Improving Outcomes After Post-Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation.

This scientific statement presents a conceptual framework for the pathophysiology of post-cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post-cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post-cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post-cardiac arrest brain injury.

Improving Outcomes After Post-Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation.

This scientific statement presents a conceptual framework for the pathophysiology of post-cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post-cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post-cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post-cardiac arrest brain injury.

Survival After Intra-Arrest Transport vs On-Scene Cardiopulmonary Resuscitation in Children.

Importance: For pediatric out-of-hospital cardiac arrest (OHCA), emergency medical services (EMS) may elect to transport to the hospital during active cardiopulmonary resuscitation (CPR) (ie, intra-arrest transport) or to continue on-scene CPR for the entirety of the resuscitative effort. The comparative effectiveness of these strategies is unclear. Objective: To evaluate the association between intra-arrest transport compared with continued on-scene CPR and survival after pediatric OHCA, and to determine whether this association differs based on the timing of intra-arrest transport. Design, Setting, and Participants: This cohort study included pediatric patients aged younger than 18 years with EMS-treated OHCA between December 1, 2005 and June 30, 2015. Data were collected from the Resuscitation Outcomes Consortium Epidemiologic Registry, a prospective 10-site OHCA registry in the US and Canada. Data analysis was performed from May 2022 to February 2024. Exposures: Intra-arrest transport, defined as an initiation of transport prior to the return of spontaneous circulation, and the interval between EMS arrival and intra-arrest transport. Main Outcomes and Measures: The primary outcome was survival to hospital discharge. Patients who underwent intra-arrest transport at any given minute after EMS arrival were compared with patients who were at risk of undergoing intra-arrest transport within the same minute using time-dependent propensity scores calculated from patient demographics, arrest characteristics, and EMS interventions. We examined subgroups based on age (<1 year vs ≥1 year). Results: Of 2854 eligible pediatric patients (median [IQR] age, 1 [0-9] years); 1691 males [59.3%]) who experienced OHCA between December 2005 and June 2015, 1892 children (66.3%) were treated with intra-arrest transport and 962 children (33.7%) received continued on-scene CPR. The median (IQR) time between EMS arrival and intra-arrest transport was 15 (9-22) minutes. In the propensity score-matched cohort (3680 matched cases), there was no significant difference in survival to hospital discharge between the intra-arrest transport group and the continued on-scene CPR group (87 of 1840 patients [4.7%] vs 95 of 1840 patients [5.2%]; risk ratio [RR], 0.81 [95% CI, 0.59-1.10]). Survival to hospital discharge was not modified by the timing of intra-arrest transport (P value for the interaction between intra-arrest transport and time to matching = .10). Among patients aged younger than 1 year, intra-arrest transport was associated with lower survival to hospital discharge (RR, 0.52; 95% CI, 0.33-0.83) but there was no association for children aged 1 year or older (RR, 1.22; 95% CI, 0.77-1.93). Conclusions and Relevance: In this cohort study of a North American OHCA registry, intra-arrest transport compared with continued on-scene CPR was not associated with survival to hospital discharge among children with OHCA. However, intra-arrest transport was associated with a lower likelihood of survival to hospital discharge among children aged younger than 1 year.

Clinicians' approach to predicting post-cardiac arrest outcomes for patients enrolled in a United States clinical trial.

PURPOSE: Perceived poor prognosis can lead to withdrawal of life-sustaining therapies (WLST) in patients who might otherwise recover. We characterized clinicians' approach to post-arrest prognostication in a multicenter clinical trial. METHODS: Semi-structured interviews were conducted with clinicians who treated a comatose post-cardiac arrest patient enrolled in the Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (ICECAP) trial (NCT04217551). Two authors independently analyzed each interview using inductive and deductive coding. The clinician reported how they arrived at a prognosis for the specific patient. We summarized the frequency with which clinicians reported using objective diagnostics to formulate their prognosis, and compared the reported approaches to established guidelines. Each respondent provided demographic information and described local neuroprognostication practices. RESULTS: We interviewed 30 clinicians at 19 US hospitals. Most claimed adherence to local hospital neuroprognostication protocols (n = 19). Prognostication led to WLST for perceived poor neurological prognosis in 15/30 patients, of whom most showed inconsistencies with guidelines or trial recommendations, respectively. In 10/15 WLST cases, clinicians reported relying on multimodal testing. A prevalent theme was the use of "clinical gestalt," defined as prognosticating based on a patient's overall appearance or a subjective impression in the absence of objective data. Many clinicians (21/30) reported using clinical gestalt for initial prognostication, with 9/21 expressing high confidence initially. CONCLUSION: Clinicians in our study state they follow neuroprognostication guidelines in general but often do not do so in actual practice. They reported clinical gestalt frequently informed early, highly confident prognostic judgments, and few objective tests changed initial impressions. Subjective prognostication may undermine well-designed trials.

Brain computed tomography after resuscitation from in-hospital cardiac arrest.

BACKGROUND: Few data characterize the role of brain computed tomography (CT) after resuscitation from in-hospital cardiac arrest (IHCA). We hypothesized that identifying a neurological etiology of arrest or cerebral edema on brain CT are less common after IHCA than after resuscitation from out-of-hospital cardiac arrest (OHCA). METHODS: We included all patients comatose after resuscitation from IHCA or OHCA in this retrospective cohort analysis. We abstracted patient and arrest clinical characteristics, as well as pH and lactate, to estimate systemic illness severity. Brain CT characteristics included quantitative measurement of the grey-to-white ratio (GWR) at the level of the basal ganglia and qualitative assessment of sulcal and cisternal effacement. We compared GWR distribution by stratum (no edema ≥1.30, mild-to-moderate <1.30 and >1.20, severe ≤1.20) and newly identified neurological arrest etiology between IHCA and OHCA groups. RESULTS: We included 2,306 subjects, of whom 420 (18.2%) suffered IHCA. Fewer IHCA subjects underwent post-arrest brain CT versus OHCA subjects (149 (35.5%) vs 1,555 (82.4%), p < 0.001). Cerebral edema for IHCA versus OHCA was more often absent (60.1% vs. 47.5%) or mild-to-moderate (34.3% vs. 27.9%) and less often severe (5.6% vs. 24.6%). A neurological etiology of arrest was identified on brain CT in 0.5% of IHCA versus 3.2% of OHCA. CONCLUSIONS: Although severe edema was less frequent in IHCA relative to OHCA, mild-to-moderate or severe edema occurred in one in three patients after IHCA. Unsuspected neurological etiologies of arrest were rarely discovered by CT scan in IHCA patients.

Duration of cardiopulmonary resuscitation and outcomes for adults with in-hospital cardiac arrest: retrospective cohort study.

OBJECTIVE: To quantify time dependent probabilities of outcomes in patients after in-hospital cardiac arrest as a function of duration of cardiopulmonary resuscitation, defined as the interval between start of chest compression and the first return of spontaneous circulation or termination of resuscitation. DESIGN: Retrospective cohort study. SETTING: Multicenter prospective in-hospital cardiac arrest registry in the United States. PARTICIPANTS: 348 996 adult patients (≥18 years) with an index in-hospital cardiac arrest who received cardiopulmonary resuscitation from 2000 through 2021. MAIN OUTCOME MEASURES: Survival to hospital discharge and favorable functional outcome at hospital discharge, defined as a cerebral performance category score of 1 (good cerebral performance) or 2 (moderate cerebral disability). Time dependent probabilities of subsequently surviving to hospital discharge or having favorable functional outcome if patients pending the first return of spontaneous circulation at each minute received further cardiopulmonary resuscitation beyond the time point were estimated, assuming that all decisions on termination of resuscitation were accurate (that is, all patients with termination of resuscitation would have invariably failed to survive if cardiopulmonary resuscitation had continued for a longer period of time). RESULTS: Among 348 996 included patients, 233 551 (66.9%) achieved return of spontaneous circulation with a median interval of 7 (interquartile range 3-13) minutes between start of chest compressions and first return of spontaneous circulation, whereas 115 445 (33.1%) patients did not achieve return of spontaneous circulation with a median interval of 20 (14-30) minutes between start of chest compressions and termination of resuscitation. 78 799 (22.6%) patients survived to hospital discharge. The time dependent probabilities of survival and favorable functional outcome among patients pending return of spontaneous circulation at one minute's duration of cardiopulmonary resuscitation were 22.0% (75 645/343 866) and 15.1% (49 769/328 771), respectively. The probabilities decreased over time and were <1% for survival at 39 minutes and <1% for favorable functional outcome at 32 minutes' duration of cardiopulmonary resuscitation. CONCLUSIONS: This analysis of a large multicenter registry of in-hospital cardiac arrest quantified the time dependent probabilities of patients' outcomes in each minute of duration of cardiopulmonary resuscitation. The findings provide resuscitation teams, patients, and their surrogates with insights into the likelihood of favorable outcomes if patients pending the first return of spontaneous circulation continue to receive further cardiopulmonary resuscitation.

A multicenter, randomized, doubleblind, placebo-controlled trial of amantadine to stimulate awakening in comatose patients resuscitated from cardiac arrest.

OBJECTIVE: We hypothesized that the administration of amantadine would increase awakening of comatose patients resuscitated from cardiac arrest. METHODS: We performed a prospective, randomized, controlled pilot trial, randomizing subjects to amantadine 100 mg twice daily or placebo for up to 7 days. The study drug was administered between 72 and 120 hours after resuscitation and patients with absent N20 cortical responses, early cerebral edema, or ongoing malignant electroencephalography patterns were excluded. Our primary outcome was awakening, defined as following two-step commands, within 28 days of cardiac arrest. Secondary outcomes included length of stay, awakening, time to awakening, and neurologic outcome measured by Cerebral Performance Category at hospital discharge. We compared the proportion of subjects awakening and hospital survival using Fisher exact tests and time to awakening and hospital length of stay using Wilcoxon rank sum tests. RESULTS: After 2 years, we stopped the study due to slow enrollment and lapse of funding. We enrolled 14 subjects (12% of goal enrollment), seven in the amantadine group and seven in the placebo group. The proportion of patients who awakened within 28 days after cardiac arrest did not differ between amantadine (n=2, 28.6%) and placebo groups (n=3, 42.9%; P>0.99). There were no differences in secondary outcomes. Study medication was stopped in three subjects (21.4%). Adverse events included a recurrence of seizures (n=2; 14.3%), both of which occurred in the placebo group. CONCLUSION: We could not determine the effect of amantadine on awakening in comatose survivors of cardiac arrest due to small sample size.

Sex-specific disparities in COVID-19 outcomes.

Objectives: Sex-specific disparities in morbidity and mortality of COVID-19 illness are not well understood. Neutralizing antibodies (Ab) may protect against severe COVID-19 illness. We investigated the association of sex with disease progression and SARS-CoV-2 Ab response. Methods: In this exploratory analysis of the phase 3, multicenter, randomized, placebo-controlled Convalescent Plasma in Outpatients (C3PO) trial, we examined whether sex was associated with progression to severe illness, defined as a composite of all-cause hospitalization, emergency/urgent care visit, or death within 15 days from study enrollment. Patients had a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test, symptom onset within 7 days, stable condition for emergency department discharge, and were either ≥50 years old or had at least one high-risk feature for disease progression. Patients received blinded convalescent plasma or placebo in a 1:1 fashion and were evaluated on days 15 and 30 after infusion. Blood samples were collected on day 0 (pre-/post-infusion), 15, and 30 to measure Ab levels with the Broad Institute using the Plaque Reduction Neutralization Test assay. Results: Of 511 patients enrolled (median age 54 [Iinterquartile range 41-62] years, 46% male, 66% white, 20% black, 3.5% Asian), disease progression occurred in 36.7% of males and 25.9% of females (unadjusted risk difference 10.8%, 95% confidence interval [CI], 2.8-18.8%). Sex-disparities did not persist when adjusted for treatment group, age, viremic status, symptom onset, and tobacco use (adjusted risk difference 5.6%, 95% confidence interval [CI], -2.2% to 13.4%), but were present in the subgroup presenting 3 or more days after symptom onset (adjusted risk difference 12.6%, 95% CI, 3.4% to 21.9%). Mean baseline Ab levels (log scale) available for 367 patients were similar between sexes (difference 0.19 log units, 95% CI, -0.08 to 0.46). The log-scale mean increase from baseline to day 15 after adjusting for treatment assignment and baseline levels was larger in males than females (3.26 vs. 2.67). A similar difference was noted when the groups were subdivided by outcome. Conclusions: Progression of COVID-19 was similar in males and females when adjusted for age, tobacco use, and viremia status in this study. However, in the cohort presenting 3 or more days after symptom onset, COVID-19 outcomes were worse in males than females. Neutralizing Ab levels increased more in males but did not correlate with sex differences in outcomes.

Prehospital Electroencephalography to Detect Traumatic Brain Injury during Helicopter Transport: A Pilot Observational Cohort Study.

OBJECTIVE: Early recognition of traumatic brain injury (TBI) is important to facilitate time-sensitive care. Electroencephalography (EEG) can identify TBI, but feasibility of EEG has not been evaluated in prehospital settings. We tested the feasibility of obtaining single-channel EEG during air medical transport after trauma. We measured association between quantitative EEG features, early blood biomarkers, and abnormalities on head computerized tomography (CT). METHODS: We performed a pilot prospective, observational study enrolling consecutive patients transported by critical care air ambulance from the scene of trauma to a Level I trauma center. During transport, prehospital clinicians placed a sensor on the patient's forehead to record EEG. We reviewed EEG waveforms and selected 90 seconds of recording for quantitative analysis. EEG data processing included fast Fourier transform to summarize component frequency power in the delta (0-4 Hz), theta (4-8 Hz), and alpha (8-13 Hz) ranges. We collected blood samples on day 1 and day 3 post-injury and measured plasma levels of two brain injury biomarkers (ubiquitin C-terminal hydrolase L1 [UCH-L1] and glial fibrillary acidic protein [GFAP]). We compared predictors between individuals with and without CT-positive TBI findings. RESULTS: Forty subjects were enrolled, with EEG recordings successfully obtained in 34 (85%). Reasons for failure included uncharged battery (n = 5) and user error (n = 1). Data were lost in three cases. Of 31 subjects with data, interpretable EEG signal was recorded in 26 (84%). Mean age was 48 (SD 16) years, 79% were male, and 50% suffered motor vehicle crashes. Eight subjects (24%) had CT-positive TBI. Subjects with and without CT-positive TBI had similar median delta power, alpha power, and theta power. UCH-L1 and GFAP plasma levels did not differ across groups. Delta power inversely correlated with UCH-L1 day 1 plasma concentration (r = -0.60, p = 0.03). CONCLUSIONS: Prehospital EEG acquisition is feasible during air transport after trauma.

Metabolic Manipulation and Therapeutic Hypothermia.

Hypothermia has multiple physiological effects, including decreasing metabolic rate and oxygen consumption (VO2). There are few human data about the magnitude of change in VO2 with decreases in core temperature. We aimed to quantify to magnitude of reduction in resting VO2 as we reduced core temperature in lightly sedated healthy individuals. After informed consent and physical screening, we cooled participants by rapidly infusing 20 mL/kg of cold (4°C) saline intravenously and placing surface cooling pads on the torso. We attempted to suppress shivering using a 1 mcg/kg intravenous bolus of dexmedetomidine followed by titrated infusion at 1.0 to 1.5 µg/(kg·h). We measured resting metabolic rate VO2 through indirect calorimetry at baseline (37°C) and at 36°C, 35°C, 34°C, and 33°C. Nine participants had mean age 30 (standard deviation 10) years and 7 (78%) were male. Baseline VO2 was 3.36 mL/(kg·min) (interquartile range 2.98-3.76) mL/(kg·min). VO2 was associated with core temperature and declined with each degree decrease in core temperature, unless shivering occurred. Over the entire range from 37°C to 33°C, median VO2 declined 0.7 mL/(kg·min) (20.8%) in the absence of shivering. The largest average decrease in VO2 per degree Celsius was by 0.46 mL/(kg·min) (13.7%) and occurred between 37°C and 36°C in the absence of shivering. After a participant developed shivering, core body temperature did not decrease further, and VO2 increased. In lightly sedated humans, metabolic rate decreases around 5.2% for each 1°C decrease in core temperature from 37°C to 33°C. Because the largest decrease in metabolic rate occurs between 37°C and 36°C, subclinical shivering or other homeostatic reflexes may be present at lower temperatures.

Simple approach to quantify hypoxic-ischemic brain injury severity from computed tomography imaging files after cardiac arrest.

BACKGROUND: Grey-white ratio (GWR) can estimate severity of cytotoxic cerebral edema secondary to hypoxic-ischemic brain injury after cardiac arrest and predict progression to death by neurologic criteria (DNC). Current approaches to calculating GWR are not standardized and have variable interrater reliability. We tested if measures of variance of brain density on early computed tomographic (CT) imaging after cardiac arrest could predict DNC. METHODS: We performed a retrospective cohort study, identifying post-arrest patients treated between 2011 and 2020 at our single center. We extracted demographic data from our registry and Digital Imaging and Communication in Medicine (DICOM) files for each patient's first brain CT. We analyzed slices 15-20 of each DICOM, corresponding to the level of the basal ganglia while accommodating differences in patient anatomy. We extracted pixel arrays and converted the radiodensities to Hounsfield units (HU). To focus on brain tissue densities, we excluded HU > 60 and < 10. We calculated the variance of each patient's HU distribution and the difference between the means of a two-group Gaussian finite mixture model. We compared these novel metrics to existing measures of cerebral edema, then randomly divided our data into 80% training and 20% test sets and used logistic regression to predict DNC. RESULTS: Of 1,133 included subjects, 457 (40%) were female, mean (standard deviation) age was 58 (16) years, and 115 (10%) progressed to DNC. CTs were obtained a median [interquartile range] of 4.2 [2.8-5.7] hours post-arrest. Our novel measures correlated weakly with GWR. HU variance, but not difference between mixture model means, differed significantly between subjects with and without sulcal or cistern effacement. GWR outperformed our novel measures in predicting progression to DNC with an area under the receiver operating characteristic curve (AUC) of 0.82, compared to HU variance (AUC = 0.73) and the difference between mixture model means (AUC = 0.56). CONCLUSION: There are differences in the distribution of HU on post-arrest CT in patients with qualitative measures of cerebral edema. Current methods to quantify cerebral edema outperform simple measures of attenuation variance on early brain CT. Further analyses could investigate if these measures of variance, or other distributional characteristics of brain density, have improved predictive performance on brain CTs obtained later in the clinical course or derived from discrete regions of anatomical interest.

Correlation of vital sign centiles with in-hospital outcomes among adults encountered by emergency medical services.

BACKGROUND: Vital signs are a critical component of the prehospital assessment. Prior work has suggested that vital signs may vary in their distribution by age. These differences in vital signs may have implications on in-hospital outcomes or be utilized within prediction models. We sought to (1) identify empirically derived (unadjusted) cut points for vital signs for adult patients encountered by emergency medical services (EMS), (2) evaluate differences in age-adjusted cutoffs for vital signs in this population, and (3) evaluate unadjusted and age-adjusted vital signs measures with in-hospital outcomes. METHODS: We used two multiagency EMS data sets to derive (National EMS Information System from 2018) and assess agreement (ESO, Inc., from 2019 to 2021) of vital signs cutoffs among adult EMS encounters. We compared unadjusted to age-adjusted cutoffs. For encounters within the ESO sample that had in-hospital data, we compared the association of unadjusted cutoffs and age-adjusted cutoffs with hospitalization and in-hospital mortality. RESULTS: We included 13,405,858 and 18,682,684 encounters in the derivation and validation samples, respectively. Both extremely high and extremely low vital signs demonstrated stepwise increases in admission and in-hospital mortality. When evaluating age-based centiles with vital signs, a gradual decline was noted at all extremes of heart rate (HR) with increasing age. Extremes of systolic blood pressure at upper and lower margins were greater in older age groups relative to younger age groups. Respiratory rate (RR) cut points were similar for all adult age groups. Compared to unadjusted vital signs, age-adjusted vital signs had slightly increased accuracy for HR and RR but lower accuracy for SBP for outcomes of mortality and hospitalization. CONCLUSIONS: We describe cut points for vital signs for adults in the out-of-hospital setting that are associated with both mortality and hospitalization. While we found age-based differences in vital signs cutoffs, this adjustment only slightly improved model performance for in-hospital outcomes.

Critical Care Management of Patients After Cardiac Arrest: A Scientific Statement From the American Heart Association and Neurocritical Care Society.

The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.

Critical Care Management of Patients After Cardiac Arrest: A Scientific Statement from the American Heart Association and Neurocritical Care Society.

The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.

Impact of Preexisting Depression and Anxiety on Hospital Readmission and Long-Term Survival After Cardiac Arrest.

BACKGROUND: While sudden cardiac arrest (CA) survivors are at risk for developing psychiatric disorders, little is known about the impact of preexisting mental health conditions on long-term survival or postacute healthcare utilization. We examined the prevalence of preexisting psychiatric conditions in CA patients who survived hospital discharge, characterized incidence and reason for inpatient psychiatry consultation during these patients' acute hospitalizations, and determined the association of pre-CA depression and anxiety with hospital readmission rates and long-term survival. We hypothesized that prior depression or anxiety would be associated with higher hospital readmission rates and lower long-term survival. METHODS: We conducted a retrospective cohort study including patients resuscitated from in- and out-of-hospital CA who survived both admission and discharge from a single hospital between January 1, 2010, and December 31, 2017. We identified patients from our prospective registry, then performed a structured chart review to abstract past psychiatric history, prescription medications for psychiatric conditions, and identify inpatient psychiatric consultations. We used administrative data to identify readmissions within 1 year and vital status through December 31, 2020. We used multivariable Cox regressions controlling for patient demographics, medical comorbidities, discharge Cerebral Performance Category and disposition, depression, and anxiety history to predict long-term survival and hospital readmission. RESULTS: We included 684 subjects. Past depression or anxiety was noted in 24% (n = 162) and 19% (n = 129) of subjects. A minority of subjects (n = 139, 20%) received a psychiatry consultation during the index hospitalization. Overall, 262 (39%) subjects had at least 1 readmission within 1 year. Past depression was associated with an increased hazard of hospital readmission (hazard ratio 1.50, 95% CI 1.11-2.04), while past anxiety was not associated with readmission. Neither depression nor anxiety were independently associated with long-term survival. CONCLUSIONS: Depression is an independent risk factor for hospital readmission in CA survivors.

Bag-Valve-Mask Ventilation and Survival From Out-of-Hospital Cardiac Arrest: A Multicenter Study.

BACKGROUND: Few studies have measured ventilation during early cardiopulmonary resuscitation (CPR) before advanced airway placement. Resuscitation guidelines recommend pauses after every 30 chest compressions to deliver ventilations. The effectiveness of bag-valve-mask ventilation delivered during the pause in chest compressions is unknown. We sought to determine: (1) the incidence of lung inflation with bag-valve-mask ventilation during 30:2 CPR; and (2) the association of ventilation with outcomes after out-of-hospital cardiac arrest. METHODS: We studied patients with out-of-hospital cardiac arrest from 6 sites of the Resuscitation Outcomes Consortium CCC study (Trial of Continuous Compressions versus Standard CPR in Patients with Out-of-Hospital Cardiac Arrest). We analyzed patients assigned to the 30:2 CPR arm with ≥2 minutes of thoracic bioimpedance signal recorded with a cardiac defibrillator/monitor. Detectable ventilation waveforms were defined as having a bioimpedance amplitude ≥0.5 Ω (corresponding to ≥250 mL VT) and a duration ≥1 s. We defined a chest compression pause as a 3- to 15-s break in chest compressions. We compared the incidence of ventilation and outcomes in 2 groups: patients with ventilation waveforms in <50% of pauses (group 1) versus those with waveforms in ≥50% of pauses (group 2). RESULTS: Among 1976 patients, the mean age was 65 years; 66% were male. From the start of chest compressions until advanced airway placement, mean±SD duration of 30:2 CPR was 9.8±4.9 minutes. During this period, we identified 26 861 pauses in chest compressions; 60% of patients had ventilation waveforms in <50% of pauses (group 1, n=1177), and 40% had waveforms in ≥50% of pauses (group 2, n=799). Group 1 had a median of 12 pauses and 2 ventilations per patient versus group 2, which had 12 pauses and 12 ventilations per patient. Group 2 had higher rates of prehospital return of spontaneous circulation (40.7% versus 25.2%; P<0.0001), survival to hospital discharge (13.5% versus 4.1%; P<0.0001), and survival with favorable neurological outcome (10.6% versus 2.4%; P<0.0001). These associations persisted after adjustment for confounders. CONCLUSIONS: In this study, lung inflation occurred infrequently with bag-valve-mask ventilation during 30:2 CPR. Lung inflation in ≥50% of pauses was associated with improved return of spontaneous circulation, survival, and survival with favorable neurological outcome.

Association of substance use with outcomes in mildly ill COVID-19 outpatients.

BACKGROUND: Smoking, alcohol use, and non-prescription drug use are associated with worsened COVID-19 outcomes in hospitalized patients. Whether there is an association between substance use and outcomes in patients with COVID-19 who visited the Emergency Department (ED) but did not require hospitalization has not been well established. We investigated whether smoking, alcohol, and non-prescription drug use were associated with worsened COVID-19 outcomes among such patients presenting to the ED. METHODS: We conducted a secondary analysis of a clinical trial which sought to determine the effect of early convalescent plasma administration in patients presenting to the ED within 7 days of onset of mild COVID-19 symptoms. The study recruited 511 participants who were aged 50 years or older or had one or more risk factors for severe COVID-19. The primary outcome was disease progression within 15 days after randomization, which was defined as a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included: no hospitalization within 30 days post-randomization, symptom worsening on the 5-category COVID-19 outpatient ordinal scale within 15 days post-randomization, and all-cause mortality. Substance use was categorized into either use or never use based on participant self-report. Logistic regression models were used to determine the association between substance use and outcomes. RESULTS: The mean age of the 511 patients enrolled was 52 years and the majority were females (274, 54%). Approximately 213 (42%) were non-Hispanic Whites, 156 (30%) Hispanics, 100 (20%) non-Hispanic Blacks, 18 (4%) non-Hispanic Asian, 8 (1%) American Indian Alaskan, and 16 (3%) unknown race. Tobacco 152 (30%) was the most common substance use reported. Alcohol use 36 (7%) and non-prescription drug use 33 (6%) were less common. Tobacco use and non-prescription drug use were associated with an increased risk for meeting the primary outcome ((tobacco: adjusted odds ratio [aOR] =2.08; 95% confidence interval [CI]: 1.37-3.15) and (drug: aOR =2.41; 95%CI: 1.17-5.00)) and increased risk for symptom worsening on the 5-category COVID-19 outpatient scale ((tobacco: aOR = 1.62; 95%CI: 1.09-2.42) and (drug: aOR = 2.32 95% CI: 1.10-4.87)) compared to non-use after adjusting for age, sex, plasma administration, and comorbidity. CONCLUSION: Tobacco and non-prescription drug use but not alcohol use were associated with worsened COVID-19 outcomes in patients who did not require hospitalization on their initial presentation. Future studies should determine the quantity, duration, and type of drug/tobacco use that may worsen COVID-19.

Comparing strategies for prehospital transport to specialty care after cardiac arrest.

Outcomes are better when patients resuscitated from out-of-hospital cardiac arrest (OHCA) are treated at specialty centers. The best strategy to transport patients from the scene of resuscitation to specialty care is unknown. METHODS: We performed a retrospective cohort study. We identified patients treated at a single specialty center after OHCA from 2010 to 2021 and used OHCA geolocations to develop a catchment area using a convex hull. Within this area, we identified short term acute care hospitals, OHCA receiving centers, adult population by census block group, and helicopter landing zones. We determined population-level times to specialty care via: (1) direct ground transport; (2) transport to the nearest hospital followed by air interfacility transfer; and (3) ground transport to air ambulance. We used an instrumental variable (IV) adjusted probit regression to estimate the causal effect of transport strategy on functionally favorable survival to hospital discharge. RESULTS: Direct transport to specialty care by ground to air ambulance had the shortest population-level times from OHCA to specialty care (median 56 [IQR 47-66] minutes). There were 1,861 patients included in IV regression of whom 395 (21%) had functionally favorable survival. Most (n = 1,221, 66%) were transported to the nearest hospital by ground EMS then to specialty care by air. Patient outcomes did not differ across transport strategies in our IV analysis. DISCUSSION: We did not find strong evidence in favor of a particular strategy for transport to specialty care after OHCA. Population level time to specialty care was shortest with ground ambulance transport to the nearest helicopter landing zone.

Diagnostic yield of computed tomography after non-traumatic out-of-hospital cardiac arrest.

AIM: Determine the frequency with which computed tomography (CT) after out-of-hospital cardiac arrest (OHCA) identifies clinically important findings. METHODS: We included non-traumatic OHCA patients treated at a single center from February 2019 to February 2021. Clinical practice was to obtain CT head in comatose patients. Additionally, CT of the cervical spine, chest, abdomen, and pelvis were obtained if clinically indicated. We identified CT imaging obtained within 24 hours of emergency department (ED) arrival and summarized radiology findings. We used descriptive statistics to summarize population characteristics and imaging results, report their frequencies and, post hoc, compared time from ED arrival to catheterization between patients who did and did not undergo CT. RESULTS: We included 597 subjects, of which 491 (82.2%) had a CT obtained. Time to CT was 4.1 hours [2.8-5.7]. Most (n = 480, 80.4%) underwent CT head, of which 36 (7.5%) had intracranial hemorrhage and 161 (33.5%) had cerebral edema. Fewer subjects (230, 38.5%) underwent a cervical spine CT, and 4 (1.7%) had acute vertebral fractures. Most subjects (410, 68.7%) underwent a chest CT, and abdomen and pelvis CT (363, 60.8%). Chest CT abnormalities included rib or sternal fractures (227, 55.4%), pneumothorax (27, 6.6%), aspiration or pneumonia (309, 75.4%), mediastinal hematoma (18, 4.4%) and pulmonary embolism (6, 3.7%). Significant abdomen and pelvis findings were bowel ischemia (24, 6.6%) and solid organ laceration (7, 1.9%). Most subjects that had CT imaging deferred were awake and had shorter time to catheterization. CONCLUSIONS: CT identifies clinically important pathology after OHCA.