Significance of body temperature in elderly patients with sepsis.

BACKGROUND: Elderly patients have a blunted host response, which may influence vital signs and clinical outcomes of sepsis. This study was aimed to investigate whether the associations between the vital signs and mortality are different in elderly and non-elderly patients with sepsis. METHODS: This was a retrospective observational study. A Japanese multicenter sepsis cohort (FORECAST, n = 1148) was used for the discovery analyses. Significant discovery results were tested for replication using two validation cohorts of sepsis (JAAMSR, Japan, n = 624; SPH, Canada, n = 1004). Patients were categorized into elderly and non-elderly groups (age ≥ 75 or < 75 years). We tested for association between vital signs (body temperature [BT], heart rate, mean arterial pressure, systolic blood pressure, and respiratory rate) and 90-day in-hospital mortality (primary outcome). RESULTS: In the discovery cohort, non-elderly patients with BT < 36.0 °C had significantly increased 90-day mortality (P = 0.025, adjusted hazard ratio 1.70, 95% CI 1.07-2.71). In the validation cohorts, non-elderly patients with BT < 36.0 °C had significantly increased mortality (JAAMSR, P = 0.0024, adjusted hazard ratio 2.05, 95% CI 1.29-3.26; SPH, P = 0.029, adjusted hazard ratio 1.36, 95% CI 1.03-1.80). These differences were not observed in elderly patients in the three cohorts. Associations between the other four vital signs and mortality were not different in elderly and non-elderly patients. The interaction of age and hypothermia/fever was significant (P < 0.05). CONCLUSIONS: In septic patients, we found mortality in non-elderly sepsis patients was increased with hypothermia and decreased with fever. However, mortality in elderly patients was not associated with BT. These results illuminate the difference in the inflammatory response of the elderly compared to non-elderly sepsis patients.

Complementary Role of Hypothermia Identification to the Quick Sequential Organ Failure Assessment Score in Predicting Patients With Sepsis at High Risk of Mortality: A Retrospective Analysis From a Multicenter, Observational Study.

BACKGROUND: Although the quick Sequential Organ Failure Assessment (qSOFA) has been recommended for identifying patients at higher risk of hospital death, it has only a 60% sensitivity for in-hospital mortality. On the other hand, hypothermia associates with increased mortality and organ failure in patients with sepsis. This study aimed to assess the predictive validity of qSOFA for identifying patients with sepsis at higher risk of multiple organ dysfunction or death and the complementary effect of hypothermia. METHODS: Patients with severe sepsis admitted to intensive care units (ICUs) were retrospectively analyzed. The predictive validities of qSOFA (≥2, positive) and the complementary effect of hypothermia (body temperature ≤36.5°C) for the identification of death or multiorgan dysfunction were evaluated. RESULTS: Of the 624 patients, 230 (36.9%) developed multiorgan dysfunction and 144 (23.1%) died within 28 days; 527 (84.5%) had a positive qSOFA. The 28-day mortality rates of patients with positive and negative qSOFA were 25.4% and 10.3%, respectively (P = .001). The rate of positive qSOFA was higher in patients with multiorgan dysfunction (sensitivity, 0.896; specificity, 0.185) and among patients who died within 28 days (sensitivity, 0.931; specificity, 0.181); 10 (6.9%) of 144 deaths were not identified. In cases of positive qSOFA without hypothermia, positive qSOFA + hypothermia, or negative qSOFA with hypothermia, the predictive value for 28-day mortality improved (sensitivity, 0.979). Among the 144 patients who died, only 3 were not identified. CONCLUSION: A qSOFA score ≥2 may identify >90% of 28-day deaths among patients with severe sepsis; hypothermia may complement the predictive ability of qSOFA.

Characteristics and outcomes of frail patients with suspected infection in intensive care units: a descriptive analysis from a multicenter cohort study.

BACKGROUND: Frailty is associated with morbidity and mortality in patients admitted to intensive care units (ICUs). However, the characteristics of frail patients with suspected infection remain unclear. We aimed to investigate the characteristics and outcomes of frail patients with suspected infection in ICUs. METHODS: This is a secondary analysis of a multicenter cohort study, including 22 ICUs in Japan. Adult patients (aged ≥16 years) with newly suspected infection from December 2017 to May 2018 were included. We compared baseline patient characteristics and outcomes among three frailty groups based on the Clinical Frailty Scale (CFS) score: fit (score, 1-3), vulnerable (score, 4), and frail (score, 5-9). We conducted subgroup analysis of patients with sepsis defined as per Sepsis-3 criteria. We also produced Kaplan-Meier survival curves for 90-day survival. RESULTS: We enrolled 650 patients with suspected infection, including 599 (92.2%) patients with sepsis. Patients with a median CFS score of 3 (interquartile range [IQR] 3-5) were included: 337 (51.8%) were fit, 109 (16.8%) were vulnerable, and 204 (31.4%) were frail. The median patient age was 72 years (IQR 60-81). The Sequential Organ Failure Assessment scores for fit, vulnerable, and frail patients were 7 (IQR 4-10), 8 (IQR 5-11), and 7 (IQR 5-10), respectively (p = 0.59). The median body temperatures of fit, vulnerable, and frail patients were 37.5 °C (IQR 36.5 °C-38.5 °C), 37.5 °C (IQR 36.4 °C-38.6 °C), and 37.0 °C (IQR 36.3 °C-38.1 °C), respectively (p < 0.01). The median C-reactive protein levels of fit, vulnerable, and frail patients were 13.6 (IQR 4.6-24.5), 12.1 (IQR 3.9-24.9), 10.5 (IQR 3.0-21.0) mg/dL, respectively (p < 0.01). In-hospital mortality did not statistically differ among the patients according to frailty (p = 0.19). Kaplan-Meier survival curves showed little difference in the mortality rate during short-term follow-up. However, more vulnerable and frail patients died after 30-day than fit patients; this difference was not statistically significant (p = 0.25). Compared with the fit and vulnerable groups, the rate of home discharge was lower in the frail group. CONCLUSION: Frail and vulnerable patients with suspected infection tend to have poor disease outcomes. However, they did not show a statistically significant increase in the 90-day mortality risk.

Impact of Body Temperature Abnormalities on the Implementation of Sepsis Bundles and Outcomes in Patients With Severe Sepsis: A Retrospective Sub-Analysis of the Focused Outcome Research on Emergency Care for Acute Respiratory Distress Syndrome, Sepsis and Trauma Study.

OBJECTIVES: To investigate the impact of body temperature on disease severity, implementation of sepsis bundles, and outcomes in severe sepsis patients. DESIGN: Retrospective sub-analysis. SETTING: Fifty-nine ICUs in Japan, from January 2016 to March 2017. PATIENTS: Adult patients with severe sepsis based on Sepsis-2 were enrolled and divided into three categories (body temperature < 36°C, 36-38°C, > 38°C), using the core body temperature at ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Compliance with the bundles proposed in the Surviving Sepsis Campaign Guidelines 2012, in-hospital mortality, disposition after discharge, and the number of ICU and ventilator-free days were evaluated. Of 1,143 enrolled patients, 127, 565, and 451 were categorized as having body temperature less than 36°C, 36-38°C, and greater than 38°C, respectively. Hypothermia-body temperature less than 36°C-was observed in 11.1% of patients. Patients with hypothermia were significantly older than those with a body temperature of 36-38°C or greater than 38°C and had a lower body mass index and higher prevalence of septic shock than those with body temperature greater than 38°C. Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores on the day of enrollment were also significantly higher in hypothermia patients. Implementation rates of the entire 3-hour bundle and administration of broad-spectrum antibiotics significantly differed across categories; implementation rates were significantly lower in patients with body temperature less than 36°C than in those with body temperature greater than 38°C. Implementation rate of the entire 3-hour resuscitation bundle + vasopressor use + remeasured lactate significantly differed across categories, as did the in-hospital and 28-day mortality. The odds ratio for in-hospital mortality relative to the reference range of body temperature greater than 38°C was 1.760 (95% CI, 1.134-2.732) in the group with hypothermia. The proportions of ICU-free and ventilator-free days also significantly differed between categories and were significantly smaller in patients with hypothermia. CONCLUSIONS: Hypothermia was associated with a significantly higher disease severity, mortality risk, and lower implementation of sepsis bundles.

Implementation of earlier antibiotic administration in patients with severe sepsis and septic shock in Japan: a descriptive analysis of a prospective observational study.

BACKGROUND: Time to antibiotic administration is a key element in sepsis care; however, it is difficult to implement sepsis care bundles. Additionally, sepsis is different from other emergent conditions including acute coronary syndrome, stroke, or trauma. We aimed to describe the association between time to antibiotic administration and outcomes in patients with severe sepsis and septic shock in Japan. METHODS: This prospective observational study enrolled 1184 adult patients diagnosed with severe sepsis based on the Sepsis-2 criteria and admitted to 59 intensive care units (ICUs) in Japan between January 1, 2016, and March 31, 2017, as the sepsis cohort of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) study. We compared the characteristics and in-hospital mortality of patients administered with antibiotics at varying durations after sepsis recognition, i.e., 0-60, 61-120, 121-180, 181-240, 241-360, and 361-1440 min, and estimated the impact of antibiotic timing on risk-adjusted in-hospital mortality using the generalized estimating equation model (GEE) with an exchangeable, within-group correlation matrix, with "hospital" as the grouping variable. RESULTS: Data from 1124 patients in 54 hospitals were used for analyses. Of these, 30.5% and 73.9% received antibiotics within 1 h and 3 h, respectively. Overall, the median time to antibiotic administration was 102 min [interquartile range (IQR), 55-189]. Compared with patients diagnosed in the emergency department [90 min (IQR, 48-164 min)], time to antibiotic administration was shortest in patients diagnosed in ICUs [60 min (39-180 min)] and longest in patients transferred from wards [120 min (62-226)]. Overall crude mortality was 23.4%, where patients in the 0-60 min group had the highest mortality (28.0%) and a risk-adjusted mortality rate [28.7% (95% CI 23.3-34.1%)], whereas those in the 61-120 min group had the lowest mortality (20.2%) and risk-adjusted mortality rates [21.6% (95% CI 16.5-26.6%)]. Differences in mortality were noted only between the 0-60 min and 61-120 min groups. CONCLUSIONS: We could not find any association between earlier antibiotic administration and reduction in in-hospital mortality in patients with severe sepsis.

Prognostic Accuracy of Quick SOFA is different according to the severity of illness in infectious patients.

BACKGROUND: Sepsis-3 proposed the quick Sequential Organ Failure Assessment (qSOFA) to identify sepsis patients likely to have poor outcome. The clinical utility of qSOFA still remains controversial because its predictive accuracy for mortality is quite different across the validation studies. We hypothesized that one of the major causes for these controversial findings was the heterogeneity in severity across the studies, and evaluated the association between severity of illness and the prognostic accuracy of qSOFA. MATERIALS AND METHODS: This was a post hoc analysis of a prospective nationwide cohort of consecutive adult patients with sepsis in 59 intensive care units in Japan. Regression trees analysis for survival was used to classify patients according to severity of illness as determined by SOFA score on registration. We conducted receiver operating characteristic (ROC) analyses and evaluated the differences in the area under the ROC curve (AUROC). As a subgroup analysis, we conducted the above evaluations in emergency department (ED) and non-ED patients separately. RESULTS: We included 1114 patients fulfilling the criteria and classified them into three subsets according to severity. The AUROC for mortality was significantly different according to the severity of illness (p = 0.007), with the highest AUROC being in the low-severity subset (patients with SOFA score ≤ 7). Interestingly, our subgroup analysis revealed that a significant difference in the AUROC of qSOFA was observed only in ED patients. CONCLUSION: This study suggested that lower severity of illness was associated with the relatively higher prognostic accuracy of qSOFA, especially in ED patients.

Characteristics, management, and in-hospital mortality among patients with severe sepsis in intensive care units in Japan: the FORECAST study.

BACKGROUND: Sepsis is a leading cause of death and long-term disability in developed countries. A comprehensive report on the incidence, clinical characteristics, and evolving management of sepsis is important. Thus, this study aimed to evaluate the characteristics, management, and outcomes of patients with severe sepsis in Japan. METHODS: This is a cohort study of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis, and Trauma (FORECAST) study, which was a multicenter, prospective cohort study conducted at 59 intensive care units (ICUs) from January 2016 to March 2017. We included adult patients with severe sepsis based on the sepsis-2 criteria. RESULTS: In total, 1184 patients (median age 73 years, interquartile range (IQR) 64-81) with severe sepsis were admitted to the ICU during the study period. The most common comorbidity was diabetes mellitus (23%). Moreover, approximately 63% of patients had septic shock. The median Sepsis-related Organ Failure Assessment (SOFA) score was 9 (IQR 6-11). The most common site of infection was the lung (31%). Approximately 54% of the participants had positive blood cultures. The compliance rates for the entire 3-h bundle, measurement of central venous pressure, and assessment of central venous oxygen saturation were 64%, 26%, and 7%, respectively. A multilevel logistic regression model showed that closed ICUs and non-university hospitals were more compliant with the entire 3-h bundle. The in-hospital mortality rate of patients with severe sepsis was 23% (21-26%). Older age, multiple comorbidities, suspected site of infection, and increasing SOFA scores correlated with in-hospital mortality, based on the generalized estimating equation model. The length of hospital stay was 24 (12-46) days. Approximately 37% of the patients were discharged home after recovery. CONCLUSION: Our prospective study showed that sepsis management in Japan was characterized by a high compliance rate for the 3-h bundle and low compliance rate for central venous catheter measurements. The in-hospital mortality rate in Japan was comparable to that of other developed countries. Only one third of the patients were discharged home, considering the aging population with multiple comorbidities in the ICUs in Japan. TRIAL REGISTRATION: UMIN-CTR, UMIN000019742 . Registered on 16 November 2015.

Worldwide Survey of the "Assessing Pain, Both Spontaneous Awakening and Breathing Trials, Choice of Drugs, Delirium Monitoring/Management, Early Exercise/Mobility, and Family Empowerment" (ABCDEF) Bundle.

OBJECTIVES: To assess the knowledge and use of the Assessment, prevention, and management of pain; spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment; Early mobility and exercise; and Family engagement and empowerment (ABCDEF) bundle to implement the Pain, Agitation, Delirium guidelines. DESIGN: Worldwide online survey. SETTING: Intensive care. INTERVENTION: A cross-sectional online survey using the Delphi method was administered to intensivists worldwide, to assess the knowledge and use of all aspects of the ABCDEF bundle. MEASUREMENT AND MAIN RESULTS: There were 1,521 respondents from 47 countries, 57% had implemented the ABCDEF bundle, with varying degrees of compliance across continents. Most of the respondents (83%) used a scale to evaluate pain. Spontaneous awakening trials and spontaneous breathing trials are performed in 66% and 67% of the responder ICUs, respectively. Sedation scale was used in 89% of ICUs. Delirium monitoring was implemented in 70% of ICUs, but only 42% used a validated delirium tool. Likewise, early mobilization was "prescribed" by most, but 69% had no mobility team and 79% used no formal mobility scale. Only 36% of the respondents assessed ICU-acquired weakness. Family members were actively involved in 67% of ICUs; however, only 33% used dedicated staff to support families and only 35% reported that their unit was open 24 hr/d for family visits. CONCLUSIONS: The current implementation of the ABCDEF bundle varies across individual components and regions. We identified specific targets for quality improvement and adoption of the ABCDEF bundle. Our data reflect a significant but incomplete shift toward patient- and family-centered ICU care in accordance with the Pain, Agitation, Delirium guidelines.

Serum neutrophil gelatinase-associated lipocalin levels predict the neurological outcomes of out-of-hospital cardiac arrest victims.

BACKGROUND: Serum neutrophil gelatinase-associated lipocalin (NGAL) is a well-known biomarker of acute kidney injury. Serum NGAL was recently proposed as a potential predictor of mortality in post cardiac arrest syndrome (PCAS) patients following out-of-hospital cardiac arrest (OHCA). However, the potential predictive value of NGAL for neurological outcomes is unknown. Therefore, we assessed the potential predictive value of NGAL for neurological outcomes after OHCA. We also compared its predictive value with that of neuron-specific enolase (NSE) as an established biomarker. METHODS: Blood samples were prospectively collected from 43 PCAS patients following OHCA. Serum NGAL was measured on days 1 and 2, and NSE was measured on day 2. These biomarkers were compared between patients with favourable (cerebral performance category [CPC] 1-2) and unfavourable (CPC 3-5) outcomes. Receiver operating characteristic (ROC) curve analysis was performed. RESULTS: Serum NGAL and NSE on day 2 (both P < 0.001), but not NGAL on day 1 (P = 0.609), were significantly different between the favourable and unfavourable groups. In ROC curve analysis, the sensitivity and specificity were 83% and 85%, respectively, for NGAL (day 2) at a cutoff value of 204 ng/mL and were 84% and 100% for NSE (day 2) at a cutoff value of 28.8 ng/mL. The area under the ROC curve of NGAL (day 2) was equivalent to that of NSE (day 2) (0.830 vs. 0.918). Additionally, the area under the ROC curve in subgroup of estimated glomerular filtration rate (eGFR) > 20 mL/min/1.73 m2 (n = 38, 0.978 vs. 0.923) showed the potential of NGAL predictability. CONCLUSIONS: Serum NGAL might predict the neurological outcomes of PCAS patients, and its predictive value was equivalent to that of NSE.

Assessment of mortality by qSOFA in patients with sepsis outside ICU: A post hoc subgroup analysis by the Japanese Association for Acute Medicine Sepsis Registry Study Group.

Quick sequential organ failure assessment (qSOFA) was proposed in the new sepsis definition (Sepsis-3). Although qSOFA was created to identify patients with suspected infection and likely to have poor outcomes, the clinical utility of qSOFA to screen sepsis has not been fully evaluated. We investigated the number of patients diagnosed as having severe sepsis who could not be identified by the qSOFA criteria and what clinical signs could complement the qSOFA score. This retrospective analysis of a multicenter prospective registry included adult patients with severe sepsis diagnosed outside the intensive care unit (ICU) by conventional criteria proposed in 2003. We conducted receiver operating characteristic (ROC) analyses to assess the predictive value for in-hospital mortality and compared clinical characteristics between survivors and non-survivors with qSOFA score ≤ 1 point (qSOFA-negative). Among 387 eligible patients, 63 (16.3%) patients were categorized as qSOFA-negative, and 10 (15.9%) of these patients died. The area under the ROC curve for the qSOFA score was 0.615, which was superior to that for the systemic inflammatory response syndrome score (0.531, P = 0.019) but inferior to that for the SOFA score (0.702, P = 0.005). Multivariate logistic regression analysis showed that hypothermia might be associated with poor outcome independently of qSOFA criteria. Our findings suggested that qSOFA had a suboptimal level of predictive value outside the ICU and could not identify 16.3% of patients who were once actually diagnosed with sepsis. Hypothermia might be associated with an increased risk of death that cannot be identified by qSOFA.

Validity of a Modified Sequential Organ Failure Assessment Score Using the Richmond Agitation-Sedation Scale.

OBJECTIVES: The Sequential Organ Failure Assessment and other severity of illness scales rely on the Glasgow Coma Scale to measure acute neurologic dysfunction, but the Glasgow Coma Scale is unavailable or inconsistently applied in some institutions. The objective of this study was to assess the validity of a modified Sequential Organ Failure Assessment that uses the Richmond Agitation-Sedation Scale instead of Glasgow Coma Scale. DESIGN: Prospective cohort study. SETTING: Medical and surgical ICUs within a large, tertiary care hospital. PATIENTS: Critically ill medical/surgical ICU patients. INTERVENTIONS: We calculated daily Sequential Organ Failure Assessment scores by using electronic medical record-derived data. By using bedside nurse-recorded Glasgow Coma Scale and Richmond Agitation-Sedation Scale measures, we calculated neurologic Sequential Organ Failure Assessment scores using the original Glasgow Coma Scale-based approach and a novel Richmond Agitation-Sedation Scale-based approach, converting the 10-point Richmond Agitation-Sedation Scale to a 4-point neurologic Sequential Organ Failure Assessment score. We assessed construct validity of Richmond Agitation-Sedation Scale-based Sequential Organ Failure Assessment by analyzing correlations with established severity of illness constructs (Acute Physiology and Chronic Health Evaluation II and Glasgow Coma Scale-based Sequential Organ Failure Assessment) and predictive validity by using logistic regression to determine whether Richmond Agitation-Sedation Scale-based Sequential Organ Failure Assessment predicts ICU, hospital, and 1-year mortality. We assessed discriminative performance with c-statistics. MEASUREMENTS AND MAIN RESULTS: Among 513 patients (5,199 patient-days), Richmond Agitation-Sedation Scale-based Sequential Organ Failure Assessment was strongly correlated with Acute Physiology and Chronic Health Evaluation II acute physiology score at enrollment (r = 0.583; 95% CI, 0.518-0.642) and daily Glasgow Coma Scale-based Sequential Organ Failure Assessment scores (r = 0.963; 95% CI, 0.956-0.968). Mean Richmond Agitation-Sedation Scale-based Sequential Organ Failure Assessment scores predicted ICU mortality (areas under the curve = 0.814)-as did mean Glasgow Coma Scale-based Sequential Organ Failure Assessment (0.799)-as well as hospital and 1-year mortality. Admission Sequential Organ Failure Assessment scores, whether using Richmond Agitation-Sedation Scale or Glasgow Coma Scale, were less accurate predictors of mortality; areas under the curves for ICU mortality for Richmond Agitation-Sedation Scale-based and Glasgow Coma Scale-based Sequential Organ Failure Assessment, for example, were 0.622 and 0.608, respectively. CONCLUSION: A modified Sequential Organ Failure Assessment score that uses bedside Richmond Agitation-Sedation Scale when Glasgow Coma Scale data are not available is a valid means of assessing daily severity of illness in the ICU and may be valuable for risk-adjustment and benchmarking purposes.

Infection site is predictive of outcome in acute lung injury associated with severe sepsis and septic shock.

BACKGROUND AND OBJECTIVE: Sepsis is a leading cause of acute lung injury (ALI); however, the characteristics and outcome of sepsis-associated ALI are poorly understood. We aimed to elucidate factors that predict patient outcome in sepsis-associated ALI. METHODS: Secondary analysis of a multicenter, prospective, observational study was performed. RESULTS: Among 624 patients with severe sepsis and septic shock, 251 (40.2%) fulfilled the definition of American-European Consensus Conference definition of ALI. All-cause 28-day and in-hospital mortalities were 30.7% and 38.6%, respectively. More than 40% of ALI patients had neurological, cardiovascular and haematological dysfunctions or disseminated intravascular coagulation, all of which were associated with higher mortality. We report a significant correlation between infection site and mortality in patients with ALI, but not in those without ALI. The proportion of ALI was significantly higher in pulmonary sepsis; further, a complication of ALI was associated with higher mortality in sepsis from pulmonary and other sources, but not in abdominal sepsis. Among the other sepsis sites, urinary tract, central nervous system, catheter-related and undetermined foci of infection had worse outcomes when associated with ALI. None of the individual severe sepsis bundles, including fluid resuscitation and early antibiotic administration, correlated with mortality. Compliance with a set of sepsis management bundles was associated with better outcomes. CONCLUSION: In severe sepsis and septic shock, the proportion and effect on outcome was not uniform among infection sites. The infection site was predictive of outcome in patients with ALI but not in those without ALI.

The Association of Fever with Total Mechanical Ventilation Time in Critically Ill Patients.

This research aims to investigate the impact of fever on total mechanical ventilation time (TVT) in critically ill patients. Subgroup analysis was conducted using a previous prospective, multicenter observational study. We included mechanically ventilated patients for more than 24 hours from 10 Korean and 15 Japanese intensive care units (ICU), and recorded maximal body temperature under the support of mechanical ventilation (MAX(MV)). To assess the independent association of MAX(MV) with TVT, we used propensity-matched analysis in a total of 769 survived patients with medical or surgical admission, separately. Together with multiple linear regression analysis to evaluate the association between the severity of fever and TVT, the effect of MAX(MV) on ventilator-free days was also observed by quantile regression analysis in all subjects including non-survivors. After propensity score matching, a MAX(MV) ≥ 37.5°C was significantly associated with longer mean TVT by 5.4 days in medical admission, and by 1.2 days in surgical admission, compared to those with MAX(MV) of 36.5°C to 37.4°C. In multivariate linear regression analysis, patients with three categories of fever (MAX(MV) of 37.5°C to 38.4°C, 38.5°C to 39.4°C, and ≥ 39.5°C) sustained a significantly longer duration of TVT than those with normal range of MAX(MV) in both categories of ICU admission. A significant association between MAX(MV) and mechanical ventilator-free days was also observed in all enrolled subjects. Fever may be a detrimental factor to prolong TVT in mechanically ventilated patients. These findings suggest that fever in mechanically ventilated patients might be associated with worse mechanical ventilation outcome.

Epidemiology of severe sepsis in Japanese intensive care units: a prospective multicenter study.

Severe sepsis is a leading cause of morbidity and mortality in the intensive care unit (ICU). We conducted a prospective multicenter study to evaluate epidemiology and outcome of severe sepsis in Japanese ICUs. The patients were registered at 15 general critical care centers in Japanese tertiary care hospitals when diagnosed as having severe sepsis. Of 14,417 patients, 624 (4.3%) were diagnosed with severe sepsis. Demographic and clinical characteristics at enrollment (Day 1), physiologic and blood variables on Days 1 and 4, and mortality were evaluated. Mean age was 69.0 years, and initial mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were 23.4 and 8.6, respectively. The 28-day mortality was 23.1%, and overall hospital mortality was 29.5%. SOFA score and disseminated intravascular coagulation (DIC) score were consistently higher in nonsurvivors than survivors on Days 1 and 4. SOFA score, DIC score on Days 1 and 4, and hospital mortality were higher in patients with than without septic shock. SOFA score on Days 1 and 4 and hospital mortality were higher in patients with than without DIC. Logistic regression analyses showed age, presence of septic shock, DIC, and cardiovascular dysfunction at enrollment to be predictors of 28-day mortality and presence of comorbidity to be an additional predictor of hospital mortality. Presence of septic shock or DIC resulted in approximately twice the mortality of patients without each factor, whereas the presence of comorbidity may be a significant predictor of delayed mortality in severe sepsis.

A multicenter, prospective evaluation of quality of care and mortality in Japan based on the Surviving Sepsis Campaign guidelines.

To elucidate the standard Surviving Sepsis Campaign (SSC) guidelines-based quality of care and mortality related to severe sepsis in Japan, we conducted a multicenter, prospective, observational study using a new web-based database between June 1, 2010, and December 31, 2011. A total of 1104 patients with severe sepsis were enrolled from 39 Japanese emergency and critical care centers. All-cause hospital mortality was 29.3% in patients with severe sepsis and 40.7% in patients with septic shock. Pulmonary, renal, hepatic, and hematological dysfunctions were associated with significantly higher mortality, and hematological dysfunction, especially coagulopathy, was associated with the highest odds ratio for mortality. Compliance with severe sepsis bundles in our study was generally low compared with that in a previous international sepsis registry study, and glycemic control was associated with lowest odds ratio for mortality. Despite higher complication rates of multiple organ dysfunction syndrome and low compliance with severe sepsis bundles on the whole, mortality in our study was similar to that in the international sepsis registry study. From these results, we concluded that our prospective multicenter study was successful in evaluating SSC guidelines-based standard quality of care and mortality related to severe sepsis in Japan. Although mortality in Japan was equivalent to that reported worldwide in the above-mentioned international sepsis registry study, compliance with severe sepsis bundles was low. Thus, there is scope for improvement in the initial treatment of severe sepsis and septic shock in Japanese emergency and critical care centers.

Effects of uninterrupted chest compressions on the rescuer's physical condition.

STUDY OBJECTIVE: Recent guidelines have emphasized the need for uninterrupted chest compressions. The purpose of this study was to evaluate the rescuer's tolerability of uninterrupted chest compressions. METHODS: Twenty-five healthy subjects performed uninterrupted chest compressions for 7 minutes at a rate of 100 compressions per minute using a training manikin. The quality of chest compressions was assessed in terms of the total number and percentage of chest compressions, compression depth, recoil distance, and duty cycle. Correct chest compression was defined as a depth of 38 to 51 mm. Physiological and laboratory parameters were measured before and after the procedure. Fatigue was measured using a numerical rating scale. Data were compared before and after the procedure. RESULTS: The participants were 10 emergency physicians and 15 medical students. The compression rate was nearly 100 compressions per minute. The number and percentage of correct compressions decreased gradually after 3 minutes. The compression depth decreased significantly after 2 minutes. The recoil distance and duty cycle were unchanged over 7 minutes. Systolic blood pressure, pulse rate, respiratory rate, numerical rating scale, serum lactate, adrenalin, and noradrenalin increased significantly after the procedure. Noradrenalin levels measured before the procedure were significantly and negatively correlated with the total number and percentage of correct compressions (r = -0.587, P = .004; r = -0.549, P = .008, respectively). CONCLUSIONS: Performing uninterrupted chest compressions for 7 minutes is an arduous procedure. Higher noradrenalin levels before the procedure might be associated with incorrect chest compressions.

[Clinical examination of 3 patients with delayed neuropsychiatric encephalopathy induced by carbon monoxide poisoning, who recovered from severe neurocognitive impairment by repetitive hyperbaric oxygen therapy].

We performed hyperbaric oxygen (HBO) therapy for 3 patients with delayed neuropsychiatric encephalopathy induced by carbon monoxide (CO) poisoning. All patients were male and around 50 years old, and they had not received HBO therapy within 24 h after CO poisoning, even though they showed severe consciousness disturbance. In these patients, delayed neuropsychiatric encephalopathy appeared about 25 days after acute CO poisoning, and HBO therapy was initiated within 8 days after disease onset. Although the condition of 2 of the patients worsened initially, they showed significant improvement of neurocognitive impairment after 30 sessions of HBO therapy. The clinical courses of these patients suggest that the effect of HBO therapy can be evaluated after 30 sessions. To evaluate the validity of the indices of the clinical effect of HBO therapy, we performed brain magnetic resonance imaging, single photon emission computed tomography, electroencephalography (EEG), and neurocognitive tests (HDS-R, and Wechsler Adult Intelligence Scale-Revised or III). Our results showed that changes in EEG signals and neurocognitive tests were closely correlated with the patients' clinical courses.

The OROCHI (Observational Research of Clinical Course After mamusHI) Study: A Prospective, Observational, Multicenter Study on the Efficacy of Mamushi (Gloydius blomhoffii) Antivenom Serum.

BACKGROUND: Evidence on the efficacy of mamushi antivenom serum is limited. OBJECTIVE: To investigate the effectiveness of mamushi (Gloydius blomhoffii) antivenom serum. METHODS: The Observational Research Of the Clinical course after mamusHI bite (OROCHI) study was a prospective multicenter study conducted at 24 hospitals in Japan. Patients hospitalized due to mamushi bite were registered. The primary endpoint was the length of hospital stay. Secondary endpoints were adverse effects, pain (numerical rating scale), and grade of swelling. We performed a cohort analysis to compare outcomes between patients treated with mamushi antivenom serum (antivenom group) and those who were not treated with the serum (no-antivenom group). RESULTS: Overall, 106 patients were registered across 18 hospitals between April 22, 2020, and October 31, 2022. Of these, 92 were eligible for the analyses, with 53 and 39 in the antivenom and no-antivenom groups. The median (interquartile) length of hospital stay was not significantly different between the antivenom and no-antivenom groups (5 (3-6) days vs. 3 (1-8) days, P = 0.369). In multivariable analysis, the adjusted odds ratio for a hospital stay of >4 days was 1.331 in patients treated with mamushi antivenom serum (95% confidence interval (CI) = 0.744‒2.015, P = 0.574) and 6.154 in patients treated with cepharanthine (95% CI = 1.442-26.258, P = 0.014). Pain and the grade of swelling were worse in the antivenom group than in the no-antivenom group up to 24 h after arrival, but there were no differences in these outcomes after 48 h. CONCLUSION: Although the effectiveness of mamushi antivenom serum in reducing the length of hospitalization was not demonstrated, beneficial effects on pain and swelling were observed.

Association of Advanced Airway Management in Preference to Intravenous Adrenaline on Neurological Outcomes Following Out-of-Hospital Cardiac Arrest.

AIM: To examine the preference for advanced airway management (AAM) or intravenous adrenaline administration (IVAd) provided by emergency medical services (EMS) for out-of-hospital cardiac arrest (OHCA) with shockable or nonshockable rhythms. METHODS: We conducted a retrospective analysis of a nationwide cohort of OHCA patients in Japan. Adult patients with witnessed collapse who were provided AAM and/or IVAd by EMS between June 2014 and December 2019 were divided into the AAM preferred group and IVAd preferred group, according to the initial advanced EMS intervention. The rates of favorable neurological outcomes (cerebral performance category 1 or 2 after 30 days) were compared between groups of patients with initial shockable or nonshockable rhythms. RESULTS: We analyzed 1365 and 9733 patients with initial shockable and nonshockable rhythms, respectively. Of these patients, 1033 (75.7%) with shockable and 7844 (80.6%) with nonshockable rhythms, respectively, were assigned to the AAM preferred group. Favorable neurological outcomes were significantly more frequent in the AAM preferred group than in the IVAd preferred group in patients with a shockable rhythm (13.6% vs 9.3%, respectively; P = 0.039), but not in those with a nonshockable rhythm (1.0% vs 0.8%, respectively; P = 0.509). Preferred AAM was independently associated with a higher probability of favorable neurological outcomes in patients with a shockable rhythm (adjusted odds ratio 1.66, 95% confidence interval 1.08-2.53, P = 0.020), but not in patients with a nonshockable rhythm. CONCLUSIONS: AAM provided by EMS in preference to IVAd was associated with the favorable neurological outcomes of OHCA patients with shockable rhythms.

Three cases of neutralization of factor Xa inhibitors with andexanet alfa under rotational thromboelastography monitoring.

Background: Factor Xa inhibitors are direct oral anticoagulants that are extremely useful in clinical applications, safe, and do not require dose adjustment. It is desirable to be able to monitor their effects in the event of hemorrhagic complications requiring neutralization. However, it is difficult to monitor their activity and neutralization using conventional coagulation tests. Case Presentation: We report three patients taking factor Xa inhibitors who underwent rotational thromboelastography (ROTEM) monitoring before and after neutralization with andexanet alfa. All three patients had hemorrhagic complications that required neutralization of their factor Xa inhibitors using andexanet alfa. One ROTEM parameter, the EXTEM clotting time (EXTEM-CT), was immediately shortened after andexanet alfa bolus administration, without subsequent extension of the EXTEM-CT assessed 4 h after the bolus dose. Conclusion: ROTEM parameters, particularly EXTEM-CT, might be useful for monitoring neutralization of factor Xa inhibitors.