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.

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.

Cyanide poisoning is a possible cause of cardiac arrest among fire victims, and empiric antidote treatment may improve outcomes.

BACKGROUND: Carbon monoxide and cyanide poisoning are important causes of death due to fire. Carbon monoxide is more regularly assessed than cyanide at the site of burn or smoke inhalation treatment due to its ease in assessment and simplicity to treat. Although several forensic studies have demonstrated the significance of cyanide poisoning in fire victims using blood cyanide levels, the association between the cause of cardiac arrest and the concentration of cyanide among fire victims has not been sufficiently investigated. This study aimed to investigate the frequency of cyanide-induced cardiac arrest in fire victims and to assess the necessity of early empiric treatment for cyanide poisoning. METHODS: This study was a retrospective analysis of fire victims with cardiac arrest at the scene who were transported to a trauma and critical care center, Kyorin University Hospital, from January 2014 to June 2017. Patients whose concentration of cyanide was measured were included. RESULTS: Five patients were included in the study; all died despite cardiopulmonary resuscitation. Three of these victims were later found to have lethal cyanide levels (>3 µg/ml). Two of the patients had non-lethal carboxyhemoglobin levels under 50% and might have been saved if hydroxocobalamin had been administered during resuscitation. CONCLUSION: According to our results, cyanide-induced cardiac arrest may be more frequently present among fire victims than previously believed, and early empiric treatment with hydroxocobalamin may improve outcomes for these victims in cases where cardiac arrest is of short duration.

Resuscitative Endovascular Balloon Occlusion of the Aorta Using a Low-Profile Device is Easy and Safe for Emergency Physicians in Cases of Life-Threatening Hemorrhage.

BACKGROUND: Bleeding from hemorrhagic shock can be immediately controlled by blocking the proximal part of the hemorrhagic point using either resuscitative thoracotomy for aortic cross-clamping or insertion of a large-caliber (10-14Fr) resuscitative endovascular balloon occlusion of the aorta (REBOA) device via the femoral artery. However, such methods are very invasive and have various complications. With recent progress in endovascular treatment, a low-profile REBOA device (7Fr) has been developed. OBJECTIVE: The objective of this study was to report our experience of this low-profile REBOA device and to evaluate the usefulness of emergency physician-operated REBOA in life-threatening hemorrhagic shock. METHODS: Ten patients with refractory hemorrhagic shock underwent REBOA using this device via the femoral artery. All REBOA procedures were performed by emergency physicians. The success rate of the insertion, vital signs, and REBOA-related complications were evaluated. RESULTS: Median age was 54 years (interquartile range 33-78 years). The causes of hemorrhagic shock were trauma (n = 4; 1 blunt and 3 penetrating), ruptured abdominal aortic aneurysm (n = 3), and obstetric hemorrhage (n = 3). Two patients had cardiopulmonary arrest upon arrival. REBOA procedure was successful in all patients, and all became hemodynamically stable to undergo definitive interventions after REBOA. There were no REBOA-related complications. The mortality rate within 24 h and 30 days was 40%. CONCLUSIONS: This REBOA device was useful for emergency physicians in life-threatening hemorrhagic shock because of its ease in handling and low invasiveness.

COAGULOPATHY PARAMETERS PREDICTIVE OF OUTCOMES IN SEPSIS-INDUCED ACUTE RESPIRATORY DISTRESS SYNDROME: A SUBANALYSIS OF THE TWO PROSPECTIVE MULTICENTER COHORT STUDIES.

ABSTRACT: Background: Although coagulopathy is often observed in acute respiratory distress syndrome (ARDS), its clinical impact remains poorly understood. Objectives: This study aimed to clarify the coagulopathy parameters that are clinically applicable for prognostication and to determine anticoagulant indications in sepsis-induced ARDS. Method: This study enrolled patients with sepsis-derived ARDS from two nationwide multicenter, prospective observational studies. We explored coagulopathy parameters that could predict outcomes in the Focused Outcome Research on Emergency Care for Acute Respiratory Distress Syndrome, Sepsis, and Trauma (FORECAST) cohort, and the defined coagulopathy criteria were validated in the Sepsis Prognostication in Intensive Care Unit and Emergency Room-Intensive Care Unit (SPICE-ICU) cohort. The correlation between anticoagulant use and outcomes was also evaluated. Results: A total of 181 patients with sepsis-derived ARDS in the FORECAST study and 61 patients in the SPICE-ICU study were included. In a preliminary study, we found the set of prothrombin time-international normalized ratio ≥1.4 and platelet count ≤12 × 10 4 /µL, and thrombocytopenia and elongated prothrombin time (TEP) coagulopathy as the best coagulopathy parameters and used it for further analysis; the odds ratio (OR) of TEP coagulopathy for in-hospital mortality adjusted for confounding was 3.84 (95% confidence interval [CI], 1.66-8.87; P = 0.005). In the validation cohort, the adjusted OR for in-hospital mortality was 32.99 (95% CI, 2.60-418.72; P = 0.002). Although patients without TEP coagulopathy showed significant improvements in oxygenation over the first 4 days, patients with TEP coagulopathy showed no significant improvement (ΔPaO 2 /FiO 2 ratio, 24 ± 20 vs. 90 ± 9; P = 0.026). Furthermore, anticoagulant use was significantly correlated with mortality and oxygenation recovery in patients with TEP coagulopathy but not in patients without TEP coagulopathy. Conclusion: Thrombocytopenia and elongated prothrombin time coagulopathy is closely associated with better outcomes and responses to anticoagulant therapy in sepsis-induced ARDS, and our coagulopathy criteria may be clinically useful.

Age-related differences in the survival benefit of the administration of antithrombin, recombinant human thrombomodulin, or their combination in sepsis.

Disseminated intravascular coagulation (DIC) is one of the major organ dysfunctions associated with sepsis. This retrospective secondary analysis comprised data from a prospective multicenter study to investigate the age-related differences in the survival benefit of anticoagulant therapy in sepsis according to the DIC diagnostic criteria. Adult patients with severe sepsis based on the Sepsis-2 criteria were enrolled and divided into the following groups: (1) anticoagulant group (patients who received anticoagulant therapy) and (2) non-anticoagulant group (patients who did not receive anticoagulant therapy). Patients in the former group were administered antithrombin, recombinant human thrombomodulin, or their combination. The increases in the risk of hospital mortality were suppressed in the high-DIC-score patients aged 60-70 years receiving anticoagulant therapy. No favorable association of anti-coagulant therapy with hospital mortality was observed in patients aged 50 years and 80 years. Furthermore, anticoagulant therapy in the lower-DIC-score range increased the risk of hospital mortality in patients aged 50-60 years. In conclusion, anticoagulant therapy was associated with decreased hospital mortality according to a higher DIC score in septic patients aged 60-70 years. Anticoagulant therapy, however, was not associated with a better outcome in relatively younger and older patients with sepsis.

Hour-1 bundle adherence was associated with reduction of in-hospital mortality among patients with sepsis in Japan.

BACKGROUND: The updated Surviving Sepsis Campaign guidelines recommend a 1-hour window for completion of a sepsis care bundle; however, the effectiveness of the hour-1 bundle has not been fully evaluated. The present study aimed to evaluate the impact of hour-1 bundle completion on clinical outcomes in sepsis patients. METHODS: This was a multicenter, prospective, observational study conducted in 17 intensive care units in tertiary hospitals in Japan. We included all adult patients who were diagnosed as having sepsis by Sepsis-3 and admitted to intensive care units from July 2019 to August 2020. Impacts of hour-1 bundle adherence and delay of adherence on risk-adjusted in-hospital mortality were estimated by multivariable logistic regression analyses. RESULTS: The final study cohort included 178 patients with sepsis. Among them, 89 received bundle-adherent care. Completion rates of each component (measure lactate level, obtain blood cultures, administer broad-spectrum antibiotics, administer crystalloid, apply vasopressors) within 1 hour were 98.9%, 86.2%, 51.1%, 94.9%, and 69.1%, respectively. Completion rate of all components within 1 hour was 50%. In-hospital mortality was 18.0% in the patients with and 30.3% in the patients without bundle-adherent care (p = 0.054). The adjusted odds ratio of non-bundle-adherent versus bundle-adherent care for in-hospital mortality was 2.32 (95% CI 1.09-4.95) using propensity scoring. Non-adherence to obtaining blood cultures and administering broad-spectrum antibiotics within 1 hour was related to in-hospital mortality (2.65 [95% CI 1.25-5.62] and 4.81 [95% CI 1.38-16.72], respectively). The adjusted odds ratio for 1-hour delay in achieving hour-1 bundle components for in-hospital mortality was 1.28 (95% CI 1.04-1.57) by logistic regression analysis. CONCLUSION: Completion of the hour-1 bundle was associated with lower in-hospital mortality. Obtaining blood cultures and administering antibiotics within 1 hour may have been the components most contributing to decreased in-hospital mortality.

Incidence and Impact of Dysglycemia in Patients with Sepsis Under Moderate Glycemic Control.

ABSTRACT: Glycemic control strategies for sepsis have changed significantly over the last decade, but their impact on dysglycemia and its associated outcomes has been poorly understood. In addition, there is controversy regarding the detrimental effects of hyperglycemia in sepsis. To evaluate the incidence and risks of dysglycemia under current strategy, we conducted a preplanned subanalysis of the sepsis cohort in a prospective, multicenter FORECAST study. A total of 1,140 patients with severe sepsis, including 259 patients with pre-existing diabetes, were included. Median blood glucose levels were approximately 140 mg/dL at 0 and 72 h indicating that blood glucose was moderately controlled. The rate of initial and late hyperglycemia was 27.3% and 21.7%, respectively. The rate of early hypoglycemic episodes during the initial 24 h was 13.2%. Glycemic control was accompanied by a higher percentage of initial and late hyperglycemia but not with early hypoglycemic episodes, suggesting that glycemic control was targeted at excess hyperglycemia. In nondiabetic patients, late hyperglycemia (hazard ratio, 95% confidence interval; P value: 1.816, 1.116-2.955, 0.016) and early hypoglycemic episodes (1.936, 1.180-3.175, 0.009) were positively associated with in-hospital mortality. Further subgroup analysis suggested that late hyperglycemia and early hypoglycemic episodes independently, and probably synergistically, affect the outcomes. In diabetic patients, however, these correlations were not observed. In conclusion, a significantly high incidence of dysglycemia was observed in our sepsis cohort under moderate glycemic control. Late hyperglycemia in addition to early hypoglycemia was associated with poor outcomes at least in nondiabetic patients. More sophisticated approaches are necessary to reduce the incidence of these serious complications.

Hyperoxemia during resuscitation of trauma patients and increased intensive care unit length of stay: inverse probability of treatment weighting analysis.

BACKGROUND: Information on hyperoxemia among patients with trauma has been limited, other than traumatic brain injuries. This study aimed to elucidate whether hyperoxemia during resuscitation of patients with trauma was associated with unfavorable outcomes. METHODS: A post hoc analysis of a prospective observational study was carried out at 39 tertiary hospitals in 2016-2018 in adult patients with trauma and injury severity score (ISS) of > 15. Hyperoxemia during resuscitation was defined as PaO2 of ≥ 300 mmHg on hospital arrival and/or 3 h after arrival. Intensive care unit (ICU)-free days were compared between patients with and without hyperoxemia. An inverse probability of treatment weighting (IPW) analysis was conducted to adjust patient characteristics including age, injury mechanism, comorbidities, vital signs on presentation, chest injury severity, and ISS. Analyses were stratified with intubation status at the emergency department (ED). The association between biomarkers and ICU length of stay were then analyzed with multivariate models. RESULTS: Among 295 severely injured trauma patients registered, 240 were eligible for analysis. Patients in the hyperoxemia group (n = 58) had shorter ICU-free days than those in the non-hyperoxemia group [17 (10-21) vs 23 (16-26), p < 0.001]. IPW analysis revealed the association between hyperoxemia and prolonged ICU stay among patients not intubated at the ED [ICU-free days = 16 (12-22) vs 23 (19-26), p = 0.004], but not among those intubated at the ED [18 (9-20) vs 15 (8-23), p = 0.777]. In the hyperoxemia group, high inflammatory markers such as soluble RAGE and HMGB-1, as well as low lung-protective proteins such as surfactant protein D and Clara cell secretory protein, were associated with prolonged ICU stay. CONCLUSIONS: Hyperoxemia until 3 h after hospital arrival was associated with prolonged ICU stay among severely injured trauma patients not intubated at the ED. TRIAL REGISTRATION: UMIN-CTR, UMIN000019588 . Registered on November 15, 2015.

Current spectrum of causative pathogens in sepsis: A prospective nationwide cohort study in Japan.

BACKGROUND: There is no one-size-fits-all empiric antimicrobial therapy for sepsis because the pathogens vary according to the site of infection and have changed over time. Therefore, updating knowledge on the spectrum of pathogens is necessary for the rapid administration of appropriate antimicrobials. OBJECTIVE: The aim of this study was to elucidate the current spectrum of pathogens and its variation by site of infection in sepsis. METHODS: This was a prospective nationwide cohort study of consecutive adult patients with sepsis in 59 intensive care units in Japan. The spectrum of pathogens was evaluated in all patients and in subgroups by site of infection. Regression analyses were conducted to evaluate the associations between the pathogens and mortality. RESULTS: The study cohort comprised 1184 patients. The most common pathogen was Escherichia coli (21.5%), followed by Klebsiella pneumoniae (9.0%). However, the pattern varied widely by site of infection; for example, gram-positive bacteria were the dominant pathogen in bone/soft tissue infection (55.7%) and cardiovascular infection (52.6%), but were rarely identified in urinary tract infection (6.4%). In contrast, gram-negative bacteria were the predominant pathogens in abdominal infection (38.4%) and urinary tract infection (72.0%). The highest mortality of 47.5% was observed in patients infected with methicillin-resistant Staphylococcus aureus, which was significantly associated with an increased risk of death (odds ratio 1.88, 95% confidence interval 1.22-2.91). CONCLUSIONS: This study revealed the current spectrum of pathogens and its variation based on the site of infection, which is essential for empiric antimicrobial therapy against sepsis.

Association between low body mass index and increased 28-day mortality of severe sepsis in Japanese cohorts.

Current research regarding the association between body mass index (BMI) and altered clinical outcomes of sepsis in Asian populations is insufficient. We investigated the association between BMI and clinical outcomes using two Japanese cohorts of severe sepsis (derivation cohort, Chiba University Hospital, n = 614; validation cohort, multicenter cohort, n = 1561). Participants were categorized into the underweight (BMI < 18.5) and non-underweight (BMI ≥ 18.5) groups. The primary outcome was 28-day mortality. Univariate analysis of the derivation cohort indicated increased 28-day mortality trend in the underweight group compared to the non-underweight group (underweight 24.4% [20/82 cases] vs. non-underweight 16.0% [85/532 cases]; p = 0.060). In the primary analysis, multivariate analysis adjusted for baseline imbalance revealed that patients in the underweight group had a significantly increased 28-day mortality compared to those in the non-underweight group (p = 0.031, adjusted odds ratio [OR] 1.91, 95% confidence interval [CI] 1.06-3.46). In a repeated analysis using a multicenter validation cohort (underweight n = 343, non-underweight n = 1218), patients in the underweight group had a significantly increased 28-day mortality compared to those in the non-underweight group (p = 0.045, OR 1.40, 95% CI 1.00-1.97). In conclusion, patients with a BMI < 18.5 had a significantly increased 28-day mortality compared to those with a BMI ≥ 18.5 in Japanese cohorts with severe sepsis.

Disseminated intravascular coagulation immediately after trauma predicts a poor prognosis in severely injured patients.

Trauma patients die from massive bleeding due to disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype in the early phase, which transforms to DIC with a thrombotic phenotype in the late phase of trauma, contributing to the development of multiple organ dysfunction syndrome (MODS) and a consequently poor outcome. This is a sub-analysis of a multicenter prospective descriptive cross-sectional study on DIC to evaluate the effect of a DIC diagnosis on the survival probability and predictive performance of DIC scores for massive transfusion, MODS, and hospital death in severely injured trauma patients. A DIC diagnosis on admission was associated with a lower survival probability (Log Rank P < 0.001), higher frequency of massive transfusion and MODS and a higher mortality rate than no such diagnosis. The DIC scores at 0 and 3 h significantly predicted massive transfusion, MODS, and hospital death. Markers of thrombin and plasmin generation and fibrinolysis inhibition also showed a good predictive ability for these three items. In conclusion, a DIC diagnosis on admission was associated with a low survival probability. DIC scores obtained immediately after trauma predicted a poor prognosis of severely injured trauma patients.

Predictors of severe sepsis-related in-hospital mortality based on a multicenter cohort study: The Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis, and Trauma study.

ABSTRACT: This study aimed to identify prognostic factors for severe sepsis-related in-hospital mortality using the structural equation model (SEM) analysis with statistical causality. Sepsis data from the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis, and Trauma study (FORECAST), a multicenter cohort study, was used. Forty seven observed variables from the database were used to construct 4 latent variables. SEM analysis was performed on these latent variables to analyze the statistical causality among these data. This study evaluated whether the variables had an effect on in-hospital mortality. Overall, 1148 patients were enrolled. The SEM analysis showed that the 72-hour physical condition was the strongest latent variable affecting mortality, followed by physical condition before treatment. Furthermore, the 72-hour physical condition and the physical condition before treatment strongly influenced the Sequential Organ Failure Assessment (SOFA) score with path coefficients of 0.954 and 0.845, respectively. The SOFA score was the strongest variable that affected mortality after the onset of severe sepsis. The score remains the most robust prognostic factor and can facilitate appropriate policy development on care.

Reevaluation for prognostic value of prognostic burn index in severe burn patients.

AIM: The prognostic burn index (PBI), which consists of half partial-thickness burn surface area plus full-thickness burn surface area and age, has been widely used to predict mortality in Japan. However, the prognostic value of PBI has not been investigated sufficiently. The purpose of the present study is to clinically reevaluate the PBI in severe burn patients. METHODS: Data of 69 severe burn patients admitted to the burn center at Kyorin University Hospital (Tokyo, Japan) from January 2008 to December 2017 were analyzed retrospectively. The primary outcome in this study was in-hospital mortality. RESULTS: The overall in-hospital mortality rate was 34.8%. There were significant differences in age, the presence of inhalation injury, total burned surface area, full-thickness burn area, burn index, and PBI between survivors and non-survivors. In logistic regression analysis, PBI was independently associated with mortality, while the presence of inhalation injury was not. A PBI above the threshold of 105 was significantly associated with in-hospital mortality. The area under the receiver operating characteristic curve for PBI was 0.85 (95% confidence interval, 0.73-0.93). CONCLUSION: The PBI could be a good prognostic indicator. A PBI above the threshold of 105 was associated with mortality among severe burn patients treated in burn-care facilities.

A Case Involving Massive Insulin Overdose: Direct and Indirect Conditions Requiring Extended Management of Serum Potassium.

BACKGROUND Insulin lowers not only blood glucose levels but also serum potassium levels by driving potassium into the cells. Hypokalemia can occur during aggressive treatment of hypoglycemia in patients with insulin overdose and is a well-documented clinical phenomenon; however, there are no studies describing delayed hyperkalemia occurring after initial treatment in patients with insulin overdose. CASE REPORT A 23-year-old male with a history of type 2 diabetes mellitus and self-medicating with insulin, attempted suicide by subcutaneously injecting 2100 units of insulin. He was admitted to our emergency department due to recurrent hypoglycemia. Continuous administration of 50% glucose and potassium via a central venous catheter was performed to maintain his glucose levels above 80 mg/dL and serum potassium level between 3.5 and 4.0 mEq/L. Because his serum potassium level exceeded 4.5 mEq/L at day 3 after admission, the dosage was adjusted accordingly. After his serum potassium level declined to 3.0 mEq/L, his potassium level abruptly increased to 6.0 mEq/L at day 5 after admission. The patient was placed on a potassium-restricted diet and administered furosemide. Potassium infusion was also discontinued. After serum potassium levels returned to the normal range without interventional therapies, the patient was discharged to home on day 14. CONCLUSIONS In cases of high-dose insulin overdose, management of hyperkalemia following recovery from hypoglycemia is a critical aspect of patient management. Conservative administration of potassium to correct initial hypokalemia may be considered in patients with high-dose insulin overdose.