An inadvertent consequence of advances in stem cell research, neuroscience, and resuscitation science has been to enable scientific insights regarding what happens to the human brain in relation to death. The scientific exploration of death is in large part possible due to the recognition that brain cells are more resilient to the effects of anoxia than assumed. Hence, brain cells become irreversibly damaged and "die" over hours to days postmortem. Resuscitation science has enabled life to be restored to millions of people after their hearts had stopped. These survivors have described a unique set of recollections in relation to death that appear universal. We review the literature, with a focus on death, the recalled experiences in relation to cardiac arrest, post-intensive care syndrome, and related phenomena that provide insights into potential mechanisms, ethical implications, and methodologic considerations for systematic investigation. We also identify issues and controversies related to the study of consciousness and the recalled experience of cardiac arrest and death in subjects who have been in a coma, with a view to standardize and facilitate future research. Keywords: death; cardiac arrest; resuscitation; death by brain death criteria; near-death experiences (NDEs); out-ofbody experiences (OBEs); external visual awareness (EVA); recalled experience of death (RED) coma; cardiopulmonary resuscitation-induced consciousness (CPRIC); post-intensive care syndrome (PICS)

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Despite improvements in cardiopulmonary resuscitation (CPR), survival and neurologic recovery after cardiac arrest remain very poor because of the impact of severe ischemia and subsequent reperfusion injury. As the likelihood of survival and favorable neurologic outcome decreases with increasing severity of ischemia during CPR, developing methods to measure the magnitude of ischemia during resuscitation, particularly cerebral ischemia, is critical for improving overall outcomes. Cerebral oximetry, which measures regional cerebral oxygen saturation (rSO 2 ) by near-infrared spectroscopy, has emerged as a potentially beneficial marker of cerebral ischemia during CPR. In numerous preclinical and clinical studies, higher rSO 2 during CPR has been associated with improved cardiac arrest survival and neurologic outcome. In this narrative review, we summarize the scientific rationale and validation of cerebral oximetry across populations and pathophysiologic states, discuss the evidence surrounding its use to predict return of spontaneous circulation, rearrest, and neurologic outcome, and provide suggestions for incorporation of cerebral oximetry into CPR practice.

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Cerebral oximetry is a non-invasive method of monitoring regional cerebral oxygenation (rSO2). rSO2 has been proposed as an alternative to end-tidal CO2 (ETCO2) as a predictor of return of spontaneous circulation (ROSC) and end-organ perfusion. Previously, we demonstrated that higher rSO2 is associated with higher rates of ROSC and improved neurologic recovery in in-hospital cardiac arrest (IHCA) patients. However, there are currently no studies examining patient-specific, pericardiac arrest variables that correlate with higher rSO2. Identifying modifiable variables can help tailor patient-specific interventions in addition to ACLS to optimize rSO2 and improve survival and neurologic recovery from IHCA. The aim of this study was to identify which clinical variables, particularly modifiable ones, are predictive of a higher rSO2. METHODS:We performed an ancillary cohort analysis of data collected as part of an ongoing multicenter prospective study of adult IHCA in 15 hospitals across the US and UK. rSO2 values were collected in real-time using a portable near-infrared spectroscopy device (SedLine, Nonin). Demographics, vitals, and labs were collected via chart review. Among 323 adult IHCA patients, under a multivariable regression model, we investigated the predictive value of age, hemoglobin (hgb), partial pressure of oxygen (PaO2), epinephrine dose, and APACHE II score for mean rSO2. Using two-sample t-tests, we also investigated the difference in mean rSO2 in relation to sex, shockable versus non-shockable rhythm, and manual versus mechanical CPR. RESULTS:We demonstrated a small, statistically significant, negative correlation for hgb (coefficient = -0.17, p = 0.03). Due to the unexpected negative correlation, an individual linear regression was performed, demonstrating no statistically significant correlation (coefficient = -0.14, p = 0.07). We did not find any statistically significant correlation with the other variables. We also did not find a statistically significant difference in mean rSO2 in relation to sex, initial rhythm, and type of CPR. CONCLUSIONS:Our study demonstrates no statistically significant correlation between PaO2, hgb, epinephrine dose, APACHE II scores, and rSO2. The lack of correlation for hgb is particularly interesting, as hgb has been demonstrated to positively correlate with rSO2 in healthy individuals. However, there are limitations to this study. Intra-cardiac paO2 and hgb were generally high in our sample size (92 mmHg and 14.0 g/dL, respectively), which may explain the lack of statistical significance. In addition, rSO2 data from each individual patient across the duration of CPR is variable, and utilizing mean rSO2 may be an oversimplification. CLINICAL IMPLICATIONS:The current standard of care is to apply a single ACLS protocol to an inherently heterogeneous group of patients undergoing cardiac arrest. As a result, there is ongoing interest in identifying modifiable variables to optimize survival and neurologic recovery. Our study demonstrates that clinical measures we expect t...