs) (Fig. 1B), and 5 after focal seizures without BTC (Fig. 1C) (average 229 vs 68 mins after seizure end, p = 0.0004). Eight of nine postictal HCVR measurements showed a decrease in HCVR slope compared to the interictal values. This attenuation was greater after FBTC seizures (1.85 + 0.5 L/min/mm Hg interictal vs 1.2 + 0.39 L/min/mm Hg, p = 0.02) vs seizures without BTC (1.60 + 0.86 L/min/mm Hg interictal vs 1.27 + 1.03 L/min/mm Hg, p =0.54).  Conclusions: Compared to the interictal state, the ventilatory response to CO2 (HCVR) is suppressed after FBTC seizures. This may contribute to severe postictal respiratory depression that is often seen after seizures.  Funding: NINDS: U01 NS090414Center for SUDEP Research: Respiratory and Arousal Mechanisms