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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., (© 2023. The Author(s).)

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.

Purpose: To investigate the effects of the selective NLRP3 inflammasome inhibitor MCC950 on post-resuscitation myocardial function and survival in a rat model of cardiopulmonary resuscitation (CPR)., Methods: Thirty-six Sprague Dawley rats were randomized into three groups: (1) MCC950, (2) control, and (3) sham. Each group consisted of a 6 h non-survival subgroup (n = 6) and a 48 h survival subgroup (n = 6). Ventricular fibrillation (VF) was induced and untreated for 6 min. CPR was initiated and continued for 8 min. Resuscitation was attempted with a 4 J defibrillation. MCC950 (10 mg/kg) or vehicle was administered via intraperitoneal injection immediately after the return of spontaneous circulation (ROSC). Myocardial function and sublingual microcirculation were measured after ROSC in the non-survival subgroups. Plasma levels of interleukin Iβ (IL-1β) and cardiac troponin I (cTnI) were measured at baseline and 6 h in the non-survival subgroups. Heart tissue was harvested to measure the NLRP3 inflammasome constituents, including NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, and IL-1β. Survival duration and neurologic deficit score (NDS) were recorded and evaluated among survival groups., Results: Post-resuscitation myocardial function and sublingual microcirculation were improved in MCC950 compared with control (p < 0.05). IL-1β and cTnI were decreased in MCC950 compared to control (p < 0.01). The MCC950 treated groups showed significantly reduced ASC, caspase-1, and IL-1β compared with the control group (p < 0.05). Survival at 48 h after ROSC was greater in MCC950 (p < 0.05) with improved NDS (p < 0.05)., Conclusion: Administration of MCC950 following ROSC mitigates post-resuscitation myocardial dysfunction and improves survival., (© 2021. The Author(s).)

Background: Although most US emergency medical services (EMS) systems collect time-to-treatment data in their electronic prehospital patient care reports (PCRs), analysis of these data seldom appears in publications. We believe EMS agencies should routinely analyze the initial time-to-treatment data for various potentially life-threatening conditions. This not only assures that protocol-required treatments have been provided but can discover avoidable delays and drive protocol/treatment priority change. Our study purpose was to analyze the interval from 9-1-1 call receipt until the first administration of naloxone to adult opioid overdose victims to demonstrate the quality assurance importance of analyzing time-to-treatment data., Methods: Retrospective analysis of intervals from 9-1-1 call receipt to initial naloxone treatment in adult opioid overdose victims. We excluded victims <18 years of age and cases where a bystander, police, or a health care worker gave naloxone before EMS arrival. We compared data collected before and during the COVID-19 pandemic to determine its effect on the analysis., Results: The mean patient age of 582 opioid overdose victims was 40.7 years [95% CI 39.6, 41.8] with 405 males (69.6%). EMS units' scene arrival was 6.7 minutes from the 9-1-1 call receipt. It took 1.8 minutes to reach the victim, and 8.6 additional minutes to administer the first naloxone regardless of administration route (70.4% intravenous, 26.1% intranasal, 2.7% intraosseous, 0.7% intramuscular). EMS personnel administered the first naloxone 17.1 minutes after the 9-1-1 call receipt, with 50.3% of the delay occurring after patient contact. There was no statistically significant difference in the times-to-treatment before vs. during the pandemic., Conclusion: The prepandemic interval from 9-1-1 call receipt until initial EMS administration of naloxone was substantial and did not change significantly during COVID-19. Our findings exemplify why EMS agencies should analyze initial time-to-treatment data, especially for life-threatening conditions, beyond assuring that protocol-required treatments have been provided. Based on our analysis, fire department crews now carry intranasal naloxone, and intranasal naloxone is given to "impaired" opioid overdose victims the first-arriving fire department or EMS personnel. We continue to collect data on intervals-to-treatment prospectively and monitor our critical process/treatment intervals using the plan-do-study-act model to improve our process/carry out change, and publish our results in a future publication.

Abstract: Aims: A rapid heart rate (HR) that occurs after cardiopulmonary resuscitation (CPR) is a short-term compensatory mechanism preserving cardiac output. However, if of long duration, it is unfavorable for myocardial function postresuscitation because of disrupted balance between myocardial oxygen supply and demand. This raises the assumption that such a sustained fast HR should be regulated. The present study aimed to investigate the follow-on effect of ivabradine (a specific inhibitor of the I f current of the sinoatrial node)-induced HR reduction (HRR) on postresuscitation myocardial function in a rat model of CPR. Methods and results: Six minutes of ventricular fibrillation and 8 min of CPR were performed on Sprague-Dawley rats. All 32 resuscitated animals were then randomized into saline and ivabradine groups, each group having nonsurvival and survival subgroups (n = 8 each). Saline or ivabradine (0.5 mL/kg) was administered at 1 h postresuscitation. Heart rate, myocardial function as expressed by cardiac output, ejection fraction, and myocardial performance index were assessed at baseline and hourly from 1 to 5 h postresuscitation. Heart rate variability was analyzed at baseline and at 1, 3, and 5 h postresuscitation. Serum epinephrine and cardiac troponin I at baseline and at 1, 3, and 5 h postresuscitation in nonsurvival subgroup were measured. Survival duration in the survival subgroup was observed. The baseline HR was approximately 390 beats/min (bpm). After resuscitation, an average increase of Δ ≈ +15 bpm (relative ratio ≈ +3.8%) with a resultant HR of 405 bpm lasting more than 5 h occurred. Ivabradine group achieved a steady HRR of Δ ≈ -30 bpm (relative ratio ≈ -7.4%) as compared with saline group ( P < 0.01). Postresuscitation myocardial function was significantly worse in the ivabradine group (all P < 0.01). Heart rate variability was significantly impaired in the ivabradine group (all P < 0.05). Serum cardiac troponin I and epinephrine concentration were significantly higher in the ivabradine group (all P < ?0.01). Survival duration was significantly shortened in the ivabradine group as compared with the saline group (388 vs. 526 min, P < ?0.01). Conclusions: Ivabradine-induced HRR increases the severity of postresuscitation myocardial dysfunction and shortens survival duration in a rat model of CPR., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Background: Although rapid response teams have been widely promoted as a strategy to reduce unexpected hospital deaths, most studies of rapid response teams have not adjusted for secular trends in mortality before their implementation. We examined whether implementation of a rapid response team was associated with a reduction in hospital mortality after accounting for preimplementation mortality trends., Methods: Among 56 hospitals in Get With The Guidelines-Resuscitation linked to Medicare, we calculated the annual rates of case mix-adjusted mortality for each hospital during 2000 to 2014. We constructed a hierarchical log-binomial regression model of mortality over time (calendar-year), incorporating terms to capture the effect of rapid response teams, to determine whether implementation of rapid response teams was associated with reduction in hospital mortality that was larger than expected based on preimplementation trends, while adjusting for hospital case mix index., Results: The median annual number of Medicare admissions was 5214 (range, 408-18 398). The median duration of preimplementation and postimplementation period was 7.6 years (≈2.5 million admissions) and 7.2 years (≈2.6 million admissions), respectively. Hospital mortality was decreasing by 2.7% annually during the preimplementation period. Implementation of rapid response teams was not associated with a change in mortality during the initial year (relative risk for model intercept, 0.98 [95% CI, 0.94-1.02]; P =0.30) or in the mortality trend (relative risk for model slope, 1.01 per year [95% CI, 0.99-1.02]; P =0.30). Among individual hospitals, implementation of a rapid response team was associated with a lower-than-expected mortality at only 4 (7.1%) and higher-than-expected mortality at 2 (3.7%) hospitals., Conclusions: Among a large and diverse sample of US hospitals, we did not find implementation of rapid response teams to be associated with reduction in hospital mortality. Studies are needed to understand best practices for rapid response team implementation, to ensure that hospital investment in these teams improves patient outcomes.

Background: Previous studies have demonstrated that inflammation and impaired microcirculation are key factors in post-resuscitation syndromes. Here, we investigated whether methylprednisolone (MP) could improve myocardial function and microcirculation by suppressing the systemic inflammatory response following cardiopulmonary resuscitation (CPR) in a rat model of cardiac arrest (CA)., Methods: Sprague-Dawley rats were randomly assigned to (1) sham, (2) control, and (3) drug groups. Ventricular fibrillation was induced and then followed by CPR. The rats were infused with either MP or vehicle at the start of CPR. Myocardial function and microcirculation were assessed at baseline and after the restoration of spontaneous circulation. Blood samples were drawn at baseline and 60-min post-resuscitation to assess serum cytokine (TNF-α, IL-1β, and IL-6) levels., Results: Myocardial function [estimated by the ejection fraction (EF), myocardial performance index (MPI), and cardiac output (CO)] improved post-ROSC in the MP group compared with those in the control group ( p < 0.05). MP decreased the levels of the aforementioned pro-inflammatory cytokines and alleviated cerebral, sublingual, and intestinal microcirculation compared with the control ( p < 0.05). A negative correlation emerged between the cytokine profile and microcirculatory blood flow., Conclusion: MP treatment reduced post-resuscitation myocardial dysfunction, inhibited pro-inflammatory cytokines, and improved microcirculation in the initial recovery phase in a CA and resuscitation animal model. Therefore, MP could be a potential clinical target for CA patients in the early phase after CPR to alleviate myocardial dysfunction and improve prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Bischof, Xu, Guo, Zheng, Ge, Hu, Georgescu Margarint, Bradley, Peberdy, Ornato, Zhu and Tang.)

The systemic inflammatory response following global myocardial ischemia/reperfusion (I/R) injury is a critical driver of poor outcomes. Both pyroptosis and necroptosis are involved in the systemic inflammatory response and contribute to regional myocardial I/R injury. This study aimed to explore the effect of necrosulfonamide (NSA) on post-resuscitation myocardial dysfunction in a rat model of cardiac arrest. Sprague-Dawley rats were randomly categorized to Sham, CPR and CPR-NSA groups. For rats in the latter two groups, ventricular fibrillation was induced without treatment for 6 min, with cardiopulmonary resuscitation (CPR) being sustained for 8 min. Rats were injected with NSA (10 mg/kg in DMSO) or vehicle at 5 min following return of spontaneous circulation. Myocardial function was measured by echocardiography, survival and neurological deficit score (NDS) were recorded at 24, 48, and 72 h after ROSC. Western blotting was used to assess pyroptosis- and necroptosis-related protein expression. ELISAs were used to measure levels of inflammatory cytokine. Rats in the CPR-NSA group were found to exhibit superior post-resuscitation myocardial function, and better NDS values in the group of CPR-NSA. Rats in the group of CPR-NSA exhibited median survival duration of 68 ± 8 h as compared to 34 ± 21 h in the CPR group. After treatment with NSA, NOD-like receptor 3 (NLRP3), GSDMD-N, phosphorylated-MLKL, and phosphorylated-RIP3 levels in cardiac tissue were reduced with corresponding reductions in inflammatory cytokine levels. Administration of NSA significantly improved myocardial dysfunction succeeding global myocardial I/R injury and enhanced survival outcomes through protective mechanisms potentially related to inhibition of pyroptosis and necroptosis pathways., (Copyright © 2022. Published by Elsevier B.V.)

Abstract: Blocking ferroptosis reduces ischemia-reperfusion injury in some pathological contexts. However, there is no evidence that ferroptosis contributes to post-resuscitation myocardial dysfunction (PRMD). Here, we evaluated the therapeutic performance of ferroptosis inhibitors (UAMC-3203 or/and Deferoxamine) on the PRMD in a rat model of cardiac arrest and surveyed the changes of essential ferroptosis markers in the myocardium. Remarkably, all treatments reduce the severity of cardiac dysfunction and microcirculation hypoperfusion after resuscitation compared with control. Consistently, we observe that the ferroptosis marker Glutathione peroxidase 4, 4-hydroxynonenal and non-heme iron altered (1 ± 0.060 vs. 0.021 ± 0.016, 1 ± 0.145 vs. 3.338 ± 0.221, 52.010 ± 3.587 ug/g vs. 70.500 ± 3.158 ug/g, all P < 0.05) in the myocardium after resuscitation. These changes were significantly suppressed by UAMC-3203 [(0.187 ± 0.043, 2.848 ± 0.169, all P < 0.05), (72.43 ± 4.920 ug/g, P  > 0.05)], or Deferoxamine (0.203 ± 0.025, 2.683 ± 0.273, 55.95 ± 2.497 ug/g, all P < 0.05). Briefly, UAMC-3203 or/and Deferoxamine improve post-resuscitation myocardial dysfunction and provide evidence of ferroptosis involvement, suggesting that ferroptosis inhibitors could potentially provide an innovative therapeutic approach for mitigating the myocardial damage caused by cardiopulmonary resuscitation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)

Cardiac arrest (CA) remains a major public health issue. Inflammatory responses with overproduction of interleukin-1β regulated by NLRP3 inflammasome activation play a crucial role in cerebral ischemia/reperfusion injury. We investigated the effects of the selective NLRP3-inflammasome inhibitor MCC950 on post-resuscitation cerebral function and neurologic outcome in a rat model of cardiac arrest. Thirty-six male rats were randomized into the MCC950 group, the control group, or the sham group (N = 12 of each group). Each group was divided into a 6 h non-survival subgroup (N = 6) and a 24 h survival subgroup (N = 6). Ventricular fibrillation (VF) was electrically induced and untreated for 6 min, followed by 8 min of precordial compressions and mechanical ventilation. Resuscitation was attempted with a 4J defibrillation. Either MCC950 (10 mg/kg) or vehicle was injected intraperitoneally immediately after the return of spontaneous circulation (ROSC). Rats in the sham group underwent the same surgical procedures without VF and CPR. Brain edema, cerebral microcirculation, plasma interleukin Iβ (IL-1β), and neuron-specific enolase (NSE) concentration were measured at 6 h post-ROSC of non-survival subgroups, while 24 h survival rate, neurological deficits were measured at 24 h post-ROSC of survival subgroups. Post-resuscitation brain edema was significantly reduced in animals treated with MCC950 (p < 0.05). Cerebral perfused vessel density (PVD) and microcirculatory flow index (MFI) values were significantly higher in the MCC950 group compared with the control group (p < 0.05). The plasma concentrations of IL-1β and NSE were significantly decreased in animals treated with MCC950 compared with the control group (p < 0.05). 24 h-survival rate and neurological deficits score (NDS) was also significantly improved in the MCC950 group compared with the control group (p < 0.05). NLRP3 inflammasome blockade with MCC950 at ROSC reduces the circulatory level of IL-1β, preserves cerebral microcirculation, mitigates cerebral edema, improves the 24 h-survival rate, and neurological deficits., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background: Several prospective studies have demonstrated that the echocardiographic detection of any myocardial activity during PEA is strongly associated with higher rates of return of spontaneous circulation (ROSC). We hypothesized that PEA represents a spectrum of disease in which not only the presence of myocardial activity, but more specifically that the degree of left ventricular (LV) function would be a predictor of outcomes. The purpose of this study was to retrospectively assess the association between LV function and outcomes in patients with OHCA., Materials and Methods: Using prospectively obtained data from an observational cohort of patients receiving focused echocardiography during cardiopulmonary resuscitation (CPR) in the Emergency Department (ED) setting, we analyzed 312 consecutive subjects with available echocardiography images with initial rhythm of PEA. We used left ventricular systolic fractional shortening (LVFS), a unidimensional echocardiographic parameter to perform the quantification of LV function during PEA. Regression analyses were performed independently to evaluate for relationships between LVFS and a primary outcome of ROSC and secondary outcome of survival to hospital admission. We analyzed LVFS both as a continuous variable and as a categorial variable using the quartiles and the median to perform multiple different comparisons and to illustrate the relationship of LVFS and outcomes of interest. We performed survival analysis using Cox proportional hazards model to evaluate the hazard corresponding to length of resuscitation., Results: We found a positive association between LVFS and the primary outcome of ROSC (OR 1.04, 95%CI 1.01-1.08), but not with the secondary outcome of survival to hospital admission (OR 1.02, 95%CI 0.96-1.08). Given that the relationship was not linear and that we observed a threshold effect in the relationship between LVFS and outcomes, we performed an analysis using quartiles of LVFS. The predicted probability of ROSC was 75% for LVFS between 23.4-96% (fourth quartile) compared to 47% for LVFS between 0-4.7% (first quartile). The hazard of not achieving ROSC was significantly greater for subjects with LVFS below the median (13.1%) compared to the subgroup with LVFS greater than 13.1% (p < 0.05), with the separation of the survival curves occurring at approximately 40 min of resuscitation duration., Conclusions: Left ventricular function measured by LVFS is positively correlated with higher probability of ROSC and may be associated with higher chances of survival in patients with PEA arrest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Brain mitochondria are more sensitive to global ischemia compared to heart mitochondria. Complex I in the electron transport chain (ETC) is sensitive to ischemic injury and is a major control point of the rate of ADP stimulated oxygen consumption. The purpose of this study was to explore whether changes in cerebral and myocardial mitochondria differ after cardiac arrest. Animals were randomized into 4 groups (n = 6): 1) Sham 2) VF 3) VF+CPR 4) ROSC 1hr. Ventricular Fibrillation (VF) was induced through a guide wire advanced from the right jugular vein into the ventricle and untreated for 8 min. Resuscitation was attempted with a 4J defibrillation after 8 min of cardiopulmonary resuscitation (CPR). Brain mitochondria and cardiac mitochondrial subpopulations were isolated. Calcium retention capacity was measured to assess susceptibility to mitochondrial permeability transition pore opening. ADP stimulated oxygen consumption and ETC activity assays were performed. Brain mitochondria are far more sensitive to injury during cardiac arrest and resuscitation compared to cardiac mitochondria. Complex I is highly sensitive to injury in brain mitochondria. With markedly decreased calcium retention capacity, mitochondria contribute to cerebral reperfusion injury. Therapeutic preservation of cerebral mitochondrial activity and mitochondrial function during cardiac arrest may improve post-resuscitation neurologic function., (Published by Elsevier Masson SAS.)

Out-of-hospital cardiac arrest (CA) is a leading cause of death in the United States. Severe post-resuscitation cerebral dysfunction is a primary cause of poor outcome. Therefore, we investigate the effects of polyethylene glycol-20k (PEG-20k), a cell impermeant, on post-resuscitation cerebral function. Thirty-two male Sprague-Dawley rats were randomized into four groups: 1) Control; 2) PEG-20k; 3) Sham control; 4) Sham with PEG-20k. To investigate blood brain barrier (BBB) permeability, ten additional rats were randomized into two groups: 1) CPR+Evans Blue (EB); 2) Sham+EB. Ventricular fibrillation was induced and untreated for 8 min, followed by 8 min of CPR, and resuscitation was attempted by defibrillation. Cerebral microcirculation was visualized at baseline, 2, 4 and 6 h after return of spontaneous circulation (ROSC). Brain edema was assessed by comparing wet-to-dry weight ratios after 6 h. S-100β, NSE and EB concentrations were analyzed to determine BBB permeability damage. For results, Post-resuscitation cerebral microcirculation was impaired compared to baseline and sham control (p < 0.05). However, dysfunction was reduced in animals treated with PEG-20k compared to control (p < 0.05). Post-resuscitation cerebral edema as measured by wet-to-dry weight ratio was lower in PEG-20k compared to control (3.23 ± 0.5 vs. 3.36 ± 0.4, p < 0.05). CA and CPR increased BBB permeability and damaged neuronal cell with associated elevation of S-100β sand NSE serum levels. PEG-20k administered during CPR improved cerebral microcirculation and reducing brain edema and injury., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background: Time to initial treatment is important in any response to out-of-hospital cardiac arrest (OHCA). The purpose of this paper was to quantify the time delay for providing initial EMS treatments supplemented by comparison with those of other EMS systems conducting clinical trials., Methods: Data were collected between 1/1/16-2/15/19. Dispatched, EMS-worked, adult OHCA cases occurring before EMS arrival were included and compared with published treatment time data. Response time and time-to-treatment intervals were profiled in both groups. Time intervals were calculated by subtracting the following timepoints from 9-1-1 call receipt: ambulance in route; at curb; patient contact; first defibrillation; first epinephrine; and first antiarrhythmic., Results: 342 subjects met study inclusion/exclusion. Mean time intervals (min [95%CI]) from 9-1-1 call receipt to the following EMS endpoints were: dispatch 0.1 [0.05-0.2]; at curb 5.0 [4.5, 5.5]; at patient 6.7 [6.1, 7.2];, first defibrillation initially shockable 11.7 [10.1, 13.3]; first epinephrine (initially shockable 15.0 [12.8, 17.2], initially non-shockable 14.8 [13.5, 15.9]), first antiarrhythmic 25.1 [22.0, 28.2]. These findings were similar to data in 5 published clinical trials involving 12,954 subjects., Conclusions: Delay to EMS treatments are common and may affect clinical outcomes. Neither Utstein out-of-hospital guidelines [1] nor U.S. Cardiac Arrest Registry to Enhance Survival (CARES) databases require capture of these elements. EMS is often not providing treatments quickly enough to optimize clinical outcomes. Further regulatory change/research are needed to determine whether OHCA outcome can be improved by novel changes such as enhancing bystander effectiveness through drone-delivered drugs/devices & real-time dispatcher direction on their use., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Accumulating evidence demonstrated that administration of ω-3 polyunsaturated fatty acid (ω-3 PUFA) or ascorbic acid (AA) following cardiac arrest (CA) improves survival. Therefore, we investigate the effects of ω-3 PUFA combined with AA on myocardial function after CA and cardiopulmonary resuscitation (CPR) in a rat model. Thirty male rats were randomized into 5 groups: (1) sham; (2) control; (3) ω-3 PUFA; (4) AA; (5) ω-3 PUFA + AA. Ventricular fibrillation (VF) was induced and untreated for 6 min followed by defibrillation after 8 min of CPR. Infusion of drug or vehicle occurred at the start of CPR. Myocardial function and sublingual microcirculation were measured at baseline and after return of spontaneous circulation (ROSC). Heart tissues and blood were collected 6 h after ROSC. Myocardial function and sublingual microcirculation improvements were seen with ω-3 PUFA or AA compared to control after ROSC (p < 0.05). ω-3 PUFA + AA shows a better myocardial function than ω-3 PUFA or AA (p < 0.05). ω-3 PUFA or AA decreases pro-inflammatory cytokines, cTnI, myocardium malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) modified proteins compared to control (p < 0.05). ω-3 PUFA and AA combined have lower MDA and 4-HNE modified proteins than alone (p < 0.05). ω-3 PUFA or AA treatment reduces the severity of post-resuscitation myocardial dysfunction, improves sublingual microcirculation, decreases lipid peroxidation and systemic inflammation in the early phase of recovery following CA and resuscitation. A combination of ω-3 PUFA and AA treatment confers an additive effect in suppressing lipid peroxidation and improving myocardial function., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The objective of this study was to investigate the effects of pharmacologically induced hypothermia with WIN55, 212-2 (WIN)on postresuscitation myocardial function, microcirculation, and metabolism-specific lipids in a rat cardiac arrest (CA) model. Ventricular fibrillation was electrically induced and untreated for 6 minutes in 24 Sprague-Dawley rats weighing 450-550 g. Cardiopulmonary resuscitation including chest compression and mechanical ventilation was then initiated and continued for 8 minutes, followed by defibrillation. At 5 minutes after restoration of spontaneous circulation (ROSC), animals were randomized into four groups: (1) normothermia with vehicle (NT); (2) physical hypothermia with vehicle (PH); (3) WIN55, 212-2 with normothermia (WN); and (4) WIN55, 212-2 with hypothermia (WH). For groups of WN and WH, WIN was administered by continuous intravenous infusion with a syringe pump for 4 hours. PH started at 5 minutes after resuscitation. NT maintained core temperature at 37°C ± 0.2°C with the aid of a heating blanket. Hypothermia groups maintained temperature at 33°C ± 0.5°C for 4 hours after ROSC. There was a significant improvement in myocardial function as measured by ejection fraction, cardiac output, and myocardial performance index in animals treated with WH and PH beginning at 1 hour after start of infusion. In the WH and PH groups, buccal microcirculation was significantly improved compared with NT and WN. Plasma at pre-CA and ROSC 4 hours was harvested for lipid metabolism. The WH group appeared to be closer to baseline than the other groups in lipid metabolism. lysophosphatidylcholine (LPC) 18:2, free fatty acid (FFA) 22:6, and ceramide (CER) (24:0) changed significantly among the lipidomic data compared with NT ( p  < 0.05). Postresuscitation hypothermia improved myocardial function and microcirculation. WH-mediated lipid metabolism had the best metabolic outcome to bring back the animals to normal metabolism, which may be protective to improve outcomes of CA. LPC 18:2, FFA 22:6, and CER (24:0) may be important predictors of outcomes of CA.

Survival after cardiac arrest requires an integrated system of people, training, equipment, and organizations working together to achieve a common goal. Part 7 of the 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care focuses on systems of care, with an emphasis on elements that are relevant to a broad range of resuscitation situations. Previous systems of care guidelines have identified a Chain of Survival, beginning with prevention and early identification of cardiac arrest and proceeding through resuscitation to post-cardiac arrest care. This concept is reinforced by the addition of recovery as an important stage in cardiac arrest survival. Debriefing and other quality improvement strategies were previously mentioned and are now emphasized. Specific to out-of-hospital cardiac arrest, this Part contains recommendations about community initiatives to promote cardiac arrest recognition, cardiopulmonary resuscitation, public access defibrillation, mobile phone technologies to summon first responders, and an enhanced role for emergency telecommunicators. Germane to in-hospital cardiac arrest are recommendations about the recognition and stabilization of hospital patients at risk for developing cardiac arrest. This Part also includes recommendations about clinical debriefing, transport to specialized cardiac arrest centers, organ donation, and performance measurement across the continuum of resuscitation situations.

Background: Currently, ≤5% of bystanders witnessing an opioid overdose (OD) in the US administer antidote to the victim. A possible model to mitigate this crisis would be a system that enables 9-1-1 dispatchers to both rapidly deliver naloxone by drone to bystanders at a suspected opioid OD and direct them to administer it while awaiting EMS arrival., Methods: A simulated 9-1-1 dispatcher directed thirty subjects via 2-way radio to retrieve naloxone nasal spray from atop a drone located outside the simulation building and then administer it using scripted instructions. The primary outcome measure was time from first contact with the dispatcher to administration of the medication., Results: All subjects administered the medication successfully. The mean time interval from 9 -1-1 contact until antidote administration was 122 [95%CI 109-134] sec. There was a significant reduction in time interval if subjects had prior medical training (p = 0.045) or had prior experience with use of a nasal spray device (p = 0.030). Five subjects had difficulty using the nasal spray and four subjects had minor physical impairments, but these barriers did not result in a significant difference in time to administration (p = 0.467, p = 0.30). A significant number of subjects (29/30 [97%], p = 0.044) indicated that they felt confident they could administer intranasal naloxone to an opioid OD victim after participating in the simulation., Conclusions: Our results suggest that bystanders can carry out 9-1-1 dispatcher instructions to fetch drone-delivered naloxone and potentially decrease the time interval to intranasal administration which supports further development and testing of a such a system., Competing Interests: Declaration of competing interest JPO reports no conflict of interest. AXY reports no conflict of interest. GM reports no conflict of interest. LKM reports no conflict of interest. AS reports no conflict of interest. JH reports no conflict of interest. SD reports no conflict of interest. LH reports no conflict of interest. SRD reports no conflict of interest. JM reports no conflict of interest. DT reports no conflict of interest. MAP reports no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Focused transthoracic echocardiography (TTE) during cardiac arrest resuscitation can enable the characterization of myocardial activity, identify potentially treatable pathologies, assist with rhythm interpretation, and provide prognostic information. However, an important limitation of TTE is the difficulty obtaining interpretable images due to external and patient-related limiting factors. Over the last decade, focused transesophageal echocardiography (TEE) has been proposed as a tool that is ideally suited to image patients in extremis-those in cardiac arrest and periarrest states. In addition to the same diagnostic and prognostic role provided by TTE images, TEE provides unique advantages including the potential to optimize the quality of chest compressions, shorten cardiopulmonary resuscitation interruptions, guide resuscitative procedures, and provides a continuous image of myocardial activity. This review discusses the rationale, supporting evidence, opportunities, and challenges, and proposes a research agenda for the use of focused TEE in cardiac arrest with the goal to improve resuscitation outcomes., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To characterize the rapid response team activations, and the patients receiving them, in the American Heart Association-sponsored Get With The Guidelines Resuscitation-Medical Emergency Team cohort between 2005 and 2015., Design: Retrospective multicenter cohort study., Setting: Three hundred sixty U.S. hospitals., Patients: Consecutive adult patients experiencing rapid response team activation., Interventions: Rapid response team activation., Measurements and Main Results: The cohort included 402,023 rapid response team activations from 347,401 unique healthcare encounters. Respiratory triggers (38.0%) and cardiac triggers (37.4%) were most common. The most frequent interventions-pulse oximetry (66.5%), other monitoring (59.6%), and supplemental oxygen (62.0%)-were noninvasive. Fluids were the most common medication ordered (19.3%), but new antibiotic orders were rare (1.2%). More than 10% of rapid response teams resulted in code status changes. Hospital mortality was over 14% and increased with subsequent rapid response activations., Conclusions: Although patients requiring rapid response team activation have high inpatient mortality, most rapid response team activations involve relatively few interventions, which may limit these teams' ability to improve patient outcomes.

Significant improvements have been achieved in cardiac arrest resuscitation and postarrest resuscitation care, but mortality remains high. Most of the poor outcomes and deaths of cardiac arrest survivors have been attributed to widespread brain injury. This brain injury, commonly manifested as a comatose state, is a marker of poor outcome and a major basis for unfavorable neurological prognostication. Accurate prognostication is important to avoid pursuing futile treatments when poor outcome is inevitable but also to avoid an inappropriate withdrawal of life-sustaining treatment in patients who may otherwise have a chance of achieving meaningful neurological recovery. Inaccurate neurological prognostication leading to withdrawal of life-sustaining treatment and deaths may significantly bias clinical studies, leading to failure in detecting the true study outcomes. The American Heart Association Emergency Cardiovascular Care Science Subcommittee organized a writing group composed of adult and pediatric experts from neurology, cardiology, emergency medicine, intensive care medicine, and nursing to review existing neurological prognostication studies, the practice of neurological prognostication, and withdrawal of life-sustaining treatment. The writing group determined that the overall quality of existing neurological prognostication studies is low. As a consequence, the degree of confidence in the predictors and the subsequent outcomes is also low. Therefore, the writing group suggests that neurological prognostication parameters need to be approached as index tests based on relevant neurological functions that are directly related to the functional outcome and contribute to the quality of life of cardiac arrest survivors. Suggestions to improve the quality of adult and pediatric neurological prognostication studies are provided.

Neurotensin is an endogenous tridecapeptide that binds to neurotensin receptors in the brain, which induce hypothermia. The aim of this study was to investigate whether the receptor agonist ABS 201 could induce therapeutic hypothermia and improve postresuscitation outcomes in a ventricular fibrillation cardiac arrest (VFCA) rat model. VF was electrically induced in 12 rats. Defibrillation was achieved after 6 min of cardiopulmonary resuscitation. After successful resuscitation, animals were randomized to receive ABS 201 (8 mg/kg/h) or placebo. Postresuscitation myocardial function and neurological deficit scores (NDS) were assessed, and postresuscitation survival duration was observed for up to 72 h. After administration of ABS 201, blood temperature decreased significantly from 37°C to 34°C, and was maintained for 2.5 h. There was a significant improvement of postresuscitation myocardial dysfunction, NDS, and survival duration in animals treated with ABS 201. These results demonstrated that ABS 201 induces therapeutic hypothermia in a VFCA rat model, ameliorates postresuscitation myocardial-neurological dysfunction, and prolongs survival duration. ABS 201 may therefore be an alternative method to induce therapeutic hypothermia with current cooling methods and improve postresuscitation outcomes.

Studies have demonstrated that vagus nerve stimulation (VNS) reduces ischemia/reperfusion injury. In this study, we investigated the protective effects of VNS in a rat model of cardiopulmonary resuscitation (CPR). We further investigated whether the beneficial effects of VNS were dependent on the alpha 7 nicotinic acetylcholine receptor (α7nAChR). Forty animals were randomized into four groups and all underwent CPR (n = 10 each): CPR alone (control); VNS during CPR; α7nAChR antagonist methyllycaconitine citrate (MLA) with VNS; α7nAChR agonist 3-(2, 4-dimethoxybenzylidene) anabaseine (GTS-21 dihydrochloride) without VNS. The right vagus nerve was exteriorized in all animals. Ventricular fibrillation was induced and untreated for 8 min. Defibrillation was attempted after 8 min of CPR. VNS was initiated at the beginning of precordial chest compressions and continued for 4 h after return of spontaneous circulation (ROSC) in both the VNS and MLA groups. Hemodynamic measurements and myocardial function, including ejection fraction and myocardial performance index, were assessed at baseline, 1 and 4 h after ROSC. The neurological deficit score was measured at 24-h intervals for a total of 72 h. The heart rate was reduced in the VNS and MLA groups, while no difference was found in mean arterial pressure between the four groups. Better post-resuscitation myocardial and cerebral function and longer duration of survival were observed in the VNS-treated animals. The protective effects of VNS could be abolished by MLA and imitated by GTS-21. In addition, VNS decreased the number of electrical shocks and the duration of CPR required. VNS improves multiple outcomes after CPR.

Background: Epinephrine administered during cardiopulmonary resuscitation (CPR) is associated with severe post-resuscitation myocardial dysfunction. We previously demonstrated that therapeutic hypothermia reduced the severity of post-resuscitation myocardial dysfunction caused by epinephrine; however, the relationship between myocardial adrenoceptor expression and myocardial protective effects by hypothermia remains unclear., Methods and Results: Rats weighing between 450 and 550 g were randomized into 5 groups: (1) normothermic placebo, (2) normothermic epinephrine, (3) hypothermic placebo, (4) hypothermic epinephrine, and (5) sham (not subject to cardiac arrest and resuscitation). Ventricular fibrillation was induced and untreated for 8 minutes for all other groups. Hypothermia was initiated coincident with the start of CPR and maintained at 33±0.2°C for 4 hours. Placebo or epinephrine was administered 5 minutes after the start of CPR and 3 minutes before defibrillation. Post-resuscitation ejection fraction was measured hourly for 4 hours then hearts were harvested. Epinephrine increased coronary perfusion pressure during CPR (27±6 mm Hg versus 21±2 mm Hg P <0.05). Post-resuscitation myocardial function was impaired in the normothermic epinephrine group compared with other groups. The concentration of myocardial cAMP doubled in the normothermic epinephrine group (655.06±447.63 μmol/L) compared with the hypothermic epinephrine group (302.51±97.98 μmol/L; P <0.05). Myocardial β 1 -adrenoceptor expression decreased with normothermia cardiac arrest but not with hypothermia regardless of epinephrine., Conclusions: Epinephrine, administered during normothermic CPR, increased the severity of post-resuscitation myocardial dysfunction. This adverse effect was inhibited by intra-arrest hypothermia resuscitation. Declined cAMP with more preserved β 1 -adrenoceptors in hypothermia-resuscitated myocardium is associated with improved post-resuscitated myocardial function in vivo., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Cardiac arrest in patients on mechanical support is a new phenomenon brought about by the increased use of this therapy in patients with end-stage heart failure. This American Heart Association scientific statement highlights the recognition and treatment of cardiovascular collapse or cardiopulmonary arrest in an adult or pediatric patient who has a ventricular assist device or total artificial heart. Specific, expert consensus recommendations are provided for the role of external chest compressions in such patients., (© 2017 American Heart Association, Inc.)

Aim: The post-cardiac arrest syndrome is a complex set of pathophysiological processes including a systemic inflammatory response. The goal of the current investigation was to test the hypothesis that early inflammatory markers are independently associated with in-hospital mortality and poor neurological outcome in patients initially resuscitated from out-of-hospital cardiac arrest., Methods: This was a preplanned analysis of data collected from a prospective observational multicenter study in adult out-of-hospital cardiac arrest patients. Blood was drawn at baseline, 12 and 24h after return of spontaneous circulation and plasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α were measured. The primary outcome measure was survival to hospital discharge. We utilized a mixed linear model to compare the levels of cytokines in survivors and non-survivors over time. We used multivariable logistic regression to assess the association between IL-6 levels and mortality., Results: A total of 102 patients were analyzed. Non-survivors and patients with poor functional outcome had statistical significant higher IL-1Ra, IL-6, IL-8, and IL-10 levels (all p<0.001) at all time points (0, 12 and 24h) compared to survivors. Baseline IL-6 levels were a good predictor of mortality (AUC=0.83 [95%CI: 0.75-0.92]). Baseline IL-6 levels were strongly associated with mortality in multivariable analysis (OR: 2.58 [95%CI: 1.93-3.45], p<0.001) but were not associated with neurological outcome in multivariable analysis (OR: 1.33 [95%CI: 0.62-2.86], p=0.47)., Conclusion: Early inflammatory markers, especially IL-6, are higher in patients with a poor outcome after OHCA. IL-6 remained associated with mortality, but not functional outcome, in multivariable analysis adjusting for patient and event characteristics., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The American Heart Association (AHA) commends the recently released Institute of Medicine (IOM) report, Strategies to Improve Cardiac Arrest Survival: A Time to Act (2015). The AHA recognizes the unique opportunity created by the report to meaningfully advance the objectives of improving outcomes for sudden cardiac arrest. For decades, the AHA has focused on the goal of reducing morbidity and mortality from cardiovascular disease though robust support of basic, translational, clinical, and population research. The AHA also has developed a rigorous process using the best available evidence to develop scientific, advisory, and guideline documents. These core activities of development and dissemination of scientific evidence have served as the foundation for a broad range of advocacy initiatives and programs that serve as a foundation for advancing the AHA and IOM goal of improving cardiac arrest outcomes. In response to the call to action in the IOM report, the AHA is announcing 4 new commitments to increase cardiac arrest survival: (1) The AHA will provide up to $5 million in funding over 5 years to incentivize resuscitation data interoperability; (2) the AHA will actively pursue philanthropic support for local and regional implementation opportunities to increase cardiac arrest survival by improving out-of-hospital and in-hospital systems of care; (3) the AHA will actively pursue philanthropic support to launch an AHA resuscitation research network; and (4) the AHA will cosponsor a National Cardiac Arrest Summit to facilitate the creation of a national cardiac arrest collaborative that will unify the field and identify common goals to improve survival. In addition to the AHA's historic and ongoing commitment to improving cardiac arrest care and outcomes, these new initiatives are responsive to each of the IOM recommendations and demonstrate the AHA's leadership in the field. However, successful implementation of the IOM recommendations will require a timely response by all stakeholders identified in the report and a coordinated approach to achieve our common goal of improved cardiac arrest outcomes., (© 2015 American Heart Association, Inc.)

Alpha-1 antitrypsin (AAT) has broad anti-inflammatory and immunomodulating properties in addition to inhibiting serine proteases. Administration of human plasma-derived AAT is protective in models of acute myocardial infarction in mice. The objective of this study was to determine the safety and tolerability of human plasma-derived AAT and its effects on the acute inflammatory response in non-AAT deficient patients with ST-segment elevation myocardial infarction (STEMI). Ten patients with acute STEMI were enrolled in an open-label, single-arm treatment study of AAT at 60 mg/kg infused intravenously within 12 hours of admission and following standard of care treatment. C-reactive protein (CRP) and plasma AAT levels were determined at admission, 72 hours, and 14 days, and patients were followed clinically for 12 weeks for the occurrence of new onset heart failure, recurrent myocardial infarction, or death. Twenty patients with STEMI enrolled in previous randomized trials with identical inclusion and/or exclusion criteria, but who received placebo, served as historical controls. Prolastin C was well tolerated and there were no in-hospital adverse events. Compared with historical controls, the area under the curve of CRP levels was significantly lower 14 days after admission in the Prolastin C group (75.9 [31.4 to 147.8] vs 205.6 [78.8 to 410.9] mg/l, p = 0.048), primarily due to a significant blunting of the increase occurring between admission and 72 hours (delta CRP +1.7 [0.2 to 9.4] vs +21.1 [3.1 to 38.0] mg/l, p = 0.007). Plasma AAT levels increased from admission (149 [116 to 189]) to 203 ([185 to 225] mg/dl) to 72 hours (p = 0.005). In conclusion, a single administration of Prolastin C in patients with STEMI is well tolerated and is associated with a blunted acute inflammatory response., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The development of advanced life support (ALS) termination of resuscitation (TOR) guidelines for out-of-hospital cardiac arrest (OHCA) seeks to improve the efficiency of scarce pre-hospital resources. However, as pre-hospital treatment for OHCA evolves and survival improves, these TOR guidelines must be reevaluated in the contemporary context of emergency medical services (EMS) providing access to advanced resuscitation care., Methods: Retrospective review of all adult (>18 years old), non-traumatic, OHCA patients (defined as patients with absence of pulse who received either CPR and/or defibrillation) treated by EMS in Richmond, VA, from January 1, 2009 to December 31, 2010. In addition to standard ALS, intra-arrest cold saline, mechanical CPR, and transportation to a comprehensive post-resuscitation center (CPRC) was provided. Patient treatment and outcomes were recorded via prehospital patient care reports and data were evaluated against previously established criteria for termination of resuscitation in an ALS EMS system. According to the aforementioned previously described criteria for TOR, patients meeting a single criterion for transport are recommended to be transported emergently to a comprehensive post-resuscitation care facility. Conversely, patients failing to meet any of the TOR criteria can be presumed to be expired without exception. Survival at 180 days was presumed when death could not be verified from publically reportable sources., Results: Of the 322 OHCA patients enrolled, the majority were male (59%), unwitnessed (52%), received no bystander CPR (67%), and presented in a non-shockable initial rhythm (79%), with an average age of 62.5 years. Overall survival was 17%, 14%, 12%, and 11% at 7, 14, 30, and 180 days, respectively. Of the 75 patients for which TOR guidelines recommended termination, none survived yielding both 100% specificity (95% CI 100-92.8%) and positive predictive value (95% CI 100-94.1%). However, TOR guidelines recommended transport of 208 of the 283 patients who died within 30 days, resulting in a sensitivity of 26.5% (95% CI 34.5-23.4%)., Conclusion: The TOR guidelines continue to have a reliable positive predictive value for death even in the setting of advanced EMS resuscitation methods and access to a CPRC. However, as the potential for survival from OHCA improves, the efficiency gained from their use is impacted greatly., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To determine the utility of an artificial neural network (ANN) in predicting cardiovascular (CV) death in patients with heart failure (HF)., Background: ANNs use weighted inputs in multiple layers of mathematical connections in order to predict outcomes from multiple risk markers. This approach has not been applied in the context of cardiopulmonary exercise testing (CPX) to predict risk in patients with HF., Methods: 2635 patients with HF underwent CPX and were followed for a mean of 29 ± 30 months. The sample was divided randomly into ANN training and testing sets to predict CV mortality. Peak VO2, VE/VCO2 slope, heart rate recovery, oxygen uptake efficiency slope, and end-tidal CO2 pressure were included in the model. The predictive accuracy of the ANN was compared to logistic regression (LR) and a Cox proportional hazards (PH) score. A multi-layer feed-forward ANN was used and was tested with a single hidden layer containing a varying number of hidden neurons., Results: There were 291 CV deaths during the follow-up. An abnormal VE/VCO2 slope was the strongest predictor of CV mortality using conventional PH analysis (hazard ratio 3.04; 95% CI 2.2-4.2, p<0.001). After training, the ANN was more accurate in predicting CV mortality compared to LR and PH; ROC areas for the ANN, LR, and PH models were 0.72, 0.70, and 0.69, respectively. Age and BMI-adjusted odds ratios were 4.2, 2.6, and 2.9, for ANN, LR, and PH, respectively., Conclusion: An ANN model slightly improves upon conventional methods for estimating CV mortality risk using established CPX responses., (Published by Elsevier Ireland Ltd.)

Both commercial aviation and resuscitation are complex activities in which team members must respond to unexpected emergencies in a consistent, high quality manner. Lives are at stake in both activities and the two disciplines have similar leadership structures, standard setting processes, training methods, and operational tools. Commercial aviation crews operate with remarkable consistency and safety, while resuscitation team performance and outcomes are highly variable. This commentary provides the perspective of two physician-pilots showing how commercial aviation training, operations, and safety principles can be adapted to resuscitation team training and performance., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Aim: Neuromuscular blockade may improve outcomes in patients with acute respiratory distress syndrome. In post-cardiac arrest patients receiving therapeutic hypothermia, neuromuscular blockade is often used to prevent shivering. Our objective was to determine whether neuromuscular blockade is associated with improved outcomes after out-of-hospital cardiac arrest., Methods: A post hoc analysis of a prospective observational study of comatose adult (>18 years) out-of-hospital cardiac arrest at 4 tertiary cardiac arrest centers. The primary exposure of interest was neuromuscular blockade for 24h following return of spontaneous circulation and primary outcomes were in-hospital survival and functional status at hospital discharge. Secondary outcomes were evolution of oxygenation (PaO2:FiO2), and change in lactate. We tested the primary outcomes of in-hospital survival and neurologically intact survival with multivariable logistic regression. Secondary outcomes were tested with multivariable linear mixed-models., Results: A total of 111 patients were analyzed. In patients with 24h of sustained neuromuscular blockade, the crude survival rate was 14/18 (78%) compared to 38/93 (41%) in patients without sustained neuromuscular blockade (p=0.004). After multivariable adjustment, neuromuscular blockade was associated with survival (adjusted OR: 7.23, 95% CI: 1.56-33.38). There was a trend toward improved functional outcome with neuromuscular blockade (50% versus 28%; p=0.07). Sustained neuromuscular blockade was associated with improved lactate clearance (adjusted p=0.01)., Conclusions: We found that early neuromuscular blockade for a 24-h period is associated with an increased probability of survival. Secondarily, we found that early, sustained neuromuscular blockade is associated with improved lactate clearance., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The purpose of this analysis was to evaluate the prognostic characteristics of peak oxygen consumption (Vo2) and the minute ventilation/carbon dioxide (VE/Vco2) slope of different peak respiratory exchange ratios (RERs) obtained from cardiopulmonary exercise testing in patients with heart failure (HF)., Background: For patients with HF, peak Vo2 and the VE/Vco2 slope are used for assessing prognosis. Peak Vo2 is assessed in association with peak RER ≥1.10, indicating maximal effort and prognostic sensitivity. Conversely, the VE/Vco2 slope provides effort-independent prognostic discrimination., Methods: Patients with HF scheduled to undergo cardiopulmonary exercise testing were enrolled. Patients were subclassified by peak RER (RER <1.00, RER 1.00 to 1.04, RER 1.05 to 1.09, RER ≥1.10) and followed for up to 3 years for major cardiac-related events (death, left ventricular assist device implantation, or cardiac transplantation)., Results: Included were 1,728 patients with HF (75% males; 40% ischemic etiology; age: 55 ± 14 years; left ventricular ejection fraction: 28 ± 10%). Two hundred seventy major events occurred, with no proportional differences across the RER subgroups. Multivariate Cox regression analysis indicated that the VE/Vco2 slope and peak Vo2 remained prognostic within each subgroup; the VE/Vco2 slope remained the strongest predictor. Receiver-operating characteristic analysis demonstrated equitable prognostic cutoffs for the VE/Vco2 slope (range: 34.9 to 35.7; area under the curve [AUC] range: 0.69 to 0.75) and peak Vo2 (range: 13.8 to 14.0 ml·kg(-1)·min(-1); AUC range: 0.68 to 0.75)., Conclusions: Peak Vo2 provided a sensitive assessment of prognosis in patients with HF in all RER subgroups. The VE/Vco2 slope provided greater prognostic discrimination in all RER subgroups. Clinical consideration may be warranted for patients with low RER, low peak Vo2, and an elevated VE/Vco2 slope., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Heart rate recovery (HRR) has been observed to be a significant prognostic measure in patients with heart failure (HF). However, the prognostic value of HRR has not been examined in regard to the level of patient effort during exercise testing. Using the peak respiratory exchange ratio (RER) and a large multicenter HF database we examined the prognostic utility of HRR., Methods: Cardiopulmonary exercise testing (CPX) was performed in 806 HF patients who then underwent an active cool-down of at least 1 min. Peak oxygen consumption (VO2), ventilatory efficiency (VE/VCO2 slope), and peak RER were determined with subjects categorized into subgroups according to peak RER (<1.00, 1.00-1.09, ≥ 1.10). HRR was defined as the difference between heart rate at peak exercise and 1 min following test termination. Patients were followed for major cardiac events for up to four years post-CPX., Results: There were 163 major cardiac events (115 deaths, 20 left ventricular assist device implantations, and 28 transplantations) during the four year tracking period. Univariate Cox regression analysis results identified HRR as a significant (p<0.05) univariate predictor of adverse events regardless of the RER achieved. Multivariate Cox regression analysis in the overall group revealed that the VE/VCO2 slope was the strongest predictor of adverse events (chi-square: 110.9, p<0.001) with both HRR (residual chi-square: 16.7, p<0.001) and peak VO2 (residual chi-square: 10.4, p<0.01) adding significant prognostic value., Conclusions: HRR after symptom-limited exercise testing performed at sub-maximal efforts using RER to categorize level of effort is as predictive as HRR after maximal effort in HF patients., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Identify the occurrence rate of post-arrest psychological distress; evaluate methodological approaches; suggest future research priorities; address clinical implications., Methods: The electronic databases PubMed/MEDLINE and PsychInfo/APA PsycNET were utilized to search for terms including 'Cardiac Arrest', 'Therapeutic Hypothermia' and 'Depression', 'Anxiety', 'Quality of Life', 'Posttraumatic Stress Disorder (PTSD)', 'Psychological Outcomes', 'Hospital Anxiety and Depression Scale (HADS)', and 'Beck Depression Inventory (BDI)'., Results: High rates of psychological distress have been reported after OHCA. Specifically, incidence rates of depression have ranged from 14% to 45%; anxiety rates have ranged from 13% to 61%; PTSD rates reportedly range from 19% to 27%. Variability between studies is likely attributable to methodological variations relating to measures used, time since arrest, and research setting., Discussion: Given the occurrence rate of psychological distress after OHCA, psychological screening and early intervention seems indicated in the cardiac arrest population. Further studies are needed to better establish occurrence rates in both inpatient and outpatient settings, determine appropriate measures and normative cut off scores, and decide on the most appropriate method of intervention., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: To determine the impact of cardiorespiratory fitness (FIT) on survival in relation to the obesity paradox in patients with systolic heart failure (HF)., Patients and Methods: We studied 2066 patients with systolic HF (body mass index [BMI] ≥18.5 kg/m(2)) between April 1, 1993 and May 11, 2011 (with 1784 [86%] tested after January 31, 2000) from a multicenter cardiopulmonary exercise testing database who were followed for up to 5 years (mean ± SD, 25.0±17.5 months) to determine the impact of FIT (peak oxygen consumption <14 vs ≥14 mL O2 ∙ kg(-1) ∙ min(-1)) on the obesity paradox., Results: There were 212 deaths during follow-up (annual mortality, 4.5%). In patients with low FIT, annual mortality was 8.2% compared with 2.8% in those with high FIT (P<.001). After adjusting for age and sex, BMI was a significant predictor of survival in the low FIT subgroup when expressed as a continuous (P=.03) and dichotomous (<25.0 vs ≥25.0 kg/m(2)) (P=.01) variable. Continuous and dichotomous BMI expressions were not significant predictors of survival in the overall and high FIT groups after adjusting for age and sex. In patients with low FIT, progressively worse survival was noted with BMI of 30.0 or greater, 25.0 to 29.9, and 18.5 to 24.9 (log-rank, 11.7; P=.003), whereas there was no obesity paradox noted in those with high FIT (log-rank, 1.72; P=.42)., Conclusion: These results indicate that FIT modifies the relationship between BMI and survival. Thus, assessing the obesity paradox in systolic HF may be misleading unless FIT is considered., (Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Cardiopulmonary exercise test (CPX) responses are strong predictors of outcomes in patients with heart failure. We recently developed a CPX score that integrated the additive prognostic information from CPX. The purpose of this study was to validate the score in a larger, independent sample of patients., Methods and Results: A total of 2625 patients with heart failure underwent CPX and were followed for cardiovascular (CV) mortality and major CV events (death, transplantation, left ventricular assist device implantation). Net reclassification improvement (NRI) for the score and each of its components were determined at 3 years. The VE/VCO2 slope was the strongest predictor of risk and was attributed a relative weight of 7, with weighted scores for abnormal heart rate recovery, oxygen uptake efficiency slope, end-tidal CO2 pressure, and peak VO2 having scores of 5, 3, 3, and 2, respectively. A summed score of >15 was associated with an annual mortality rate of 12.2% and a relative risk >9 for total events, whereas a score of <5 was associated with an annual mortality rate of 1.2%. The composite score was the most accurate predictor of CV events among all CPX responses considered (C indexes, 0.70 for CV mortality and 0.72 for the composite outcome). Each component of the score provided significant NRI compared with peak VO2 (category-free NRI, 0.61-0.77), and the score provided significant NRI above clinical risk factors for both CV events and mortality (NRI, 0.63 and 0.65 for CPX score compared with clinical variables alone)., Conclusions: These results validate the application of a simple, integrated multivariable score based on readily available CPX responses.

Objectives: To determine the rate of appropriate documentation of endotracheal tube (ET) position confirmation in the American Heart Association's Get With the Guidelines-Resuscitation (GWTG-R) and to determine whether outcomes of patients who experience in-hospital cardiac arrest differ in relation to documentation rate., Design: Analysis of data from the GWTG-R, a prospective observational registry of in-hospital cardiac arrest and resuscitation., Setting: Database containing clinical information from the 507 hospitals participating in the GWTG-R., Patients: Adults resuscitated after in-hospital cardiac arrest., Measurements: The rate of appropriate documentation of ET position confirmation, defined as the use of capnography or an esophageal detector device (EDD); relationship between appropriate documentation of ET position confirmation and return of spontaneous circulation (ROSC) or survival to hospital discharge. Proportions with 95% CI are reported for prevalence data. Binary logistic regression was used to determine the relationship between appropriate documentation of ET position confirmation and outcome (ROSC, survival to hospital discharge). Adjusted and unadjusted odds ratios are reported., Main Results: Of the 176,054 patients entered into the GWTG-R database, 75,777 had an ET placed. For 13,263 (17.5%) of these patients, ET position confirmation was not documented in the chart. Auscultation alone was documented in 19,480 (25.7%) cases. Confirmation of ET position by capnography or EDD was documented in 43,034 (56.8%) cases. ROSC occurred in 39,063 (51.6%), and 13,474 (17.8%) survived to discharge. Patients whose ET position was confirmed by capnography or EDD were more likely to have ROSC (adjusted OR 1.229 [1.179, 1.282]) and to survive to hospital discharge (adjusted OR 1.093 [1.033, 1.157])., Conclusion: Documentation of ET position confirmation in patients who experience cardiac arrest is suboptimal. Appropriate documentation of ET position confirmation in the GWTG-R is associated with greater likelihood of ROSC and survival to hospital discharge., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The objective of the study is to assess the role of cardiopulmonary exercise testing (CPX) variables, including peak oxygen consumption (VO(2)), which is the most recognized CPX variable, the minute ventilation/carbon dioxide production (VE/VCO(2)) slope, the oxygen uptake efficiency slope (OUES), and exercise oscillatory ventilation (EOV) in a current meta-analysis investigating the prognostic value of a broader list of CPX-derived variables for major adverse cardiovascular events in patients with HF. A search for relevant CPX articles was performed using standard meta-analysis methods. Of the initial 890 articles found, 30 met our inclusion criteria and were included in the final analysis. The total subject populations included were as follows: peak VO(2) (7,319), VE/VCO(2) slope (5,044), EOV (1,617), and OUES (584). Peak VO(2), the VE/VCO(2) slope and EOV were all highly significant prognostic markers (diagnostic odds ratios ≥ 4.10). The OUES also demonstrated promise as a prognostic marker (diagnostic odds ratio = 8.08) but only in a limited number of studies (n = 2). No other independent variables (including age, ejection fraction, and beta-blockade) had a significant effect on the meta-analysis results for peak VO(2) and the VE/VCO(2) slope. CPX is an important component in the prognostic assessment of patients with HF. The results of this meta-analysis strongly confirm this and support a multivariate approach to the application of CPX in this patient population.

New variables obtained from cardiopulmonary exercise testing (CPX) have received attention in recent years, in particular the partial pressure of end-tidal carbon dioxide (P(ET) CO(2) ). The purpose of this study was to therefore comprehensively assess the ability of resting and exercise P(ET) CO(2) to predict major cardiac events in a heart failure (HF) cohort referred for CPX. A total of 963 patients with systolic HF undergoing symptom-limited CPX were included in the analysis. Resting and exercise P(ET) CO(2) along with other CPX variables were determined, and patients were followed for major adverse events. With regard to resting measures, multivariate analysis revealed that left ventricular ejection fraction was the most robust prognostic marker (P<.001) while resting P(ET) CO(2) added significant predictive value and was retained in the regression (P<.001). When exercise data were considered, the multivariate analysis revealed that the P(ET) CO(2) apex during exercise added predictive value and was retained (P<.05). In what is the largest evaluation of P(ET) CO(2) in the assessment of systolic HF patients to date, the authors substantiate prior (smaller) studies showing prognostic utility of P(ET) CO(2) , both as a resting measure (an important potential screening tool) and during exercise. These data add to the rationale to incorporate P(ET) CO(2) as a routine monitoring component in HF management., (© 2012 Wiley Periodicals, Inc.)

Background: Minute ventilation/CO(2) production (VE/Vco(2)) slope is an index determined by cardiopulmonary exercise testing, which incorporates pertinent cardiac, pulmonary, and skeletal muscle physiology into a substantive composite assessment. The VE/Vco(2) slope has many applications, including utility as a well-validated prognostic gauge for patients with heart failure (HF). In this study, we combine VE/Vco(2) slope with systolic blood pressure, creating a novel index that we labeled ventilatory power. Ventilatory power links the combined physiology inherent in the VE/Vco(2) slope to peripheral pressure, adding an additional dimension pertinent to HF assessment. Whereas the related concept of circulatory power links peak oxygen consumption with peak systolic blood pressure as a prognostic index, we hypothesized that ventilatory power would provide greater prognostic discrimination than VE/Vco2 slope, peak oxygen consumption, and circulatory power for patients with systolic HF., Methods and Results: Patients with systolic HF (left ventricular ejection fraction ≤35%) underwent symptom-limited cardiopulmonary exercise testing as part of routine management and were followed for up to 4 years for major cardiac events (mortality, left ventricular assist device implantation, and heart transplantation). Eight hundred seventy-five patients with HF (left ventricular ejection fraction, 26±9%; mean age, 55±14) were studied. Cardiopulmonary exercise testing indices peak oxygen consumption, VE/Vco(2) slope, circulatory power, and ventilatory power were all predictive of cardiac events (P<0.001). Multivariate analysis demonstrated that ventilatory power was the strongest indicator of prognosis., Conclusions: Although circulatory power and traditional cardiopulmonary exercise testing parameters can be used to predict prognosis among patients with HF, ventilatory power provides relatively greater prognostic discrimination and may constitute a relatively more useful composite tool.

Introduction: While the medical management strategy for patients with heart failure (HF) has dramatically changed, cardiopulmonary exercise testing (CPX) procedures and the data obtained have remained relatively stable. We are unaware of any previous investigation that has assessed differences in the prognostic utility of CPX in HF according to time period, reflecting differences in the clinical management of systolic HF., Methods: Subjects (n = 381) underwent CPX between April 1, 1993, and December 31, 2005, and the remaining 511 were tested between January 1, 2006, and October 28, 2010. Peak oxygen uptake ((Equation is included in full-text article.)O2) and the minute ventilation/carbon dioxide production ((Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2) slope were ascertained for all tests., Results: Both the (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 slope and peak (Equation is included in full-text article.)O2 were strong univariate predictors of adverse events in both subgroups. In the multivariate analysis, the (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 slope was the strongest predictive marker while peak (Equation is included in full-text article.)O2 added predictive value and was retained in the regression for all scenarios. In subjects undergoing CPX before 2006, a (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 slope 45 or greater and a peak (Equation is included in full-text article.)O2 of less than 10 mL · kg · min generated a hazard ratio of 4.2 (95% CI: 1.9-9.1, P < .001) when considering only mortality as an endpoint. In subjects undergoing CPX after 2006, a (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 slope 45 or greater and a peak (Equation is included in full-text article.)O2 of less than 10 mL · kg · min generated a hazard ratio of 8.2 (95% CI: 4.7-14.3, P < .001) when considering only mortality as an endpoint., Conclusion: The results of this study indicate that CPX continues to be a valuable clinical assessment in the present-day HF management.