Abstracts

Rationale: Seizures with periods of apnea and hypoventilation are common following severe traumatic brain injury (TBI) and are part of our severe TBI model. We observed that induction of apnea with hypoventilation after seizure acutely interrupted seizures, leading us to hypothesize that apnea and hypoventilation (A/H) may reduce seizure duration throughout the 24-hour experiment. Though inhaled CO₂ has been previously demonstrated to have anti-convulsant properties in children, the effects of the timing of apnea and hypoventilation on seizure duration and localization and in a severe TBI model has not been studied and may inform the pathophysiology and treatment of severe TBI.

Methods: Male, Yorkshire piglets aged 7 or 30 days were anesthetized with a seizure-permissive anesthetic regimen to induce cortical impact, mass effect, subdural hematoma, and seizure induction with kainic acid (42 - 63 mg/kg, in subdural blood) on the right hemisphere. Apnea and hypoventilation were induced either before (n = 3) or after (n = 4) seizure induction. EEG was recorded pre-injury and 7-21 hours post-injury while piglets were sedated and mechanically ventilated. Seizures were defined as paroxysmal spikes at ≥ 2 Hz for ≥ 10 seconds. Ictal spike trains were defined as paroxysmal spikes at 0.15-1.9 Hz for ≥ 10 seconds. The effect of time, A/H timing, and the interaction on time in seizure, time in ictal spikes, and location of seizure were tested via a mixed model ANOVA followed by post-hoc tests.

Results: Apnea and hypoventilation (A/H) induced after seizure reduced time in seizure compared to apnea and hypoventilation prior to seizure (main effect of A/H, P = 0.03; A/H x time interaction, P = 0.02). At 4-6 hours post-seizure induction, the percent of time spent in seizure was less with apnea and hypoventilation after seizure induction vs. before (27.3 + 6.4 vs. 98.2 + 1.4%, P = 0.03). After 8-10 hours, seizures transitioned to spike trains (P = 0.02). Time spent in spike trains did not differ between groups (P = 0.7). In subjects with apnea and hypoventilation before seizure induction, seizures were localized in the hemisphere ipsilateral to the injury (P = 0.002), however in subjects with A/H after seizure initiation, the seizures were localized in the contralateral hemisphere (P = 0.002).  

Conclusions: Apnea and hypoventilation after seizure induction interrupted seizure, reducing seizure duration and shifting the seizure to the contralateral hemisphere. Apnea and hypoventilation may serve as an inherent protective mechanism in infants and toddlers with severe TBI. Future work will analyze subjects that had all injuries except apnea and hypoventilation and will analyze end tidal CO₂, blood gases, lactate, and pH among all groups. The presence and timing of apnea and hypoventilation may influence the role of traumatic seizures in driving pathophysiology and influence the pattern and extent of tissue damage after severe TBI.

Funding: Please list any funding that was received in support of this abstract.: This study was facilitated by: NICHD K01HD083759 and NICHD R01HD099397; Summer Training as Research Scholars (STaRS) Program Grant from the NIH.