Association of Interictal Respiratory Variability and Severity of Postictal Hypoxemia After Generalized Convulsive...

Severe hypoxemia after generalized convulsive seizures (GCSs) can trigger neural injury and is a potential biomarker for sudden unexpected death in epilepsy (SUDEP). Some degree of variability in interbreath interval is normal, but increased variability may suggest dysfunctional breathing control and may be associated with severe postictal hypoxemia. We evaluated the relationship between interictal breathing variability and severity and duration of hypoxemia after GCS.

We prospectively collected video-EEG, respiratory flow and effort, pulse oximetry (SpO₂), and ECG from people with epilepsy (PWE). Measures of interictal interbreath interval variability (coefficient of variation, root mean square of successive differences [RMSSD], and long-term [SD-2] variability from Poincaré plots) from interictal asleep and awake periods and other relevant variables were evaluated as covariates for primary outcomes: (1) hypoxemia duration (length of time SpO₂ <90%) and (2) severity of hypoxemia (SpO₂ nadir), and secondary outcome: occurrence of combined prolonged and pronounced hypoxemia. Univariable and multivariable models were created for primary outcomes, but only univariable analyses were performed for the secondary outcome.

Of 2,506 participants enrolled, 257 (141 [∼54%] female; mean age = 37.9 years) had ≥1 GCS, but only 152 GCS in 123 had evaluable respiratory data. Multivariable model for hypoxemia duration showed that SpO₂ nadir (mean ratio [MR] = 0.88, 95% CI 0.81-0.96, p = 0.002) and SD-2 of the awake interbreath interval (MR = 1.06, 95% CI 1.01-1.13, p = 0.04) were significantly associated. RMSSD of the non-REM interbreath interval (mean difference = -5.01, 95% CI -8.10 to -1.93, p = 0.002) was the only variable significantly associated with hypoxemia severity after controlling for duration of postictal generalized EEG suppression, SD-2 of the awake interbreath interval, and body mass index. Univariable analyses for combined prolonged and pronounced hypoxemia showed SD-2 of the awake interbreath interval, temporal lobe epilepsy, ictal central apnea, and a shorter tonic phase duration were significantly associated.

Measures of interictal respiratory variability are associated with severe and prolonged hypoxemia after GCS. Increased interictal respiratory variability suggests baseline respiratory dysregulation in some PWE and may be a surrogate for SUDEP risk.