OBJECTIVES:To evaluate the cost-effectiveness of implementing an extracorporeal cardiopulmonary resuscitation (ECPR) strategy for refractory out-of-hospital cardiac arrest (OHCA) compared with current practice in Singapore, where it is not routinely used. DESIGN:We performed a simulation-based cost-effectiveness analysis using a decision tree to model acute phase and a Markov model for long-term outcomes over a lifetime horizon, from a healthcare provider perspective. SETTING:Singapore healthcare system. PATIENTS:Nontraumatic adult OHCA patients from Singapore with initial shockable rhythm and no prehospital return of spontaneous circulation were analyzed. INTERVENTIONS:We modeled the implementation of an ECPR strategy and compared it with current practice using only conventional cardiopulmonary resuscitation. Transition probabilities of existing practice were derived from the nationwide Singapore OHCA registry (Pan-Asian Resuscitation Outcomes Study: PAROS), (2010-2016), while ECPR outcomes were based on the Comprehensive Registry of Intensive Care for OHCA Survival in Osaka (Osaka CRITICAL study) (2012-2019). Costs and quality-adjusted life-years (QALYs) were compared between strategies, with scenario analyses conducted to assess the impact of lower age eligibility thresholds and increased transport time to extracorporeal membrane oxygenation-capable hospitals. Incremental cost-effectiveness ratios (ICERs) were estimated using a willingness-to-pay threshold of S$45,000 per QALY. MEASUREMENTS AND MAIN RESULTS:A total of 1462 OHCA cases from Singapore were analyzed; the mean age of patients was 57 years (sd, 11 yr), and 87% were male. In base-case analysis, ICER was estimated at $34,320/QALY, with a positive net monetary benefit of $8,532. Scenario analyses demonstrated that an age-restricted ECPR strategy (< 65 yr) yielded a similar ICER ($33,469/QALY) to the base case. In contrast, incorporating a 10-minute transport extension slightly exceeded the willingness-to-pay threshold ($47,158/QALY). CONCLUSIONS:In this modeling study, adopting an ECPR strategy for OHCA in Singapore was likely to be cost-effective across different age-based eligibility thresholds; however, it was sensitive to delays in transport time. Further implementation research is important to guide scale-up and policy decisions.

Abstract Background A lower serum lactate/albumin ratio has been linked to favorable outcomes in critically ill patients. Objective We investigated whether the serum lactate/albumin ratio could predict the likelihood of benefiting from targeted temperature management (TTM) after out‐of‐hospital cardiac arrest (OHCA). Methods Using a nationwide Japanese registry, we reviewed patients aged ≥18 years with OHCA of medical cause who received TTM during the study period. The patients were grouped by serum lactate/albumin ratio quartile at hospital arrival (first quartile, ≤1.77, n = 219; second quartile, 1.77 to ≤2.59, n = 211; third quartile, 2.59 to ≤3.62, n = 212; fourth quartile, >3.62, n = 191) for targeted temperatures of ≤34°C and ≥35°C. The primary outcome was 30‐day survival with favorable neurological outcomes, defined as Cerebral Performance Category scores of 1 or 2. Results The targeted temperature was ≤34°C in 833 patients and ≥35°C in 437 patients. Multivariable logistic regression analysis in the ≤34°C subgroup illustrated that patients in the second [adjusted odds ratio (AOR) = 0.60, 95% confidence interval (CI) = 0.36–0.99], third (AOR = 0.24, 95% CI = 0.14–0.39), and fourth quartiles (AOR = 0.12, 95% CI = 0.06–0.22) had lower odds of favorable neurological outcomes than those in the first quartile. Similar results were obtained in the ≥35°C subgroup (p for interaction = 0.86). Conclusions Among patients who received TTM after OHCA, those in the lowest serum lactate/albumin ratio quartile at hospital admission experienced significantly better neurological outcomes.

OBJECTIVES:To evaluate temporal trends in clinical outcomes among nontraumatic out-of-hospital cardiac arrest (OHCA) patients transported to critical care medical centers (CCMCs) in Japan. DESIGN:Retrospective cohort study. SETTING:Nationwide multicenter registry involving CCMCs in Japan, which are government-designated advanced emergency care institutions specializing in intensive resuscitation and post-cardiac arrest management. Data were obtained from the Japanese Association for Acute Medicine OHCA (JAAM-OHCA) registry from June 1, 2014, to December 31, 2022. PATIENTS:Adult patients (≥ 18 yr old) with nontraumatic OHCA who were transported to CCMCs and had Utstein-style prehospital data available. Patients were categorized into three calendar periods (2014-2016, 2017-2019, and 2020-2022) for temporal comparison. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Among 61,725 eligible patients, the proportion with favorable neurologic outcomes decreased from 3.6% (2014-2016) to 3.3% (2017-2019) and further to 2.5% (2020-2022). Using multivariable logistic regression, the adjusted odds ratios (aORs) for favorable neurologic outcome were 1.01 (95% CI, 0.89-1.15) in 2017-2019 and 0.83 (95% CI, 0.72-0.94) in 2020-2022, compared with 2014-2016. Similarly, 30-day survival declined during the same period, from 6.9% to 6.8% and 5.4%. In most predefined subgroups, similar trends were observed. In contrast, neurologic outcomes improved among candidates for extracorporeal cardiopulmonary resuscitation (ECPR), with an aOR of 1.43 (95% CI, 1.06-1.93) in 2020-2022 compared with 2014-2016. CONCLUSIONS:Outcomes among OHCA patients transported to CCMCs remained stable until 2019 but declined during the COVID-19 pandemic period. However, improved outcomes among patients eligible for ECPR suggest that timely and targeted post-arrest interventions may improve outcomes in selected populations.

Predicting postpartum hemorrhage risk can be useful in clinical settings. We aimed to develop and validate a clinical prediction model for postpartum hemorrhage in patients who undergo elective cesarean section. This retrospective observational study included patients who underwent elective cesarean section between January 2008 and September 2021. The primary outcome to be predicted was postpartum hemorrhage, defined as blood loss of ≥ 1500 mL during surgery. We used data prior to January 2018 for the development cohort and after for the validation cohort. We then constructed a multivariate logistic regression model. The model performance, including discrimination and calibration, was evaluated and its diagnostic ability was assessed. Of the 4070 patients, 860 (21.0

BACKGROUND:Severe traumatic brain injury (TBI) remains a major cause of death and disability worldwide. Secondary brain injury due to hypoxia, hypotension, and intracranial hypertension worsens outcomes. The hybrid emergency room (ER) system integrates computed tomography, interventional radiology, and surgery in one suite, enabling an immediate diagnosis and intervention without patient transfer. This study evaluated its long-term effects on functional outcomes in severe TBI. METHODS:This retrospective before-after study included patients with severe TBI (defined as Head Abbreviated Injury Scale ≥ 3, Glasgow Coma Scale [GCS] ≤ 8) admitted to Osaka General Medical Center between 2007 and 2019. Patients were classified into conventional (2007-2011) and hybrid ER (2011-2019) groups. The primary outcome was long-term functional status at follow-up assessed by the Glasgow Outcome Scale-Extended (GOS-E). The secondary outcome was GOS-E at hospital discharge. Multivariate logistic regression adjusted for age, GCS, and Injury Severity Score. An exploratory assessment of psychological and quality-of-life measures among long-term survivors was also performed. RESULTS:A total of 127 patients were analyzed. The hybrid ER group had significantly shorter times to computed tomography (11 min vs. 27 min; p < 0.001) and surgery (48 min vs. 69 min; p < 0.001). Favorable outcomes (GOS-E ≥ 5) were more frequent in the hybrid ER group at discharge (37% vs. 16%) and follow-up (52% vs. 39%). After adjustment for major prognostic factors, management in the hybrid ER group was associated with favorable functional outcomes (adjusted OR 4.47; 95% CI 1.47-13.60; p = 0.008). The exploratory findings on psychological and quality-of-life outcomes were descriptive with no formal conclusions drawn, owing to the limited sample size and low response rate. CONCLUSION:Hybrid ER management was associated with more favorable long-term functional outcomes compared with conventional management. The wide confidence intervals and differences in follow-up duration between groups preclude definitive conclusions; however, these findings are consistent with a sustained benefit of early integrated trauma care and warrant further prospective investigation.

Aim: We aimed to assess the association between base excess (BE) levels and neurological outcomes in patients with out-of-hospital cardiac arrest (OHCA), accounting for the time from cardiac arrest onset to blood sampling. Methods: This multicentre study was conducted in Osaka, Japan, and enrolled consecutive patients with OHCA who were transported to 16 medical centres between 2012 and 2021. Patients aged ≥ 18 years with witnessed OHCA and available BE measurements upon hospital arrival were examined. Patients were stratified into Q1 (BE ≤ −21.1 mmol/L), Q2 (−21.1 < BE ≤ −15.7 mmol/L), Q3 (−15.7 < BE ≤ −10.4 mmol/L) and Q4 (BE > −10.4 mmol/L) groups based on BE levels. The primary outcome was 1-month survival with a favourable neurological outcome (Cerebral Performance Category scale score: 1 or 2). Results: Among the 23,854 patients with OHCA, only 6066 were included in the final analysis. Approximately 3.2 %, 4.7 %, 9.9 % and 23.7 % of patients in the Q1, Q2, Q3 and Q4 groups, respectively, achieved favourable neurological outcomes at 1 month. Compared with Q4, the adjusted odds ratio for a favourable neurological outcome in Q1 was 0.13. Subgroup analysis revealed a significant interaction between prehospital return of spontaneous circulation (ROSC) and neurological outcomes; neurological outcomes worsened as BE decreased in patients with ROSC but not in those without ROSC. Conclusion: Lower BE levels upon hospital arrival are associated with poorer neurological outcomes and may serve as prognostic indicators in patients with OHCA who achieved prehospital ROSC.

AbstractBackgroundWarfarin, a vitamin K antagonist, is widely used for preventing and treating thromboembolic diseases. While guidelines exist for managing elevated prothrombin time‐international normalized ratio (INR) in patients on warfarin, the treatment for warfarin overdose in these patients is yet to be standardized.Case PresentationA 41‐year‐old woman ingested 230 mg of warfarin with suicidal intent, along with other medications. Initially unconscious, her INR was 1.0, and laboratory results were normal. Prophylactic continuous menaquinone‐4, vitamin K2, injections were administered before the INR increased. After stopping vitamin K2 72 h later, her INR rose to 1.8, but she recovered without severe coagulopathy or bleeding, despite a high initial warfarin concentration.ConclusionThis is the first case of warfarin overdose managed with prophylactic vitamin K2 injections before INR elevation, successfully preventing severe complications. Prophylactic vitamin K infusion may be a practical approach for warfarin overdose treatment in non‐dependent patients.

Background The causes underlying out‐of‐hospital cardiac arrest (OHCA) are rarely investigated. This study aimed to investigate causes of OHCA in CRITICAL (Comprehensive Registry of In‐Hospital Intensive Care for OHCA Survival), a multicenter OHCA registry in Osaka, Japan. Methods Nontraumatic patients with OHCA (by CARES [Cardiac Arrest Registry to Enhance Survival] criteria) aged 18 to 90 years between July 1, 2012 and December 31, 2020 were included. By Japanese law, all patients with OHCA (resuscitated or not) must be transported to the emergency department where death is declared if resuscitation is unsuccessful; this latter group was considered presumed sudden cardiac deaths whereas those surviving to hospitalization were considered resuscitated OHCA. We compared underlying causes of OHCA in presumed sudden cardiac deaths, survivors of OHCA (alive 30 days after the event), and nonsurvivors of OHCA (died during hospitalization). Causes were confirmed when autopsy or postresuscitation hospital workup was performed and probable when determined by attending physician impression (partial workup). Results Of 12 252 total OHCAs, 8005 (65.3%) were. presumed sudden cardiac deaths, 4247 (34.7%) were resuscitated, and 1293 (10.6%) were survivors. Resuscitated OHCA cardiac causes comprised 73.2% (n=3110) and noncardiac causes 26.8% (n=1137). Cardiac cause, most commonly acute coronary syndrome, was more prevalent in survivors of OHCA than nonsurvivors (85.7% [n=1137] versus 67.8% [n=2002]; P<0.001). Although 40.4% of the survived at 30 days cases were acute coronary syndrome, cerebrovascular disease accounted for 9.8% of nonsurvivors of OHCA and nearly one fifth (n=144, 17.8%) of middle‐aged cases. Conclusions Cardiac cause was more common in survivors than cases dying in the emergency room (sudden deaths) or in hospital after initial resuscitation (nonsurvivors of OHCA). Causes in nonsurvivors of OHCA who died in hospital were more heterogeneous than those of survivors of OHCA, especially cerebrovascular emergencies.

Extracorporeal cardiopulmonary resuscitation (ECPR) requires advanced skills for induction and management. This study evaluated whether the outcomes of ECPR differ by institutional volume. Using the Japanese Association for Acute Medicine–Out-of-Hospital Cardiac Arrest (JAAM-OHCA) registry, we analyzed adult patients (aged ≥18 years) who received ECPR between 2014 and 2020, focusing on 30 day in-hospital survival and favorable neurologic prognosis at 30 days defined as Cerebral Performance Category (CPC) 1–2. Facilities were categorized into tertiles by annual ECPR volume. Multivariable logistic regression examined outcomes across low (≤4.7 cases/year), medium (4.8–7.8 cases/year), and high (≥7.9 cases/year) volume groups. A total of 1,759 patients from 83 centers were included, with an overall 30 day survival of 21.1% and CPC 1–2 rate of 10.1%. We observed no statistically significant differences in the respective rates of 30 day survival and neurologic outcomes in the medium ECPR volume group (adjusted odds ratios 1.09 [95% confidence interval {CI}, 0.82–1.47] and 0.85 [0.56–1.26]) and higher ECPR volume group (adjusted odds ratios 1.27 [95% CI, 0.95–1.70] and 1.11 [0.75–1.63]) compared with the lower ECPR volume group. These findings suggest that ECPR outcomes for out-of-hospital cardiac arrest are not significantly affected by institutional ECPR volume.

BACKGROUND:Acute coronary syndrome (ACS) requires prompt diagnosis and treatment. Although "OPQRST" (Onset, Provocation, Quality, Region/Radiation, Symptoms, and Time) is commonly used, the evidence linking emergency department (ED) chest pain characteristics to ACS remains inconclusive. This study evaluated detailed symptoms in ED patients with and without ACS using a broad chest pain registry with symptom data. METHODS AND RESULTS:This single-center prospective study was conducted at Rakuwakai-Otowa Hospital in Kyoto, Japan, as a pilot study for a multicenter registry. We enrolled 420 consecutive adult patients presenting with chest pain at the ED from June 2022 to May 2023. Baseline characteristics (including symptoms) and outcomes were recorded. Of the 420 patients, 65 (15.5%) were diagnosed with ACS. Patients with and without ACS differed in the proportion with sudden onset (58.5% vs. 27.6%, respectively), radiation to the tooth (9.2% vs. 0.6%, respectively), and cold sweat (diaphoresis; 44.6% vs. 16.9%, respectively). In the overall population, positive likelihood ratios were 2.12 (95% confidence interval [CI] 1.63-2.76) for sudden onset, 16.38 (95% CI 3.38-79.41) for radiation to the tooth, and 2.64 (95% CI 1.85-3.77) for diaphoresis. CONCLUSIONS:This study in a suburban area of Japan (one of the most super-aged societies) identified key chest pain characteristics in a broad chest pain cohort (i.e., sudden onset, radiation to the tooth, and diaphoresis) that may help with the rapid triage and diagnosis of ACS.

Background: The patients most likely to benefit from targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA) are unknown. We investigated whether a lower serum lactate/albumin ratio (SLAR) at hospital arrival was associated with favorable neurological outcomes in patients receiving TTM after OHCA. Methods: Using the nationwide registry led by the Japanese Association for Acute Medicine, we reviewed the records of adults aged ≥18 years with OHCA who received TTM after the return of spontaneous circulation between June 1, 2014, and December 31, 2022. SLAR was recorded at hospital arrival. Patients with OHCA caused by trauma such as falls, hanging, drowning, poisoning, burns, or asphyxia were excluded, as were patients with missing data, those who received extracorporeal membrane oxygenation, and those for whom the time the emergency call to the measurement of laboratory data exceeded 120 min. The primary outcome was 30-day survival with favorable neurological outcome, defined as cerebral performance category scale 1 or 2. The enrolled patients were categorized according to the quartiles of SLAR for targeted temperatures of ≤34°C (n = 833; first quartile: SLAR ≤ 1.73, n = 209; second quartile: 1.73 < SLAR ≤ 2.54, n = 208; third quartile: 2.54 < SLAR ≤ 3.53, n = 209; fourth quartile: SLAR > 3.53, n = 207) and ≥35°C (n = 437; first quartile: SLAR ≤ 1.85, n = 111; second quartile: 1.85< SLAR ≤ 2.68, n = 108; third quartile: 2.68< SLAR ≤ 3.75, n = 109; fourth quartile: SLAR > 3.75, n = 109). Multivariable logistic regression analysis was performed to adjust for critical factors. Results: In patients with targeted temperature ≤ 34°C, the likelihood of favorable neurological outcomes was lower in the second (adjusted odds ratio [AOR] = 0.59, 95% confidence interval [CI] = 0.35–0.98), third (AOR = 0.25, 95% CI = 0.15–0.42), and fourth quartiles (AOR = 0.10, 95% CI = 0.05–0.18) than in the first quartile. In the group with target temperature ≥ 35°C, the likelihood of favorable neurological outcomes was similarly lower in the second (AOR = 0.38, 95% CI = 0.19–0.74), third (AOR = 0.19, 95% CI = 0.09–0.40), and fourth quartiles (AOR = 0.07, 95% CI = 0.03–0.17) than in the first quartile. Conclusions: A lower SLAR at hospital arrival was significantly associated with better neurological outcomes in patients receiving TTM after OHCA regardless of the targeted temperature.

INTRODUCTION:Temperature control is a fundamental intervention for neuroprotection following resuscitation from cardiac arrest. However, evidence regarding the efficacy of hypothermia in post-cardiac arrest syndrome (PCAS) remains unclear. Retrospective studies suggest that the clinical effectiveness of hypothermia may depend on the severity of PCAS. The R-CAST OHCA trial aims to compare the efficacy of hypothermia versus normothermia in improving 30-day neurological outcomes in patients with moderately severe PCAS following out-of-hospital cardiac arrest. METHODS AND ANALYSIS:The multicentre, single-blind, parallel-group, superiority, randomised controlled trial (RCT) is conducted with the participation of 35 emergency and critical care centres and/or intensive care units at academic and non-academic hospitals. The study enrols moderately severe PCAS patients, defined as those with a revised post-Cardiac Arrest Syndrome for induced Therapeutic Hypothermia score of 5.5-15.5. A target number of 380 participants will be enrolled. Participants are randomised to undergo either hypothermia or normothermia within 3 hours after return of spontaneous circulation. Patients in the hypothermia group are cooled and maintained at 34°C until 28 hours post-randomisation, followed by rewarming to 37°C at a rate of 0.25°C/hour. Patients in the normothermia group are maintained at normothermia (36.5°C-37.7°C). Total periods of intervention, including the cooling, maintenance and rewarming phases, will occur 40 hours after randomisation. Other treatments for PCAS can be determined by the treating physicians. The primary outcome is a favourable neurological outcome, defined as Cerebral Performance Category 1 or 2 at 30 days after randomisation and compared using an intention-to-treat analysis. ETHICS AND DISSEMINATION:This study has been approved by the Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital, Ethics Committee (approval number: R2201-001). Written informed consent is obtained from all participants or their authorised surrogates. Results will be disseminated via publications and presentations. TRIAL REGISTRATION NUMBER:jRCT1062220035.

Background The International Liaison Committee on Resuscitation (ILCOR) Research and Registries Committee previously reported 2015 data on systems of care and outcomes for out-of-hospital cardiac arrest (OHCA) from 16 registries and 2015 to 2017 data from 15 registries. To describe updated data on OHCA, we report the characteristics of OHCAs from 2018 through 2021. Methods We invited national and regional population-based OHCA registries to participate voluntarily and included emergency medical services-treated OHCAs. We collected descriptive summary data of core elements of the Utstein OHCA registry template from 2018 through 2021 at each registry. Results Thirteen national and five regional registries from North America, Europe, Asia, and Oceania were included in this report. The provision of bystander cardiopulmonary resuscitation ranged from 9.6% to 83.8% (median 61.7%) and shocks by public access automated external defibrillator from 0.5% to 11.7% (median 2.3%) in 2021. Survival to hospital discharge or 30-day survival for bystander-witnessed shockable OHCA ranged from 19.9% to 44.4% (median 28.3%), and neurologically favourable outcome ranged from 9.5% to 35.1% (median 22.0%) in 2021. The majority of registries showed that survival and favourable neurological outcomes were lower in the 2020-2021 COVID-19 pandemic period compared with those in 2018-2019. Conclusion This report from ILCOR presents summary data for OHCA systems of care and outcomes from 2018 through 2021 from 18 national and regional OHCA registries worldwide. We observed a persisting wide variability in OHCA characteristics and outcomes across registries and the potential impact of the COVID-19 pandemic within registries.

BACKGROUND:Prompt automated external defibrillator (AED) use and shock delivery are crucial for improving outcomes in patients with out-of-hospital cardiac arrest (OHCA). This study was aimed at elucidating the current patterns of AED use by lay rescuers in Japan and exploring the associated factors by lay rescuer type. METHODS:In this observational study, data from the All-Japan Utstein Registry, a nationwide population-based registry of OHCAs, were analyzed. Patients with OHCA due to nonexternal causes that were witnessed by citizens were included. The primary outcome was AED use, defined as AED pad application, by each bystander witness type. As an exploratory analysis, we performed a multivariable logistic regression analysis of factors that could be associated with AED use. RESULTS:In total, 33,426 individuals with OHCAs witnessed by citizens were included. Of these individuals, 20,410 were male (61.1%) with a median (interquartile range [IQR]) age of 80 (70, 87) years. AEDs were used in 12.6% of all OHCAs witnessed by citizens; and in 1.1%, 22.5%, and 37.7% of OHCAs witnessed by family members, citizens in public, and others, respectively. Regarding the OHCAs witnessed by citizens in public, female sex, weekends, and nighttime were associated with decreased AED use. Regardless of the witness type, dispatcher instructions and delays in response time were associated with increased AED use. CONCLUSION:We elucidated the current patterns of AED use in Japan by using a nationwide population-based OHCA registry. We found that patient characteristics and various situational and systemic factors can influence AED use by citizens.

AIM:To evaluate the impact of the COVID-19 pandemic on favourable neurological outcome after out-of-cardiac arrest (OHCA) witnessed by emergency medical services (EMS) personnels in Japan. METHODS:We conducted an interrupted time series analysis (ITSA) using a prospective, nationwide, population-based registry in Japan to assess 30-day favourable neurological outcome (Cerebral Performance Category 1 or 2), prehospital return of spontaneous circulation (ROSC), and 30-day survival among adult patients with EMS-witnessed OHCA during the pre-pandemic (January 2016-March 2020) and pandemic (April 2020-December 2021) periods. Subgroup analyses were performed by stratifying regions based on state of emergency declaration status. A controlled ITSA was conducted to compare outcome trends between areas with and without significant COVID-19 spread. RESULTS:In total, 58,315 adult patients with EMS-witnessed OHCA were identified. Favourable neurological outcome significantly declined during the pandemic (relative risk [RR], 0.80; 95 % CI, 0.71-0.91; p < 0.001). Prehospital ROSC and 30-day survival also decreased significantly (p < 0.05). In subgroup analyses, favourable neurological outcome declined in areas affected by COVID-19 spread (p < 0.001), while no significant change was observed in unaffected areas (p = 0.243). The controlled ITSA revealed a significantly greater decline in favourable neurological outcome in areas with COVID-19 spread compared with unaffected areas (RR, 0.77; 95 % CI, 0.60-0.98; p = 0.035). CONCLUSION:Favourable neurological outcomes among patients with EMS-witnessed OHCA in Japan were lower during the COVID-19 pandemic, particularly in regions affected by COVID-19 spread.