AWAreness during REsuscitation - II: A Multi-Center Study of Consciousness and Awareness in Cardiac Arrest
INTRODUCTION/BACKGROUND:Cognitive activity and awareness during cardiac arrest (CA) are reported but ill understood. This first of a kind study examined consciousness and its underlying electrocortical biomarkers during cardiopulmonary resuscitation (CPR). METHODS:) monitoring into CPR during in-hospital CA (IHCA). Survivors underwent interviews to examine for recall of awareness and cognitive experiences. A complementary cross-sectional community CA study provided added insights regarding survivors' experiences. RESULTS:=43%) normal EEG activity (delta, theta and alpha) consistent with consciousness emerged as long as 35-60 minutes into CPR. CONCLUSIONS:Consciousness. awareness and cognitive processes may occur during CA. The emergence of normal EEG may reflect a resumption of a network-level of cognitive activity, and a biomarker of consciousness, lucidity and RED (authentic "near-death" experiences).
A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome from COVID-19
Toward harmonization of strategies for investigating lucidity in AD/ADRD: A preliminary research framework
Episodes of lucidity (ELs) in Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD), have garnered increasing attention as an important area of research. Efforts to study lucidity suffer from a lack of clear definitional criteria, inconsistent conceptualization, and diverse approaches to operationalizing features of these events. To advance systematic investigation of ELs in AD/ADRD, there is a need for clarity and precision in labeling event attributes, markers, and specific measurement strategies that enable operational harmonization across distinct approaches to investigating the relatively broad and nascent phenomenon. To that end, we propose a preliminary research framework to guide harmonization of approaches to investigating ELs in AD/ADRD. Our goal is to provide an initial schematic that encourages uniform labeling of operational decisions about ELs.
CPR-related cognitive activity, consciousness, awareness and recall, and its management: A scoping review
Background/UNASSIGNED:There are increasing numbers of reports of cognitive activity, consciousness, awareness and recall related to cardiopulmonary resuscitation (CPR) and interventions such as the use of sedative and analgesic drugs during CPR. Objectives/UNASSIGNED:This scoping review aims to describe the available evidence concerning CPR-related cognitive activity, consciousness, awareness and recall and interventions such as the use of sedative and analgesic drugs during CPR. Methods/UNASSIGNED:A literature search was conducted of Medline, Embase and CINAHL from inception to 21 October 2021. We included case studies, observational studies, review studies and grey literature. Results/UNASSIGNED:We identified 8 observational studies including 40,317 patients and 464 rescuers, and 26 case reports including 33 patients. The reported prevalence of CPR-induced consciousness was between 0.23% to 0.9% of resuscitation attempts, with 48-59% of experienced professional rescuers surveyed estimated to have observed CPR-induced consciousness. CPR-induced consciousness is associated with professional rescuer CPR, witnessed arrest, a shockable rhythm, increased return of spontaneous circulation (ROSC), and survival to hospital discharge when compared to patients without CPR-induced consciousness. Few studies of sedation for CPR-induced consciousness were identified. Although local protocols for treating CPR-induced consciousness exist, there is no widely accepted guidance. Conclusions/UNASSIGNED:CPR-related cognitive activity, consciousness, awareness and recall is uncommon but increasingly reported by professional rescuers. The data available was heterogeneous in nature and not suitable for progression to a systematic review process. Although local treatment protocols exist for management of CPR-induced consciousness, there are no widely accepted treatment guidelines. More studies are required to investigate the management of CPR-induced consciousness.
Guidelines and standards for the study of death and recalled experiences of death--a multidisciplinary consensus statement and proposed future directions
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.
Cerebral oximetry: a developing tool for monitoring cerebral oxygenation during cardiopulmonary resuscitation
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 (rSO2 ) by near-infrared spectroscopy, has emerged as a potentially beneficial marker of cerebral ischemia during CPR. In numerous preclinical and clinical studies, higher rSO2 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.
Pharmacologic neuroprotection in ischemic brain injury after cardiac arrest
Cardiac arrest has many implications for morbidity and mortality. Few interventions have been shown to improve return of spontaneous circulation (ROSC) and long-term outcomes after cardiac arrest. Ischemic-reperfusion injury upon achieving ROSC creates an imbalance between oxygen supply and demand. Multiple events occur in the postcardiac arrest period, including excitotoxicity, mitochondrial dysfunction, and oxidative stress and inflammation, all of which contribute to ongoing brain injury and cellular death. Given that complex pathophysiology underlies global brain hypoxic ischemia, neuroprotective strategies targeting multiple stages of the neuropathologic cascade should be considered as a means of mitigating secondary neuronal injury and improving neurologic outcomes and survival in cardiac arrest victims. In this review article, we discuss a number of different pharmacologic agents that may have a potential role in targeting these injurious pathways following cardiac arrest. Pharmacologic therapies most relevant for discussion currently include memantine, perampanel, magnesium, propofol, thiamine, methylene blue, vitamin C, vitamin E, coenzyme Q10 , minocycline, steroids, and aspirin.
Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19
BACKGROUND:Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS:In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS:The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS:In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).
Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19
BACKGROUND:Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS:In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS:The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. CONCLUSIONS:In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.).
Outcomes among Hospitalized Chronic Kidney Disease Patients with COVID-19
Background/UNASSIGNED:Patients with CKD ha ve impaired immunity, increased risk of infection-related mortality, and worsened COVID-19 outcomes. However, data comparing nondialysis CKD and ESKD are sparse. Methods/UNASSIGNED:Patients with COVID-19 admitted to three hospitals in the New York area, between March 2 and August 27, 2020, were retrospectively studied using electronic health records. Patients were classified as those without CKD, those with nondialysis CKD, and those with ESKD, with outcomes including hospital mortality, ICU admission, and mortality rates. Results/UNASSIGNED:Of 3905 patients, 588 (15%) had nondialysis CKD and 128 (3%) had ESKD. The nondialysis CKD and ESKD groups had a greater prevalence of comorbidities and higher admission D-dimer levels, whereas patients with ESKD had lower C-reactive protein levels at admission. ICU admission rates were similar across all three groups (23%-25%). The overall, unadjusted hospital mortality was 25%, and the mortality was 24% for those without CKD, 34% for those with nondialysis CKD, and 27% for those with ESKD. Among patients in the ICU, mortality was 56%, 64%, and 56%, respectively. Although patients with nondialysis CKD had higher odds of overall mortality versus those without CKD in univariate analysis (OR, 1.58; 95% CI, 1.31 to 1.91), this was no longer significant in fully adjusted models (OR, 1.11; 95% CI, 0.88 to 1.40). Also, ESKD status did not associate with a higher risk of mortality compared with non-CKD in adjusted analyses, but did have reduced mortality when compared with nondialysis CKD (OR, 0.57; 95% CI, 0.33 to 0.95). Mortality rates declined precipitously after the first 2 months of the pandemic, from 26% to 14%, which was reflected in all three subgroups. Conclusions/UNASSIGNED:In a diverse cohort of patients with COVID-19, we observed higher crude mortality rates for patients with nondialysis CKD and, to a lesser extent, ESKD, which were not significant after risk adjustment. Moreover, patients with ESKD appear to have better outcom es than those with nondialysis CKD.