Abstract Sun202: Post-resuscitation Sedation with Dexmedetomidine during Targeted Normothermia Enhances EEG Recovery and Improves Survival in Mice

Abstract

Introduction: Neurological recovery after cardiac arrest (CA) remains poor. While majority of comatose post-arrest patients are sedated, its benefits under normothermia remain unclear. This study examined whether sedation improves outcomes after resuscitation under normothermic conditions. Hypothesis: Post-CA sedation modulates cerebral physiology and improves neurological outcomes in normothermic mice. Methods: Adult male C57BL/6J mice underwent CA induced by potassium chloride injection and were resuscitated after 10 minutes. Mice were randomized into five groups: control (normothermia without sedation); dexmedetomidine (2 μg/kg/h), ketamine (10 mg/kg/h), or propofol (2 mg/kg/h) sedation under normothermic conditions; and a hypothermia group without sedation. Sedatives were administered subcutaneously via osmotic pumps for 24 hours starting 10 minutes post-resuscitation. In the control and sedation groups, esophageal temperature was maintained at 36°C for 2 hours during oxygenation via tracheal intubation. After extubation, mice were placed in cages and maintained at 33°C with rectal temperature for 4 more hours, then housed at 33°C for up to 48 hours. The hypothermia group was kept 3°C lower for the first 6 hours, then at 30°C. EEGs were recorded continuously for 48 hours using implanted telemetry transmitters. Results: Dexmedetomidine sedation significantly improved 10-day survival under normothermia (3/11 vs. control 1/11; P = 0.021), while ketamine and propofol showed no benefit (ketamine: 1/11, P = 0.96; propofol: 2/11, P = 0.091) compared to normothermia control without sedation. Hypothermia without sedation markedly improved survival (6/11 vs. 1/11; P = 0.0034). Dexmedetomidine and propofol accelerated recovery from EEG suppression and enhanced gamma-band activity at 6 hours, suggesting better cortical recovery. In contrast, hypothermia suppressed EEG activity during the first 6 hours. Body temperature regulation differed significantly: mice in the control and ketamine groups experienced a rapid rise in body temperature after 6 hours shortly before their death, while temperature remained relatively stable in the dexmedetomidine and hypothermia groups. Conclusion: Dexmedetomidine improved survival under normothermia, possibly through both neurophysiological and thermoregulatory mechanisms. In contrast, ketamine did not yield benefits. Post-resuscitation sedation may improve outcomes by optimizing neurophysiological recovery.