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Background: Anoxic brain injury is a common cause of death following out-of-hospital cardiac arrest (OHCA). Cerebral oximetry provides a real-time tool to brain ischemia. Little is known about the course of cerebral oximetry and its relationship to outcome following OHCA. Methods: We conducted a pilot cohort study during OHCA to evaluate the course and prognosis related to cerebral oximetry in a single US EMS agency. Cerebral oximetry was applied by first responders at the outset of EMS resuscitation using the Nonin SenSmart Model X-100 Universal Oximetry System. EMS providers were blinded to oximeter information. The oximeter recording was linked to the defibrillator recording and the OHCA clinical registry, which includes the outcomes of return of spontaneous circulation (ROSC) and survival to hospital discharge with good function as determined by Cerebral Performance Category (CPC) of 1 or 2. We evaluated the variability of cerebral oximetry over time and the relationship between oximetry and outcome according to ROSC and survival status. Results: Of the 100 eligible OHCA events, 81 had complete oximeter and defibrillator information. Average age was 62, 43% were female, 14% presented with ventricular fibrillation, 49% (n=40) achieved ROSC, and 16% (n=13) survived (all with CPC of 1 or 2). Average initial cerebral oxygen saturation was 46% (SD 15) among all cases and among those requiring resuscitation >10 minutes. Among those with ongoing resuscitation, mean oximetry was 49% at 5 minutes and 51% at 10 minutes. The average change in oximetry during resuscitation was 8% with 59% demonstrating an increase in oximetry, 32% a decrease, and 9% no change. Brain oximetry increased 10% following ROSC. Initial cerebral oximetry was 53% (SD 18) among survivors versus 44% (SD 15) among non-survivors (p=0.1). When stratified by groups defined by ROSC and survival, initial brain oximetry was 43% among those without ROSC, 46% among those who achieved ROSC but did not survive, and 53% among those who survived (p=0.1 test for trend). Conclusion: Cerebral oximetry can be deployed by first responders in OHCA. Cerebral oximetry exhibits some variability during the course of resuscitation and increases with ROSC. Whether cerebral oximetry can be used to guide care is uncertain.