The dynamic pathophysiology of post cardiac arrest brain injury: “time is brain”

To review the time dependent nature of postcardiac arrest brain injury (PCABI) while contextualizing clinical trial evidence. PCABI represents a dynamic entity with respect to its pathophysiology. Intuitively, PCABI pathophysiology has been characterized focusing on mechanisms associated with cerebral ischemia. Interventions that augment cerebral oxygen delivery, such as increasing mean arterial pressure, have garnered interest. Regrettably, these trials have not demonstrated improved outcomes. At the core of this conundrum is the time dependent nature of PCABI pathophysiology with trials employing interventions approximately 4-6 h after return of spontaneous circulation (ROSC). This therapeutic window is likely far past the efficacy period of resumption of oxygen delivery to the ischemic brain. Thus, we suggest compartmentalizing PCABI into four phases: circulatory arrest; intra-arrest physiology; immediate reperfusion; and delayed reperfusion. Culprit mechanisms are discussed for each phase with contextualization of recent trial results. PCABI has dynamic pathophysiology and restoration of cerebral oxygen delivery in a delayed manner from ROSC has diminished efficacy. PCABI pathophysiology must be viewed in a time dependent manner and interventions aimed at restoring cerebral oxygen delivery are likely only to be efficacious if applied immediately after ROSC.