Impact of center volume on in-hospital mortality in adult patients with out­of­hospital cardiac arrest resuscitated using extracorporeal cardiopulmonary resuscitation: a secondary analysis of the SAVE-J II study.

Recently, patients with out-of-hospital cardiac arrest (OHCA) refractory to conventional resuscitation have started undergoing extracorporeal cardiopulmonary resuscitation (ECPR). However, the mortality rate of these patients remains high. This study aimed to clarify whether a center ECPR volume was associated with the survival rates of adult patients with OHCA resuscitated using ECPR. This was a secondary analysis of a retrospective multicenter registry study, the SAVE-J II study, involving 36 participating institutions in Japan. Centers were divided into three groups according to the tertiles of the annual average number of patients undergoing ECPR: high-volume (≥ 21 sessions per year), medium-volume (11-20 sessions per year), or low-volume (< 11 sessions per year). The primary outcome was survival rate at the time of discharge. Patient characteristics and outcomes were compared among the three groups. Moreover, a multivariable-adjusted logistic regression model was applied to study the impact of center ECPR volume. A total of 1740 patients were included in this study. The center ECPR volume was strongly associated with survival rate at the time of discharge; furthermore, survival rate was best in high-volume compared with medium- and low-volume centers (33.4%, 24.1%, and 26.8%, respectively; P = 0.001). After adjusting for patient characteristics, undergoing ECPR at high-volume centers was associated with an increased likelihood of survival compared to middle- (adjusted odds ratio 0.657; P = 0.003) and low-volume centers (adjusted odds ratio 0.983; P = 0.006). The annual number of ECPR sessions was associated with favorable survival rates and lower complication rates of the ECPR procedure.Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041577 (unique identifier: UMIN000036490).

External validation of the rCAST for patients after in-hospital cardiac arrest: a multicenter retrospective observational study.

No established predictive or risk classification tool exists for the neurological outcomes of post-cardiac arrest syndrome (PCAS) in patients with in-hospital cardiac arrest (IHCA). This study aimed to investigate whether the revised post-cardiac arrest syndrome for therapeutic hypothermia score (rCAST), which was developed to estimate the prognosis of PCAS patients with out-of-hospital cardiac arrest (OHCA), was applicable to patients with IHCA. A retrospective, multicenter observational study of 140 consecutive adult IHCA patients admitted to three intensive care units. The area under the receiver operating characteristic curves (AUCs) of the rCAST for poor neurological outcome and mortality at 30 days were 0.88 (0.82-0.93) and 0.83 (0.76-0.89), respectively. The sensitivity and specificity of the risk classification according to rCAST for poor neurological outcomes were 0.90 (0.83-0.96) and 0.67 (0.55-0.79) for the low, 0.63 (0.54-0.74) and 0.67 (0.55-0.79) for the moderate, and 0.27 (0.17-0.37) and 1.00 (1.00-1.00) for the high-severity grades. All 22 patients classified with a high-severity grade showed poor neurological outcomes. The rCAST showed excellent predictive accuracy for neurological prognosis in patients with PCAS after IHCA. The rCAST may be useful as a risk classification tool for PCAS after IHCA.

Effect of prehospital high-dose glucocorticoid on hemodynamics in patients resuscitated from out-of-hospital cardiac arrest: a sub-study of the STEROHCA trial.

BACKGROUND: Following resuscitated out-of-hospital cardiac arrest (OHCA), inflammatory markers are significantly elevated and associated with hemodynamic instability and organ dysfunction. Vasopressor support is recommended to maintain a mean arterial pressure (MAP) above 65 mmHg. Glucocorticoids have anti-inflammatory effects and may lower the need for vasopressors. This study aimed to assess the hemodynamic effects of prehospital high-dose glucocorticoid treatment in resuscitated comatose OHCA patients. METHODS: The STEROHCA trial was a randomized, placebo-controlled, phase 2 trial comparing one prehospital injection of methylprednisolone 250 mg with placebo immediately after resuscitated OHCA. In this sub-study, we included patients who remained comatose at admission and survived until intensive care unit (ICU) admission. The primary outcome was cumulated norepinephrine use from ICU admission until 48 h reported as mcg/kg/min. Secondary outcomes included hemodynamic status characterized by MAP, heart rate, vasoactive-inotropic score (VIS), and the VIS/MAP-ratio as well as cardiac function assessed by pulmonary artery catheter measurements. Linear mixed-model analyses were performed to evaluate mean differences between treatment groups at all follow-up times. RESULTS: A total of 114 comatose OHCA patients were included (glucocorticoid: n = 56, placebo: n = 58) in the sub-study. There were no differences in outcomes at ICU admission. From the time of ICU admission up to 48 h post-admission, patients in the glucocorticoid group cumulated a lower norepinephrine use (mean difference - 0.04 mcg/kg/min, 95% CI - 0.07 to - 0.01, p = 0.02). Moreover, after 12-24 h post-admission, the glucocorticoid group demonstrated a higher MAP with mean differences ranging from 6 to 7 mmHg (95% CIs from 1 to 12), a lower VIS (mean differences from - 4.2 to - 3.8, 95% CIs from - 8.1 to 0.3), and a lower VIS/MAP ratio (mean differences from - 0.10 to - 0.07, 95% CIs from - 0.16 to - 0.01), while there were no major differences in heart rate (mean differences from - 4 to - 3, 95% CIs from - 11 to 3). These treatment differences between groups were also present 30-48 h post-admission but to a smaller extent and with increased statistical uncertainty. No differences were found in pulmonary artery catheter measurements between groups. CONCLUSIONS: Prehospital treatment with high-dose glucocorticoid was associated with reduced norepinephrine use in resuscitated OHCA patients. TRIAL REGISTRATION: EudraCT number: 2020-000855-11; submitted March 30, 2020. URL: https://www. CLINICALTRIALS: gov ; Unique Identifier: NCT04624776.

Changes in temporal muscle dimensions and their clinical impact in out-of-hospital cardiac arrest survivors.

Objective: This study investigates temporal muscle atrophy in out-of-hospital cardiac arrest patients post-resuscitation, seeking associations with neurological outcomes and factors associated with atrophy. Methods: Using data from six Japanese intensive care units, adult patients' post-resuscitation who underwent head computed tomography scans on admission and two to five days post-admission were assessed. Temporal muscle area, thickness, and density were quantified from a single cross-sectional image. Patients were categorized into 'atrophy' or 'no atrophy' groups based on median daily temporal muscle atrophy rates. The primary outcome was changes in temporal muscle dimensions between admission and follow-up two to five days later. Secondary outcomes included assessing the impact of temporal muscle atrophy on 30-day survival, as well as identifying any clinical factors associated with temporal muscle atrophy. Results: A total of 185 patients were analyzed. Measurements at follow-up revealed significant decreases in temporal muscle area (214 vs. 191 mm2, p < 0.001), thickness (4.9 vs. 4.7 mm, p < 0.001), and density (46 vs. 44 HU, p < 0.001) compared to those at admission. The median daily rate for temporal muscle area atrophy was 2.0% per day. There was no significant association between temporal muscle atrophy and 30-day survival (hazard ratios, 0.71; 95% CI, 0.41-1.23, p = 0.231). Multivariable logistic regression found no clinical factors significantly associated with temporal muscle atrophy. Conclusions: Temporal muscle atrophy in post-resuscitation patients occurs rapidly at 2.0% per day. However, there was no significant association with 30-day mortality or any identified clinical factors. Further investigation into its long-term functional implications is warranted.

Cardiac power output is associated with cardiovascular related mortality in the ICU in post-cardiac arrest patients.

AIM: Although brain injury is the main determinant of poor outcome following cardiac arrest (CA), cardiovascular failure is the leading cause of death within the first days after CA. However, it remains unclear which hemodynamic parameter is most suitable for its early recognition. We investigated the association of cardiac power output (CPO) with early mortality in intensive care unit (ICU) after CA and with mortality related to post-CA cardiovascular failure. METHODS: Retrospective analysis of adult comatose survivors of CA admitted to the ICU of a University Hospital. Exclusion criteria were treatment with extracorporeal cardiopulmonary resuscitation, ECMO or intra-aortic balloon pump. We retrieved CA characteristics; we recorded mean arterial pressure, cardiac output, CPO (as derived parameter) and the vasoactive-inotropic score for the first 72 hours after ROSC, at intervals of 8 hours. ICU death was defined as related to post-CA cardiovascular failure when death occurred as a direct consequence of shock, secondary CA or fatal arrhythmia, or related to neurological injury if this led to withdrawal of life-sustaining therapy or brain death. RESULTS: Among the 217 patients (median age 66 years, 65% male, 61.8% out-of-hospital CA), 142 (65.4%) died in ICU: 99 (69.7%) patients died from neurological injury and 43 (30.3%) from cardiovascular-related causes. Comparing the evolution over time of CPO between survivors and non-survivors, a statistically significant difference was found only at +8 hours after CA (p = 0.0042). In multivariable analysis, CPO at 8-hour was significantly associated with cardiovascular-related mortality (p = 0.007). CONCLUSIONS: In post-CA patients, the 8-hour CPO is an independent factor associated with ICU cardiovascular-related mortality.

Multiorgan failure in patients after out of hospital resuscitation: a retrospective single center study.

BACKGROUND: Information on extracerebral system dysfunction is important for assessing the needs of critically ill patients after cardiac arrest. AIMS: To describe the prevalence of organ dysfunction and patient severity after out of hospital cardiac arrest (OHCA) using scores commonly used in intensive care and the association between these and mortality. METHODS: Retrospective analysis of observational data collected in real time in a tertiary medical center where care withdrawal is mostly illegal. Adult patients after nontraumatic OHCA with ROSC who survived for more than two hours were included. Primary outcome-prevalence of organ failure, based on common definitions for organ dysfunction, in the 1 days of hospitalization. Secondary outcomes-rates of survival to hospital discharge and survival with a good neurological outcome (CPC 1 or 2), and associations between organ dysfunction SOFA and APACHE-II scores and outcomes. Associations were assessed using fisher's exact test for categorical variables and Mann-Whitney and T test for continuous variables. Multivariable models were also constructed for all measurements showing associations in previous tests. For severity scores compatibility, we used receiver-operating curve (ROC). RESULTS: Overall 369 patients (median age 75 years, 65% male) were included. Most arrests (64%) were witnessed, bystander CPR was provided in 15%. Median call to arrival time was 4 min. The presenting rhythm was asystole in 48% and VT/VF in 22%. Cardiovascular causes of arrest predominated (48%, n = 178). The median length of hospitalization was 5 days. Overall 28% of the patients (n = 98) survived to hospital discharge, mostly with a good neurological status (18.7%, n = 57). The rates of organ dysfunction were: hemodynamic instability 65% (n = 247), respiratory dysfunction 94% (n = 296), kidney dysfunction 70% (n = 259), hepatic dysfunction 14% (n = 50). The median SOFA score on day 1 was 9 and the median APACHE II score was 34. Modeling was limited by missing data. Neurological dysfunction (i.e. GCS and seizures) and kidney injury were consistently correlated with the outcomes in the multivariable models. Severity of critical illness assessed by above scoring systems correlated with mortality (all ROC curves had an AUC ranging between 0.728 and 0.849). CONCLUSIONS: Multiorgan failure is common after ROSC (1-4). Therefore, the management of patients after ROSC may require advanced multidisciplinary care. Scores describing the severity of critical illness should be routinely reported in resuscitation research. Our unique setting where withdrawal of care is illegal, allows assessment of extremely ill patients and may assist in defining margins for futility.

External Validation of the CAST and rCAST Score in Patients With Out-of-Hospital Cardiac Arrest Who Underwent Extracorporeal Cardiopulmonary Resuscitation: A Secondary Analysis of the SAVE-J II Study.

BACKGROUND: Risk stratification is important in patients with post-cardiac arrest syndrome. The Post-Cardiac Arrest Syndrome for Therapeutic Hypothermia (CAST) and revised CAST (rCAST) scores have been well validated for predicting neurological outcomes, particularly for conventionally resuscitated patients with post-cardiac arrest syndrome. However, no studies have evaluated patients undergoing extracorporeal cardiopulmonary resuscitation. METHODS AND RESULTS: Adult patients with out-of-hospital cardiac arrest who underwent extracorporeal cardiopulmonary resuscitation were analyzed in this retrospective observational multicenter cohort study. We validated the accuracy of the CAST/rCAST scores for predicting neurological outcomes at 30 days. Moreover, we compared the predictive performance of these scores with the TiPS65 risk score derived from patients with out-of-hospital cardiac arrest who were resuscitated using extracorporeal cardiopulmonary resuscitation. A total of 1135 patients were analyzed. The proportion of patients with favorable neurological outcomes was 16.6%. In the external validation, the area under the receiver operating characteristic curve of the CAST score was significantly higher than that of the rCAST score (area under the receiver operating characteristic curve 0.677 versus 0.603; P<0.001), but there was no significant difference with that of the TiPS65 score (versus 0.633; P=0.154). Both CAST/rCAST risk scores showed good calibration (Hosmer-Lemeshow test: P=0.726 and 0.674), and the CAST score showed significantly better predictability in net reclassification compared with the rCAST (P<0.001) and TiPS65 scores (P=0.001). CONCLUSIONS: The prognostic accuracy of the CAST score was significantly better than that of other risk scores in net reclassification. The CAST score may help to predict neurological outcomes in patients with out-of-hospital cardiac arrest who undergo extracorporeal cardiopulmonary resuscitation. However, the predictive value of the CAST score was not sufficiently high for clinical application. REGISTRATION: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041577; Unique identifier: UMIN000036490.

Prediction of the neurological outcomes post-cardiac arrest: A prospective validation of the CAST and rCAST.

INTRODUCTION: The neurologic prognosis of out-of-hospital cardiac arrest (OHCA) patients in whom return of spontaneous circulation (ROSC) is achieved remains poor. The aim of this study was to externally and prospectively validate two scoring systems developed by us: the CAST score, a scoring system to predict the neurological prognosis of OHCA patients undergoing targeted temperature management (TTM), and a simplified version of the same score developed for improved ease of use in clinical settings, the revised CAST (rCAST) score. METHODS: This study was a prospective, multicenter, observational study conducted using the SOS KANTO 2017 registry, an OHCA registry involving hospitals in the Kanto region (including Tokyo) of Japan. The primary outcome was favorable neurological outcome (defined as Cerebral Performance Category score of 1 or 2) at 30 days and the secondary outcomes were favorable neurological outcome at 90 days and survival at 30 and 90 days. The predictive accuracies of the original CAST (oCAST) and rCAST scores were evaluated by using area under the receiver operating characteristic curve (AUC). RESULTS: Of 9909 OHCA patients, 565 showed ROSC and received TTM. Of these, we analyzed the data of 259 patients in this study. The areas under the receiver operating characteristic curve (AUCs) of the oCAST and rCAST scores for predicting a favorable neurological outcome at 30 days were 0.86 and 0.87, respectively, and those for predicting a favorable neurological outcome at 90 days were 0.87 and 0.88, respectively. The rCAST showed a higher predictive accuracy for the neurological outcome as compared with the NULL-PLEASE score. The patients with a favorable neurological outcome who had been classified into the high severity group based on the rCAST tended to have hypothermia at hospital arrival and to not show any signs of loss of gray-white matter differentiation on brain CT. Neurological function at 90 days was correlated with the rCAST (r = 0.63, p < 0.001). CONCLUSIONS: rCAST showed high predictive accuracy for the neurological prognosis of OHCA patients managed by TTM, comparable to that of the oCAST score. The scores on the rCAST were strongly correlated with the neurological functions at 90 days, implying that the rCAST is a useful scale for assessing the severity of brain injury after cardiac arrest.

Impact of blood pressure targets on central hemodynamics during intensive care after out-of-hospital cardiac arrest.

OBJECTIVES: The aim was to investigate the advanced hemodynamic effects of the two MAP-targets during intensive care on systemic hemodynamics in comatose patients after cardiac arrest. DESIGN: Secondary analysis of a randomized controlled trial. SETTING: Primary vasopressor used was per protocol norepinephrine. Hemodynamic monitoring was done with pulmonary artery catheters (PAC) and measurements were made on predefined time points. The primary endpoint of this substudy was the difference in cardiac index within 48 h from a repeated measurements-mixed model. Secondary endpoints included systemic vascular resistance index (SVRI), heart rate, and stroke volume index. PATIENTS: Comatose survivors after out-of-hospital cardiac arrest. INTERVENTIONS: The "Blood pressure and oxygenations targets after out-of-hospital cardiac arrest (BOX)"-trial was a randomized, controlled, double-blinded, multicenter-study comparing targeted mean arterial pressure (MAP) of 63 mmHg (MAP63) vs 77 mmHg (MAP77). MEASUREMENTS AND MAIN RESULTS: Among 789 randomized patients, 730 (93%) patients were included in the hemodynamic substudy. From PAC-insertion (median 1 hours after ICU-admission) and the next 48 hours, the MAP77-group received significantly higher doses of norepinephrine (mean difference 0.09 µg/kg/min, 95% confidence interval (CI) 0.07-0.11, pgroup < 0.0001). Cardiac index was significantly increased (0.20 L/min/m2 (CI 0.12-0.28), pgroup < 0.0001) as was SVRI with an overall difference of (43 dynes m2/s/cm5 (CI 7-79); pgroup = 0.02). Heart rate was increased in the MAP77-group (4 beats/minute; CI 2-6, pgroup < 0.003), but stroke volume index was not (pgroup = 0.10). CONCLUSIONS: Targeted MAP at 77 mmHg compared to 63 mmHg resulted in a higher dose of norepinephrine, increased cardiac index and SVRI. Heart rate was also increased, but stroke volume index was not affected by a higher blood pressure target.

Wolf Creek XVII Part 1: The future of cardiac arrest resuscitation.

The Wolf Creek Conference, initiated in 1975, is a well-established tradition providing a unique forum for robust intellectual exchange between thought leaders and scientists from academia and industry focused on advancing the science and practice of cardiac arrest resuscitation. The Wolf Creek XVII Conference was hosted by the Max Harry Weil Institute for Critical Care Research and Innovation in Ann Arbor, Michigan, USA on June 15-17, 2023. A major focus of the conference proceedings was to identify and prioritize the knowledge gaps, barriers to translation, and research priorities for six major domains in the field of resuscitation: (1) automated cardiac arrest diagnosis, (2) amplifying lay-responder response, (3) mobile AEDs, (4) physiology-guided CPR, (5) extracorporeal support, and (6) neuroprotection. In addition, industry scientists were given the opportunity to present and discuss cutting edge innovations. Finally, building off of the conference's theme of "The Future of Cardiac Arrest Resuscitation", the Weil Institute introduced the "Wolf Creek Innovator in Cardiac Arrest and Resuscitation Award" to recognize early career investigators who were challenging current paradigms in resuscitation science. Similar to the early Wolf Creek Conferences, the goal was to fuel active discussion and debate among leading experts to determine where future research efforts should be focused. This manuscript provides an overview of the Wolf Creek XVII conference, and the individual manuscripts within this special edition of Resuscitation Plus describe the conference proceedings and outcomes in more detail. It is our intent that these publications will provide a roadmap for important academic and commercial advances in the field of cardiac arrest resuscitation.

Prehospital high-dose methylprednisolone in resuscitated out-of-hospital cardiac arrest patients (STEROHCA): a randomized clinical trial.

PURPOSE: Patients who are successfully resuscitated following out-of-hospital cardiac arrest (OHCA) are still at a high risk of neurological damage and death. Inflammation and brain injury are components of the post-cardiac arrest syndrome, and can be assessed by systemic interleukin 6 (IL-6) and neuron-specific enolase (NSE). Anti-inflammatory treatment with methylprednisolone may dampen inflammation, thereby improving outcome. This study aimed to determine if prehospital high-dose methylprednisolone could reduce IL-6 and NSE in comatose OHCA patients. METHODS: The STEROHCA trial was a randomized, blinded, placebo-controlled, phase II prehospital trial performed at two cardiac arrest centers in Denmark. Resuscitated comatose patients with suspected cardiac etiology were randomly assigned 1:1 to a single intravenous injection of 250 mg methylprednisolone or placebo. The co-primary outcome was reduction of IL-6 and NSE-blood levels measured daily for 72 h from admission. The main secondary outcome was survival at 180 days follow-up. RESULTS: We randomized 137 patients to methylprednisolone (n = 68) or placebo (n = 69). We found reduced IL-6 levels (p < 0.0001) in the intervention group, with median (interquartile range, IQR) levels at 24 h of 2.1 pg/ml (1.0; 7.1) and 30.7 pg/ml (14.2; 59) in the placebo group. We observed no difference between groups in NSE levels (p = 0.22), with levels at 48 h of 18.8 ug/L (14.4; 24.6) and 14.8 ug/L (11.2; 19.4) in the intervention and placebo group, respectively. In the intervention group, 51 (75%) patients survived and 44 (64%) in the placebo group. CONCLUSION: Prehospital treatment with high-dose methylprednisolone to resuscitated comatose OHCA patients, resulted in reduced IL-6 levels after 24 h, but did not reduce NSE levels.

Wolf Creek XVII Part 2: The origin, evolution, and impact of the Wolf Creek Conference.

The Wolf Creek Conference is a seminal meeting of resuscitation researchers that has significantly influenced scientific advances and patient care in the field of cardiac arrest resuscitation over nearly half a century. Originating in 1975 at the Wolf Creek Lodge in Georgia, the conference was founded by Drs. James Elam, James Jude, and Peter Safar with the aim of improving clinical practices in cardiopulmonary resuscitation (CPR) by stimulating laboratory and clinical research. Over 17 conferences to date, the scope has broadened to encompass the growing field of resuscitation science, participation has expanded to include thought leaders and scientists from both academia and industry, and the proceedings have catalyzed numerous innovations in field. This narrative review highlights the genesis, objectives, proceedings, and impact of the Wolf Creek Conference from 1975 to the present.

Serial assessments of cardiac output and mixed venous oxygen saturation in comatose patients after out-of-hospital cardiac arrest.

AIM: To assess the association with outcomes of cardiac index (CI) and mixed venous oxygen saturation (SvO2) in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). METHODS: In the cohort study of 789 patients included in the "BOX"-trial, 565 (77%) patients were included in this hemodynamic substudy (age 62 ± 13 years, male sex 81%). Pulmonary artery catheters were inserted shortly after ICU admission. CI and SvO2 were measured as soon as possible in the ICU and until awakening or death. The endpoints were all-cause mortality at 1 year and renal failure defined as need for renal replacement therapy. RESULTS: First measured CI was median 1.7 (1.4-2.1) l/min/m2, and first measured SvO2 was median 67 (61-73) %. CI < median with SvO2 > median was present in 222 (39%), and low SvO2 with CI < median was present in 59 (11%). Spline analysis indicated that SvO2 value < 55% was associated with poor outcome. Low CI at admission was not significantly associated with mortality in multivariable analysis (p = 0.14). SvO2 was significantly inversely associated with mortality (hazard ratioadjusted: 0.91 (0.84-0.98) per 5% increase in SvO2, p = 0.01). SvO2 was significantly inversely associated with renal failure after adjusting for confounders (ORadjusted: 0.73 [0.62-0.86] per 5% increase in SvO2, p = 0.001). The combination of lower CI and lower SvO2 was associated with higher risk of mortality (hazard ratioadjusted: 1.54 (1.06-2.23) and renal failure (ORadjusted: 5.87 [2.34-14.73]. CONCLUSION: First measured SvO2 after resuscitation from OHCA was inversely associated with mortality and renal failure. If SvO2 and CI were below median, the risk of poor outcomes increased significantly. REGISTRATION: The BOX-trial is registered at clinicaltrials.gov (NCT03141099, date 2017-30-04, retrospectively registered).

Effect of adjuvant thiamine and ascorbic acid administration on the neurologic outcomes of out-of-hospital cardiac arrest patients: A before-and-after study.

AIM: This study aimed to evaluate the impact of early thiamine and ascorbic acid administration on the neurologic outcome in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM). METHODS: This before-and-after cohort study used data extracted from two hospitals of the Korean Hypothermia Network prospective registry. The treatment group incorporated patients enrolled from December 2019 to May 2021, that received intravenous thiamine (200 mg) and ascorbic acid (3 g) at 12-hour intervals for a total of six doses. The control group incorporated those enrolled from May 2018 to November 2019. The one-month good neurologic outcome, defined as a Cerebral Performance Category score ≤ 2, between the groups was evaluated using inverse probability of treatment weighting (IPTW). RESULTS: Among the 234 OHCA survivors with TTM, 102 were included in the treatment group and 132 were included in the control group. The one-month (31.4 % vs. 29.5 %, respectively; P = 0.76) good neurologic outcome rates did not differ between the treatment and control groups. After adjusting using the IPTW, vitamin supplementation was not associated with good neurologic outcome (odds ratio [OR], 1.134; 95 % confidence interval [CI], 0.644-1.999; P = 0.66). In subgroup analysis, vitamin administration was significantly associated with a good neurologic outcome in older (≥65 years) patients (adjusted OR, 5.53; 95 % CI, 1.21-25.23; P = 0.03). CONCLUSION: Adjuvant thiamine and ascorbic acid administration in OHCA survivors with TTM did not improve their neurologic outcome after one month. Further clinical trials are warranted.

Blood Pressure and Oxygen Targets on Kidney Injury After Cardiac Arrest.

BACKGROUND: Acute kidney injury (AKI) represents a common and serious complication to out-of-hospital cardiac arrest. The importance of post-resuscitation care targets for blood pressure and oxygenation for the development of AKI is unknown. METHODS: This is a substudy of a randomized 2-by-2 factorial trial, in which 789 comatose adult patients who had out-of-hospital cardiac arrest with presumed cardiac cause and sustained return of spontaneous circulation were randomly assigned to a target mean arterial blood pressure of either 63 or 77 mm Hg. Patients were simultaneously randomly assigned to either a restrictive oxygen target of a partial pressure of arterial oxygen (Pao2) of 9 to 10 kPa or a liberal oxygenation target of a Pao2 of 13 to 14 kPa. The primary outcome for this study was AKI according to KDIGO (Kidney Disease: Improving Global Outcomes) classification in patients surviving at least 48 hours (N=759). Adjusted logistic regression was performed for patients allocated to high blood pressure and liberal oxygen target as reference. RESULTS: The main population characteristics at admission were: age, 64 (54-73) years; 80% male; 90% shockable rhythm; and time to return of spontaneous circulation, 18 (12-26) minutes. Patients allocated to a low blood pressure and liberal oxygen target had an increased risk of developing AKI compared with patients with high blood pressure and liberal oxygen target (84/193 [44%] versus 56/187 [30%]; adjusted odds ratio, 1.87 [95% CI, 1.21-2.89]). Multinomial logistic regression revealed that the increased risk of AKI was only related to mild-stage AKI (KDIGO stage 1). There was no difference in risk of AKI in the other groups. Plasma creatinine remained high during hospitalization in the low blood pressure and liberal oxygen target group but did not differ between groups at 6- and 12-month follow-up. CONCLUSIONS: In comatose patients who had been resuscitated after out-of-hospital cardiac arrest, patients allocated to a combination of a low mean arterial blood pressure and a liberal oxygen target had a significantly increased risk of mild-stage AKI. No difference was found in terms of more severe AKI stages or other kidney-related adverse outcomes, and creatinine had normalized at 1 year after discharge. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03141099.

Rapid rewarming rate associated with favorable neurological outcomes in patients with post-cardiac arrest syndrome patients treated with targeted temperature management.

Aim: To determine whether the rewarming rate is associated with neurological outcomes in patients with post-cardiac arrest syndrome treated with targeted temperature management (TTM) at 34°C. Methods: We conducted a retrospective analysis of a nationwide cohort study of out-of-hospital cardiac arrest in Japan. Adult patients who experienced a return of spontaneous circulation and completed TTM at 34°C between June 2014 and December 2019 were divided equally into three groups (slow, moderate, and rapid) according to their rewarming rates from 34°C to 36°C. The rates of favorable neurological outcomes (Cerebral Performance Category of 1-2 after 30 days) were compared among the groups, and the adjusted odds ratios for a favorable neurological outcome were calculated for the groups. Results: We analyzed 348, 357, and 358 patients in the slow, moderate, and rapid groups, respectively. The periods of rewarming from 34°C to 36°C were 41.9 ± 10.5, 22.4 ± 1.8, and 12.2 ± 3.6 h, respectively. The number of favorable neurological outcomes after 30 days was 121 (34.8%), 125 (35.0%), and 147 (41.1%), respectively, with no significant differences among the three groups (p = 0.145). Rapid rewarming was independently associated with a favorable neurological outcome compared with slow rewarming (adjusted odds ratio 1.57 [95% confidence interval 1.04-2.37]; p = 0.031). Conclusions: Rapid rewarming after TTM at 34°C was associated with a more favorable neurological outcome than slow rewarming.

Comparison of Prognostic Performance between Procalcitonin and Procalcitonin-to-Albumin Ratio in Post Cardiac Arrest Syndrome.

(1) Background: Post-cardiac arrest syndrome (PCAS) is a type of global ischemic reperfusion injury that occurs after the return of spontaneous circulation (ROSC). The procalcitonin to albumin ratio (PAR) has been studied as an independent prognostic factor of various diseases. There are no previous studies of PAR in patients with PCAS. We assessed if PAR is more effective than procalcitonin (PCT) in predicting prognosis for patients with PCAS. (2) Methods: This retrospective cohort study included a total of 187 patients with PCAS after non-traumatic out-of-hospital cardiac arrest (OHCA) between January 2016 and December 2020. Multivariate logistic regression analysis was conducted to assess the association between PAR and PCAS prognosis. The predictive performance of PAR was compared with PCT via the receiver-operating characteristic (ROC) analysis and DeLong test.; (3) Results: PAR at 24 and 48 h after hospital admission were independently associated with one-month neurological outcome (OR: 1.167, 95% CI: 1.023-1.330; OR: 1.077, 95% CI: 1.012-1.146, p < 0.05). By ROC analysis, PAR showed better performance over PCT at 48 h after admission in predicting one-month CPC (0.763 vs. 0.772, p = 0.010). (4) Conclusions: Our findings suggest that PAR at 48 h after admission is more effective in predicting a one-month neurological outcome than PCT at 48 h after admission in patients with PCAS after OHCA.

Harnessing the therapeutic potential of mesenchymal stem cell-derived exosomes in cardiac arrest: Current advances and future perspectives.

BACKGROUND: Cardiac arrest (CA), characterized by sudden onset and high mortality rates, is one of the leading causes of death globally, with a survival rate of approximately 6-24%. Studies suggest that the restoration of spontaneous circulation (ROSC) hardly improved the mortality rate and prognosis of patients diagnosed with CA, largely due to ischemia-reperfusion injury. MAIN BODY: Mesenchymal stem cells (MSCs) exhibit self-renewal and strong potential for multilineage differentiation. Their effects are largely mediated by extracellular vesicles (EVs). Exosomes are the most extensively studied subgroup of EVs. EVs mainly mediate intercellular communication by transferring vesicular proteins, lipids, nucleic acids, and other substances to regulate multiple processes, such as cytokine production, cell proliferation, apoptosis, and metabolism. Thus, exosomes exhibit significant potential for therapeutic application in wound repair, tissue reconstruction, inflammatory reaction, and ischemic diseases. CONCLUSION: Based on similar pathological mechanisms underlying post-cardiac arrest syndrome involving various tissues and organs in many diseases, the review summarizes the therapeutic effects of MSC-derived exosomes and explores the prospects for their application in the treatment of CA.

Prevalence, reasons, and timing of decisions to withhold/withdraw life-sustaining therapy for out-of-hospital cardiac arrest patients with extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is rapidly becoming a common treatment strategy for patients with refractory cardiac arrest. Despite its benefits, ECPR raises a variety of ethical concerns when the treatment is discontinued. There is little information about the decision to withhold/withdraw life-sustaining therapy (WLST) for out-of-hospital cardiac arrest (OHCA) patients after ECPR. METHODS: We conducted a secondary analysis of data from the SAVE-J II study, a retrospective, multicenter study of ECPR in Japan. Adult patients who underwent ECPR for OHCA with medical causes were included. The prevalence, reasons, and timing of WLST decisions were recorded. Outcomes of patients with or without WLST decisions were compared. Further, factors associated with WLST decisions were examined. RESULTS: We included 1660 patients in the analysis; 510 (30.7%) had WLST decisions. The number of WLST decisions was the highest on the first day and WSLT decisions were made a median of two days after ICU admission. Reasons for WLST were perceived unfavorable neurological prognosis (300/510 [58.8%]), perceived unfavorable cardiac/pulmonary prognosis (105/510 [20.5%]), inability to maintain extracorporeal cardiopulmonary support (71/510 [13.9%]), complications (10/510 [1.9%]), exacerbation of comorbidity before cardiac arrest (7/510 [1.3%]), and others. Patients with WLST had lower 30-day survival (WLST vs. no-WLST: 36/506 [7.1%] vs. 386/1140 [33.8%], p < 0.001). Primary cerebral disorders as cause of cardiac arrest and higher severity of illness at intensive care unit admission were associated with WLST decisions. CONCLUSION: For approximately one-third of ECPR/OHCA patients, WLST was decided during admission, mainly because of perceived unfavorable neurological prognoses. Decisions and neurological assessments for ECPR/OHCA patients need further analysis.

Inflammatory response after out-of-hospital cardiac arrest-Impact on outcome and organ failure development.

BACKGROUND: Post-cardiac arrest syndrome that occurs in out-of-hospital cardiac arrest (OHCA) patients is characterized by inflammatory response. We conducted a scoping review of current evidence regarding several inflammatory markers' usefulness for assessment of patient outcome and illness severity. We also discuss the proposed underlying mechanisms leading to inflammatory response after OHCA. METHODS: We searched the MEDLINE, PubMed Central, Cochrane CENTRAL and Web of Science Core Collection databases with the following search terms: ("inflammation" OR "cytokines") AND "out-of-hospital cardiac arrest." Each inflammatory marker found was combined with "out-of-hospital cardiac arrest" using "AND" to find further relevant studies. We included original studies measuring inflammatory markers in adult OHCA patients that assessed their prognostic capabilities for mortality, neurological outcome, or organ failure severity. RESULTS: Fifty-nine studies met the inclusion criteria, covering in total 65 different markers. Interleukin-6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP) were the most studied markers, and they were associated with poor outcomes in 13/15, 13/14 and 11/17 studies, respectively. Based on area under the receiver operating characteristic curve (AUC) value, the time point of best discriminatory capacity for poor outcome was ICU admission for IL-6 (median AUC 0.78, range 0.71-0.98) and day one after OHCA for PCT (median AUC 0.84, range 0.61-0.98). Seven studies reported AUCs for CRP (range 0.52-0.76) with no measurement time point being superior to others. The association of IL-6 and PCT with outcome appeared stronger in studies with more severely ill patients. Studies reported conflicting results regarding each marker's association with organ failure severity. CONCLUSION: Inflammatory markers are potentially useful for early risk stratification after OHCA. PCT and IL-6 have moderate prognostic value during the first 24 h of the ICU stay. Predictive accuracy appears to be associated with the study overall event rate.