Review of Temperature Management in Traumatic Brain Injuries.

Therapeutic hypothermia (TH) for severe traumatic brain injury has seen restricted application due to the outcomes of randomized controlled trials (RCTs) conducted since 2000. In contrast with earlier RCTs, recent trials have implemented active normothermia management in control groups, ensuring comparable intensities of non-temperature-related therapeutic interventions, such as neurointensive care. This change in approach may be a contributing factor to the inability to establish the efficacy of TH. Currently, an active temperature management method using temperature control devices is termed "targeted temperature management (TTM)". One of the goals of TTM for severe traumatic brain injury is the regulation of increased intracranial pressure, employing TTM as a methodology for intracranial pressure management. Additionally, fever in traumatic brain injury has been acknowledged as contributing to poor prognosis, underscoring the importance of proactively preventing fever. TTM is also employed for the preemptive prevention of fever in severe traumatic brain injury. As an integral component of current neurointensive care, it is crucial to precisely delineate the targets of TTM and to potentially apply them in the treatment of severe traumatic brain injury.

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

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

Fluid balance during acute phase extracorporeal cardiopulmonary resuscitation and outcomes in OHCA patients: a retrospective multicenter cohort study.

OBJECTIVE: The association between fluid balance and outcomes in patients who underwent out-of-hospital cardiac arrest (OHCA) and received extracorporeal cardiopulmonary resuscitation (ECPR) remains unknown. We aimed to examine the above relationship during the first 24 h following intensive care unit (ICU) admission. METHODS: We performed a secondary analysis of the SAVE-J II study, a retrospective multicenter study involving OHCA patients aged ≥ 18 years treated with ECPR between 2013 and 2018 and who received fluid therapy following ICU admission. Fluid balance was calculated based on intravenous fluid administration, blood transfusion, and urine output. The primary outcome was in-hospital mortality. The secondary outcomes included unfavorable outcome (cerebral performance category scores of 3-5 at discharge), acute kidney injury (AKI), and need for renal replacement therapy (RRT). RESULTS: Overall, 959 patients met our inclusion criteria. In-hospital mortality was 63.6%, and the proportion of unfavorable outcome at discharge was 82.0%. The median fluid balance in the first 24 h following ICU admission was 3673 mL. Multivariable analysis revealed that fluid balance was significantly associated with in-hospital mortality (odds ratio (OR), 1.04; 95% confidence interval (CI), 1.02-1.06; p < 0.001), unfavorable outcome (OR, 1.03; 95% CI, 1.01-1.06; p = 0.005), AKI (OR, 1.04; 95% CI, 1.02-1.05; p < 0.001), and RRT (OR, 1.05; 95% CI, 1.03-1.07; p < 0.001). CONCLUSIONS: Excessive positive fluid balance in the first day following ICU admission was associated with in-hospital mortality, unfavorable outcome, AKI, and RRT in ECPR patients. Further investigation is warranted.

A Seasonal Variation of Clinical and Neurological Outcomes in Patients with Out-of-Hospital Cardiac Arrest Treated with Extracorporeal Cardiopulmonary Resuscitation: A Secondary Data Analysis of the SaveJ II Study.

The prognosis for patients with out-of-hospital cardiac arrest (OHCA) has been reported to be worse in the cold season. On the other hand, it is unclear whether a similar trend exists in OHCA patients who are treated with extracorporeal cardiopulmonary resuscitation (ECPR). This study was a retrospective multicenter registry study. We examined the association between ECPR and season. We compared the prognosis in four seasonal groups according to the day of occurrence. Multivariable logistic regression analysis was performed for the assessment of clinical and neurological outcomes. A total of 2024 patients with OHCA who received ECRP were included. There were no significant differences in in-hospital mortality (p = 0.649) and in the rate of favorable neurological outcome (p = 0.144). In the multivariable logistic regression, the seasonal factor was not significantly associated with worse in-hospital mortality (p = 0.855) and favorable neurological outcomes (p = 0.807). In this study, there was no seasonal variation in OHCA patients with ECPR.

Association between pupillary examinations and prognosis in patients with out-of-hospital cardiac arrest who underwent extracorporeal cardiopulmonary resuscitation: a retrospective multicentre cohort study.

BACKGROUND: In some cases of patients with out-of-hospital cardiac arrest (OHCA) who underwent extracorporeal cardiopulmonary resuscitation (ECPR), negative pupillary light reflex (PLR) and mydriasis upon hospital arrival serve as common early indicator of poor prognosis. However, in certain patients with poor prognoses inferred by pupil findings upon hospital arrival, pupillary findings improve before and after the establishment of ECPR. The association between these changes in pupillary findings and prognosis remains unclear. This study aimed to clarify the association of pupillary examinations before and after the establishment of ECPR in patients with OHCA showing poor pupillary findings upon hospital arrival with their outcomes. To this end, we analysed retrospective multicentre registry data involving 36 institutions in Japan, including all adult patients with OHCA who underwent ECPR between January 2013 and December 2018. We selected patients with poor prognosis inferred by pupillary examinations, negative pupillary light reflex (PLR) and pupil mydriasis, upon hospital arrival. The primary outcome was favourable neurological outcome, defined as Cerebral Performance Category 1 or 2 at hospital discharge. Multivariable logistic regression analysis was performed to evaluate the association between favourable neurological outcome and pupillary examination after establishing ECPR. RESULTS: Out of the 2,157 patients enrolled in the SAVE-J II study, 723 were analysed. Among the patients analysed, 74 (10.2%) demonstrated favourable neurological outcome at hospital discharge. Multivariable analysis revealed that a positive PLR at ICU admission (odds ration [OR] = 11.3, 95% confidence intervals [CI] = 5.17-24.7) was significantly associated with favourable neurological outcome. However, normal pupil diameter at ICU admission (OR = 1.10, 95%CI = 0.52-2.32) was not significantly associated with favourable neurological outcome. CONCLUSION: Among the patients with OHCA who underwent ECPR and showed poor pupillary examination findings upon hospital arrival, 10.2% had favourable neurological outcome at hospital discharge. A positive PLR after the establishment of ECPR was significantly associated with favourable neurological outcome.

Factors associated with favourable neurological outcomes following cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A retrospective multi-centre cohort study.

Aim: To investigate the factors associated with favourable neurological outcomes in adult patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA). Methods: This retrospective observational study used secondary analysis of the SAVE-J II multicentre registry data from 36 institutions in Japan. Between 2013 and 2018, 2157 patients with OHCA who underwent ECPR were enrolled in SAVE-J II. A total of 1823 patients met the study inclusion criteria. Adult patients (aged ≥ 18 years) with OHCA, who underwent ECPR before admission to the intensive care unit, were included in our secondary analysis. The primary outcome was a favourable neurological outcome at hospital discharge, defined as a Cerebral Performance Category score of 1 or 2. We used a multivariate logistic regression model to examine the association between factors measured at the incident scene or upon hospital arrival and favourable neurological outcomes. Results: Multivariable analysis revealed that shockable rhythm at the scene [odds ratio (OR); 2.11; 95% confidence interval (CI), 1.16-3.95] and upon hospital arrival (OR 2.59; 95% CI 1.60-4.30), bystander CPR (OR 1.63; 95% CI 1.03-1.88), body movement during resuscitation (OR 7.10; 95% CI 1.79-32.90), gasping (OR 4.33; 95% CI 2.57-7.28), pupillary reflex on arrival (OR 2.93; 95% CI 1.73-4.95), and male sex (OR 0.43; 95% CI 0.24-0.75) significantly correlated with neurological outcomes. Conclusions: Shockable rhythm, bystander CPR, body movement during resuscitation, gasping, pupillary reflex, and sex were associated with favourable neurological outcomes in patients with OHCA treated with ECPR.

Impact of Lactate Clearance on Clinical and Neurological Outcomes of Patients With Out-of-Hospital Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation: A Secondary Data Analysis.

OBJECTIVES: Serial evaluations of lactate concentration may be more useful in predicting outcomes in patients with out-of-hospital cardiac arrest (OHCA) than a single measurement. This study aimed to evaluate the impact of lactate clearance (LC) on clinical and neurologic outcomes in patients with OHCA who underwent extracorporeal cardiopulmonary resuscitation (ECPR). DESIGN: Retrospective multicenter observational study. SETTING: Patients with OHCA receiving ECPR at 36 hospitals in Japan between January 1, 2013, and December 31, 2018. PATIENTS: This study evaluated 1227 patients, with lactateinitial assessed upon emergency department admission and lactatesecond measured subsequently. To adjust for the disparity in the time between lactate measurements, the modified 6-hour LC was defined as follows: ([lactateinitial-lactatesecond]/lactateinitial) × 100 × (6/the duration between the initial and second measurements [hr]). The patients were divided into four groups according to the modified 6-hour LC with an equivalent number of patients among LC quartiles: Q1 (LC < 18.8), Q2 (18.8 < LC < 59.9), Q3 (60.0 < LC < 101.2), and Q4 (101.2 < LC). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The 30-day survival rates increased as the 6-hour LC increased (Q1, 21.2%; Q2, 36.8%; Q3, 41.4%; Q4, 53.6%; p for trend < 0.001). In the multivariate analysis, the modified 6-hour LC was significantly associated with a 30-day survival rate (adjusted odds ratio [AOR], 1.003; 95% CI, 1.001-1.005; p < 0.001) and favorable neurologic outcome (AOR, 1.002; 95% CI, 1.000-1.004; p = 0.027). CONCLUSIONS: In patients with OHCA who underwent ECPR, an increase in the modified 6-hour LC was associated with favorable clinical and neurologic outcome. Thus, LC can be a criterion to assess whether ECPR should be continued.

Overview and future prospects of out-of-hospital cardiac arrest registries in Japan.

Aim: Out-of-hospital cardiac arrest (OHCA) is a life-threatening emergency with high mortality. The "chain of survival" is critical to improving patient outcomes. To develop and enhance this chain of survival, measuring and monitoring the resuscitation processes and outcomes are essential for quality assurance. In Japan, several OHCA registries have successfully been implemented at both local and national levels. We aimed to review and summarise the conception, strengths, and challenges of OHCA registries in Japan. Method and results: The following representing registries in Japan were reviewed: the All-Japan Utstein registry, the Utstein Osaka Project/the Osaka-CRITICAL study, the SOS-KANTO study, the JAAM-OHCA study, and the SAVE-J II study. The All-Japan Utstein registry, operated by the Fire and Disaster Management Agency of Japan and one of the largest nationwide population-based registries in the world, collects data concerning all patients with OHCA in Japan, excluding in-hospital data. Other research- and hospital-based registries collect detailed out-of-hospital and in-hospital data. The Osaka-CRITICAL study and the SOS-KANTO study are organized at regional levels, and hospitals in the Osaka prefecture and in the Kanto area participate in these registries. The JAAM-OHCA study is managed by the Japanese Association of Acute Medicine and includes 107 hospitals throughout Japan. The Save-J II study focuses on patients with OHCA treated with extracorporeal cardiopulmonary resuscitation. Conclusion: Each OHCA registry has its own philosophy, strengths, perspectives, and challenges; however, all have been successful in contributing to the improvement of emergency medical service (EMS) systems through the quality improvement process. These registries are expected to be further utilized to enhance EMS systems and improve outcomes for patients with OHCA, while also contributing to the field of resuscitation science.

Optimal chest compression for cardiac arrest until the establishment of ECPR: Secondary analysis of the SAVE-J II study.

INTRODUCTION: The widespread incorporation of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest requires the delivery of effective and high-quality chest compressions prior to the initiation of ECPR. The aim of this study was to evaluate and compare the effectiveness of mechanical and manual chest compressions until the initiation of ECPR. METHODS: This study was a secondary analysis of the Japanese retrospective multicenter registry "Study of Advanced Life Support for Ventricular Fibrillation by Extracorporeal Circulation II (SAVE-J II)". Patients were divided into two groups, one receiving mechanical chest compressions and the other receiving manual chest compressions. The primary outcome measure was mortality at hospital discharge, while the secondary outcome was the cerebral performance category (CPC) score at discharge. RESULTS: Of the 2157 patients enrolled in the SAVE-J II trial, 453 patients (329 in the manual compression group and 124 in the mechanical compression group) were included in the final analysis. Univariate analysis showed a significantly higher mortality rate at hospital discharge in the mechanical compression group compared to the manual compression group (odds ratio [95% CI] = 2.32 [1.34-4.02], p = 0.0026). Multivariate analysis showed that mechanical chest compressions were an independent factor associated with increased mortality at hospital discharge (adjusted odds ratio [95% CI] = 2.00 [1.11-3.58], p = 0.02). There was no statistically significant difference in CPC between the two groups. CONCLUSION: For patients with out-of-hospital cardiopulmonary arrest who require ECPR, extreme caution should be used when performing mechanical chest compressions.

Prophylactic distal perfusion catheter and survival in patients with out-of-hospital cardiac arrest: Secondary analysis of the SAVE-J II study.

PURPOSE: The effect of a prophylactic distal perfusion catheter (DPC) after extracorporeal cardiopulmonary resuscitation (ECPR) in patients with out-of-hospital cardiac arrest (OHCA) remains unclear. Therefore, we aimed to clarify the association between prophylactic DPC and prognosis in patients with OHCA undergoing ECPR. MATERIALS AND METHODS: A secondary analysis of the Study of Advanced Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan (SAVE-J II) database was performed to compare groups of patients with and without prophylactic DPCs. A multivariate analysis of survival at discharge was performed using factors that were significant in the two-arm comparison. RESULTS: A total of 2044 patients were included in the analysis after excluding those who met the exclusion criteria. Survival at discharge was observed in 548 (26.9%) patients. In total, 100 (4.9%) patients developed limb ischemia, among whom 14 (0.7%) required therapeutic intervention. Multivariate analysis showed that prophylactic DPC did not result in a significant difference in survival at discharge (odds ratio: 0.898 [0.652-1.236], p = 0.509). CONCLUSIONS: The implementation of prophylactic DPC after ECPR for patients with OHCA may not contribute to survival at discharge.

Risk factors for bleeding complications in patients undergoing extracorporeal cardiopulmonary resuscitation following out-of-hospital cardiac arrest: a secondary analysis of the SAVE-J II study.

BACKGROUND: Bleeding is the most common complication in out-of-hospital cardiac arrest (OHCA) patients receiving extracorporeal cardiopulmonary resuscitation (ECPR). No studies comprehensively described the incidence rate, timing of onset, risk factors, and treatment of bleeding complications in OHCA patients receiving ECPR in a multicenter setting with a large database. This study aimed to analyze the risk factors of bleeding during the first day of admission and to comprehensively describe details of bleeding during hospitalization in patients with OHCA receiving ECPR in the SAVE-J II study database. METHODS: This study was a secondary analysis of the SAVE-J II study, which is a multicenter retrospective registry study from 36 participating institutions in Japan in 2013-2018. Adult OHCA patients who received ECPR were included. The primary outcome was the risk factor of bleeding complications during the first day of admission. The secondary outcomes were the details of bleeding complications and clinical outcomes. RESULTS: A total of 1,632 patients were included. Among these, 361 patients (22.1%) had bleeding complications during hospital stay, which most commonly occurred in cannulation sites (14.3%), followed by bleeding in the retroperitoneum (2.8%), gastrointestinal tract (2.2%), upper airway (1.2%), and mediastinum (1.1%). These bleeding complications developed within two days of admission, and 21.9% of patients required interventional radiology (IVR) or/and surgical interventions for hemostasis. The survival rate at discharge of the bleeding group was 27.4%, and the rate of favorable neurological outcome at discharge was 14.1%. Multivariable logistic regression analysis showed that the platelet count (< 10 × 104/µL vs > 10 × 104/µL) was significantly associated with bleeding complications during the first day of admission (adjusted odds ratio [OR]: 1.865 [1.252-2.777], p = 0.002). CONCLUSIONS: In a large ECPR registry database in Japan, up to 22.1% of patients experienced bleeding complications requiring blood transfusion, IVR, or surgical intervention for hemostasis. The initial platelet count was a significant risk factor of early bleeding complications. It is necessary to lower the occurrence of bleeding complications from ECPR, and this study provided an additional standard value for future studies to improve its safety.

Etiology-Based Prognosis of Extracorporeal CPR Recipients After Out-of-Hospital Cardiac Arrest: A Retrospective Multicenter Cohort Study.

BACKGROUND: A better understanding of the relative contributions of various factors to patient outcomes is essential for optimal patient selection for extracorporeal CPR (ECPR) therapy for patients with out-of-hospital cardiac arrest (OHCA). However, evidence on the prognostic comparison based on the etiologies of cardiac arrest is limited. RESEARCH QUESTION: What is the etiology-based prognosis of patients undergoing ECPR for OHCA? STUDY DESIGN AND METHODS: This retrospective multicenter registry study involved 36 institutions in Japan and included all adult patients with OHCA who underwent ECPR between January 2013 and December 2018. The primary etiology for OHCA was determined retrospectively from all hospital-based data at each institution. We performed a multivariable logistic regression model to determine the association between etiology of cardiac arrest and two outcomes: favorable neurologic outcome and survival at hospital discharge. RESULTS: We identified 1,781 eligible patients, of whom 1,405 (78.9%) had cardiac arrest because of cardiac causes. Multivariable logistic regression analysis for favorable neurologic outcome showed that accidental hypothermia (adjusted OR, 5.12; 95% CI, 2.98-8.80; P < .001) was associated with a significantly higher rate of favorable neurologic outcome than cardiac causes. Multivariable logistic regression analysis for survival showed that accidental hypothermia (adjusted OR, 5.19; 95% CI, 3.15-8.56; P < .001) had significantly higher rates of survival than cardiac causes. Acute aortic dissection/aneurysm (adjusted OR, 0.07; 95% CI, 0.02-0.28; P < .001) and primary cerebral disorders (adjusted OR, 0.12; 95% CI, 0.03-0.50; P = .004) had significantly lower rates of survival than cardiac causes. INTERPRETATION: In this retrospective multicenter cohort study, although most patients with OHCA underwent ECPR for cardiac causes, accidental hypothermia was associated with favorable neurologic outcome and survival; in contrast, acute aortic dissection/aneurysm and primary cerebral disorders were associated with nonsurvival compared with cardiac causes.

Prognostic Significance of Signs of Life in Out-of-Hospital Cardiac Arrest Patients Undergoing Extracorporeal Cardiopulmonary Resuscitation.

OBJECTIVES: Signs of life (SOLs) during cardiac arrest (gasping, pupillary light reaction, or any form of body movement) are suggested to be associated with favorable neurologic outcomes in out-of-hospital cardiac arrest (OHCA). While data has demonstrated that extracorporeal cardiopulmonary resuscitation (ECPR) can improve outcomes in cases of refractory cardiac arrest, it is expected that other contributing factors lead to positive outcomes. This study aimed to investigate whether SOL on arrival is associated with neurologic outcomes in patients with OHCA who have undergone ECPR. DESIGN: Retrospective multicenter registry study. SETTING: Thirty-six facilities participating in the Study of Advanced life support for Ventricular fibrillation with Extracorporeal circulation in Japan II (SAVE-J II). PATIENTS: Consecutive patients older than 18 years old who were admitted to the Emergency Department with OHCA between January 1, 2013, and December 31, 2018, and received ECPR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were classified into two groups according to the presence or absence of SOL on arrival. The primary outcome was a favorable neurologic outcome (Cerebral Performance Category 1 or 2) at discharge. Of the 2157 patients registered in the SAVE-J II database, 1395 met the inclusion criteria, and 250 (17.9%) had SOL upon arrival. Patients with SOL had more favorable neurologic outcomes than those without SOL (38.0% vs. 8.1%; p < 0.001). Multivariate analysis showed that SOL on arrival was independently associated with favorable neurologic outcomes (odds ratio, 5.65 [95% CI, 3.97-8.03]; p < 0.001). CONCLUSIONS: SOL on arrival was associated with favorable neurologic outcomes in patients with OHCA undergoing ECPR. In patients considered for ECPR, the presence of SOL on arrival can assist the decision to perform ECPR.

The association between blood glucose levels on arrival at the hospital and patient outcomes after out-of-hospital cardiac arrest: A multicenter cohort study.

BACKGROUND: This study aimed to investigate the association between blood glucose levels on arrival at the hospital and 1-month survival and favorable neurological outcomes in patients with OHCA using a large Japanese dataset. METHODS: This study was a secondary analysis of data from the JAAM-OHCA Registry. Adult (≥18 years) patients with witnessed OHCA transported to emergency departments and registered in the database from June 2014 to December 2019 were included in the study. The primary and secondary endpoints were 1-month survival and 1-month favorable neurological outcomes (Glasgow-Pittsburgh Cerebral Performance Category score 1 or 2), respectively. Patients were categorized into the following four groups based on blood glucose levels on arrival at the hospital: <80 mg/dL, 80-179 mg/dL, 180-299 mg/dL, and ≥300 mg/dL. RESULTS: This study included 11,387 patients. Survival rates were 1.3%, 3.1%, 7.0%, and 5.7% in the <80 mg/dL, 80-179 mg/dL, 180-299 mg/dL, and ≥ 300 mg/dL blood glucose groups, respectively. The rates of favorable neurological outcomes in each group were 0.4%, 1.5%, 3.3%, and 2.5%, respectively. Multivariable analysis showed that 180-299 mg/dL glucose was significantly associated with 1-month survival and favorable neurological outcomes compared with 80-179 mg/dL glucose (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.34-2.31; p < 0.001 and OR, 1.52; 95 % Cl, 1.02-2.25; p = 0.035, respectively). In this study, blood glucose levels with the best outcomes likely ranged from 200 to 250 mg/dL based on the cubic spline regression model. CONCLUSIONS: Blood glucose level of 180-299 mg/dL on arrival at the hospital was significantly associated with 1-month survival and favorable neurological outcomes compared to blood glucose level of 80-179 mg/dL in patients with OHCA.

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

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

Intra-aortic balloon pump in patients with extracorporeal cardiopulmonary resuscitation after cardiac arrest caused by acute coronary syndrome.

BACKGROUND: This study evaluated the association between intra-aortic balloon pump (IABP) use in patients with out-of-hospital cardiac arrest (OHCA) caused by acute coronary syndrome (ACS) who received extracorporeal cardiopulmonary resuscitation (ECPR) and 30-day outcomes. METHODS: This study was a secondary analysis of data from the SAVE-J II study, a retrospective, multicenter registry study involving 36 participating institutions in Japan. Patients with cardiac arrest caused by ACS who received ECPR were divided into two groups depending on whether or not they received IABP. The primary outcome was 30-day survival. Subgroup analysis was performed to detect what type of patients were mostly associated with improved outcomes. RESULTS: Of 2,157 patients registered in the SAVE-J II study, 877 patients were enrolled in this study, 702 patients in the IABP group and 175 patients in the non-IABP group. Multivariable logistic regression analysis did not reveal a significant difference in 30-day survival (OR 1.37, 95% CI 0.91-2.07, p = 0.13). In the subgroup analysis, 30-day survival among patients without percutaneous coronary intervention (PCI) and stenosis of multiple coronary vessels were associated with IABP use. CONCLUSIONS: IABP use in patients with OHCA with ACS who received ECPR is not associated with 30-day survival. The use of IABP in patients who did not have PCI and have multiple coronary vessel stenoses warrants further study.

Low-flow time and outcomes in out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation.

INTRODUCTION: In out-of-hospital cardiac arrest (OHCA) patients with extracorporeal cardiopulmonary resuscitation (ECPR), the association between low-flow time, the duration between the initiation of conventional cardiopulmonary resuscitation and the establishment of ECPR, and outcomes has not been clearly determined. METHODS: This was a secondary analysis of the retrospective multicenter registry in Japan. This study registered patients ≥18 years old who were admitted to the emergency department for OHCA and underwent ECPR between January, 2013 and December, 2018. Low-flow time was defined as the time from initiation of conventional cardiopulmonary resuscitation to the establishment of ECPR, and patients were categorized into two groups according to the visualized association of the restricted cubic spline curve. The primary outcome was survival discharge. Cubic spline analyses and multivariable logistic regression analyses were performed to assess the nonlinear associations between low-flow time and outcomes. RESULTS: A total of 1,524 patients were included. The median age was 60 years, and the median low-flow time was 52 (42-53) mins. The overall survival at hospital discharge and favorable neurological outcomes were 27.8% and 14.2%, respectively. The cubic spline analysis showed a decreased trend of survival discharge rates and favorable neurological outcomes with shorter low-flow time between 20 and 60 mins, with little change between the following 60 and 80 mins. The multivariable logistic regression analyses showed that patients with long low-flow time (>40 mins) compared to those with short low-flow time (0-40 mins) had significantly worse survival (adjusted odds ratio 0.42; 95% confidence intervals, 0.31-0.57) and neurological outcomes (0.65; 0.45-0.95, respectively). CONCLUSIONS: The survival discharge and neurological outcomes of patients with low-flow time shorter than 40 min are better than those of patients with longer low-flow time.

Validation of Machine Learning Models for Craniofacial Growth Prediction.

This study identified the most accurate model for predicting longitudinal craniofacial growth in a Japanese population using statistical methods and machine learning. Longitudinal lateral cephalometric radiographs were collected from 59 children (27 boys and 32 girls) with no history of orthodontic treatment. Multiple regression analysis, least absolute shrinkage and selection operator, radial basis function network, multilayer perceptron, and gradient-boosted decision tree were used. The independent variables included 26 coordinated values of skeletal landmarks, 13 linear skeletal parameters, and 17 angular skeletal parameters in children ages 6 to 12 years. The dependent variables were the values of the 26 coordinated skeletal landmarks, 13 skeletal linear parameters, and 17 skeletal angular parameters at 13 years of age. The difference between the predicted and actual measured values was calculated using the root-mean-square error. The prediction model for craniofacial growth using the least absolute shrinkage and selection operator had the smallest average error for all values of skeletal landmarks, linear parameters, and angular parameters. The highest prediction accuracies when predicting skeletal linear and angular parameters for 13-year-olds were 97.87% and 94.45%, respectively. This model incorporates several independent variables and is useful for future orthodontic treatment because it can predict individual growth.

Association between body mass index and clinical outcomes in patients with out-of-hospital cardiac arrest undergoing extracorporeal cardiopulmonary resuscitation: A multicenter observational study.

Background: We examined the association between body mass index (BMI) and outcomes in patients with out-of-hospital cardiac arrest (OHCA) undergoing extracorporeal cardiopulmonary resuscitation (ECPR). Methods: We retrospectively analyzed the database of an observational multicenter cohort in Japan. Adult patients with OHCA of cardiac etiology who received ECPR between 2013 and 2018 were categorized as follows: underweight, BMI < 18.5; normal weight, BMI = 18.5-24.9; overweight, BMI = 25-29.9; and obese, BMI ≥ 30 kg/m2. The primary outcome was in-hospital mortality; secondary outcomes were unfavorable neurological outcomes at discharge (cerebral performance category ≥ 3) and ECPR-related complications. BMI's association with outcomes was assessed using a logistic regression model adjusted for age, sex, comorbidities, witness/bystander CPR, initial rhythm, prehospital return of spontaneous circulation, and low-flow time. Results: In total, 1,044 patients were analyzed. Their median age was 61 (IQR, 49-69) years; the median BMI was 24.2 (21.5-26.9) kg/m2. The overall rates of in-hospital mortality, unfavorable neurological outcome, and ECPR-related complications were 62.2%, 79.9%, and 31.7%, respectively. In multivariate analysis, the overweight and obese groups had higher in-hospital mortality odds than the normal BMI group (odds ratio [95%CI], 1.37 [1.02-1.85], p = 0.035; and 2.09 [1.31-3.39], p < 0.001, respectively). The odds ratio for unfavorable neurological outcomes increased more in the obese than in the normal BMI group (3.17 [1.69-6.49], p < 0.001). ECPR-related complications were not significantly different among groups. Conclusions: In OHCA patients undergoing ECPR, a BMI ≥ 25 kg/m2 was associated with increased in-hospital mortality, and a BMI ≥ 30 kg/m2 was also associated with a worse neurological outcome.

Association between neuromuscular blocking agent use and outcomes among out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation and target temperature management: A secondary analysis of the SAVE-J II study.

Background: Neuromuscular blocking agents are used to control shivering in cardiac arrest patients treated with target temperature management. However, their effect on outcomes in patients treated with extracorporeal cardiopulmonary resuscitation is unclear. Methods: This study was a secondary analysis of the SAVE-J II study, a retrospective multicenter study of 2175 out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation in Japan. We classified patients into those who received neuromuscular blocking agents and those who did not and compared in-hospital mortality and incidence rates of favorable neurological outcome and in-hospital pneumonia between the groups using multivariable regression models and stabilized inverse probability weighting with propensity scores. Results: Six hundred sixty patients from the SAVE-J II registry were analyzed. Neuromuscular blocking agents were used in 451 patients (68.3%). After adjusting for potential confounders, neuromuscular blocking agents use was not significantly associated with in-hospital mortality (aHR 0.88; 95% CI, 0.67-1.14), favorable neurological outcome (aOR 0.85; 95% CI, 0.60-1.11), or pneumonia (aOR 1.52; 95% CI, 0.85-2.71). The results for in-hospital mortality (aHR 0.89; 95% CI, 0.64-1.25), favorable neurological outcome (aOR 0.94; 95% CI, 0.59-1.48) and pneumonia (aOR 1.59; 95% CI, 0.74-3.41) were similar after weighting was performed. Conclusions: Although data on the rationale for using neuromuscular blocking agents were unavailable, their use was not significantly associated with outcomes in out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation and targeted temperature management. Neuromuscular blocking agents should be used based on individual clinical indications.