Monday, May 12, 2025
5/12/2025
Role of Sedation in the Post-Cardiac Arrest Neurological Recovery - Sudden cardiac arrest (CA) is a leading cause of death. Despite advances in cardiopulmonary resuscitation (CPR) methods, only 10-20% of adult CA victims survive to hospital discharge. Neurologic injury is the main cause of death and reason to withdraw care in patients who initially achieve return of spontaneous circulation (ROSC) after CA. Although mild hypothermia has been widely adopted to improve neurologic recovery after ROSC, recent evidence refuted its efficacy leading to a new guideline that does not recommend hypothermia any longer. Because majority of comatose post-CA patients are sedated regardless of temperature management, precise impact of sedation on post-CA neurologic recovery is unknown. Studies excluding post-CA patients suggest that sedation provides very poor sleep quality, leading to a significant push to minimize sedation in ICU. On the other hand, post-CA sedation may exert neuroprotective effects. Cerebrovascular dysregulation is a common feature of post-CA encephalopathy and associated with poor outcomes. Sedation may normalize cerebral metabolism by concurrently modulating energy demand and cerebral blood flow (CBF) after CA. Further studies are needed to elucidate the role of sedation on neurologic recovery after CA. Quantitative electroencephalogram (EEG) is widely used for post-CA neuroprognostication. Recent studies showed that induction of slow-wave activities on EEG by propofol early after ROSC is associated with favorable neurologic outcomes in post-CA patients. Anesthesia-activated neurons (AANs) in hypothalamus are activated by diverse classes of anesthetic agents to produce slow-delta oscillations. However, physiological role of slow-wave oscillation, especially in post-ischemic brain, is unknown. In recently published studies related to this proposal, we evaluated the effects of sedation on outcomes after CA in hypothermia (33°C)-treated mice. We observed that, compared to hypothermia without sedation after CA, hypothermia with sedation with an intravenous infusion of propofol or dexmedetomidine (DEX) attenuated cerebral hyperemia, induced higher slow wave EEG power after ROSC, and improved neurological outcomes and survival in male and female mice. In new preliminary studies, post-CA sedation with ketamine infusion failed to improve survival, whereas chemogenetic activation of AANs after ROSC induced slow wave sleep and tended to improve survival rates in mice. Based on these results, we hypothesize that post-CA sedation during hypothermia improves neurological recovery after CA by promoting electrophysiological recovery and preventing dysregulation of cerebrovascular function and metabolism. To address this hypothesis, specifically, we propose to determine the effects of post-CA sedation with propofol or dexmedetomidine during normothermia, to characterize the effects of post-CA sedation with ketamine on neurologic outcomes, and to elucidate the role of slow-wave oscillation in the neuroprotective effects of post-CA sedation. While most post-CA patients are sedated, how sedation alters neurologic outcomes remains largely unknown. The proposed studies will fill the knowledge gap and seek to optimize sedation in post-CA care.
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