Severe Postictal Hypoventilation Is Associated with Delayed Recovery of Consciousness After Generalized Convulsive Seizures: Failure of co2-induced Arousal?
Abstract number :
1.192
Submission category :
2. Translational Research / 2A. Human Studies
Year :
2024
Submission ID :
758
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Rup Sainju, MBBS – University of Iowa
Paula Lee, MD – University of Iowa
Deidre Dragon, BS – University of Iowa
Harold Winnike, RRT – University of Iowa
Justin Kuhn, BS RRT, RPFT, RRT-ACCS/NPS, AE-C – University of Iowa
Jennie Michelson, Research specialist – University of Iowa
Johnson Hampson, MSBME – University of Texas, UT Health Houston
Samden Lhatoo, MD, FRCP – University of Texas Health Science Center at Houston
Linder Wendt, MS – University of Iowa
Patrick Ten Eyck, PhD – University of Iowa
George Richerson, MD, PhD – University of Iowa
Gordon Buchanan, MD, PhD – University of Iowa
Brian Gehlbach, MD – University of Iowa
Rationale: Postictal impairment of breathing, cardiovascular control and arousal often precede documented SUDEP cases. Seizures can inhibit serotonergic neurons in the brainstem resulting in attenuation of central respiratory CO2 chemoreception (CCR). The objective of this study was to examine the relationship between the severity of postictal hypoventilation and duration of severe depression of consciousness after GCS in patients admitted to an epilepsy monitoring unit. Here we tested the hypothesis that seizures impair the ability of hypercapnia (mediated by serotonergic neurons in the medullary and midbrain raphe) to stimulate breathing and to hasten recovery of consciousness.
Methods: Epilepsy patients 18 years or older were monitored with continuous video-EEG, EKG, respiratory impedance plethysmography, airflow, pulse oximetry, and transcutaneous (Tc) CO2. Primary outcome variables were time to earliest sign of recovery of consciousness (ROC) and duration of postictal immobility (PI). The interictal hypercapnic ventilatory response (HCVR), a measure of CCR, was performed in a subset of patients with derivation of HCVR slope (∆ minute ventilation/∆ end-tidal CO2).
Spearman’s rho was calculated for correlational analysis. Generalized linear models with gamma regression were used for univariate and multivariate models. Optimal multivariate models were selected based on Akaike Information Criterion.
Results: Of 117 GCS recorded in 68 patients, 42 GCS had adequate TcCO2 and video-EEG data for detailed assessment of semiology. HCVR was measured in 28 subjects. Duration of postictal TcCO2 rise (defined as time between elevation of TcCO2 10% above to the point when it returns to < 10% above the baseline level) was significantly associated with time to ROC in both univariate (Mean ratio 1.12, 95% CI 0.99 to 1.29, p = 0.044) and multivariate models (Mean ratio 1.15, 95% CI 1.04-1.28, p = 0.008) (Table 1, Figure 1). Likewise, preictal TcCO2 level was associated with duration of PI in univariate (Mean ratio 1.09, 95% CI 1.01-1.17, p = 0.029) and multivariate (Mean ratio 1.10, 95% CI 1.03-1.17, p = 0.007) models. The two outcome variables were closely related (Spearman’s rho = 0.824, p = < 0.001), while HCVR slope was negatively related to duration (Spearman’s rho = -0.444, p = 0.023) and magnitude of postictal TcCO2 rise (Spearman’s rho = -0.542, p = 0.006).
Conclusions: Our results indicate that severe postictal hypoventilation is independently associated with prolonged depression of consciousness after GCS. Delayed recovery of consciousness despite elevated TcCO2 provides indirect evidence for impairment of CO2 induced arousal after GCS. Preictal TcCO2 level, a proxy of CCR, was a significant predictor of duration of PI, providing additional support for our hypothesis. Our findings are consistent with seizure-induced inhibition of serotonin neurons in the medulla and midbrain responsible for CCR and CO2-induced arousal, respectively.
Funding: NINDS- R01 NS113764-01
Translational Research