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Objective: The Efficacy of Inhaled Hydrogen on Neurologic Outcome Following Brain Ischemia During Post-Cardiac Arrest Care (HYBRID) II trial (jRCTs031180352) suggested that hydrogen inhalation may reduce post-cardiac arrest brain injury (PCABI). However, the combination of hypothermic target temperature management (TTM) and hydrogen inhalation on outcomes is unclear. The aim of this study was to investigate the combined effect of hydrogen inhalation and hypothermic TTM on outcomes after out-of-hospital cardiac arrest (OHCA)., Design: Post hoc analysis of a multicenter, randomized, controlled trial., Setting: Fifteen Japanese ICUs., Patients: Cardiogenic OHCA enrolled in the HYBRID II trial., Interventions: Hydrogen mixed oxygen (hydrogen group) versus oxygen alone (control group)., Measurements and Main Results: TTM was performed at a target temperature of 32-34°C (TTM32-TTM34) or 35-36°C (TTM35-TTM36) per the institutional protocol. The association between hydrogen + TTM32-TTM34 and 90-day good neurologic outcomes was analyzed using generalized estimating equations. The 90-day survival was compared between the hydrogen and control groups under TTM32-TTM34 and TTM35-TTM36, respectively. The analysis included 72 patients (hydrogen [ n = 39] and control [ n = 33] groups) with outcome data. TTM32-TTM34 was implemented in 25 (64%) and 24 (73%) patients in the hydrogen and control groups, respectively ( p = 0.46). Under TTM32-TTM34, 17 (68%) and 9 (38%) patients achieved good neurologic outcomes in the hydrogen and control groups, respectively (relative risk: 1.81 [95% CI, 1.05-3.66], p < 0.05). Hydrogen + TTM32-TTM34 was independently associated with good neurologic outcomes (adjusted odds ratio 16.10 [95% CI, 1.88-138.17], p = 0.01). However, hydrogen + TTM32-TTM34 did not improve survival compared with TTM32-TTM34 alone (adjusted hazard ratio: 0.22 [95% CI, 0.05-1.06], p = 0.06)., Conclusions: Hydrogen + TTM32-TTM34 was associated with improved neurologic outcomes after cardiogenic OHCA compared with TTM32-TTM34 monotherapy. Hydrogen inhalation is a promising treatment option for reducing PCABI when combined with TTM32-TTM34., Competing Interests: Dr. Tamura’s institution received funding from the Taiyo Nippon Sanso Corporation, the Japanese Society for Promotion of Science, and the Marumo Memorial Foundation Grant for Emergency Medicine Research. Drs. Tamura and Suzuki disclosed off-label use of hydrogen gas. Dr. Narumiya disclosed work for hire. Dr. Homma has disclosed that he does not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

We report the feasibility and recommend the potential efficacy of a bolus intravenous potassium chloride during out-of-hospital cardiac arrest with recurrent ventricular fibrillation following an acute coronary syndrome in a man in his 40's., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: The high incidence of morbidity and mortality associated with the post-cardiac arrest (CA) period highlights the need for novel therapeutic interventions to improve the outcome of out-of-hospital cardiac arrest (OHCA) patients admitted to the intensive care unit (ICU). The aim of this study is to assess the ability of high-dose intravenous vitamin C (Vit-C) to improve post-CA shock., Methods and Analysis: This is a single-blind, open-label, multicentre, randomised controlled trial, involving 234 OHCA patients with post-CA shock planned to be enrolled in 10 French ICUs. Patients will be randomised to receive standard-of-care (SOC) or SOC with early high-dose intravenous Vit-C administration (200 mg/kg per day, within 6 hours after return of spontaneous circulation, for 3 days). The primary endpoint is the cumulative incidence of vasopressor withdrawal at 72 hours after enrolment, with death considered as a competing event. The main secondary endpoints are neurological outcome, mortality due to refractory shock, vasopressor-free days and organ failure monitored by the sequential organ failure assessment score., Ethics and Dissemination: The study protocol was approved by a French Ethics Committee (EC) on 21 February 2023 ( Comité de Protection des Personnes Ile de France 1 , Paris, France). Due to the short enrolment period to avoid any delay in treatment, the EC approved the study inclusion before informed consent was obtained. As soon as possible, patient and their relative will be asked for their deferred informed consent. The data from the study will be disseminated through conference presentations and peer-reviewed publications., Trial Registration Number: NCT05817851., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Opioid-associated out-of-hospital cardiac arrest (OA-OHCA) is a subset of cardiac arrests that could benefit from measures outside of standard Advanced Cardiac Life Support (ACLS), such as naloxone., Study Objectives: In this study, we sought to examine whether OHCA patients chosen for naloxone therapy by emergency medical services (EMS) clinicians in a system with high rates of opioid overdose would have increased rates of return of spontaneous circulation (ROSC) and survival to hospital discharge., Methods: The study took place in an urban EMS system with a high prevalence of opioid overdose. Paramedics could administer naloxone in cardiac arrest in addition to ACLS. It was often administered based on clinical gestalt for suspected OA-OHCA. The outcomes of OHCA patients who received naloxone were compared against those who received usual care in both an adjusted and unadjusted fashion. Lastly, we created a logistic regression model to test for an independent association of naloxone administration on ROSC and survival to hospital discharge., Results: A consecutive sample of 769 OHCA patients was obtained, of which 175 (23%) received naloxone. On average, patients who received naloxone had significantly fewer comorbidities and were younger. There was no difference in ROSC, survival to hospital discharge, or modified Rankin Scores. Using logistic regression modeling, there was no statistically significant effect of naloxone administration on these outcomes., Conclusion: OHCA patients who received naloxone, despite being younger and having fewer comorbidities, had similar outcomes compared to those who received usual care. The difference in baseline characteristics suggests that paramedic gestalt reasonably selected for OA-OHCA., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eric Quinn, Emily Murphy, Daniel Du Pont, Paul Comber, Marley Blood, Aman Shah, Alexander Kuc, Krystal Hunter, and Gerard Carroll were all employed by the academic health system where this study took place. The authors have no other financial, personal, or competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The post-cardiac arrest syndrome (PCAS) after out-of-hospital cardiac arrest (OHCA) is characterized by a series of pathological events, including inflammation. In the randomized "STERoid for OHCA" (STEROHCA) trial, prehospital high-dose glucocorticoid decreased interleukin (IL) 6 and C-reactive protein levels following resuscitated OHCA. The aim of this predefined sub-study was to assess the inflammatory response the first three days of admission., Methods: The STEROHCA trial enrolled 137 OHCA patients randomized to either a single prehospital injection of methylprednisolone 250 mg or placebo. Inflammatory markers, including pro- and anti-inflammatory cytokines, were analyzed in plasma samples, from 0-, 24-, 48-, and 72 h post-admission. Mixed-model analyses were applied using log-transformed data to assess group differences., Results: The 137 patients included in this sub-study had a median age of 67 years (57 to 74), and the 180-day survival rates were 75% (n = 51/68) and 64% (n = 44/69) in the glucocorticoid and placebo group, respectively. A total of 130 (95%) patients had at least one plasma sample available. The anti-inflammatory cytokine IL-10 was increased at hospital admission in the glucocorticoid group (ratio 2.74 (1.49-5.05), p = 0.006), but the intervention showed the strongest effect after 24 h, decreasing pro-inflammatory levels of IL-6 (ratio 0.06 (0.03-0.10), p < 0.001), IL-8 (ratio 0.53 (0.38-0.75), p < 0.001), macrophage chemokine protein-1 (MCP-1, ratio 0.02 (0.13-0.31), p < 0.001), macrophage inflammatory protein-1-beta (MIP-1b, ratio 0.28 (0.18-0.45), p < 0.001), and tumor necrosis factor-α (TNF-α, ratio 0.6 (0.4-0.8), p = 0.01)., Conclusion: Administering high-dose glucocorticoid treatment promptly after resuscitation from OHCA influenced the inflammatory response with a reduction in several systemic proinflammatory cytokines after 24 h., Trial Registration: EudraCT number: 2020-000855-11; submitted March 30, 2020. URL: https://www., Clinicaltrials: gov; Unique Identifier: NCT04624776., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [The corresponding author (LERO) received salary support from a grant provided by the Research Foundation of Rigshospitalet (E-22652-04). The study, including the salary of RPB, received backing from a grant from the Novo Nordisk Foundation (NNF20OC0064043) under the supervision of CH. Additionally, CH benefits from an unrestricted grant from the Lundbeck Foundation (R186-2015–2132), received a speaker honorarium from Abiomed during the study, and holds positions as a board member of the European Society of Cardiology and chair of the Danish Heart Foundation. JK is supported by an unrestricted grant from the Novo Nordisk Foundation (NNF17OC0028706) and serves on two Data Safety Monitoring Boards for the IVIO trial (as chair) and the COCA trial without financial compensation. JEM received research grants from Abiomed and the Novo Nordisk Foundation outside the current study, speaker honorariums from Abiomed, Abbott, and Boehringer Ingelheim, and attended meetings with support from Abiomed. FF is backed by a research grant from the Novo Nordisk Foundation (NNF19OC0055142). RFS received grants from the Lundbeck Foundation, Danish Heart Foundation, and Sygeforsikringen Danmark Research Fund, all unrelated to the present study. The remaining authors have no disclosures to report.]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Early administration of adrenaline is associated with improved survival after out-of-hospital cardiac arrest (OHCA). Delays in vascular access may impact the timely delivery of adrenaline. Novel methods for administering adrenaline before vascular access may enhance survival. The objective of this study was to determine whether an initial intramuscular (IM) adrenaline dose followed by standard IV/IO adrenaline is associated with improved survival after OHCA., Methods Study Design: We conducted a before-and-after study of the implementation of an early, first-dose IM adrenaline EMS protocol for adult OHCAs. The pre-intervention period took place between January 2010 and October 2019. The post-intervention period was between November 2019 and May 2024., Setting: Single-center urban, two-tiered EMS agency., Participants: Adult, nontraumatic OHCA meeting criteria for adrenaline use., Intervention: Single dose (5 mg) IM adrenaline. All other care, including subsequent IV or IO adrenaline, followed international guidelines., Main Outcomes and Measures: The primary outcome was survival to hospital discharge. Secondary outcomes were time from EMS arrival to the first dose of adrenaline, survival to hospital admission, and favorable neurologic function at discharge., Results: Among 1405 OHCAs, 420 (29.9%) received IM adrenaline and 985 (70.1%) received usual care. Fifty-two patients received the first dose of adrenaline through the IV or IO route within the post-intervention period and were included in the standard care group analysis. Age was younger and bystander CPR was higher in the IM adrenaline group. All other characteristics were similar between IM and standard care cohorts. Time to adrenaline administration was faster for the IM cohort [(median 4.3 min (IQR 3.0-6.0) vs. 7.8 min (IQR 5.8-10.4)]. Compared with standard care, IM adrenaline was associated with improved survival to hospital admission (37.1% vs. 31.6%; aOR 1.37, 95% CI 1.06-1.77), hospital survival (11.0% vs 7.0%; aOR 1.73, 95% CI 1.10-2.71) and favorable neurologic status at hospital discharge (9.8% vs 6.2%; aOR 1.72, 95% CI 1.07-2.76)., Conclusion: In this single-center before-and-after implementation study, an initial IM dose of adrenaline as an adjunct to standard care was associated with improved survival to hospital admission, survival to hospital discharge, and functional survival. A randomized controlled trial is needed to fully assess the potential benefit of IM adrenaline delivery in OHCA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Out-of-hospital cardiac arrest (OHCA) complicated by refractory ventricular fibrillation (VF) is associated with poor outcome. Beta-1-receptor selective blockade might overcome refractory VF and improve survival. This trial investigates the efficacy and safety of prehospital landiolol in OHCA and refractory VF., Methods: In this randomized, double-blind, placebo-controlled pilot trial, patients with OHCA and recurrent or refractory VF (at least 3 defibrillation attempts and last rhythm shockable), pretreated with epinephrine and amiodarone, were allocated to receive add-on treatment with landiolol or placebo. Landiolol was given as a 20 mg bolus infusion. The primary efficacy outcome was time from trial drug infusion to sustained return of spontaneous circulation (ROSC). Safety outcomes included the onset of bradycardia and asystole., Results: A total of 36 patients were enrolled, 19 were allocated to the landiolol group and 17 to the placebo group. Time from trial drug infusion to sustained ROSC was similar between treatment groups (39 min [landiolol] versus 41 min [placebo]). Sustained ROSC was numerically lower in the landiolol group compared with the placebo group (7 patients [36.8%] versus 11 patients [64.7%], respectively). Asystole within 15 min of trial drug infusion occurred significantly more often in the landiolol group than in the placebo group (7 patients [36.8%] and 0 patients [0.0%], respectively)., Conclusion: In patients with OHCA and refractory VF who are pretreated with epinephrine and amiodarone, add-on bolus infusion of landiolol 20 mg did not lead to a shorter time to sustained ROSC compared with placebo. Landiolol might be associated with bradycardia and asystole., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Importance: The incidence of opioid-associated out-of-hospital cardiac arrest (OA-OHCA) has grown from less than 1% of OHCA in 2000 to between 7% and 14% of OHCA in recent years; American Heart Association (AHA) protocols suggest that emergency medical service (EMS) clinicians consider naloxone in OA-OHCA. However, it is unknown whether naloxone improves survival in these patients or in patients with undifferentiated OHCA., Objective: To evaluate the association of naloxone with clinical outcomes in patients with undifferentiated OHCA., Design, Setting, and Participants: Retrospective cohort study of EMS-treated patients aged 18 or older who received EMS treatment for nontraumatic OHCA in 3 Northern California counties between 2015 and 2023. Data were analyzed using propensity score-based models from February to April 2024., Exposure: EMS administration of naloxone., Main Outcomes and Measures: The primary outcome was survival to hospital discharge; the secondary outcome was sustained return of spontaneous circulation (ROSC). Covariates included patient and cardiac arrest characteristics (eg, age, sex, nonshockable rhythm, any comorbidity, unwitnessed arrest, and EMS agency) and EMS clinician determination of OHCA cause as presumed drug-related., Results: Among 8195 patients (median [IQR] age, 65 [51-78] years; 5540 male [67.6%]; 1304 Asian, Native Hawaiian, or Pacific Islander [15.9%]; 1119 Black [13.7%]; 2538 White [31.0%]) with OHCA treated by 5 EMS agencies from 2015 to 2023, 715 (8.7%) were believed by treating clinicians to have drug-related OHCA. Naloxone was administered to 1165 patients (14.2%) and was associated with increased ROSC using both nearest neighbor propensity matching (absolute risk difference [ARD], 15.2%; 95% CI, 9.9%-20.6%) and inverse propensity-weighted regression adjustment (ARD, 11.8%; 95% CI, 7.3%-16.4%). Naloxone was also associated with increased survival to hospital discharge using both nearest neighbor propensity matching (ARD, 6.2%; 95% CI, 2.3%-10.0%) and inverse propensity-weighted regression adjustment (ARD, 3.9%; 95% CI, 1.1%-6.7%). The number needed to treat with naloxone was 9 for ROSC and 26 for survival to hospital discharge. In a regression model that assessed effect modification between naloxone and presumed drug-related OHCA, naloxone was associated with improved survival to hospital discharge in both the presumed drug-related OHCA (odds ratio [OR], 2.48; 95% CI, 1.34-4.58) and non-drug-related OHCA groups (OR, 1.35; 95% CI, 1.04-1.77)., Conclusions and Relevance: In this retrospective cohort study, naloxone administration as part of EMS management of OHCA was associated with increased rates of ROSC and increased survival to hospital discharge when evaluated using propensity score-based models. Given the lack of clinical practice data on the efficacy of naloxone in OA-OHCA and OHCA in general, these findings support further evaluation of naloxone as part of cardiac arrest care.

Background: Neuromuscular blocking agents (NMBAs) can control shivering during targeted temperature management (TTM) of patients with cardiac arrest. However, the effectiveness of NMBA use during TTM on neurologic outcomes remains unclear. We aimed to evaluate the association between NMBA use during TTM and favorable neurologic outcomes after out-of-hospital cardiac arrest (OHCA)., Materials and Methods: A multicenter, prospective, observational cohort study from 2019 to 2021. It included OHCA patients who received TTM after hospitalization. We conducted overlap weight propensity-score analyses after multiple imputation to evaluate the effect of NMBAs during TTM. The primary outcome was a favorable neurological outcome, defined as a cerebral performance category of 1 or 2 at discharge. Subgroup analyses were conducted based on initial monitored rhythm and brain computed tomography findings., Results: Of the 516 eligible patients, 337 received NMBAs during TTM. In crude analysis, the proportion of patients with favorable neurological outcome was significantly higher in the NMBA group (38.3% vs. 16.8%; risk difference (RD): 21.5%; 95% confidence interval (CI): 14.0% to 29.1%). In weighted analysis, a significantly higher proportion of patients in the NMBA group had a favorable neurological outcome compared to the non-NMBA group (32.7% vs. 20.9%; RD: 11.8%; 95% CI: 1.2% to 22.3%). In the subgroup with an initial shockable rhythm and no hypoxic encephalopathy, the NMBA group showed significantly higher proportions of favorable neurological outcomes., Conclusions: The use of NMBAs during TTM was significantly associated with favorable neurologic outcomes at discharge for OHCA patients. NMBAs may have benefits in selected patients with initial shockable rhythm and without poor prognostic computed tomography findings., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest and funding support., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background & Objective: Despite their continued use, the effectiveness and safety of vasopressors in post-cardiac arrest patients remain controversial. This study examined the efficacy of various vasopressors in cardiac arrest patients in terms of clinical, morbidity, and mortality outcomes., Methods: A comprehensive literature search was performed using online databases (MeSH terms: MEDLINE (Ovid), CENTRAL (Cochrane Library), Embase (Ovid), CINAHL, Scopus, and Google Scholar) from 1997 to 2023 for relevant English language studies. The primary outcomes of interest for this study included short-term survival leading to death, return of spontaneous circulation (ROSC), survival to hospital discharge, neurological outcomes, survival to hospital admission, myocardial infarction, and incidence of arrhythmias., Results: In this meta-analysis, 26 studies, including 16 RCTs and ten non-RCTs, were evaluated. The focus was on the efficacy of epinephrine, vasopressin, methylprednisolone, dopamine, and their combinations in medical emergencies. Epinephrine treatment was associated with better odds of survival to hospital discharge (OR = 1.52, 95%CI [1.20, 1.94]; p < 0.001) and achieving ROSC (OR = 3.60, 95% CI [3.45, 3.76], P < 0.00001)) over placebo but not in other outcomes of interest such as short-term survival/ death at 28-30 days, survival to hospital admission, or neurological function. In addition, our analysis indicates non-superiority of vasopressin or epinephrine vasopressin-plus-epinephrine therapy over epinephrine monotherapy except for survival to hospital admission where the combinatorial therapy was associated with better outcome (0.76, 95%CI [0.64, 0.92]; p = 0.004). Similarly, we noted the non-superiority of vasopressin-plus-methylprednisolone versus placebo. Finally, while higher odds of survival to hospital discharge (OR = 3.35, 95%CI [1.81, 6.2]; p < 0.001) and ROSC (OR = 2.87, 95%CI [1.97, 4.19]; p < 0.001) favoring placebo over VSE therapy were observed, the risk of lethal arrhythmia was not statistically significant. There was insufficient literature to assess the effects of dopamine versus other treatment modalities meta-analytically., Conclusion: This meta-analysis indicated that only epinephrine yielded superior outcomes among vasopressors than placebo, albeit limited to survival to hospital discharge and ROSC. Additionally, we demonstrate the non-superiority of vasopressin over epinephrine, although vasopressin could not be compared to placebo due to the paucity of data. The addition of vasopressin to epinephrine treatment only improved survival to hospital admission., (© 2024. The Author(s).)

Background: This study compared out-of-hospital cardiac arrest (OHCA) patient outcomes based on intravenous (IV) access and prehospital epinephrine use., Methods: A retrospective study in Ulsan, South Korea, from January 2017 to December 2022, analyzed adult nontraumatic OHCA cases. Patients were grouped: Group 1 (no IV attempts), Group 2 (failed IV access), Group 3 (successful IV access without epinephrine), and Group 4 (successful IV access with epinephrine), with comparisons using logistic regression analysis., Results: Among 2,656 patients, Group 4 had significantly lower survival to hospital discharge (adjusted OR 0.520, 95% CI 0.346-0.782, p = 0.002) and favorable neurological outcomes (adjusted OR 0.292, 95% CI 0.140-0.611, p = 0.001) than Group 1. Groups 2 and 3 showed insignificant survival to hospital discharge (adjusted OR 0.814, 95% CI 0.566-1.171, p = 0.268) and (adjusted OR 1.069, 95% CI 0.810-1.412, p = 0.636) and favorable neurological outcomes (adjusted OR 0.585, 95% CI 0.299-1.144, p = 0.117) and (adjusted OR 1.075, 95% CI 0.689-1.677, p = 0.751). In the shockable rhythm group, Group 3 had better survival to hospital discharge (adjusted OR 1.700, 95% CI 1.044-2.770, p = 0.033)., Conclusions: Successful IV access with epinephrine showed worse outcomes in both rhythm groups than no IV attempts. Outcomes for failed IV and successful IV access without epinephrine were inconclusive. Importantly, successful IV access without epinephrine showed favorable survival to hospital discharge in the shockable rhythm group, warranting further research into IV access for fluid resuscitation in shockable rhythm OHCA patients., (© 2024. The Author(s).)

Introduction: Epinephrine and norepinephrine are the two most commonly used prehospital vasopressors in the United States. Prior studies have suggested that use of a post-ROSC epinephrine infusion may be associated with increased rearrest and mortality in comparison to use of norepinephrine. We used target trial emulation methodology to compare the rates of rearrest and mortality between the groups of OHCA patients receiving these vasopressors in the prehospital setting., Methods: Adult (18-80 years of age) non-traumatic OHCA patients in the 2018-2022 ESO Data Collaborative datasets with a documented post-ROSC norepinephrine or epinephrine infusion were included in this study. Logistic regression modeling was used to evaluate the association between vasopressor agent and outcome using two sets of covariables. The first set of covariables included standard Utstein factors, the dispatch to ROSC interval, the ROSC to vasopressor interval, and the follow-up interval. The second set added prehospital systolic blood pressure and SpO 2 values. Kaplan-Meier time-to-event analysis was also conducted and the vasopressor groups were compared using a multivariable Cox regression model., Results: Overall, 1,893 patients treated by 309 EMS agencies were eligible for analysis. 1,010 (53.4%) received an epinephrine infusion and 883 (46.7%) received a norepinephrine infusion as their initial vasopressor. Adjusted analyses did not discover an association between vasopressor agent and rearrest (aOR: 0.93 [0.72, 1.21]) or mortality (aOR: 1.00 [0.59, 1.69])., Conclusions: In this multi-agency target trial emulation, the use of a post-resuscitation epinephrine infusion was not associated with increased odds of rearrest in comparison to the use of a norepinephrine infusion., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘RPC is an employee of ESO. The aims of this investigation were reviewed by an independent committee before access to the data was granted. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the results reported in this paper.’., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (© 2024. The Author(s).)

Introduction: Shock after resuscitation from out-of-hospital cardiac arrest (OHCA) is often treated with vasopressors. We examined whether infusion of epinephrine versus norepinephrine was associated with prehospital rearrest and neurologically favorable survival among OHCA patients., Methods: This retrospective study included OHCA cases in Seattle, Washington from 2014-2021 who had return of spontaneous circulation (ROSC) followed by vasopressor infusion. Our primary exposure was infusion of epinephrine or norepinephrine. Our primary outcome was prehospital rearrest. Secondary outcomes included survival and neurologically favorable outcome (Cerebral Performance Category score of 1 or 2). We used multivariable logistic regression to test associations between exposures and outcomes adjusting for key covariates., Results: Of 451 OHCA patients with ROSC followed by vasopressor infusion, 253 (56%) received norepinephrine and 198 (44%) received epinephrine infusions. Those who received epinephrine were older (median 66 [interquartile ranges {IQR} 53-79] vs 63 [IQR 47-75] years), but otherwise had similar baseline characteristics. Patients who received epinephrine were twice as likely to rearrest (55% vs 25%). After adjustment, the difference in rearrest rates between epinephrine and norepinephrine persisted (OR 3.28, 95%CI 2.25-5.08), and the odds of pulses at hospital arrival were lower in the epinephrine group (OR 0.52 95%CI 0.32-0.83). After adjustment, there was no difference in neurologically favorable survival, survival to hospital admission, or survival to discharge., Conclusion: Patients who received epinephrine infusions after ROSC suffered prehospital rearrest more frequently than those who received norepinephrine. Survival and neurological status at hospital discharge were similar. Future trials should examine the optimal approach to hemodynamic management for post-OHCA shock.

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., (© 2023. The Author(s).)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Epinephrine continues to be a fundamental part of the Advanced Cardiac Life Support algorithm despite a lack of evidence that it improves neurologically intact survival. Our aim was both to identify a potential upper limit of epinephrine use in resuscitations and to demonstrate real-world epinephrine use in different patient subgroups., Methods: This was a single-center, retrospective cohort study, conducted between August 1, 2016-July 1, 2021, of patients with medical cardiac arrest who were administered a known number of epinephrine doses. The primary outcome was neurologically intact discharge defined by a modified Rankin scale ≤3, with secondary outcomes of comparing epinephrine doses by age, rhythm, and emergency medical services vs emergency department administration of epinephrine., Results: The study included 1,330 patients, with 184 patients (13.8%) surviving to neurologically intact discharge. The primary outcome of neurologically intact discharge was found in 89 (65.4%) patients in the zero epinephrine dose group, 75 (20.0%) in the 1-3 dose group, 15 (4.3%) in the 4-6 dose group, and one (0.002%) in the ≥7 dose group ( P  < 0.001). Patients received similar amounts of epinephrine when stratified by age, while patients with shockable rhythms received more epinephrine than patients with non-shockable rhythms., Conclusion: There was a significant decrease in neurologically intact discharge with increasing number of epinephrine doses, and our data suggests that seven or more doses of epinephrine is almost always futile. While further prospective studies are needed, clinicians should consider epinephrine doses when weighing the futility or benefit of continued resuscitation efforts., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.

Introduction: The optimum route for drug administration in cardiac arrest is unclear. Recent data suggest that use of the intraosseous route may be increasing. This study aimed to explore changes over time in use of the intraosseous and intravenous drug routes in out-of-hospital cardiac arrest in England., Methods: We extracted data from the UK Out-of-Hospital Cardiac Arrest Outcomes registry. We included adult out-of-hospital cardiac arrest patients between 2015-2020 who were treated by an English Emergency Medical Service that submitted vascular access route data to the registry. The primary outcome was any use of the intraosseous route during cardiac arrest. We used logistic regression models to describe the association between time (calendar month) and intraosseous use., Results: We identified 75,343 adults in cardiac arrest treated by seven Emergency Medical Service systems between January 2015 and December 2020. The median age was 72 years, 64% were male and 23% presented in a shockable rhythm. Over the study period, the percentage of patients receiving intraosseous access increased from 22.8% in 2015 to 42.5% in 2020. For each study-month, the odds of receiving any intraosseous access increased by 1.019 (95% confidence interval 1.019 to 1.020, p < 0.001). This observed effect was consistent across sensitivity analyses. We observed a corresponding decrease in use of intravenous access., Conclusion: In England, the use of intraosseous access in out-of-hospital cardiac arrest has progressively increased over time. There is an urgent need for randomised controlled trials to evaluate the clinical effectiveness of the different vascular access routes in cardiac arrest., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CDD, RF, CJ, JPN, GDP and KC are co-investigators of the PARAMEDIC-3 trial (a randomised controlled trial of the IV versus IO route for vascular access in out-of-hospital cardiac arrest). JPN is Editor in Chief and GDP is an editor of Resuscitation. CDD and KC are editorial board members of Resuscitation., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Amiodarone and lidocaine have not been shown to have a clear survival benefit compared to placebo for out-of-hospital cardiac arrest (OHCA). However, randomized trials may have been impacted by delayed administration of the study drugs. We sought to evaluate how timing from emergency medical services (EMS) arrival on scene to drug administration affects the efficacy of amiodarone and lidocaine compared to placebo., Method: This is a secondary analysis of the 10-site, 55-EMS-agency double-blind randomized controlled amiodarone, lidocaine, or placebo in OHCA study. We included patients with initial shockable rhythms who received the study drugs of amiodarone, lidocaine, or placebo before achieving return of spontaneous circulation. We performed logistic regression analyses evaluating survival to hospital discharge and secondary outcomes of survival to admission and functional survival (modified Rankin scale score ≤ 3). We evaluated the samples stratified by early (<8 min) and late administration groups (≥8 min). We compared outcomes for amiodarone and lidocaine compared to placebo and adjust for potential confounders., Results: There were 2802 patients meeting inclusion criteria, with 879 (31.4%) in the early (<8 min) and 1923 (68.6%) in the late (≥8 min) groups. In the early group, patients receiving amiodarone, compared to placebo, had significantly higher survival to admission (62.0% vs. 48.5%, p = 0.001; adjusted OR [95% CI] 1.76 [1.24-2.50]), survival to discharge (37.1% vs. 28.0%, p = 0.021; 1.56 [1.07-2.29]), and functional survival (31.6% vs. 23.3%, p = 0.029; 1.55 [1.04-2.32]). There were no significant differences with early lidocaine compared to early placebo (p > 0.05). Patients in the late group who received amiodarone or lidocaine had no significant differences in outcomes at discharge compared to placebo (p > 0.05)., Conclusions: The early administration of amiodarone, particularly within 8 min, is associated with greater survival to admission, survival to discharge, and functional survival compared to placebo in patients with an initial shockable rhythm., (© 2023 Society for Academic Emergency Medicine.)

Background: Epinephrine is the most commonly used drug in out-of-hospital cardiac arrest (OHCA) resuscitation, but evidence supporting its efficacy is mixed., Research Question: What are the comparative efficacy and safety of standard dose epinephrine, high-dose epinephrine, epinephrine plus vasopressin, and placebo or no treatment in improving outcomes after OHCA?, Study Design and Methods: In this systematic review and network meta-analysis of randomized controlled trials, we searched six databases from inception through June 2022 for randomized controlled trials evaluating epinephrine use during OHCA resuscitation. We performed frequentist random-effects network meta-analysis and present ORs and 95% CIs. We used the the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate the certainty of evidence. Outcomes included return of spontaneous circulation (ROSC), survival to hospital admission, survival to discharge, and survival with good functional outcome., Results: We included 18 trials (21,594 patients). Compared with placebo or no treatment, high-dose epinephrine (OR, 4.27; 95% CI, 3.68-4.97), standard-dose epinephrine (OR, 3.69; 95% CI, 3.32-4.10), and epinephrine plus vasopressin (OR, 3.54; 95% CI, 2.94-4.26) all increased ROSC. High-dose epinephrine (OR, 3.53; 95% CI, 2.97-4.20), standard-dose epinephrine (OR, 3.00; 95% CI, 2.66-3.38), and epinephrine plus vasopressin (OR, 2.79; 95% CI, 2.27-3.44) all increased survival to hospital admission as compared with placebo or no treatment. However, none of these agents may increase survival to discharge or survival with good functional outcome as compared with placebo or no treatment. Compared with placebo or no treatment, standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm (OR, 2.10; 95% CI, 1.21-3.63), but not in those with shockable rhythm (OR, 0.85; 95% CI, 0.39-1.85)., Interpretation: Use of standard-dose epinephrine, high-dose epinephrine, and epinephrine plus vasopressin increases ROSC and survival to hospital admission, but may not improve survival to discharge or functional outcome. Standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm, but not those with shockable rhythm., Trial Registry: Center for Open Science: https://osf.io/arxwq., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: B. S. reports receiving funding from PIPRA AG, outside of the submitted work. B. H. reports receiving research support from Abbott, Edwards Lifesciences, Boston Scientific, and Bayer, outside of the submitted work. L. M. is associate editor of Intensive Care Medicine. E. F. reports receiving personal fees from ALung Technologies, Baxter, Boehringer-Ingelheim, Fresenius Medical Care, MC3 Cardiopulmonary, and Vasomune, outside of the submitted work. D. B. receives research support from ALung Technologies, outside of the submitted work, and has been on the medical advisory boards for Abiomed, Xenios, Medtronic, LivaNova, Inspira, and Cellenkos. S. C. reports receiving research support from Zoll Medical Inc., outside of the submitted work. N. D. F. reports consulting for Baxter and Xenios, outside of the submitted work. C. S. is associate editor of Intensive Care Medicine. G. D. P. receives support from Elsevier for roles as an editor for Resuscitation and editor-in-chief of Resuscitation Plus. J. P. N. receives support from Elsevier for his role as editor-in-chief of Resuscitation. None declared (S. M. F., R. M., B. R., P. D. S., A. T., S. L. M., C. V., D. C. S., S. L., J. S., P. D.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: Examining the association of time to treatment (drug or placebo) with survival to hospital discharge and neurologic outcome., Design: Post hoc analysis of the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, Placebo randomized controlled trial., Setting: Emergency medical services enrolled patients with out-of-hospital cardiac arrest (OHCA) at multiple North American sites., Patients: Adults with nontraumatic OHCA and an initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia refractory to at least one defibrillation attempt were included., Interventions: None., Measurements and Main Results: We used logistic regression to examine the association of time to treatment with survival to hospital discharge and favorable neurologic status at discharge (modified Rankin Scale ≤ 3) for the three treatment groups including an interaction term between treatment and time to treatment to determine the effect of time on treatment effects. Time to treatment data were available for 2,994 out of 3,026 patients (99%). The proportion of patients who survived to hospital discharge decreased as time to drug administration increased, in amiodarone (odds ratio [OR], 0.91; 95% CI, 0.90-0.93 per min), lidocaine (OR, 0.93; 95% CI, 0.91-0.96), and placebo (OR, 0.91; 95% CI, 0.90-0.93). Comparing amiodarone to placebo, there was improved survival at all times of drug administration (OR, 1.32; 95% CI, 1.05-1.65). Comparing lidocaine to placebo, survival was not different with shorter times to drug administration (< 11 min), whereas survival was higher with lidocaine at longer times to drug administration with an interaction between treatment effect and time to treatment (p = 0.048). Survival with good neurologic outcome showed similar results for all analyses., Conclusions: Survival and favorable neurologic outcomes decreased with longer times to drug administration. Amiodarone improved survival at all time points whereas lidocaine improved survival only at later time points, compared with placebo., Competing Interests: Dr. Cheskes’ institution received funding from the Heart and Stroke Foundation of Canada, Zoll Medical, and the Cardiac Arrhythmia Network of Canada; he disclosed that he is on the Advisory Board of Drone Delivery Canada. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Introduction: The benefits and risks of the intraosseous (IO) route for vascular access in patients with out-of-hospital cardiac arrest (OHCA) remain controversial. This study compares the success rates of establishing the access route, epinephrine administration rates, and time-to-epinephrine between adult patients with OHCA with IO access and those with intravenous (IV) access established by paramedics in the prehospital setting., Methods: This was a retrospective study conducted by the San-Min station of Taoyuan Fire Department. Data for IV access were collected between January 1, 2020, and December 31, 2020. Data for IO access were collected between January 1, 2021, and March 10, 2021. Inclusion criteria were adult patients with OHCA who received on-scene resuscitation attempts and in whom either IV or IO route access was established by paramedics. Exclusion criteria were missing data, return of spontaneous circulation before establishing vascular access, cardiac arrest en route to hospital, patients not resuscitated, and OHCA unidentified by the dispatcher. Exposure was defined as IV route vs. IO route (EZ-IO®). The outcome measurements were per-patient based success rates of route establishment (successes/attempts), administration rates of epinephrine (epinephrine administered per case/enrolled OHCAs), and odds ratios of IV versus IO on epinephrine administration. We used nonparametric Mann-Whitney rank sum tests for the analysis in continuous variables and Fisher's exact tests for the analysis of categorical variables and the outcomes. Firth logistic regression method was used for sparse data. Factors associated with epinephrine administration other than vascular access were also analyzed. Time-to-epinephrine (defined as time from paramedic arrival to epinephrine injection) was reviewed and calculated by two independent observers and the Kaplan-Meier method was used to compare the two access routes., Results: A total of 112 adult patients were enrolled in the analysis, including 71 men and 41 women, with an average age of 67 years. There were 90 IV access cases and 22 IO access cases. The groups were compared for median success rates of route establishment (33% vs. 100%, P < 0.001) and administration rates of epinephrine (52% vs. 100%, P < 0.001). The adjusted odds ratio of IO versus IV was 32.445, 95% confidence interval (CI) of 1.844-570.861. Time-to-epinephrine was significantly shorter in the cumulative time-event analysis by the Kaplan-Meier method (P < 0.001)., Conclusion: The IO route was significantly associated with higher success rates of route establishment, epinephrine administration, and shorter time-to-epinephrine in the prehospital resuscitation of adult patients with OHCA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Out-of-hospital cardiac arrest (OHCA) has a poor prognosis, with an overall survival rate of about 5% at discharge. Shockable rhythm cardiac arrests (ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT)) have a better prognosis. In case of shockable rhythm, treatment is based on defibrillation, and thereafter, in case of failure of 3 external electric shocks (EES), on direct intravenous administration of 300 mg amiodarone, or lidocaine when amiodarone is unavailable or inefficient. During surgical procedures under extracorporeal circulation, a high potassium cardioplegia solution is administered to interrupt cardiac activity and facilitate surgical procedure. By extension, direct intravenous administration of potassium chloride (KCl) has been shown to convert VF, resulting in return to a hemodynamically efficient organized heart rate within a few minutes. The aim of this study is to provide clinical evidence that direct intravenous injection of KCl, into a patient presenting with OHCA due to refractory VF although 3 EES, should interrupt this VF and then allow rapid restauration of an organized heart rhythm, and thus return of spontaneous circulation (ROSC)., Methods: A multicenter, prospective, single group, phase 2 study will be conducted on 81 patients presenting with refractory VF. After failure of 3 EES, each patient will receive direct intravenous injection of 20 mmol KCl instead of amiodarone. The primary outcome will be survival rate at hospital admission. Major secondary outcomes will include ROSC and time to ROSC in the prehospital setting, number of VF recidivism after KCl injection, survival rate at hospital discharge with a good neurologic prognostic, and survival rate 3 months after hospital discharge with a good neurologic prognostic., Results: No patient is currently included in the study., Discussion: Conventional guideline strategy based on antiarrhythmic drug administration, i.e. amiodarone or lidocaine, for OHCA due to shockable rhythm, has not yet demonstrated an increase in survival at hospital admission or at hospital discharge. This may be related to the major cardiodepressant effect of those drugs., Trial Registration: ClinicalTrials.gov Identifier: NCT04316611. Registered on March 2020. AP-HP180577 / N° EUDRACT: 2019-002544-24. Funded by the French Health Ministry. https://clinicaltrials.gov/ct2/show/NCT04316611., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jouffroy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Over the past decades, international guidelines for cardiopulmonary resuscitation (CPR) have changed the recommendation for alternative routes for drug administration. Until now, evidence for the substantial superiority of one route with respect to treatment outcome after CPR has been lacking. The present study compares the effects of intravenous (IV), intraosseous (IO) and endotracheal (ET) adrenaline application during CPR in out-of-hospital cardiac arrest (OHCA) on clinical outcomes within the database of the German Resuscitation Registry (GRR)., Methods: This registry analysis was based on the GRR cohort of 212,228 OHCA patients between 1989 and 2020. Inclusion criteria were: OHCA, application of adrenaline, and out-of-hospital CPR. Excluded from the study were patients younger than 18 years, those who had trauma or bleeding as suspected causes of cardiac arrest, and incomplete data sets. The clinical endpoint was hospital discharge with good neurological outcome [cerebral performance category (CPC) 1/2]. Four routes of adrenaline administration were compared: IV, IO, IO + IV, ET + IV. Group comparisons were done using matched-pair analysis and binary logistic regression., Results: In matched-pair group comparisons of the primary clinical outcome hospital discharge with CPC 1/2, the IV group (n = 2416) showed better results compared to IO (n = 1208), [odds ratio (OR): 2.43, 95% confidence interval (CI): 1.54-3.84, p < 0.01] and when comparing IV (n = 8706) to IO + IV (n = 4353), [OR: 1.33, 95% CI: 1.12-1.59, p < 0.01]. In contrast, no significant difference was found between IV (n = 532) and ET + IV (n = 266), [OR: 1.26, 95% CI: 0.55-2.90, p = 0.59]. Concurrently, binary logistic regression yielded a highly significant effect of vascular access type (χ² = 67.744(3), p < 0.001) on hospital discharge with CPC1/2, with negative effects for IO (regression coefficient (r.c.) = - 0.766, p = 0.001) and IO + IV (r.c. = - 0.201, p = 0,028) and no significant effect for ET + IV (r.c. = 0.117, p = 0.770) compared to IV., Conclusions: The GRR data, collected over a period of 31 years, seem to emphasize the relevance of an IV access during out-of-hospital CPR, in the event that adrenaline had to be administered. IO administration of adrenaline might be less effective. ET application, though removed in 2010 from international guidelines, could gain importance as an alternative route again., (© 2023. The Author(s).)

Aim: To investigate how the inflammatory response after out-of-hospital cardiac arrest (OHCA) is modulated by blocking IL-6-mediated signalling with tocilizumab, and to relate induced changes to clinical status, myocardial- and brain injury., Methods: This is a preplanned substudy of the IMICA trial (ClinicalTrials.gov, NCT03863015). Upon admission 80 comatose OHCA patients were randomized to infusion of tocilizumab or placebo. Inflammation was characterized by a cytokine assay, CRP, and leukocyte differential count; myocardial injury by TnT and NT-proBNP; brain injury by neuron-specific enolase (NSE) and Neurofilament Light chain (NFL), while sequential organ assessment (SOFA) score and Vasoactive-Inotropic Score (VIS) represented overall clinical status., Results: Responses for IL-5, IL-6, IL-17, neutrophil as well as monocyte counts, and VIS were affected by tocilizumab treatment (all p < 0.05), while there was no effect on levels of NFL. IL-5 and IL-6 were substantially increased by tocilizumab, while IL-17 was lowered. Neutrophils and monocytes were lower at 24 and 48 hours, and VIS was lower at 24 hours, for the tocilizumab group compared to placebo. Multiple correlations were identified for markers of organ injury and clinical status versus inflammatory markers; this included correlations of neutrophils and monocytes with TnT, NSE, NFL, SOFA- and VIS score for the tocilizumab but not the placebo group. NT-proBNP, NFL and SOFA score correlated with CRP in both groups., Conclusions: Treatment with tocilizumab after OHCA modulated the inflammatory response with notable increases for IL-5, IL-6, and decreases for neutrophils and monocytes, as well as reduced vasopressor and inotropy requirements., Competing Interests: Conflicts of interest MASM, MB, SW, JG, LERO, JJ, MF, JHT, RFS, JK, CH declares no conflicts of interest. ASPM has after the completion of the trial been employed by Novo Nordisk, Denmark., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Refractory ventricular fibrillation (VF) and pulseless ventricular tachycardia (pVT) cardiac arrest describes a subset of patients who do not respond to standard Advanced Cardiac Life Support (ACLS) interventions and are associated with poor outcomes. Esmolol administration and vector change defibrillation have shown promise in improving outcomes in these patients, however evidence is limited., Objectives: This study compares clinical outcomes between patients with prehospital refractory VF/pVT who received an Emergency Medical Service (EMS) bundle, comprised of esmolol administration, vector change defibrillation, and dose-capped epinephrine at 3 mg, to patients who received standard ACLS interventions., Methods: This multicenter, retrospective, cohort study evaluated medical records between October 18, 2017 and March 15, 2022. Patients were enrolled if they experienced a prehospital cardiac arrest with the rhythm VF or pVT, had received at least three standard defibrillations, at least 3 mg of epinephrine, and 300 mg of amiodarone. Patients who received the EMS bundle after its implementation were compared to patients who received standard ACLS interventions prior to its implementation. The primary outcome was sustained return of spontaneous circulation (ROSC), defined as ROSC lasting 20 min without recurrence of cardiac arrest. Secondary outcomes included the incidence of any ROSC, survival to hospital arrival, survival at hospital discharge, and neurologically intact survival at hospital discharge., Results: Eighty-three patients were included in the study. Thirty-six were included in the pre-EMS bundle group and 47 patients were included in the post-EMS bundle group. Patients in the pre-EMS bundle group achieved significantly higher rates of sustained ROSC (58.3% vs 17%, p < 0.001), any ROSC (66.7% vs 19.1%, p < 0.001), and survival to hospital arrival (55.6% vs 17%, p < 0.001). The rates of survival to hospital discharge (16.7% vs 6.4%, p = 0.17) and neurologically intact survival at hospital discharge (5.9% vs 4.3%, p = 1.00) were not significantly different between groups., Conclusions: Patients who received the EMS bundle achieved sustained ROSC significantly less often and were less likely to have pulses at hospital arrival. The incidence of neurologically intact survival was low and similar between groups., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The efficacy and safety of epinephrine in patients with out-of-hospital cardiac arrest (OHCA) remains controversial. The meta-analysis was used to comprehensively appraise the influence of epinephrine in OHCA patients., Methods: We searched all randomized controlled and cohort studies published by PubMed, EMBASE, and Cochrane Library from the inception to August 2022 on the prognostic impact of epinephrine on patients with OHCA. Survival to discharge was the primary outcome, while the return of spontaneous circulation (ROSC) and favorable neurological outcome were secondary outcomes., Results: The meta-analysis included 18 studies involving 863,952 patients. OHCA patients with adrenaline had an observably improved chance of ROSC (RR 2.81; 95% CI 2.21-3.57; P = 0.001) in randomized controlled studies, but the difference in survival to discharge (RR 1.27; 95% CI 0.58-2.78; P = 0.55) and favorable neurological outcomes (RR 1.21; 95% CI 0.90-1.62; P = 0.21) between the two groups was not statistically significant. In cohort studies, the rate of ROSC (RR 1.62; 95% CI 1.14-2.30; P = 0.007) increased significantly with the adrenaline group, while survival to discharge (RR 0.73; 95% CI 0.55-0.98; P = 0.03) and favorable cerebral function (RR 0.42; 95% CI 0.30-0.58; P = 0.001) were lower than the non-adrenaline group., Conclusion: We found that both the randomized controlled trials (RCTs) and cohort studies showed that adrenaline increased ROSC in OHCA patients. However, they were unable to agree on a long-term prognosis. The cohort studies showed that adrenaline had an adverse effect on the long-term prognosis of OHCA patients (discharge survival rate and good neurological prognosis), but adrenaline had no adverse effect in the RCTs. In addition to the differences in research methods, there are also some potential confounding factors in the included studies. Therefore, more high-quality studies are needed to fully confirm the effect of adrenaline on the long-term results of OHCA., (© 2022. The Author(s).)

Background: Post-cardiac arrest, outcomes for most patients are poor, regardless of setting. Many patients who do achieve spontaneous return of circulation require vasopressor therapy to maintain organ perfusion. There is some evidence to support the use of corticosteroids in cardiac arrest., Research Question: Assess the efficacy and safety of corticosteroids in patients following in- and out-of-hospital cardiac arrest., Study Design and Methods: We searched databases CINAHL, EMBASE, LILACS, MEDLINE, Web of Science, CENTRAL, ClinicalTrails.gov, and ICTRP. We included randomized controlled trials (RCTs) that examined the efficacy and safety of corticosteroids, as compared to placebo or usual care in patients post-cardiac arrest. We pooled estimates of effect size using random effects meta-analysis and report relative risk (RR) with 95% confidence intervals (CIs). We assessed risk of bias (ROB) for the included trials using the modified Cochrane ROB tool and rated the certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation methodology., Results: We included 8 RCTs (n = 2213 patients). Corticosteroids administered post-cardiac arrest had an uncertain effect on mortality measured at the longest point of follow-up (RR 0.96, 95% CI 0.90-1.02, very low certainty, required information size not met using trial sequential analysis). Corticosteroids probably increase return of spontaneous circulation (ROSC) (RR 1.32, 95% CI 1.18-1.47, moderate certainty) and may increase the likelihood of survival with good functional outcome (RR 1.49, 95% CI 0.87-2.54, low certainty). Corticosteroids may decrease the risk of ventilator associated pneumonia (RR 0.76, 95% CI 0.46-1.09, low certainty), may increase renal failure (RR 1.29, 95% CI 0.84-1.99, low certainty), and have an uncertain effect on bleeding (RR 2.04, 95% CI 0.53-7.84, very low certainty) and peritonitis (RR 10.54, 95% CI 2.99-37.19, very low certainty)., Conclusions: In patients during or after cardiac arrest, corticosteroids have an uncertain effect on mortality but probably increase ROSC and may increase the likelihood of survival with good functional outcome at hospital discharge. Corticosteroids may decrease ventilator associated pneumonia, may increase renal failure, and have an uncertain effect on bleeding and peritonitis. However, the pooled evidence examining these outcomes was sparse and imprecision contributed to low or very low certainty of evidence., (© 2023. The Author(s).)

Background: Cardiac arrest guidelines recommend epinephrine every 3-5 minutes during cardiac arrest resuscitation. However, it is unclear if multiple epinephrine doses are associated with improved outcomes. The objective of this study was to determine if a single-dose epinephrine protocol was associated with improved survival compared to traditional multidose protocols., Methods: We conducted a pre-post study across five North Carolina EMS agencies from 11/1/2016 to 10/29/2019. Patients ≥18 years old with attempted resuscitation for non-traumatic prehospital cardiac arrest were included. Data were collected 1 year before and after implementation of the single-dose epinephrine protocol. Prior to implementation, all agencies used a multidose epinephrine protocol. The Cardiac Arrest Registry to Enhance Survival (CARES) was used to obtain patient outcomes. Study outcomes were survival to hospital discharge (primary) and return of spontaneous circulation (ROSC). Analysis was by intention to treat. Outcomes were compared pre- vs. post-implementation using generalized estimating equations to account for clustering within EMS agencies. Adjusted analyses included age, sex, race, shockable vs. non-shockable rhythm, witnessed arrest, automatic external defibrillator availability, EMS response interval, and bystander cardiopulmonary resuscitation., Results: During the study period there were 1,690 encounters (899 pre- and 791 post-implementation). The population was 74.7% white, 61.1% male, and had a median age of 65 (IQR 53-76) years. Survival to hospital discharge was similar pre- vs. post-implementation [13.6% (122/899) vs. 15.4% (122/791); OR 1.19, 95%CI 0.89-1.59]. However, ROSC was more common post-implementation [42.3% (380/899) vs. 32.5% (257/791); OR 0.66, 95%CI 0.54-0.81]. After adjusting for covariates, the single-dose protocol was associated with similar survival to discharge rates (aOR 0.88, 95%CI 0.77-1.29), but with decreased ROSC rates (aOR 0.58, 95%CI 0.47-0.72)., Conclusion: A prehospital single-dose epinephrine protocol was associated with similar survival to hospital discharge, but decreased ROSC rates compared to the traditional multidose epinephrine protocol.

Introduction: Recent clinical trials have failed to identify a benefit of antiarrhythmic administration during cardiac arrest. However, little is known regarding the time to administration of antiarrhythmic drugs in clinical practice or its impact on return of spontaneous circulation (ROSC). We utilized a national EMS registry to evaluate the time of drug administration and association with ROSC., Methods: We utilized the 2018 and 2019 NEMSIS datasets, including all non-traumatic, adult 9-1-1 EMS activations for cardiac arrests with initial shockable rhythm and that received an antiarrhythmic. We calculated the time from 9-1-1 call to administration of antiarrhythmic. We excluded cases with erroneous time stamps. Stratified by initial antiarrhythmic (amiodarone and lidocaine), we created a mixed-effect logistic regression model evaluating the association between every 5-minute increase in time to antiarrhythmic and ROSC. We modeled EMS agency as a random intercept and adjusted for confounders., Results: There were 449,630 adults, non-traumatic cardiac arrests identified with 11,939 meeting inclusion criteria. 9,236 received amiodarone and 1,327 received lidocaine initially. The median time in minutes to initial dose for amiodarone was 19.9 minutes (IQR 15.8-25.6) and for lidocaine was 19.5 minutes (IQR 15.2-25.4). Increasing time to initial antiarrhythmic was associated with decreased odds of ROSC for both amiodarone (aOR 0.9; 95% CI 0.9-0.94) and lidocaine (aOR 0.9; 95% CI 0.8-0.97)., Conclusion: Time to administration of anti-arrhythmic medication varied, but most patients received the first dose of anti-arrhythmic drug more than 19 minutes after the initial 9-1-1 call. Longer time to administration of an antiarrhythmic in patients with an initial shockable rhythm was associated with decreased ROSC rates.

Background: Previously conducted physician-centered trials on the usefulness of vasopressin have yielded negative results; thus, patient-oriented trials have been warranted. We hypothesize that Augmented-Medication CardioPulmonary Resuscitation could be helpful for selected patients with out-of-hospital cardiac arrest (OHCA)., Methods: This is a double-blind, single-center, randomized, placebo-controlled trial conducted in the emergency department in a tertiary, university-affiliated hospital in Seoul, Korea. A total of 148 adults with non-traumatic OHCA who had initial diastolic blood pressure (DBP) < 20 mm Hg via invasive arterial monitoring during the early cardiac compression period were randomly assigned to two groups. Patients received a dose of 40 IU of vasopressin or placebo with initial epinephrine. The primary endpoint was a sustained return of spontaneous circulation. Secondary endpoints were survival discharge, and neurologic outcomes at discharge., Results: Of the 180 included patients, 32 were excluded, and 148 were enrolled in the trial. A sustained return of spontaneous circulation was achieved by 27 patients (36.5%) in the vasopressin group and 24 patients (32.4%) in the control group (risk difference, 4.1%; P = .60). Survival discharge and good neurologic outcomes did not differ between groups. The trial group had significantly higher median DBPs during resuscitation than the control group (16.0 vs. 14.5 mm Hg, P < 0.01). There was no difference in end-tidal carbon dioxide, acidosis, and lactate levels at baseline, 10 min, and end-time., Conclusion: Among patients with refractory vasodilatory shock in OHCA, administration of vasopressin, compared with placebo, did not significantly increase the likelihood of return of spontaneous circulation., (© 2022. The Author(s).)

Objective: The Calcium for Out-of-hospital Cardiac Arrest (COCA) trial was recently conducted and published. This pre-planned sub-study evaluated the effect of calcium in patients with pulseless electrical activity (PEA) including subgroup analyses based on electrocardiographic characteristics potentially associated with hyperkalemia and ischemia., Methods: Patients aged ≥ 18 years were included if they had a non-traumatic out-of-hospital cardiac arrest and received adrenaline. The trial drug consisted of calcium chloride (5 mmol) or saline placebo given after the first, and again after the second, dose of adrenaline for a maximum of two doses. This sub-study analyzed patients with PEA as their last known rhythm prior to receiving the trial drug. Outcomes were return of spontaneous circulation and survival at 30 days., Results: 104 patients were analyzed. In the calcium group, 9 patients (20 %) achieved return of spontaneous circulation vs 23 patients (39 %) in the placebo group (risk ratio 0.51; 95 %CI 0.26, 1.00). Subgroup analyses based on electrocardiographic characteristics potentially associated with hyperkalemia and ischemia showed similar results. At 30 days, 1 patient (2.2 %) was alive in the calcium group while 8 patients (13.6 %) were alive in the placebo group (risk ratio 0.16; 95 %CI 0.02, 1.26)., Conclusion: In adults with out-of-hospital cardiac arrest presenting with PEA, effect estimates suggested harm of calcium administration as compared to placebo but with wide confidence intervals. Results were consistent for patients with electrocardiographic characteristics potentially associated with hyperkalemia and ischemia. The results do not support calcium administration based strictly on electrocardiographic findings seen during out-of-hospital cardiac arrest., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Recent evidence showing the clinical effectiveness of drug therapy in cardiac arrest has led to renewed interest in the optimal route for drug administration in adult out-of-hospital cardiac arrest. Current resuscitation guidelines support use of the intravenous route for intra-arrest drug delivery, with the intraosseous route reserved for patients in whom intravenous access cannot be established. We sought to evaluate current evidence on drug route for administration of cardiac arrest drugs, with a specific focus on the intravenous and intraosseous route. We identified relevant animal, manikin, and human studies through targeted searches of MEDLINE in June 2022. Across pre-hospital systems, there is wide variation in use of the intraosseous route. Early administration of cardiac arrest drugs is associated with improved patient outcomes. Challenges in obtaining intravenous access mean that the intraosseous access may facilitate earlier drug administration. However, time from administration to the central circulation is unclear with pharmacokinetic data limited mainly to animal studies. Observational studies comparing the effect of intravenous and intraosseous drug administration on patient outcomes are challenging to interpret because of resuscitation time bias and other confounders. To date, no randomised controlled trial has directly compared the effect on patient outcomes of intraosseous compared with intravenous drug administration in cardiac arrest. The International Liaison Committee on Resuscitation has described the urgent need for randomised controlled trials comparing the intravenous and intraosseous route in adult out-of-hospital cardiac arrest. Ongoing clinical trials will directly address this knowledge gap., Competing Interests: Conflicts of interest: GDP is chief investigator of the PARAMEDIC-3 trial. JPN, AW, and KC are funded PARAMEDIC-3 trials co-investigators. NR is principal investigator of PARAMEDIC-3 for the Welsh Ambulance Service. JPN and GDP are editors of Resuscitation. KC is an editorial board member of Resuscitation., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Administration of epinephrine has been associated with worse neurological outcomes for survivors of out-of-hospital cardiac arrest. The publication of the 2018 PARAMEDIC-2 trial, a randomized and double-blind study of epinephrine in out-of-hospital cardiac arrest, provides the strongest evidence to date that epinephrine increases return of spontaneous circulation (ROSC) but not neurologically intact survival. This study aims to determine if Emergency Medical Services (EMS) cardiac arrest protocols have changed since the publication of PARAMEDIC-2., Methods: States in the US utilizing mandatory or model state-wide EMS protocols, including Washington DC, were included in this study. The nontraumatic cardiac arrest protocol as of January 1, 2018 was compared to the protocol in effect on January 1, 2021 to determine if there was a change in the administration of epinephrine. Protocols were downloaded from the relevant state EMS website. If a protocol could not be obtained, the state medical director was contacted., Results: A 2021 state-wide protocol was found for 32/51 (62.7%) states. Data from 2018 were available for 21/51 (41.2%) states. Of the 11 states without data from 2018, all follow Advanced Cardiac Life Support (ACLS) guidelines in the 2021 protocol. Five (15.6%) of the states with a state-wide protocol made a change in the cardiac arrest protocols. Maximum cumulative epinephrine dose was limited to 4mg in Maryland and 3mg in Vermont. Rhode Island changed epinephrine in shockable rhythms to be administered after three cycles of cardiopulmonary resuscitation (CPR) and an anti-arrhythmic. Rhode Island also added an epinephrine infusion as an option. No states removed epinephrine administration from their cardiac arrest protocol. Simple statistical analysis was performed with Microsoft Excel., Conclusion: Several states have adjusted cardiac arrest protocols since 2018. The most frequent change was limiting the maximum cumulative dosage of epinephrine. One state changed timing of epinephrine dosing depending on the rhythm and also provided an option of an epinephrine infusion in place of bolus dosing. While the sample size is small, these changes may reflect the future direction of prehospital cardiac arrest protocols. Significant limitations apply, including the exclusion of local and regional protocols which are more capable of quickly adjusting to new research. Additionally, this study is only focused on EMS in the United States.

Background: Patients resuscitated from out-of-hospital cardiac arrest (OHCA) have a high morbidity and mortality risk and often develop post-cardiac arrest syndrome (PCAS) involving systemic inflammation. The severity of the inflammatory response is associated with adverse outcome, with anoxic irreversible brain injury as the leading cause of death following resuscitated OHCA. The study aimed to investigate the anti-inflammatory and neuroprotective effect of pre-hospital administration of a high-dose glucocorticoid following OHCA., Methods: The study is an investigator-initiated, randomized, multicenter, single-blinded, placebo-controlled, clinical trial. Inclusion will continue until one hundred twenty unconscious OHCA patients surviving a minimum of 72 h are randomized. Intervention is a 1:1 randomization to an infusion of methylprednisolone 250 mg following a minimum of 5 min of sustained return of spontaneous circulation in the pre-hospital setting. Methylprednisolone will be given as a bolus infusion of 1 × 250 mg (1 × 4 mL) over a period of 5 min. Patients allocated to placebo will receive 4 mL of isotonic saline (NaCl 0.9%). Main eligibility criteria are OHCA of presumed cardiac cause, age ≥ 18 years, Glasgow Coma Scale ≤ 8, and sustained ROSC for at least 5 min. Co-primary endpoint: Reduction of interleukin-6 and neuron-specific-enolase. Secondary endpoints: Markers of inflammation, brain, cardiac, kidney and liver damage, hemodynamic and hemostatic function, safety, neurological function at follow-up, and mortality. A research biobank is set up with blood samples taken daily during the first 72 h from hospitalization to evaluate primary and secondary endpoints., Discussion: We hypothesize that early anti-inflammatory steroid treatment in the pre-hospital setting can mitigate the progression of PCAS following resuscitated OHCA. Primary endpoints will be assessed through analyses of biomarkers for inflammation and neurological damage taken during the first 72 h of admission., Trial Registration: EudraCT number: 2020-000855-11 ; submitted March 30, 2020 ClinicalTrials.gov Identifier: NCT04624776; submitted October 12, 2020, first posted November 10, 2020., (© 2022. The Author(s).)

Background: Out-of-hospital cardiac arrest (OHCA) with shockable rhythms, including ventricular fibrillation and pulseless ventricular tachycardia, is associated with better prognosis and neurological outcome than OHCA due to other rhythms. Antiarrhythmic drugs, including lidocaine and amiodarone, are often used for defibrillation. This study aimed to compare the effects of lidocaine and amiodarone on the prognosis and neurological outcome of patients with OHCA due to shockable rhythms in a real-world setting., Methods: We conducted a retrospective observational study using a multicenter OHCA registry of 91 participating hospitals in Japan. We included adult patients with shockable rhythms, such as ventricular fibrillation and pulseless ventricular tachycardia, who were administered either lidocaine or amiodarone. The primary outcome was 30-day survival, and the secondary outcome was a good neurological outcome at 30 days. We compared the effects of lidocaine and amiodarone for patients with OHCA due to shockable rhythms for these outcomes using logistic regression analysis after propensity score matching (PSM)., Results: Of the 51,199 patients registered in the OHCA registry, 1970 patients were analyzed. In total, 105 patients (5.3%) were administered lidocaine, and 1865 (94.7%) were administered amiodarone. After performing PSM with amiodarone used as the reference, the odds ratios and 95% confidence intervals of lidocaine use for 30-day survival and 30-day good neurological outcome were 1.44 (0.58-3.61) and 1.77 (0.59-5.29), respectively., Conclusion: The use of lidocaine and amiodarone for patients with OHCA due to shockable rhythms within a real-world setting showed no significant differences in short-term mortality or neurological outcome. There is no evidence that either amiodarone or lidocaine is superior in treatment; thus, either or both drugs could be administered., (© 2022. The Author(s).)

Objective: Current guidelines for cardiopulmonary resuscitation (CPR) recommend that standard-dose epinephrine be administered every 3-5 minutes during cardiac arrest. However, there is a knowledge gap regarding the optimal epinephrine dosing interval. This study aimed to examine the association between epinephrine dosing intervals and outcomes after out-of-hospital cardiac arrest (OHCA)., Methods: This was a nationwide population-based observational study using data from a Japanese government-led registry of OHCA, including patients who experienced OHCA in Japan from 2011 to 2017. We defined the epinephrine dosing interval as the time interval between the first epinephrine administration and return of spontaneous circulation in the prehospital setting, divided by the total number of epinephrine doses. The primary outcome was 1-month neurologically favorable survival., Results: A total of 10,965 patients (mean (SD) age, 75.8 (14.3) years; 59.8% male) were included. The median epinephrine dosing interval was 3.5 minutes (IQR, 2.5-4.5; mean (SD), 3.6 (1.8)). Only approximately half of the patients received epinephrine administration with a standard dosing interval, as recommended in the current CPR guidelines. After multivariable adjustment, compared with the standard dosing interval, neither shorter nor longer epinephrine dosing intervals were associated with neurologically favorable survival after OHCA (Short vs Standard: adjusted OR 0.87 [95%CI 0.66-1.15]; and Long vs Standard: adjusted OR 1.08 [95%CI 0.76-1.55]). Similar associations were observed in propensity score-matched analyses., Conclusions: The epinephrine dosing interval was not associated with 1-month neurologically favorable survival after OHCA. Our findings do not deny the recommended epinephrine dosing interval in the current CPR guidelines.

Objective: Clinical trials for patients with shock-refractory out-of-hospital cardiac arrest (OHCA), including the Amiodarone, Lidocaine or Placebo (ALPS) trial, have been unable to demonstrate definitive benefit after treatment with antiarrhythmic drugs. A Bayesian approach, combining the available evidence, may yield additional insights., Methods: We conducted a reanalysis of the ALPS trial comparing treatment with amiodarone or lidocaine with placebo in patients with OHCA following shock-refractory ventricular fibrillation or ventricular tachycardia (VF/VT). We used Bayesian regression to assess the probability of improved survival or improved neurological outcome on the 7-point modified Rankin Scale. We derived weak, moderate and strong priors from a previous clinical trial., Results: The original ALPS trial randomised 3026 adult patients with OHCA to amiodarone (n=974, survival to hospital discharge 24.4%), lidocaine, (n=993, survival 23.7%) or placebo (n=1059, survival 21.0%). In our reanalysis the probability of improved survival from amiodarone ranged from 83% (strong prior) to 95% (weak prior) compared with placebo and from 78% (strong) to 90% (weak) for lidocaine-an estimated improvement in survival of 2.9% (IQR 1.4%-3.8%) for amiodarone and 1.7% (IQR 0.84%-3.2%) for lidocaine over placebo (moderate prior). The probability of improved neurological outcome from amiodarone ranged from 96% (weak) to 99% (strong) compared with placebo and from 88% (weak) to 96% (strong) for lidocaine., Conclusions: In a Bayesian reanalysis of patients with shock-resistant VF/VT OHCA, treatment with amiodarone had high probabilities of improved survival and neurological outcome, while treatment with lidocaine had a more modest benefit., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The Calcium for Out-of-hospital Cardiac Arrest (COCA) trial was a randomized, placebo-controlled, double-blind trial of calcium for out-of-hospital cardiac arrest. The primary and secondary outcomes have been reported previously. This article describes the long-term outcomes of the trial., Methods: Patients aged ≥18 years were included if they had a non-traumatic out-of-hospital cardiac arrest during which they received adrenaline. The trial drug consisted of calcium chloride (5 mmol) or saline placebo given after the first dose of adrenaline and again after the second dose of adrenaline for a maximum of two doses. This article presents pre-specified analyses of 6-month and 1-year outcomes for survival, survival with a favorable neurological outcome (modified Rankin Scale of 3 or less), and health-related quality of life., Results: A total of 391 patients were analyzed. At 1 year, 9 patients (4.7%) were alive in the calcium group while 18 (9.1%) were alive in the placebo group (risk ratio 0.51; 95% confidence interval 0.24, 1.09). At 1 year, 7 patients (3.6%) were alive with a favorable neurological outcome in the calcium group while 17 (8.6%) were alive with a favorable neurological outcome in the placebo group (risk ratio 0.42; 95% confidence interval 0.18, 0.97). Outcomes for health-related quality of life likewise suggested harm of calcium but results were imprecise with wide confidence intervals., Conclusions: Effect estimates remained constant over time suggesting harm of calcium but with wide confidence intervals. The results do not support calcium administration during out-of-hospital cardiac arrest., Trial Registration: ClinicalTrials.gov-number, NCT04153435., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Targeted temperature management at 33 °C (TTM33) has been employed in effort to mitigate brain injury in unconscious survivors of out-of-hospital cardiac arrest (OHCA). Current guidelines recommend prevention of fever, not excluding TTM33. The main objective of this study was to investigate if TTM33 is associated with mortality in patients with vasopressor support on admission after OHCA., Methods: We performed a post hoc analysis of patients included in the TTM-2 trial, an international, multicenter trial, investigating outcomes in unconscious adult OHCA patients randomized to TTM33 versus normothermia. Patients were grouped according to level of circulatory support on admission: (1) no-vasopressor support, mean arterial blood pressure (MAP) ≥ 70 mmHg; (2) moderate-vasopressor support MAP < 70 mmHg or any dose of dopamine/dobutamine or noradrenaline/adrenaline dose ≤ 0.25 µg/kg/min; and (3) high-vasopressor support, noradrenaline/adrenaline dose > 0.25 µg/kg/min. Hazard ratios with TTM33 were calculated for all-cause 180-day mortality in these groups., Results: The TTM-2 trial enrolled 1900 patients. Data on primary outcome were available for 1850 patients, with 662, 896, and 292 patients in the, no-, moderate-, or high-vasopressor support groups, respectively. Hazard ratio for 180-day mortality was 1.04 [98.3% CI 0.78-1.39] in the no-, 1.22 [98.3% CI 0.97-1.53] in the moderate-, and 0.97 [98.3% CI 0.68-1.38] in the high-vasopressor support groups with regard to TTM33. Results were consistent in an imputed, adjusted sensitivity analysis., Conclusions: In this exploratory analysis, temperature control at 33 °C after OHCA, compared to normothermia, was not associated with higher incidence of death in patients stratified according to vasopressor support on admission. Trial registration Clinical trials identifier NCT02908308 , registered September 20, 2016., (© 2022. The Author(s).)

Background: Ischemic brain injury is a major hurdle that limits the survival of resuscitated out-of-hospital cardiac arrest (OHCA)., Methods: The aim of this study is to assess the feasibility and potential for reduction of ischemic brain injury in adult OHCA patients treated with high- or low-dose Neu2000K, a selective blocker of N-methyl-D-aspartate (NMDA) type 2B receptor and also a free radical scavenger, or given placebo. This study is a phase II, multicenter, randomized, double-blinded, prospective, intention-to-treat, placebo-controlled, three-armed, safety and efficacy clinical trial. This trial is a sponsor-initiated trial supported by GNT Pharma. Successfully resuscitated OHCA patients aged 19 to 80 years would be included. The primary outcome is blood neuron-specific enolase (NSE) level on the 3rd day. The secondary outcomes are safety, efficacy defined by study drug administration within 4 h in > 90% of participants, daily NSE up to 5th day, blood S100beta, brain MRI apparent diffusion coefficient imaging, cerebral performance category (CPC), and Modified Rankin Scale (mRS) at 5th, 14th, and 90th days. Assuming NSE of 42 ± 80 and 80 ± 80 μg/L in the treatment (high- and low-dose Neu2000K) and control arms with 80% power, a type 1 error rate of 5%, and a 28% of withdrawal prior to the endpoint, the required sample size is 150 patients., Discussion: The AWAKE trial explores a new multi-target neuroprotectant for the treatment of resuscitated OHCA patients., Trial Registration: ClinicalTrials.gov NCT03651557 . Registered on August 29, 2018., (© 2022. The Author(s).)

Aims: The delayed administration of epinephrine has been proven to worsen the neurological outcomes of patients with out-of-hospital cardiac arrest (OHCA) and shockable rhythm or asystole. We aimed to investigate whether the delayed administration of epinephrine might also worsen the neurological outcomes of patients with witnessed OHCA and initial pulseless electrical activity (PEA)., Methods and Results: The JAAM-OHCA Registry is a multicentre registry including OHCA patients between 2014 and 2017. Patients with emergency medical services (EMS)-treated OHCA and initial PEA rhythm were included. The primary exposure was the time from the EMS call to the administration of epinephrine. The secondary exposure was the time to epinephrine dichotomized as early (≤15 min) or delayed (>15 min). The primary outcome was the achievement of a favourable neurological outcome, defined as Cerebral Performance Categories Scale 1-2 at 30 days after OHCA. Out of 34 754 patients with OHCA, 3050 patients were included in the present study. After adjusting for potential confounders, the delayed administration of the epinephrine was associated with a lower likelihood of achieving a favourable neurological outcome [adjusted odds ratio (OR) 0.96; 95% confidence interval (CI) 0.93-0.99; P = 0.016]. The percentage of patients who achieved a favourable neurological outcome in the delayed epinephrine group was lower than that in the early epinephrine group (1.3% vs. 4.7%; adjusted OR 0.33; 95% CI 0.15-0.72; P = 0.005). A restricted cubic spline analysis demonstrated that delayed epinephrine administration could decrease the likelihood of achieving a favourable neurological outcome; this was significant within the first 10 min., Conclusions: The delayed administration of epinephrine was associated with worse neurological outcomes in patients with witnessed OHCA patients with initial PEA., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Importance: No large randomised controlled trial has assessed the potential benefits on neurologic outcomes of prehospital sodium bicarbonate administration in patients with nontraumatic out-of-hospital cardiac arrest (OHCA)., Objective: To obtain information of assistance in designing a randomised controlled trial of bicarbonate therapy after OHCA in specific patient subgroups., Design: We conducted two, separate, simultaneous, retrospective studies of two distinct, unlinked datasets., Setting and Participants: One dataset was a French nationwide population-based registry (RéAC Registry, French dataset) and the other was a randomised controlled trial comparing continuous to interrupted chest compressions in North America (ROC-CCC trial, North-American dataset)., Intervention: We investigated whether prehospital bicarbonate administration was associated with better neurologic outcomes., Outcome Measures and Analyses: The main outcome measure was the functional outcome at hospital discharge. To adjust for potential confounders, we conducted a nested propensity-score-matched analysis with inverse probability-of-treatment weighting., Main Results: In the French dataset, of the 54 807 patients, 1234 (2.2%) received sodium bicarbonate and 450 were matched. After propensity-score matching, sodium bicarbonate was not associated with a higher likelihood of favourable functional outcomes on day 30 [adjusted odds ratio (aOR), 0.912; 95% confidence interval (95%CI), 0.501-1.655]. In the North-American dataset, of the 23 711 included patients, 4902 (20.6%) received sodium bicarbonate and 1238 were matched. After propensity-score matching, sodium bicarbonate was associated with a lower likelihood of favourable functional outcomes at hospital discharge (aOR, 0.45; 95% CI, 0.34-0.58)., Conclusion: In patients with OHCA, prehospital sodium bicarbonate administration was not associated with neurologic outcomes in a French dataset and was associated with worse neurologic outcomes in a North-American dataset. Given the considerable variability in sodium bicarbonate use by different prehospital care systems and the potential resuscitation-time bias in the present study, a large randomised clinical trial targeting specific patient subgroups may be needed to determine whether sodium bicarbonate has a role in the prehospital management of prolonged OHCA., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)