Temperature difference between jugular bulb and pulmonary artery is associated with neurological outcome in patients with severe traumatic brain injury: A post hoc analysis of a brain hypothermia study.

BACKGROUND: The purpose of this study was to examine whether the temperature difference between the jugular bulb and pulmonary artery (ΔTjb-pa) is associated with the neurological outcome of patients with severe traumatic brain injury (TBI). METHODS: We conducted a post hoc analysis of a multicenter randomized controlled trial of mild therapeutic hypothermia (TH, 32.0-34.0°C) or fever control (FC, 35.5-37.0°C) for the patients with severe TBI. ΔTjb-pa averaged every 12 h and the variation in ΔTjb-pa were compared between patients with favorable (n = 39) and unfavorable (n = 37) neurological outcomes. These values were also compared in the TH and FC subgroups. RESULTS: The average ΔTjb-pa values in patients with favorable and unfavorable outcomes were 0.24 ± 0.23 and 0.06 ± 0.36°C, respectively (P < 0.001). ΔTjb-pa trended significantly higher in the favorable outcome patients than in the unfavorable outcome patients throughout the 120 h after onset of severe TBI (P < 0.001). The variation in ΔTjb-pa from 0 to 72 h was significantly lower in the favorable outcome patients than in the unfavorable outcome patients (0.8 ± 0.8 vs 1.8 ± 2.5°C, respectively, P = 0.013). From 72 to 120 h, there was no significant difference in the variation in ΔTjb-pa. Significant differences between patients with favorable and unfavorable outcomes in ΔTjb-pa and the variation in ΔTjb-pa were similar in the TH subgroup, but not evident in the FC subgroup. CONCLUSIONS: A reduction in ΔTjb-pa and greater variation in ΔTjb-pa were associated with an unfavorable outcome in patients with severe TBI, especially those treated with TH. When treating severe TBI patients, it is important to understand that there will be differences in temperature reflecting the brain environment and the systemic temperature, depending on the severity and outcome of TBI during TH.

Benefits of Hypothermia for Young Patients with Acute Subdural Hematoma: A Computed Tomography Analysis of the Brain Hypothermia Study.

Therapeutic hypothermia for severe traumatic brain injury (TBI) has been repeatedly studied, but no past studies have assessed the detailed head computed tomography (CT) findings. We sought to investigate individual CT findings of severe TBI patients treated with targeted temperature management utilizing the head CT database obtained from the Brain Hypothermia study. Enrolled patients underwent either mild therapeutic hypothermia (32.0°C-34.0°C) or fever control (35.5°C-37.0°C). We assessed individual head CT images on arrival and after rewarming and investigated the correlations with outcomes. The initial CT data were available for 125 patients (hypothermia group = 80, fever control group = 45). Baseline characteristics and CT findings, such as hematoma thickness and midline shift, were similar in all aspects between the two groups. The favorable outcomes in the hypothermia and fever control groups were 38 (47.5%) and 24 (53.3%; p = 0.53) for all 125 patients, respectively; 21 (46.7%) vs. 10 (38.5%; p = 0.50) for 71 patients with acute subdural hematoma (SDH), respectively; and 12 (75.0%) vs. 4 (36.4%; p = 0.045) in 27 young adults (≤50 years) with acute SDH, respectively. There was a trend toward favorable outcomes for earlier time to reach 35.5°C (190 vs. 377 min, p = 0.052) and surgery (155 vs. 180 min, p = 0.096) in young patients with acute SDH. The second CT image revealed progression of the brain injury. This study demonstrated the potential benefits of early hypothermia in young patients with acute SDH, despite no difference in CT findings between the two groups. However, the small number of cases involved hindered the drawing of definitive conclusions. Future studies are warranted to validate the results.

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.

Comparison of high-flow nasal cannula oxygen therapy and non-invasive ventilation as first-line therapy in respiratory failure: a multicenter retrospective study.

AIM: To identify which subgroups of respiratory failure could benefit more from high-flow nasal cannula oxygen therapy (HFNC) or non-invasive ventilation (NIV). METHODS: We undertook a multicenter retrospective study of patients with acute respiratory failure (ARF) who received HFNC or NIV as first-line respiratory support between January 2012 and December 2017. The adjusted odds ratios (OR) with 95% confidence intervals (CI) for HFNC versus NIV were calculated for treatment failure and 30-day mortality in the overall cohort and in patient subgroups. RESULTS: High-flow nasal cannula oxygen therapy and NIV were used in 200 and 378 patients, and the treatment failure and 30-day mortality rates were 56% and 34% in the HFNC group and 41% and 39% in the NIV group, respectively. The risks of treatment failure and 30-day mortality were not significantly different between the two groups. In subgroup analyses, HFNC was associated with increased risk of treatment failure in patients with cardiogenic pulmonary edema (adjusted OR 6.26; 95% CI, 2.19-17.87; P < 0.01) and hypercapnia (adjusted OR 3.70; 95% CI, 1.34-10.25; P = 0.01), but the 30-day mortality was not significantly different in these subgroups. High-flow nasal cannula oxygen therapy was associated with lower risk of 30-day mortality in patients with pneumonia (adjusted OR 0.43; 95% CI, 0.19-0.94; P = 0.03) and in patients without hypercapnia (adjusted OR 0.51; 95% CI, 0.30-0.88; P = 0.02). CONCLUSION: High-flow nasal cannula oxygen therapy could be more beneficial than NIV in patients with pneumonia or non-hypercapnia, but not in patients with cardiogenic pulmonary edema or hypercapnia.

Prognostic Significance of the Difference Between Mixed and Jugular Venous Oxygen Saturation After Severe Traumatic Brain Injury: A Post Hoc Analysis of the Brain Hypothermia Study.

BACKGROUND: In patients postcardiac arrest, it has been reported that the small value of the difference between mixed venous oxygen saturation (Svo2) and jugular venous oxygen saturation (Sjvo2) is associated with poor neurologic outcome. However, the importance of the difference between mixed venous oxygen saturation and jugular venous oxygen saturation (ΔSo2 [v - jv]) remains unknown in severe traumatic brain injury (TBI). The aim of this study was to examine whether ΔSo2 (v - jv) is associated with neurologic outcome and mortality in patients with severe TBI. METHODS: We conducted post hoc analyses of the Brain Hypothermia Study, a multicenter randomized controlled trial of mild therapeutic hypothermia for the treatment of severe TBI. The value of ΔSo2(v - jv) on day 1 and day 3 was compared between survivors (n = 65) and nonsurvivors (n = 25) or between patients with favorable (n = 47) and unfavorable (n = 43) neurologic outcomes. RESULTS: The reduction in ΔSo2 (v - jv) on day 3 was -2.0% (range, -6.9% to 6.5%) in the nonsurvivor group and 6.3% (range, -2.5% to 16.7%) in the survivor group. The difference was statistically significant (P = 0.03). The same tendencies were observed in the nonsurvivor group on day 1 and in the unfavorable neurologic outcome group on day 1 and day 3, but the difference was not significant. CONCLUSIONS: The reduction in ΔSo2(v - jv) on day 3 was associated with high mortality in patients with severe TBI.

Mechanisms Associated with the Adverse Vascular Consequences of Rapid Posthypothermic Rewarming and Their Therapeutic Modulation in Rats.

We previously demonstrated that rapid posthypothermic rewarming in noninjured animals was capable of damaging cerebral arterioles both at endothelial and smooth muscle levels. Such adverse consequences could be prevented with antioxidants, suggesting the involvement of free radicals. In this study, we further investigate the mechanisms associated with free radicals production by using two radical scavengers, superoxide dismutase (SOD) and catalase. Employing rats, the cerebral vascular response was evaluated at 2, 3, and 4 hours after onset of hypothermia. Before rapid rewarming, SOD treatment, but not catalase, preserved the NO-mediated dilation induced by acetylcholine (ACh). On the contrary, catalase preserved the hypercapnia-induced relaxation of the smooth muscle cells, whereas SOD offered only partial protection. Adding SOD to catalase treatment offered no additional benefit. These results suggest that rapid posthypothermic rewarming impairs ACh- and hypercapnia-induced vasodilation through different subcellular mechanisms. In the case of diminished vascular response to ACh, it appears to act on the endothelial front primarily by superoxide anions, as evidenced by its full preservation after SOD treatment. In terms of impaired dilation to hypercapnia, hydrogen peroxide and/or its derivatives are the likely candidates in targeting the smooth muscle cells. The partial protection of SOD to hypercapnia-induced dilation is believed to be the reduced amount of superoxide that would otherwise spontaneously dismutate to produce hydrogen peroxide. Although SOD exerts some indirect influence on the hydrogen peroxide production downstream, catalase apparently has no influence on upstream superoxide production.

Hyperoxemia during the hyperacute phase of aneurysmal subarachnoid hemorrhage is associated with delayed cerebral ischemia and poor outcome: a retrospective observational study.

OBJECTIVE: The harmful effects of hyperoxemia have been reported in critically ill patients with various disorders, including those with brain injuries. However, the effect of hyperoxemia on aneurysmal subarachnoid hemorrhage (aSAH) patients is unclear. In this study the authors aimed to determine whether hyperoxemia during the hyperacute or acute phase in patients with aSAH is associated with delayed cerebral ischemia (DCI) and poor neurological outcome. METHODS: In this single-center retrospective study, data from patients with aSAH treated between January 2011 and June 2017 were reviewed. The patients were classified into groups according to whether they experienced DCI (DCI group and non-DCI group) and whether they had a poor outcome at discharge (poor outcome group and favorable outcome group). The background characteristics and time-weighted average (TWA) PaO2 during the first 24 hours after arrival at the treatment facility (TWA24h-PaO2) and between the first 24 hours after arrival and day 6 (TWA6d-PaO2), the hyperacute and acute phases, respectively, were compared between the groups. Factors related to DCI and poor outcome were evaluated with logistic regression analyses. RESULTS: Of 197 patients with aSAH, 42 patients experienced DCI and 82 patients had a poor outcome at discharge. TWA24h-PaO2 was significantly higher in the DCI group than in the non-DCI group (186 [141-213] vs 161 [138-192] mm Hg, p = 0.029) and in the poor outcome group than in the favorable outcome group (176 [154-205] vs 156 [136-188] mm Hg, p = 0.004). TWA6d-PaO2 did not differ significantly between the groups. Logistic regression analyses revealed that higher TWA24h-PaO2 was an independent risk factor for DCI (OR 1.09, 95% CI 1.01-1.17, p = 0.037) and poor outcome (OR 1.17, 95% CI 1.06-1.29, p = 0.002). CONCLUSIONS: Hyperoxemia during the first 24 hours was associated with DCI and a poor outcome in patients with aSAH. Excessive oxygen therapy might have an adverse effect in the hyperacute phase of aSAH.

Impact of type of emergency department on the outcome of out-of-hospital cardiac arrest: a prospective cohort study.

AIM: To assess whether the outcomes of out-of-hospital cardiac arrest (OHCA) differ between patients treated at tertiary or secondary emergency medical facilities. METHODS: Data from the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest (JAAM-OHCA) registry between June 2014 and December 2015 were analyzed and compared between patients treated at tertiary (tertiary group) and secondary (secondary group) emergency medical facilities. The primary outcome of this study was a favorable neurological outcome at 1 and 3 months after OHCA, defined as a Glasgow-Pittsburgh cerebral performance category of 1 or 2. RESULTS: Between June 2014 and December 2015, a total of 13,491 patients with OHCA were registered in the JAAM-OHCA registry. Of these, 12,836 were eligible in the present analysis, with 11,583 in the tertiary group and 1,253 in the secondary group. The proportions of patients with favorable neurological outcomes in the tertiary group were significantly higher than those in the secondary group at 1 (4.7% versus 2.0%, P < 0.001) and 3 (3.5% versus 1.6%, P < 0.001) months after OHCA. Even after adjusting for baseline characteristics of patients, treatment at a tertiary emergency medical facility was independently associated with favorable neurological outcomes at 1 (odds ratio, 2.856, 95% confidence interval, 1.429-5.710; P = 0.003) and 3 (odds ratio, 2.462, 95% confidence interval, 1.203-5.042; P = 0.014) months after OHCA. CONCLUSION: The neurological outcomes of patients with OHCA treated at tertiary emergency medical facilities were better than those of patients treated at secondary emergency medical facilities.

Comparison between the Bouchama and Japanese Association for Acute Medicine Heatstroke Criteria with Regard to the Diagnosis and Prediction of Mortality of Heatstroke Patients: A Multicenter Observational Study.

BACKGROUND: This study aims to compare the Bouchama heatstroke (B-HS) and Japanese Association for Acute Medicine heatstroke (JAAM-HS) criteria with regard to the diagnosis and prediction of mortality and neurological status of heatstroke patients. METHODS: This multicenter observational study recruited eligible patients from the emergency departments of 110 major hospitals in Japan from 1 July to 30 September, 2014. RESULTS: A total of 317 patients (median age, 65 years; interquartile range, 39-80 years) were included and divided into the B-HS, JAAM-HS, and non-HS groups, with each group consisting of 97, 302, and 15 patients, respectively. The JAAM-HS (1.0; 95% confidence interval [CI], 0.87-1.0) and B-HS (0.29; 95% CI, 0.14-0.49) criteria showed high and low sensitivity to mortality, respectively. Similarly, the JAAM-HS (1.0; 95% CI, 0.93-1.0) and B-HS (0.35; 95% CI, 0.23-0.49) criteria showed high and low sensitivity to poor neurological status, respectively. Meanwhile, the sequential organ failure assessment (SOFA) scores demonstrated good accuracy in predicting mortality among heat-related illness (HRI) patients. However, both JAAM-HS and B-HS criteria could not predict in-hospital mortality. The AUC of the SOFA score for mortality was 0.83 (day 3) among the HRI patients. The patients' neurological status was difficult to predict using the JAAM-HS and B-HS criteria. Concurrently, the total bilirubin level could relatively predict the central nervous system function at discharge. CONCLUSIONS: The JAAM-HS criteria showed high sensitivity to mortality and could include all HRI patients who died. The JAAM-HS criterion was considered a useful tool for judgement of admission at ED. Further investigations are necessary to determine the accuracy of both B-HS and JAAM-HS criteria in predicting mortality and neurological status at discharge.

Mild decrease in heart rate during early phase of targeted temperature management following tachycardia on admission is associated with unfavorable neurological outcomes after severe traumatic brain injury: a post hoc analysis of a multicenter randomized controlled trial.

BACKGROUND: The association between isolated admission heart rate (HR) and prognosis has been discussed, but not that between gross HR change and neurological outcome in patients with severe traumatic brain injury (TBI). In the acute phase of severe TBI, HR is influenced by several factors (e.g., pain, sympathetic activation, hypovolemia, fever, body temperature). Therefore, admission HR and gross HR change should be examined in patients with TBI treated with a well-designed protocol, such as was done in the Brain Hypothermia (B-HYPO) Study. METHODS: This was a post hoc analysis of the B-HYPO Study, which was conducted as a prospective, multicenter, randomized controlled trial in patients with severe TBI receiving mild therapeutic hypothermia (MTH; 32.0 °C-34.0 °C) or fever control (35.5 °C-37.0 °C) in Japan. Patients with MTH were examined, and HR change (%HR) in the early MTH phase was calculated as follows: [admission HR - HR at day 1]/admission HR × 100. Patients were divided into six groups, using admission HR (< 80, 80-99, ≤ 100) and median of %HR; i.e., group (Admission HR < 80 and %HR ≥ 18.6); group (Admission HR < 80 and %HR < 18.6); group (Admission HR 80-99 and %HR ≥ 18.6); group (Admission HR 80-99 and %HR < 18.6); group (Admission HR ≥100 and %HR ≥ 18.6); and group (Admission HR ≥100 and %HR < 18.6). The primary outcome was an adjusted predicted probability of unfavorable neurological outcome at 6 months after TBI according to Glasgow Outcome Scale score, which is a measure of functional recovery and defined as severe disability, persistent vegetative state, and death. RESULTS: Overall, 79 patients with MTH (52.7% of the original trial) were examined; among these, unfavorable neurological outcomes were observed in 53.2%. Among all the groups, group (Admission HR ≥100 and %HR < 18.6) exhibited the highest proportion of unfavorable outcomes, and 82.3% of patients had an adjusted predicted probability of unfavorable outcomes, whereas those in group (Admission HR < 80 and %HR ≥ 18.6) developed only 22.8% (p = 0.04). CONCLUSIONS: Mild HR decrease during the early phase of targeted temperature management following tachycardia at admission can be associated with unfavorable neurological outcomes after severe TBI.

Evaluation of a Novel Classification of Heat-Related Illnesses: A Multicentre Observational Study (Heat Stroke STUDY 2012).

The Japanese Association for Acute Medicine Committee recently proposed a novel classification system for the severity of heat-related illnesses. The illnesses are simply classified into three stages based on symptoms and management or treatment. Stages I, II, and III broadly correspond to heat cramp and syncope, heat exhaustion, and heat stroke, respectively. Our objective was to examine whether this novel severity classification is useful in the diagnosis by healthcare professionals of patients with severe heat-related illness and organ failure. A nationwide surveillance study of heat-related illnesses was conducted between 1 June and 30 September 2012, at emergency departments in Japan. Among the 2130 patients who attended 102 emergency departments, the severity of their heat-related illness was recorded for 1799 patients, who were included in this study. In the patients with heat cramp and syncope or heat exhaustion (but not heat stroke), the blood test data (alanine aminotransferase, creatinine, blood urea nitrogen, and platelet counts) for those classified as Stage III were significantly higher than those of patients classified as Stage I or II. There were no deaths among the patients classified as Stage I. This novel classification may avoid underestimating the severity of heat-related illness.

Slow rewarming improved the neurological outcomes of prolonged mild therapeutic hypothermia in patients with severe traumatic brain injury and an evacuated hematoma.

Mild therapeutic hypothermia (MTH) is expected to improve the neurological outcomes of patients with severe traumatic brain injury (TBI). However, there are no standard protocols for managing the temperature of patients with severe TBI in order to improve their neurological outcomes. We conducted a post hoc analysis of the B-HYPO study, a randomized controlled trial of MTH in patients with TBI in Japan. We evaluated the impact of MTH methods on neurological outcomes. Ninety-seven patients who received MTH were included in the present analyses. The neurological outcomes were compared among subgroups of patients divided by cutoff values for the induction, maintenance, and rewarming times of MTH in all patients, in patients with diffuse injury, and in patients with an evacuated hematoma. The proportion of patients with a good neurological outcome was significantly different between patients with an evacuated hematoma divided into subgroups by the cutoff value of rewarming time of 48 h (>48 h vs. ≤ 48 h: 65% vs. 22%; odds ratio: 6.61; 95% confidence interval: 1.13-38.7, P = 0.0498). Slow rewarming for >48 h might improve the neurological outcomes of prolonged MTH in patients with TBI and an evacuated hematoma. Further studies are needed to investigate the optimal rewarming protocol in patients with TBI.

Early enteral nutrition is associated with reduced in-hospital mortality from sepsis in patients with sarcopenia.

PURPOSE: To determine whether the association of early enteral nutrition (EEN) with mortality from sepsis differs between patients with and without sarcopenia. MATERIALS AND METHODS: We retrospectively reviewed septic patients treated at our centre between January 2010 and August 2017. The skeletal muscle area (SMA) at the level of the third lumbar vertebra was measured with CT on admission, and sarcopenia was defined as SMA < 80% of the predicted value. Patients were divided into two subgroups (sarcopenic and non-sarcopenic patients), and in-hospital mortality was compared in patients treated with and without EEN within each subgroup. We used logistic regression to examine factors associated with in-hospital mortality in each subgroup. RESULTS: EEN was administered to 35/91 sarcopenic patients and 43/100 non-sarcopenic patients. In-hospital mortality did not differ between non-sarcopenic patients with EEN and those without EEN (16% vs 16%, P = 0.947), but was significantly lower in sarcopenic patients with EEN than in those without EEN (9% vs 34%, P = 0.005). Logistic regression showed that EEN was independently associated with reduced in-hospital mortality in sarcopenic patients (OR 0.18, 95% CI 0.05-0.71, P = 0.014), but not in non-sarcopenic patients. CONCLUSIONS: EEN may be more beneficial in sarcopenic patients.

A novel early risk assessment tool for detecting clinical outcomes in patients with heat-related illness (J-ERATO score): Development and validation in independent cohorts in Japan.

BACKGROUND: We sought to develop a novel risk assessment tool to predict the clinical outcomes after heat-related illness. METHODS: Prospective, multicenter observational study. Patients who transferred to emergency hospitals in Japan with heat-related illness were registered. The sample was divided into two parts: 60% to construct the score and 40% to validate it. A binary logistic regression model was used to predict hospital admission as a primary outcome. The resulting model was transformed into a scoring system. RESULTS: A total of 3,001 eligible patients were analyzed. There was no difference in variables between development and validation cohorts. Based on the result of a logistic regression model in the development phase (n = 1,805), the J-ERATO score was defined as the sum of the six binary components in the prehospital setting (respiratory rate≥22 /min, Glasgow coma scale<15, systolic blood pressure≤100 mmHg, heart rate≥100 bpm, body temperature≥38°C, and age≥65 y), for a total score ranging from 0 to 6. In the validation phase (n = 1,196), the score had excellent discrimination (C-statistic 0.84; 95% CI 0.79-0.89, p<0.0001) and calibration (P>0.2 by Hosmer-Lemeshow test). The observed proportion of hospital admission increased with increasing J-ERATO score (score = 0, 5.0%; score = 1, 15.0%; score = 2, 24.6%; score = 3, 38.6%; score = 4, 68.0%; score = 5, 85.2%; score = 6, 96.4%). Multivariate analyses showed that the J-ERATO score was an independent positive predictor of hospital admission (adjusted OR, 2.43; 95% CI, 2.06-2.87; P<0.001), intensive care unit (ICU) admission (3.73; 2.95-4.72; P<0.001) and in-hospital mortality (1.65; 1.18-2.32; P = 0.004). CONCLUSIONS: The J-ERATO score is simply assessed and can facilitate the identification of patients with higher risk of heat-related hospitalization. This scoring system is also significantly associated with the higher likelihood of ICU admission and in-hospital mortality after heat-related hospitalization.

Variability in Treatment for Carbon Monoxide Poisoning in Japan: A Multicenter Retrospective Survey.

BACKGROUND: The aim of this study was to identify practice differences in the treatment of carbon monoxide (CO) poisoning with or without hyperbaric oxygen (HBO2) therapy in Japan. MATERIALS AND METHODS: Using an online survey website (Google form), we created a questionnaire and invited interested institutions to join the COP-J Study, a prospective observational study of CO poisoning in Japan. RESULTS: Forty-eight (63%) of 76 institutions replied to the questionnaire. Thirty-three institutions (69%) administered HBO2 therapy to patients with CO poisoning, and 15 institutions (31%) did not. Consciousness disturbance on arrival, exposure to CO for a long time, and elevation of arterial carboxyhemoglobin (CO-Hb) were the major indications for HBO2 therapy. The maximum therapeutic pressures were 2.0, 2.5, and 2.8 atmospheres absolute (ATA) at 19 (58%), 6 (18%), and 8 (24%) institutions, respectively. The number of HBO2 sessions on the first day was 1-3, and 1-7 sessions were administered on days 2-7. Seventeen (35%) institutions treated patients with delayed neurological sequelae (DNS) and 15 of them used HBO2 therapy for DNS. CONCLUSIONS: This survey indicates that HBO2 therapy for CO poisoning was varied in both the indications and practice regimens used in Japan.

Prognostic significance of disseminated intravascular coagulation in patients with heat stroke in a nationwide registry.

PURPOSE: Heat stroke (HS) induces disseminated intravascular coagulation (DIC); however, the prognostic significance of DIC in patients with HS has not yet been fully assessed in large populations. The aim of this study was to examine the prognostic significance of DIC in patients with HS using a nationwide registry. MATERIALS AND METHODS: Data regarding HS were obtained and analyzed from three prospective, observational, multicenter HS registries (HSRs): 2010, 2012, and 2014. Univariate and multivariate analyses were performed to identify independent predictors of hospital death. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) diagnostic criteria, with a total score≥4 implying a DIC diagnosis. RESULTS: In total, 705 (median age, 68years; 501 men) were included in this study. Hospital mortality was 7.1% (50 patients). Multiple regression analysis revealed that hospital mortality was significantly associated with presence of DIC (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.09-4.27; p=0.028). Mortality worsened as the DIC score increased, and increased remarkably to approximately 10% when the DIC score was 2. CONCLUSIONS: Presence of DIC was an independent prognostic factor of hospital mortality in patients with HS. Hematological dysfunction represents potential target for specific therapies in HS.

Therapeutic hypothermia in patients with coagulopathy following severe traumatic brain injury.

BACKGROUND: Coagulopathy in traumatic brain injury (TBI) has been associated with poor neurological outcomes and higher in-hospital mortality. In general principle of trauma management, hypothermia should be prevented as it directly worsens coagulopathy. Therefore, we examined the safety of mild therapeutic hypothermia (MTH) in patients with coagulopathy following severe TBI. METHODS: We re-evaluated the brain hypothermia (B-HYPO) study data based on coagulopathy and compared the Glasgow Outcome Scale scores and survival rates at 6 months using per protocol analyses. Coagulopathy was defined as an activated partial thromboplastin time (APTT) > 60 s and/or fibrin/fibrinogen degradation product levels (FDP) > 90 µg/mL on admission. Baseline characteristics, coagulation parameters, and outcomes were compared between the control and MTH groups with or without coagulopathy. RESULTS: In patients with coagulopathy, 12 patients were allocated to the control group (35.5-37.0 °C) and 20 patients to the MTH group (32-34 °C). In patients without coagulopathy, 28 were allocated to the control group and 59 patients were allocated to the MTH group. In patients with coagulopathy, favorable neurological outcomes and survival rates were comparable between the control and MTH groups (33.3% vs. 35.0%, P = 1.00; 50.0% vs. 60.0%, P = 0.72) with no difference in complication rates. On admission, no significant differences in APTT or FDP levels were observed between the two groups; however, APTT was significantly prolonged in the MTH group compared to the control group on day 3. DISCUSSION: Based on our study, MTH did not seem to negatively affect the outcomes in patients with coagulopathy following severe TBI on admission; therefore, the present study indicates that MTH may be applicable even in patients with severe TBI and coagulopathy. CONCLUSIONS: Our study suggests that in comparison to control, MTH does not worsen the outcome of patients with coagulopathy following severe TBI. TRIAL REGISTRATION: UMIN-CTR, No. C000000231 , Registered 13 September 2005.

Early-Stage Hyperoxia Is Associated with Favorable Neurological Outcomes and Survival after Severe Traumatic Brain Injury: A Post-Hoc Analysis of the Brain Hypothermia Study.

The effects of hyperoxia on the neurological outcomes of patients with severe traumatic brain injury (TBI) are still controversial. We examined whether the partial pressure of arterial oxygen (PaO2) and hyperoxia were associated with neurological outcomes and survival by conducting post-hoc analyses of the Brain Hypothermia (B-HYPO) study, a multi-center randomized controlled trial of mild therapeutic hypothermia for severe TBI. The differences in PaO2 and PaO2/fraction of inspiratory oxygen (P/F) ratio on the 1st day of admission were compared between patients with favorable (n = 64) and unfavorable (n = 65) neurological outcomes and between survivors (n = 90) and deceased patients (n = 39). PaO2 and the P/F ratio were significantly greater in patients with favorable outcomes than in patients with unfavorable neurological outcomes (PaO2: 252 ± 122 vs. 202 ± 87 mm Hg, respectively, p = 0.008; P/F ratio: 455 ± 171 vs. 389 ± 155, respectively, p = 0.022) and in survivors than in deceased patients (PaO2: 242 ± 117 vs. 193 ± 75 mm Hg, respectively, p = 0.005; P/F ratio: 445 ± 171 vs. 370 ± 141, respectively, p = 0.018). Similar tendencies were observed in subgroup analyses in patients with fever control and therapeutic hypothermia, and in patients with an evacuated mass or other lesions (unevacuated lesions). PaO2 was independently associated with survival (odds ratio 1.008, p = 0.037). These results suggested that early-stage hyperoxia might be associated with favorable neurological outcomes and survival following severe TBI.

Association between Blood Glucose Levels the Day after Targeted Temperature Initiation and Outcome in Traumatic Brain Injury: A Post-Hoc Analysis of the B-HYPO Study.

We investigated associations between blood glucose levels and clinical outcomes in participants of the multi-center randomized controlled Brain-Hypothermia (B-HYPO) study. Patients with severe traumatic brain injury (TBI, Glasgow Coma Scale 4-8) were assigned to therapeutic hypothermia (TH, 32-34°C, n = 98) or fever control (35.5-37.0°C, n = 50) groups. TH patients were cooled as soon as possible for ≥72 h and rewarmed at a rate of <1°C/d. We recorded blood glucose (BG) levels on days 0, 1, and 3 after treatment initiation, and day 1 after rewarming. The Glasgow Outcome Scale was assessed at 6 months. Median BG levels decreased from day 0 to day 1 (163 vs. 132 mg/dL, p = 0.0062) in the fever control group. In contrast, a decrease was observed from day 1 to day 3 (157.5 vs. 126 mg/dL, p < 0.001) in the TH group. Day 1 BG was higher in the TH group compared with the fever control group (p = 0.0252). At day 0, BG levels were higher in non-survivors compared with survivors across all patients (p = 0.0035), the TH group (p = 0.0125), and the non-surgical group (p = 0.0236). Higher day 1 BG levels were observed in non-survivors compared with survivors across all patients (p = 0.0071), the fever control group (p = 0.0495), and the surgical group (p = 0.0364). In the TH group, the initial stress hyperglycemia was sustained the next day after TH induction. Day 1 BG predicted outcome in TBI patients with TH and fever control. Our findings indicate the significance of BG control particularly during TH treatment.