A prehospital risk assessment tool predicts clinical outcomes in hospitalized patients with heat-related illness: a Japanese nationwide prospective observational study.

We previously developed a risk assessment tool to predict outcomes after heat-related illness (J-ERATO score), which consists of six binary prehospital vital signs. We aimed to evaluate the ability of the score to predict clinical outcomes for hospitalized patients with heat-related illnesses. In a nationwide, prospective, observational study, adult patients hospitalized for heat-related illnesses were registered. A binary logistic regression model and receiver operating characteristic (ROC) curve analysis were used to assess the relationship between the J-ERATO and survival at hospital discharge as a primary outcome. Among eligible patients, 1244 (93.0%) survived to hospital discharge. Multivariable logistic regression analysis revealed that the J-ERATO was an independent predictor for survival to discharge (adjusted odds ratio [OR] 0.47; 95% confidence interval [CI] 0.37-0.59) and occurrence of disseminated intravascular coagulation (DIC) on day 1 (adjusted OR 2.07; 95% CI 1.73-2.49). ROC analyses revealed an optimal J-ERATO cut-off of 5 for prediction of mortality at discharge (area under the curve [AUC] 0.742; 95% CI 0.691-0.787) and DIC development on day 1 (AUC 0.723; 95% CI 0.684-0.758). The J-ERATO obtained before transportation could be helpful in predicting the severity and mortality of hospitalized patients with heat-related illnesses.

Influence of the coronavirus disease 2019 (COVID-19) pandemic on the incidence of heat stroke and heat exhaustion in Japan: a nationwide observational study based on the Heatstroke STUDY 2019 (without COVID-19) and 2020 (with COVID-19).

AIM: To assess heat stroke and heat exhaustion occurrence and response during the coronavirus disease 2019 pandemic in Japan. METHODS: This retrospective, multicenter, registry-based study describes and compares the characteristics of patients between the months of July and September in 2019 and 2020. Factors affecting heat stroke and heat exhaustion were statistically analyzed. Cramér's V was calculated to determine the effect size for group comparisons. We also investigated the prevalence of mask wearing and details of different cooling methods. RESULTS: No significant differences were observed between 2019 and 2020. In both years, in-hospital mortality rates just exceeded 8%. Individuals >65 years old comprised 50% of cases and non-exertional onset (office work and everyday life) comprised 60%-70%, respectively. The recommendations from the Working Group on Heat Stroke Medicine given during the coronavirus disease pandemic in 2019 had a significant impact on the choice of cooling methods. The percentage of cases, for which intravascular temperature management was performed and cooling blankets were used increased, whereas the percentage of cases in which evaporative plus convective cooling was performed decreased. A total of 49 cases of heat stroke in mask wearing were reported. CONCLUSION: Epidemiological assessments of heat stroke and heat exhaustion did not reveal significant changes between 2019 and 2020. The findings suggest that awareness campaigns regarding heat stroke prevention among the elderly in daily life should be continued in the coronavirus disease 2019 pandemic. In the future, it is also necessary to validate the recommendations of the Working Group on Heatstroke Medicine.

Association between active cooling and lower mortality among patients with heat stroke and heat exhaustion.

Body cooling is recommended for patients with heat stroke and heat exhaustion. However, differences in the outcomes of patients who do or do not receive active cooling therapy have not been determined. The best available evidence supporting active cooling is based on a case series without comparison groups; thus, the effectiveness of this method in improving patient prognoses cannot be appropriately quantified. Therefore, we compared the outcomes of heat stroke patients receiving active cooling with those of patients receiving rehydration-only therapy. This prospective observational multicenter registry-based study of heat stroke and heat exhaustion patients was conducted in Japan from 2010 to 2019. The patients were stratified into the "severe" group or the "mild-to-moderate" group, per clinical findings on admission. After conducting multivariate logistic regression analyses, we compared the prognoses between patients who received "active cooling + rehydration" and patients who received "rehydration only," with in-hospital death as the endpoint. Sex, age, onset situation (i.e., exertional or non-exertional), core body temperature, liver damage, renal dysfunction, and disseminated intravascular coagulation were considered potential covariates. Among those who received active cooling and rehydration-only therapy, the in-hospital mortality rates were 21.5% and 35.5%, respectively, for severe patients (n = 231) and 3.9% and 5.7%, respectively, for mild-to-moderate patients (n = 578). Rehydration-only therapy was associated with a higher in-hospital mortality in patients with severe heat illness (adjusted odds ratio [aOR], 3.29; 95% confidence interval [CI], 1.21-8.90), whereas the cooling methods were not associated with lower in-hospital mortality in patients with mild-to-moderate heat illness (aOR, 2.22; 95% CI, 0.92-5.84). Active cooling was associated with lower in-hospital mortality only in the severe group. Our results indicated that active cooling should be recommended as an adjunct to rehydration-only therapy for patients with severe heat illness.

Association between frailty and mortality among patients with accidental hypothermia: a nationwide observational study in Japan.

BACKGROUND: Frailty has been associated with a risk of adverse outcomes, and mortality in patients with various conditions. However, there have been few studies on whether or not frailty is associated with mortality in patients with accidental hypothermia (AH). In this study, we aim to determine this association in patients with AH using Japan's nationwide registry data. METHODS: The data from the Hypothermia STUDY 2018&19, which included patients of ≥18 years of age with a body temperature of ≤35 °C, were obtained from a multicenter registry for AH conducted at 120 institutions throughout Japan, collected from December 2018 to February 2019 and December 2019 to February 2020. The clinical frailty scale (CFS) score was used to determine the presence and degree of frailty. The primary outcome was the comparison of mortality between the frail and non-frail patient groups. RESULTS: In total, 1363 patients were included in the study, of which 920 were eligible for the analysis. The 920 patients were divided into the frail patient group (N = 221) and non-frail patient group (N = 699). After 30-days of hospitalization, 32.6% of frail patients and 20.6% of non-frail patients had died (p < 0.001). Frail patients had a significantly higher risk of 90-day mortality (Hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.25-2.17; p < 0.001). Based on the Cox proportional hazards analysis using multiple imputation, after adjustment for age, potassium level, lactate level, pH value, sex, CPK level, heart rate, platelet count, location of hypothermia incidence, and rate of tracheal intubation, the HR was 1.69 (95% CI, 1.25-2.29; p < 0.001). CONCLUSIONS: This study showed that frailty was associated with mortality in patients with AH. Preventive interventions for frailty may help to avoid death caused by AH.

Emergency lower gastrointestinal endoscopy performed safely in a COVID-19 patient on extracorporeal membrane oxygenation (ECMO) with hemorrhagic shock.

Emergency endoscopy in coronavirus disease 2019 (COVID-19) patients should be avoided whenever possible to ensure the safety of medical staff; however, it may be unavoidable in some cases. We report a case of emergency lower gastrointestinal endoscopy performed with full personal protective equipment in a patient on extracorporeal membrane oxygenation with severe COVID-19 pneumonia admitted in a restricted area under negative pressure in the intensive care unit. To avoid the risk of fecal-oral transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the procedure, the patient's lower body was covered with a 2 m2 vinyl sheet with an aperture (diameter, approximately 2 cm). None of the medical staff involved exhibited any signs of SARS-CoV-2 infection after the procedure. Although patients with severe COVID-19 pneumonia on extracorporeal membrane oxygenation have a high risk of bleeding, we believe that emergency lower endoscopy can be safely performed in such patients by reducing exposure to dispersed feces and using full personal protective equipment.

Machine learning-based mortality prediction model for heat-related illness.

In this study, we aimed to develop and validate a machine learning-based mortality prediction model for hospitalized heat-related illness patients. After 2393 hospitalized patients were extracted from a multicentered heat-related illness registry in Japan, subjects were divided into the training set for development (n = 1516, data from 2014, 2017-2019) and the test set (n = 877, data from 2020) for validation. Twenty-four variables including characteristics of patients, vital signs, and laboratory test data at hospital arrival were trained as predictor features for machine learning. The outcome was death during hospital stay. In validation, the developed machine learning models (logistic regression, support vector machine, random forest, XGBoost) demonstrated favorable performance for outcome prediction with significantly increased values of the area under the precision-recall curve (AUPR) of 0.415 [95% confidence interval (CI) 0.336-0.494], 0.395 [CI 0.318-0.472], 0.426 [CI 0.346-0.506], and 0.528 [CI 0.442-0.614], respectively, compared to that of the conventional acute physiology and chronic health evaluation (APACHE)-II score of 0.287 [CI 0.222-0.351] as a reference standard. The area under the receiver operating characteristic curve (AUROC) values were also high over 0.92 in all models, although there were no statistical differences compared to APACHE-II. This is the first demonstration of the potential of machine learning-based mortality prediction models for heat-related illnesses.

Accidental hypothermia: Factors related to a prolonged hospital stay - A nationwide observational study in Japan.

BACKGROUND: The incidence of accidental hypothermia (AH) is low, and the length of hospital stay in patients with AH remains poorly understood. The present study explored which factors were related to prolonged hospitalization among patients with AH using Japan's nationwide registry data. METHODS: The data from the Hypothermia STUDY 2018, which included patients ≥18 years old with a body temperature ≤ 35 °C, were obtained from a multicenter registry for AH conducted at 89 institutions throughout Japan, collected from December 1, 2018, to February 28, 2019. The patients were divided into a "short-stay patients" group (within 7 days) and "long-stay patients" group (more than 7 days). A logistic regression analysis after multiple imputation was performed to obtain odds ratios (ORs) for prolonged hospitalization with age, frailty, location, causes underlying the hypothermia, temperature, pH, potassium level, and disseminated intravascular coagulation (DIC) score as independent variables. RESULTS: In total, 656 patients were included in the study, of which 362 were eligible for the analysis. The median length of hospital stay was 17 days. Of the 362 patients, 265 (73.2%) stayed in the hospital for more than 7 days. The factors associated with prolonged hospitalization were frailty (OR, 2.11; 95% confidence interval [CI], 1.09-4.10; p = 0.027), the occurrence of indoor (OR, 3.20; 95% CI, 1.58-6.46; p = 0.001), alcohol intoxication (OR, 0.17; 95% CI, 0.05-0.56; p = 0.004), pH (OR, 0.07; 95% CI, 0.01-0.76; p = 0.029), potassium level (OR, 1.36; 95% CI, 1.00-1.85; p = 0.048), and DIC score (OR, 1.54; 95% CI, 1.13-2.10; p = 0.006). CONCLUSIONS: Frailty, indoor situation, alcohol intoxication, pH value, potassium level, and DIC score were factors contributing to prolonged hospitalization in patients with AH. Preventing frailty may help reduce the length of hospital stay in patients with AH. In addition, measuring the pH value and potassium level by an arterial blood gas analysis at the ED is recommended for the early evaluation of AH.

Polymerase-chain reaction testing to prevent hospital-acquired severe acute respiratory syndrome coronavirus 2 infection in Shinjuku, an epicenter in Tokyo: The Tokyo Women's Medical University model.

Hospital-acquired severe acute respiratory virus coronavirus 2 (SARS-CoV-2) infection is a healthcare challenge. We hypothesized that polymerase chain reaction testing of symptomatic triaged outpatients and all inpatients before hospitalization in Shinjuku, a coronavirus disease 2019 (COVID-19) epicenter in Tokyo, using the Tokyo Women's Medical University (TMWU) model would be feasible and efficient at preventing COVID-19. This retrospective study enrolled 2981 patients from March to May 2020. The prevalence of SARS-CoV-2 infection was 1.81% (95% credible interval [CI]: 0.95-3.47%) in triaged symptomatic outpatients, 0.04% (95% CI: 0.0002-0.2%) in scheduled asymptomatic inpatients, 3.78% (95% CI: 1.82-7.26%) in emergency inpatients, and 2.4% (95% CI: 1.49-3.82%) in symptomatic patients. There were no cases of hospital-acquired SARS-CoV-2 infection. This shows that the TWMU model could prevent hospital-acquired SARS-CoV-2 infection and is feasible and effective in reducing the impact of SARS-CoV-2 infection in the hospitals.

Clinical characteristics, prognostic factors, and outcomes of heat-related illness (Heatstroke Study 2017-2018).

AIM: Heat-related illness is common, but its epidemiology and pathological mechanism remain unclear. The aim of this study was to report current clinical characteristics, prognostic factors, and outcomes of heat-related illness in Japan. METHODS: We undertook a prospective multicenter observational study in Japan. Only hospitalized patients with heat-related illness were enrolled from 1 July to 30 September 2017 and 1 July to 30 September 2018. RESULTS: A total of 763 patients were enrolled in the study. Median age was 68 years (interquartile range, 49-82 years) and median body temperature on admission was 38.2°C (interquartile range, 36.8-39.8°C). Non-exertional cause was 56.9% and exertional cause was 40.0%. The hospital mortality was 4.6%. The median Japanese Association for Acute Medicine disseminated intravascular coagulation (JAAM DIC), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores on admission were 1 (0-2), 4 (2-6), and 13 (8-22), respectively. To predict hospital mortality, areas under the receiver operating characteristic curves were 0.776 (JAAM DIC score), 0.825 (SOFA), and 0.878 (APACHE II). There were 632 cases defined as heatstroke by JAAM heat-related illness criteria, 73 cases diagnosed as having DIC. A total of 16.6% patients had poor neurological outcome (modified Rankin Scale ≥ 4) at hospital discharge. In the multivariate analysis, Glasgow Coma Scale and platelets were independent predictors of mortality. Type of heatstroke, Glasgow Coma Scale, and platelets were independent predictors of poor neurological outcome. Body temperature was not associated with mortality or poor neurological outcome. CONCLUSIONS: In this study, hospital mortality of heat-related illness was <5%, one-sixth of the patients had poor neurological outcome. The APACHE II, SOFA, and JAAM DIC scores predicted hospital mortality. Body temperature was not associated with mortality or poor neurological outcome.

Dual-Phase Computed Tomography Angiography Enhances Detection of Contrast Extravasation in Subarachnoid Hemorrhage.

BACKGROUND: Contrast-enhanced computed tomography angiography (CTA) can be used to detect contrast extravasation in intracerebral hemorrhage. However, investigation for contrast extravasation in subarachnoid hemorrhage (SAH) is insufficient. We evaluated the efficacy of dual-phase CTA to improve evaluation of contrast extravasation in SAH. METHODS: We retrospectively evaluated 35 patients with SAH who underwent contrast-enhanced dual-phase CTA within 24 hours from onset. The second-phase scan was performed 8 or 15 seconds following the usual CTA. The frequency of contrast extravasation was compared between phases. We also recorded the time from onset, coma level, interventional treatment, and early mortality. RESULTS: Of 35 patients (22.9%) with SAH, 8 showed contrast extravasation in the second phase compared with 3 in the first phase. Contrast extravasation was correlated with clinical coma level (P < 0.05), and all contrast extravasation was found within 6 hours from onset. Early mortality, treatment decision, and hematoma distribution type did not correlate with existence of contrast extravasation. We also observed 4 cases of secondary subpial hematoma due to SAH, with 3 showing extravasation in both phases. CONCLUSIONS: Dual-phase CTA with a short interval enhances detection frequency of contrast extravasation in SAH and might be a better evaluation tool for SAH.

Confirmed cardiac output on emergency medical services arrival as confounding by indication: an observational study of prehospital airway management in patients with out-of-hospital cardiac arrest.

OBJECTIVES: Many registry studies on patients with out-of-hospital cardiac arrest (OHCA) have reported that conventional bag-valve-mask (BVM) ventilation is independently associated with favourable outcomes. This study aimed to compare the data of patients with OCHA with confirmed cardiac output on emergency medical services (EMS) arrival and consider the confounding factors in prehospital airway management studies. METHODS: This was a cohort study using the registry data for survivors after out-of hospital cardiac arrest in the Kanto region at 2012 in Japan (SOS-KANTO 2012). Survivors who received advanced airway management (AAM) group and a BVM group were compared for confirmed cardiac output on EMS arrival and neurolgical outcome at 1 month. Favourable neurological outcome was defined as a score of one or two on the Cerebral Performance Categories Scale. Multivariable logistic regression was used to adjust the neurological outcome by age, gender, cardiac aetiology, witnessed arrest, shockable rhythm, cardiopulmonary resuscitation performed by a bystander, BVM at prehospital ventilation and presence of confirmed cardiac output on EMS arrival. RESULTS: A total of 16 452 patients were enrolled in the SOS-KANTO 2012 study, and of those data 12 867 were analysed; 5893 patients comprised the AAM group and 6974 comprised the BVM group. Of the study participants, 386 (2.9%) had confirmed cardiac output on EMS arrival; 340 (2.6%) of the entire study group had a favourable neurological outcome. The proportion of patients with confirmed cardiac output on EMS arrival was significantly higher in the BVM group (272: 3.9%) than in the AAM group (114: 1.9%) (95% CI: 1.65 to 2.25). The proportion of patients with favourable neurological outcomes was 30% (117/386) in those with cardiac output on EMS arrival compared with 1.8% (223/12481) in those without. The OR for a good neurological outcome with BVM decreased from 3.24 (2.49 to 4.20) to 2.60 (1.97 to 3.44) when confirmed cardiac output on EMS arrival was added to the multivariable model analysis. CONCLUSION: Confirmed cardiac output on EMS arrival should be considered as confounding by indication in observational studies of prehospital airway management.

Mathematical modeling of septic shock based on clinical data.

BACKGROUND: Mathematical models of diseases may provide a unified approach for establishing effective treatment strategies based on fundamental pathophysiology. However, models that are useful for clinical practice must overcome the massive complexity of human physiology and the diversity of patients' environmental conditions. With the aim of modeling a complex disease, we choose sepsis, which is highly complex, life-threatening systemic disease with high mortality. In particular, we focused on septic shock, a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. Our model includes cardiovascular, immune, nervous system models and a pharmacological model as submodels and integrates them to create a sepsis model based on pathological facts. RESULTS: Model validation was done in two steps. First, we established a model for a standard patient in order to confirm the validity of our approach in general aspects. For this, we checked the correspondence between the severity of infection defined in terms of pathogen growth rate and the ease of recovery defined in terms of the intensity of treatment required for recovery. The simulations for a standard patient showed good correspondence. We then applied the same simulations to a patient with heart failure as an underlying disease. The model showed that spontaneous recovery would not occur without treatment, even for a very mild infection. This is consistent with clinical experience. We next validated the model using clinical data of three sepsis patients. The model parameters were tuned for these patients based on the model for the standard patient used in the first part of the validation. In these cases, the simulations agreed well with clinical data. In fact, only a handful parameters need to be tuned for the simulations to match with the data. CONCLUSIONS: We have constructed a model of septic shock and have shown that it can reproduce well the time courses of treatment and disease progression. Tuning of model parameters for each patient could be easily done. This study demonstrates the feasibility of disease models, suggesting the possibility of clinical use in the prediction of disease progression, decisions on the timing of drug dosages, and the estimation of time of infection.

Association of the time to first epinephrine administration and outcomes in out-of-hospital cardiac arrest: SOS-KANTO 2012 study.

OBJECTIVE: This study assessed the association between the timing of first epinephrine administration (EA) and the neurological outcomes following out-of-hospital cardiac arrests (OHCAs) with both initial shockable and non-shockable rhythms. METHODS: This was a post-hoc analysis of a multicenter prospective cohort study (SOS-KANTO 2012), which registered OHCA patients in the Kanto region of Japan from January 2012 to March 2013. We included consecutive adult OHCA patients who received epinephrine. The primary result included 1-month favorable neurological outcomes defined as cerebral performance category (CPC) 1 or 2. Secondary results included 1-month survival and return of spontaneous circulation (ROSC) after arrival at the hospital. Multivariable logistic regression analysis determined the association between delay per minute of the time from call to first EA in both pre- or in-hospital settings and outcomes. RESULTS: Of the 16,452 patients, 9344 were eligible for our analyses. In univariable analysis, the delay in EA was associated with decreased favorable neurological outcomes only when the initial rhythm was a non-shockable rhythm. In multivariable analyses, delay in EA was associated with decreased ROSC (adjusted odds ratio [OR] for one minute delay, 0.97; 95% confidence interval [CI], 0.96-0.98) and 1-month survival (adjusted OR, 0.95; 95% CI, 0.92-0.97) when the initial rhythm was a non-shockable rhythm, whereas during a shockable rhythm, delay in EA was not associated with decreased ROSC and 1-month survival. CONCLUSIONS: While assessing the effectiveness of epinephrine for OHCA, we should consider the time-limited effects of epinephrine. Additionally, consideration of early EA based on the pathophysiology is needed.

Association Between Therapeutic Hypothermia and Outcomes in Patients with Non-shockable Out-of-Hospital Cardiac Arrest Developed After Emergency Medical Service Arrival (SOS-KANTO 2012 Analysis Report).

BACKGROUND/OBJECTIVE: The outcomes of patients with non-shockable out-of-hospital cardiac arrest (non-shockable OHCA) are poorer than those of patients with shockable out-of-hospital cardiac arrest (shockable OHCA). In this retrospective study, we selected patients from the SOS-KANTO 2012 study with non-shockable OHCA that developed after emergency medical service (EMS) arrival and analyzed the effect of therapeutic hypothermia (TH) on non-shockable OHCA patients. METHODS: Of 16,452 patients who have definitive data on the 3-month outcome in the SOS-KANTO 2012 study, we selected 241 patients who met the following criteria: age ≥ 18 years, normal spontaneous respiration or palpable pulse upon emergency medical services arrival, no ventricular fibrillation or pulseless ventricular tachycardia before hospital arrival, and achievement of spontaneous circulation without cardiopulmonary bypass. Patients were divided into two groups based on the presence or absence of TH and were analyzed. RESULTS: Of the 241 patients, 49 underwent TH. Univariate analysis showed that the 1-/3-month survival rates and favorable 3-month cerebral function outcome rates in the TH group were significantly better than the non-TH group (46% vs 19%, respectively, P < 0.001, 35% vs 12%, respectively, P < 0.001, 20% vs 7%, respectively, P = 0.01). Multivariate logistic regression analysis showed that TH was a significant, independent prognostic factor for cerebral function outcome. CONCLUSIONS: In this study, TH was an independent prognostic factor for the 3-month cerebral function outcome. Even in patients with non-shockable OHCA, TH may improve outcome if the interval from the onset of cardiopulmonary arrest is relatively short, and adequate cardiopulmonary resuscitation is initiated immediately after onset.

Renal Function and Outcome of Out-of-Hospital Cardiac Arrest　- Multicenter Prospective Study (SOS-KANTO 2012 Study).

BACKGROUND: Renal dysfunction is associated with increased cardiovascular-related mortality, but its impact on outcome of out-of-hospital cardiac arrest (OHCA) remains unclear. We assessed whether post-OHCA outcome correlated with renal function early after OHCA. Methods and Results: Of the 16,452 registered patients in the SOS-KANTO 2012 Study, 5,112 cardiogenic OHCA adults with creatinine measurement (mean age, 72 years; male, 64%) were examined. First-obtained creatinine was used to assess eGFR. Associations between eGFR groups, ≥60 (n=997), 45-59 (n=1,311), 30-44 (n=1,441), and <30 mL/min/1.73 m2(n=1,363), and 3-month survival and neurological outcomes were examined. Favorable neurological outcome was defined as cerebral performance categories 1 or 2. Survival rate (15.1%, 9.7%, 3.9%, and 2.9%; P<0.001) and proportion of favorable neurological outcome (12.3%, 7.4%, 2.6%, and 2.2%; P<0.001) were determined for eGFR groups ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively. The survival rate decreased with eGFR (<60 mL/min/1.73 m2), and survival adjusted OR were 0.74 (95% CI: 0.54-1.03), 0.42 (95% CI: 0.28-0.62), and 0.43 (95% CI: 0.28-0.68) for eGFR 45-59, 30-44, and <30 mL/min/1.73 m2, respectively. The adjusted OR for favorable neurological outcome also decreased with eGFR: 0.74 (95% CI: 0.52-1.06), 0.40 (95% CI: 0.25-0.64), and 0.48 (95% CI: 0.29-0.81), respectively. CONCLUSIONS: An independent and graded association was observed between decreased eGFR and 3-month survival and proportion of favorable neurological outcome in cardiogenic OHCA patients.

Mechanical Cardiopulmonary Resuscitation and Hospital Survival Among Adult Patients With Nontraumatic Out-of-Hospital Cardiac Arrest Attending the Emergency Department: A Prospective, Multicenter, Observational Study in Japan (SOS-KANTO [Survey of Survivors after Out-of-Hospital Cardiac Arrest in Kanto Area] 2012 Study).

BACKGROUND: Mechanical cardiopulmonary resuscitation (mCPR) for patients with out-of-hospital cardiac arrest attending the emergency department has become more widespread in Japan. The objective of this study is to determine the association between the mCPR in the emergency department and clinical outcomes. METHODS AND RESULTS: In a prospective, multicenter, observational study, adult patients with out-of-hospital cardiac arrest with sustained circulatory arrest on hospital arrival were identified. The primary outcome was survival to hospital discharge. The secondary outcomes included a return of spontaneous circulation and successful hospital admission. Multivariate analyses adjusted for potential confounders and within-institution clustering effects using a generalized estimation equation were used to analyze the association of the mCPR with outcomes. Between January 1, 2012 and March 31, 2013, 6537 patients with out-of-hospital cardiac arrest were eligible; this included 5619 patients (86.0%) in the manual CPR group and 918 patients (14.0%) in the mCPR group. Of those patients, 28.1% (1801/6419) showed return of spontaneous circulation in the emergency department, 20.4% (1175/5754) had hospital admission, 2.6% (168/6504) survived to hospital discharge, and 1.2% (75/6419) showed a favorable neurological outcome at 1 month after admission. Multivariate analyses revealed that mCPR was associated with a decreased likelihood of survival to hospital discharge (adjusted odds ratio, 0.40; 95% confidence interval, 0.20-0.78; P=0.005), return of spontaneous circulation (adjusted odds ratio, 0.71; 95% confidence interval, 0.53-0.94; P=0.018), and hospital admission (adjusted odds ratio, 0.57; 95% confidence interval, 0.40-0.80; P=0.001). CONCLUSIONS: After accounting for potential confounders, the mCPR in the emergency department was associated with decreased likelihoods of good clinical outcomes after adult nontraumatic out-of-hospital cardiac arrest. Further studies are needed to clarify circumstances in which mCPR may benefit these patients.

Hyperfibrinolysis in severe isolated traumatic brain injury may occur without tissue hypoperfusion: a retrospective observational multicentre study.

BACKGROUND: Hyperfibrinolysis is a critical complication in severe trauma. Hyperfibrinolysis is traditionally diagnosed via elevated D-dimer or fibrin/fibrinogen degradation product levels, and recently, using thromboelastometry. Although hyperfibrinolysis is observed in patients with severe isolated traumatic brain injury (TBI) on arrival at the emergency department (ED), it is unclear which factors induce hyperfibrinolysis. The present study aimed to investigate the factors associated with hyperfibrinolysis in patients with isolated severe TBI. METHODS: We conducted a multicentre retrospective review of data for adult trauma patients with an injury severity score ≥ 16, and selected patients with isolated TBI (TBI group) and extra-cranial trauma (non-TBI group). The TBI group included patients with an abbreviated injury score (AIS) for the head ≥ 4 and an extra-cranial AIS < 2. The non-TBI group included patients with an extra-cranial AIS ≥ 3 and head AIS < 2. Hyperfibrinolysis was defined as a D-dimer level ≥ 38 mg/L on arrival at the ED. We evaluated the relationships between hyperfibrinolysis and injury severity/tissue injury/tissue perfusion in TBI patients by comparing them with non-TBI patients. RESULTS: We enrolled 111 patients in the TBI group and 126 in the non-TBI group. In both groups, patients with hyperfibrinolysis had more severe injuries and received transfusion more frequently than patients without hyperfibrinolysis. Tissue injury, evaluated on the basis of lactate dehydrogenase and creatine kinase levels, was associated with hyperfibrinolysis in both groups. Among patients with TBI, the mortality rate was higher in those with hyperfibrinolysis than in those without hyperfibrinolysis. Tissue hypoperfusion, evaluated on the basis of lactate level, was associated with hyperfibrinolysis in only the non-TBI group. Although the increase in lactate level was correlated with the deterioration of coagulofibrinolytic variables (prolonged prothrombin time and activated partial thromboplastin time, decreased fibrinogen levels, and increased D-dimer levels) in the non-TBI group, no such correlation was observed in the TBI group. CONCLUSIONS: Hyperfibrinolysis is associated with tissue injury and trauma severity in TBI and non-TBI patients. However, tissue hypoperfusion is associated with hyperfibrinolysis in non-TBI patients, but not in TBI patients. Tissue hypoperfusion may not be a prerequisite for the occurrence of hyperfibrinolysis in patients with isolated TBI.

Association between cardiopulmonary resuscitation duration and one-month neurological outcomes for out-of-hospital cardiac arrest: a prospective cohort study.

BACKGROUND: The duration of cardiopulmonary resuscitation (CPR) is an important factor associated with the outcomes for an out-of-hospital cardiac arrest. However, the appropriate CPR duration remains unclear considering pre- and in-hospital settings. The present study aimed to evaluate the relationship between the CPR duration (including both the pre- and in-hospital duration) and neurologically favorable outcomes 1-month after cardiac arrest. METHODS: Data were utilized from a prospective multi-center cohort study of out-of-hospital cardiac arrest patients transported to 67 emergency hospitals between January 2012 and March 2013 in the Kanto area of Japan. A total of 3,353 patients with out-of-hospital cardiac arrest (age ≥18 years) who underwent CPR by emergency medical service personnel and achieved the return of spontaneous circulation in a pre- or in-hospital setting were analyzed. The primary outcome was a 1-month favorable neurological outcome. Logistic regression analysis was performed to estimate the influence of cardiopulmonary resuscitation duration. The CPR duration that achieved a cumulative proportion >99% of cases with a 1-month neurologically favorable outcome was determined. RESULTS: Of the 3,353 eligible cases, pre-hospital return of spontaneous circulation was obtained in 1,692 cases (50.5%). A total of 279 (8.3%) cases had a 1-month neurologically favorable outcome. The CPR duration was significantly and inversely associated with 1-month neurologically favorable outcomes with adjustment for pre- and in-hospital confounders (adjusted odds ratio: 0.911, per minute, 95% CI: 0.892-0.929, p < 0.001). After 30 min of CPR, the probability of a 1-month neurologically favorable outcome decreased from 8.3 to 0.7%. At 45 min of CPR, the cumulative proportion for a 1-month neurologically favorable outcome reached >99%. CONCLUSIONS: The CPR duration was independently and inversely associated with 1-month neurologically favorable outcomes after out-of-hospital cardiac arrest. The CPR duration required to achieve return of spontaneous circulation in >99% of out-of-hospital cardiac arrest patients with a 1-month favorable neurological outcome was 45 min, considering both pre- and in-hospital settings.

Early Lactate Clearance Is Associated With Improved Outcomes in Patients With Postcardiac Arrest Syndrome: A Prospective, Multicenter Observational Study (SOS-KANTO 2012 Study).

OBJECTIVES: To determine whether early lactate reduction is associated with improved survival and good neurologic outcome in patients with out-of-hospital cardiac arrest. DESIGN: Ad hoc data analysis of a prospective, multicenter observational study. SETTING: Out-of-hospital cardiac arrest patients at 67 emergency hospitals in Kanto, Japan between January 2012 and March 2013. PATIENTS: Adult patients with out-of-hospital cardiac arrest admitted to the hospital after successful resuscitation were identified. INTERVENTIONS: Blood lactate concentrations were measured at hospital admission and 6 h after hospital admission. Early lactate clearance was defined as the percent change in lactate level 6 h after a baseline measurement. MEASUREMENTS AND MAIN RESULTS: The 543 patients (mean age, 65 ± 16 yr; 72.6% male) had a mean lactate clearance of 42.4% ± 53.7%. Overall 30-day survival and good neurologic outcome were 47.1% and 27.4%, respectively. The survival proportion increased with increasing lactate clearance (quartile 1, 29.4%; quartile 2, 42.6%; quartile 3, 51.5%; quartile 4, 65.2%; p < 0.001). Multivariate logistic regression analysis showed that lactate clearance quartile was an independent predictor of the 30-day survival and good neurologic outcome. In the Cox proportional hazards model, the frequency of mortality during 30 days was significantly higher for patients with lactate clearance in quartile 1 (hazard ratio, 3.12; 95% CI, 2.14-4.53), quartile 2 (hazard ratio, 2.13; 95% CI, 1.46-3.11), and quartile 3 (hazard ratio, 1.49; 95% CI, 1.01-2.19) than those with lactate clearance in quartile 4. Furthermore, multivariate logistic regression analysis revealed that lactate clearance was a significant predictor of good neurologic outcome at 30 days after hospital admission. CONCLUSIONS: Effective lactate reduction over the first 6 hours of postcardiac arrest care was associated with survival and good neurologic outcome independently of the initial lactate level.