Intra-individual Variability of Hypercapnic Ventilatory Response over Time in Patients with Epilepsy
Abstract number :
3.092
Submission category :
2. Translational Research / 2A. Human Studies
Year :
2022
Submission ID :
2204885
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:27 AM
Authors :
Rup Sainju, MBBS – University of Iowa Hospitals and Clinics; Deidre Dragon, BBS – Neurology – University of Iowa Hospitals and Clinics; Justin Kuhn, RRT – Institute of Clinical and Translational Science – University of Iowa; Patrick Ten Eyck, PhD – Institute of Clinical and Translational Science – University of Iowa; George Richerson, MD, PhD – Neurology – University of Iowa Hospitals and Clinics; Brian Gehlbach, MD – Internal Medicine – University of Iowa Hospitals and Clinics
Rationale: An attenuated hypercapnic ventilatory response (HCVR), a measure of central CO2 chemosensitivity, in patients with epilepsy is associated with severe postictal hypoventilation after generalized convulsive seizures. Thus, it is a potential biomarker for SUDEP risk, and can be measured noninvasively as an outpatient. Prior studies in populations without epilepsy suggest genetic factors are a major determinant of HCVR, while environmental and acquired factors can also influence both intra and inter-individual variability of HCVR when measured repeatedly over a short-term. Given lack of data on stability of intra-individual HCVR in patients with epilepsy, we evaluated this in a prospective study.
Methods: This is a prospective study evaluating stability of intra-individual HCVR over a short-term in patients with epilepsy aged >18 years at the University of Iowa Hospitals and Clinics. Subjects underwent HCVR measurement at baseline, and repeat testing every 6 months for 2 years. HCVR was measured by a modified hyperoxic CO2 rebreathing technique using an Ultima PFX Respiratory Gas Analyzer. HCVR testing started with measurement of baseline minute ventilation (VE), end-tidal (ET) CO2 and ETO2 in room air. Then, subjects switched to two 5-liter rebreathing bags prefilled with 50% O2, 6% CO2, balance N2. Subjects were asked to take 2 deep breaths and then breathe as they felt comfortable until the end of the test. Given our previous experience of measuring HCVR in this population, we modified our previous protocol by changing target ETCO2 from 55 mm Hg to a higher level as one of the endpoints for the test. Hence, the test was terminated if: (a) ETCO2 > 20 mm Hg higher than baseline but minimally 60 mm Hg, (b) ETCO2 > 65 mm Hg, (c) VE > 100 L/min, (d) ETO2 < 160 mm Hg, or (e) subject intolerance. HCVR slope (∆VE/∆ETCO2) was calculated by simple linear regression. We plan to use generalized linear mixed model to evaluate stability of HCVR slope over four time points spanning 2 years. Herein, using paired t-test we compared HCVR slopes at baseline and repeat testing 6 months later.
Results: A total of 57 subjects (21 women) have been enrolled so far. Seventeen subjects have completed repeat testing at 6 months. Of 17 repeated tests, 2 were discarded due to technical error. Therefore, 15 subjects were included in this interim analysis. HCVR slopes at baseline ranged 0.07 to 2.33 (1.58 + 0.60) L/min/mm Hg vs at 6-month follow up ranged 0.73 to 2.74 (1.58 + 0.60) L/min/mm Hg. Paired t-test showed no significant change between baseline and follow up measurements (p=0.98, mean difference = 0.003 L/min/mm Hg) (Figure 1).
Conclusions: These preliminary results suggest intra-individual HCVR remains stable over the course of 6 months. It remains unclear if this holds true during a longer follow up period, or if it is altered in patients depending on seizure history.
Funding: NIH: R01 NS113764-01
Translational Research