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.

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.

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.

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.

A pilot study of quantitative capillary refill time to identify high blood lactate levels in critically ill patients.

INTRODUCTION: We developed a new device to quantify capillary refill time (CRT) by applying the pulse oximeter principle, and evaluated the correlation between quantitative CRT (Q-CRT) and hypoperfusion status, as represented by blood lactate levels, in critically ill patients. METHODS: A pilot study was undertaken in the intensive care unit (ICU) in a tertiary emergency medical centre. While the pulse oxygen saturation sensor was placed on the finger of the patients, transmitted light intensity (TLI) was measured with a pulse oximeter (OLV-3100; Nihon Kohden, Tokyo, Japan) before and during compression of the finger. Q-CRT was defined as the interval from the release of compression to the time when TLI reached 90% of baseline. RESULTS: Q-CRT was analysed in a total of 57 waveforms among 23 patients and statistically correlated with lactate levels (Spearman's rank correlation coefficient, 0.681; p<0.001). The cut-off value of Q-CRT for predicting a lactate level of ≥2.0 mmol/L was 6.81 s (area under the curve (AUC) (95% CI 1.000 (1.000 to 1.000), p<0.001), and the value for predicting a lactate level of ≥4.0 mmol/L was 7.27 s (AUC=0.989 (95% CI 0.954 to 1.000), p<0.001). CONCLUSIONS: Q-CRT correlated with blood lactate levels in this pilot study. The most useful threshold for Q-CRT was ∼6-8 s. Further study is needed to investigate the potential role of this modality as a non-invasive predictor of hypoperfusion in the emergency department, ICU and operating room settings.

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.

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.

A multicenter, prospective validation study of the Japanese Association for Acute Medicine disseminated intravascular coagulation scoring system in patients with severe sepsis.

INTRODUCTION: To validate the Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) scoring system in patients with severe sepsis, we conducted a multicenter, prospective study at 15 critical care centers in tertiary care hospitals. METHODS: This study included 624 severe sepsis patients. JAAM DIC was scored on the day of diagnosis of severe sepsis (day 1) and day 4. Scores for disease severity and organ dysfunction were also evaluated. RESULTS: The prevalence of JAAM DIC was 46.8% (292/624), and 21% of the DIC patients were scored according to the reduction rate of platelets. The JAAM DIC patients were more seriously ill and exhibited more severe systemic inflammation, a higher prevalence of multiple organ dysfunction syndrome (MODS) and worse outcomes than the non-DIC patients. Disease severity, systemic inflammation, MODS and the mortality rate worsened in accordance with an increased JAAM DIC score on day 1. The Kaplan-Meier curves demonstrated lower 1-year survival in the JAAM DIC patients than in those without DIC (log-rank test P<0.001). The JAAM DIC score on day 1 (odds ratio=1.282, P<0.001) and the Delta JAAM DIC score (odds ratio=0.770, P<0.001) were independent predictors of 28-day death. Dynamic changes in the JAAM DIC score from days 1 to 4 also affected prognoses. The JAAM DIC scoring system included all patients who met the International Society on Thrombosis and Haemostasis overt DIC criteria on day 1. The International Society on Thrombosis and Haemostasis scoring system missed a large number of nonsurvivors recognized by the JAAM scoring system. CONCLUSIONS: The JAAM DIC scoring system exhibits good prognostic value in predicting MODS and poor prognosis in patients with severe sepsis and can detect more patients requiring treatment. Conducting repeated daily JAAM scoring increases the ability to predict the patient's prognosis.

The impact of body temperature abnormalities on the disease severity and outcome in patients with severe sepsis: an analysis from a multicenter, prospective survey of severe sepsis.

INTRODUCTION: Abnormal body temperatures (Tb) are frequently seen in patients with severe sepsis. However, the relationship between Tb abnormalities and the severity of disease is not clear. This study investigated the impact of Tb on disease severity and outcomes in patients with severe sepsis. METHODS: We enrolled 624 patients with severe sepsis and grouped them into 6 categories according to their Tb at the time of enrollment. The temperature categories (≤ 35.5 °C, 35.6-36.5 °C, 36.6-37.5 °C, 37.6-38.5 °C, 38.6-39.5 °C, ≥ 39.6 °C) were based on the temperature data of the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring. We compared patient characteristics, physiological data, and mortality between groups. RESULTS: Patients with Tb of ≤ 36.5 °C had significantly worse sequential organ failure assessment (SOFA) scores when compared with patients with Tb >37.5 °C on the day of enrollment. Scores for APACHE II were also higher in patients with Tb ≤ 35.5 °C when compared with patients with Tb >36.5 °C. The 28-day and hospital mortality was significantly higher in patients with Tb ≤ 36.5 °C. The difference in mortality rate was especially noticeable when patients with Tb ≤ 35.5 °C were compared with patients who had Tb of >36.5 °C. Although mortality did not relate to Tb ranges of ≥ 37.6 °C as compared to reference range of 36.6-37.5 °C, relative risk for 28-day mortality was significantly greater in patients with 35.6-36.5 °C and ≤ 35.5 °C (odds ratio; 2.032, 3.096, respectively). When patients were divided into groups based on the presence (≤ 36.5 °C, n = 160) or absence (>36.5 °C, n = 464) of hypothermia, disseminated intravascular coagulation (DIC) as well as SOFA and APACHE II scores were significantly higher in patients with hypothermia. Patients with hypothermia had significantly higher 28-day and hospital mortality rates than those without hypothermia (38.1% vs. 17.9% and 49.4% vs. 22.6%, respectively). The presence of hypothermia was an independent predictor of 28-day mortality, and the differences between patients with and without hypothermia were observed irrespective of the presence of septic shock. CONCLUSIONS: In patients with severe sepsis, hypothermia (Tb ≤ 36.5 °C) was associated with increased mortality and organ failure, irrespective of the presence of septic shock. TRIAL REGISTRATION: UMIN-CTR ID UMIN000008195.

The estimation of tissue loss during tangential hydrosurgical debridement.

The preservation of healthy tissue during surgical debridement is desirable as this may improve clinical outcomes. This study has estimated for the first time the amount of tissue lost during debridement using the VERSAJET system of tangential hydrosurgery. A multicenter, prospective case series was carried out on 47 patients with mixed wound types: 21 (45%) burns, 13 (28%) chronic wounds, and 13 (28%) acute wounds. Overall, 44 (94%) of 47 patients achieved appropriate debridement after a single debridement procedure as verified by an independent photographic assessment. The percentage of necrotic tissue reduced from a median of 50% to 0% (P < 0.001). Median wound area and depth increased by only 0.3 cm (6.8%) and 0.5 mm (25%), respectively. Notably, 43 (91%) of 47 wounds did not progress into a deeper compartment, indicating a high degree of tissue preservation.

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.