The neurological phoenix: multimodal strategies for brain recovery and prognostication in post-cardiac arrest syndrome—a 2025 clinical framework

Post-cardiac arrest brain injury remains the leading cause of mortality and morbidity in comatose survivors despite successful resuscitation. This review synthesizes contemporary evidence from the 2025 European Resuscitation Council and European Society of Intensive Care Medicine guidelines, the 2024–2025 International Liaison Committee on Resuscitation recommendations, and recent randomized controlled trials to provide clinicians with a practical framework emphasizing cerebral protection, multimodal monitoring, and reliable prognostication while minimizing premature withdrawal of life-sustaining therapy. Core interventions include targeted oxygenation with peripheral oxygen saturation between 94 and 98% and normocapnia with partial pressure of carbon dioxide between 35 and 45 mm of mercury, individualized perfusion targeting mean arterial pressure of 60–65 mm of mercury, active fever prevention with core temperature maintained at or below 37.5 degrees Celsius for 36–72 h without routine hypothermia, continuous electroencephalography monitoring with treatment of seizures but no prophylactic antiseizure drugs, short-acting sedation enabling neurological assessment, and multimodal neuroprognostication performed at least 72 h post-return of spontaneous circulation requiring concordant predictors across multiple domains. A disciplined multimodal approach utilizing precision in gas exchange and perfusion, rigorous fever prevention, electroencephalography-guided seizure management, and cautious delayed prognostication offers the optimal pathway to meaningful neurological recovery in post-cardiac arrest syndrome.