中田 孝明

INTRODUCTION: Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. Although most patients with COVID-19 develop asymptomatic or mild disease, some patients develop severe disease. The effectiveness of various therapeutic agents, including antiviral drugs, steroids, and anti-inflammatories for COVID-19, have been being confirmed. The effect of administering steroids in early disease is unclear. This study therefore aimed to evaluate the effectiveness and risk of exacerbation of steroids administered preceding antiviral drugs in patients with COVID-19 pneumonia. METHODS: This retrospective, single-center, observational study included consecutive patients with COVID-19 between March 2020 and March 2021. Patients were divided into a steroids-first group and antiviral-drugs-first group. Mortality, duration of hospitalization, incidence rate and duration of intensive care unit (ICU) admission, intubation, and extracorporeal membrane oxygenation (ECMO) induction of the two groups were compared. RESULTS: A total of 258 patients were admitted during the study period. After excluding patients who received symptomatic treatment only, who were taking immunosuppressive drugs, or who were administered antiviral drugs only, 68 patients were included in the analysis, 16 in the steroids-first group and 52 in the antiviral-drugs-first group. The rate of intubation, ICU admission and ECMO induction were significantly higher in the steroids-first group than in the antiviral-drugs-first group (81.3% vs. 33.3, p<0.001, 75.0% vs. 29.4%, p = 0.001, and 31.3% vs. 7.8%, p = 0.017, respectively). Furthermore, patients who received steroids within ten days after starting antiviral drugs had significantly lower rates of ICU admission, intubation, and ECMO induction. (81.3% vs. 42.9% p = 0.011, 75.0% vs. 37.1% p = 0.012, and 31.3% vs. 8.6% p = 0.039, respectively). CONCLUSIONS: Administering steroids prior to antiviral drugs soon after symptom onset can aggravate disease severity. When administration of steroids is considered soon after symptom onset, it may be safer to initiate antiviral drugs first.

Rapid response system(RRS)が起動された入院患者において、入院診療科区分と心停止発症との関連について検討した。対象患者は314名、入院診療科は内科系122名、外科系153名、循環器系39名であった。3群間の背景因子の比較では、年齢、RRS起動以前のICU入室歴に有意差を認め、内科系で年齢が若く、外科系でICU入室歴の頻度が高かった。主要評価項目のmedical emergency team接触時の心停止は、単変量解析で3群間に有意な差を認め、循環器系で頻度が最も高かった。背景因子を調整した解析においても、循環器系の診療科区分は有意に心停止と関連していた。副次評価項目である重症例と28日死亡に関する解析では、診療科区分間で有意な差を認めなかった。循環器系診療科区分の入院患者は予期せぬ院内心停止発症のリスクが高いため、通常のRRSに加えて、さらなる予防策を講じる必要があると考えられた。

Although several studies have reported on the clinical and epidemiological characteristics of the patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinical course of the most severe cases requiring treatment in ICU have been insufficiently reported. A 73-year-old man traveling on a cruise ship with history of hypertension and dyslipidemia developed high fever, dyspnea and cough after 7 days of steroid treatment for sudden sensorineural hearing loss, and tested positive for SARS-CoV-2 in sputa polymerase chain reaction (PCR) examination. His respiratory function deteriorated despite treatments with lopinavir/ritonavir, oseltamivir, azithromycin and meropenem at a regional hospital. He was intubated and transferred to the ICU in the tertiary university hospital on day 10 (ICU day 1). Interferon beta-1b subcutaneous injection was initiated immediately to enhance anti-viral therapy, and favipiravir on ICU day 10 upon availability. Progression of organ dysfunctions necessitated inhalation of nitrogen oxide for respiratory dysfunction, noradrenaline for cardiovascular dysfunction and continuous renal replacement therapy for renal dysfunction. His blood samples PCR also tested positive for SARS-CoV-2, indicating viremia, concomitantly with elevated IL-6 levels. VV-ECMO was initiated after sudden exacerbation of respiratory dysfunction on ICU day 7 to maintain oxygenation. The sustained excessive inflammatory cytokines in the present case might have led to the exacerbation of the disease, requiring vigorous organ support therapies to allow for survival and recovery from the rapid progression of multiple organ dysfunctions and severe respiratory failure.

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.

BACKGROUND: Multiple organ dysfunction syndrome (MODS) is a predominant cause of death in acute respiratory distress syndrome (ARDS). Disseminated intravascular coagulation (DIC) is recognized as a syndrome that frequently develops MODS. To test the hypothesis that DIC scores are useful for predicting MODS development and that DIC is associated with MODS, we retrospectively analyzed the data of a prospective, multicenter study on ARDS. METHODS: Patients who met the Berlin definition of ARDS were included. DIC scores as well as the disease severity and the development of MODS on the day of the diagnosis of ARDS (day 0) and day 3 were evaluated. The primary and secondary outcomes were the development of MODS and the hospital mortality. RESULTS: In the 129 eligible patients, the prevalence of DIC was 45.7% (59/129). DIC patients were more seriously ill and exhibited a higher prevalence of MODS on days 0 and 3 than non-DIC patients. The DIC scores on day 0 detected the development of MODS with good area under the receiver operating characteristic curve (0.714, p<.001). DIC on day 0 was significantly associated with MODS on days 0 and 3 (odds ratio 1.53 and 1.34, respectively). Patients with persistent DIC from days 0 to 3 had higher rates of both MODS on day 3 (p=.035) and hospital mortality (p=.031) than the other patients. CONCLUSIONS: DIC scores were able to predict MODS, and DIC was associated with MODS during the early stage of ARDS. Persistent DIC may also have role in this association.

BACKGROUND: Whether hospital bed number and rapid response system (RRS) call rate is associated with the clinical outcomes of patients who have RRS activations is unknown. We test a hypothesis that hospital volume and RRS call rates are associated with the clinical outcomes of patients with RRSs. METHODS: This is a retrospective chart analysis of an existing dataset associated with In-Hospital Emergency Registry in Japan. In the present study, 4818 patients in 24 hospitals from April 2014 to March 2018 were analyzed. Primary outcome variable was an unplanned intensive care unit (ICU) admission after RRS activation. RESULTS: In the primary analysis of the study using a multivariate analysis adjusting potential confounding factors, higher RRS call rate was significantly associated with decreased unplanned ICU admissions (P < 0.0001, Odds ratio [OR] 0.95, 95% confidence interval [CI] 0.92-0.98), but there was no significant association of hospital volume with unplanned ICU admissions (P = 0.44). In the secondary analysis of the study, there was a non-significant trend of increased cardiac arrest on arrival at the location of the RRS provider at large-volume hospitals (P = 0.084, OR 1.16, 95% CI 0.98-1.38). Large-volume hospitals had a significantly higher 1-month mortality rate (P = 0.0040, OR 1.10, 95% CI 1.03-1.18). CONCLUSION: Hospitals with increased RRS call rates had significantly decreased unplanned ICU admission in patients who had RRS activations. Patients who had RRS activations at large-volume hospitals had an increased 1-month mortality rate.

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.

AIM: We compared the outcomes between patients who experienced out-of-hospital cardiac arrest at private residences and public locations to investigate whether patient and bystander characteristics can explain the poorer outcomes of out-of-hospital cardiac arrests at private residences. METHODS: Adult patients with intrinsic out-of-hospital cardiac arrest (n = 6,191, age ≥18 years) were selected from a prospectively collected Japanese database (January 2012 and March 2013). Patients were grouped according to arrest location into private-residence or control (e.g., public station or road, workplace, school, and other public locations) groups. The primary outcome was a favourable neurological outcome 1 month after out-of-hospital cardiac arrest. RESULTS: The arrest location and initial cardiac rhythm had interaction effects on the outcome. After adjusting for patient and bystander characteristics and relative to the control group, a significantly poorer 1-month neurological outcome was observed in the private-residence group if the initial cardiac rhythm was non-shockable (odds ratio: 0.36, 95% confidence interval: 0.24-0.54), while it was not significant if the initial cardiac rhythm was shockable (odds ratio: 1.16, 95% confidence interval: 0.74-1.84). CONCLUSIONS: Patients with out-of-hospital cardiac arrest at private residences had poorer outcomes than those with out-of-hospital cardiac arrest at public locations, even after adjusting for patient and bystander characteristics, if the initial cardiac rhythm was non-shockable. Our results suggest that poorer patient and bystander characteristics do not completely explain the poorer outcomes of out-of-hospital cardiac arrests; there may be unknown mechanisms through which the location of cardiac arrest affect the outcomes.

PURPOSE: Acute respiratory distress syndrome (ARDS) remains a major cause of death. Epidemiology should be continually examined to refine therapeutic strategies for ARDS. We aimed to elucidate demographics, treatments, and outcomes of ARDS in Japan. METHODS: This is a prospective cohort study for ARDS. We included adult patients admitted to intensive care units through emergency and critical care departments who satisfied the American-European Consensus Conference (AECC) acute lung injury (ALI) criteria. In addition, the fulfillment of the Berlin definition was assessed. Logistic regression analyses were used to examine the association of independent variables with outcomes. RESULTS: Our study included 166 patients with AECC ALI from 34 hospitals in Japan; among them, 157 (94.6%) fulfilled the Berlin definition. The proportion of patients with PaO2/FIO2 ≤ 100, patients under invasive positive pressure ventilation (IPPV), and in-hospital mortality was 39.2%, 92.2%, and 38.0% for patients with AECC ALI and 38.9%, 96.8%, and 37.6% for patients with Berlin ARDS, respectively. The area of lung infiltration was independently associated with outcomes of ARDS. Low-mid-tidal volume ventilation was performed in 75% of patients under IPPV. Glucocorticoid use was observed in 54% patients, and it was positively associated with mortality. CONCLUSIONS: Our study included a greater percentage of patients with ARDS with high severity and found that the overall mortality was 38%. The management of ARDS in Japan was characterized by high the utilization rate of glucocorticoids, which was positively associated with mortality.

INTRODUCTION: Polymyxin B hemoperfusion (PMX-HP) is an adjuvant therapy for sepsis or septic shock that removes circulating endotoxin. However, PMX-HP has seldom achieved expectations in randomized trials targeting nonspecific overall sepsis patients. If used in an optimal population, PMX-HP may be beneficial. This study aimed to identify the optimal population for PMX-HP in patients with septic shock. METHODS: We used a prospective nationwide cohort targeting consecutive adult patients with severe sepsis (Sepsis-2) in 59 intensive care units in Japan. Associations between PMX-HP therapy and in-hospital mortality were assessed using multivariable Cox proportional hazard regression models. To identify best targets for PMX-HP, we developed a non-linear restricted cubic spline model including two-way interaction term (treatment × Acute Physiology and Chronic Health Evaluation [APACHE] II score/Sequential Organ Failure Assessment [SOFA] score) and three-way interaction term (treatment × age × each score). RESULTS: The final study cohort comprised 741 sepsis patients (92 received PMX-HP, 625 did not). Cox proportional hazards regression model adjusted for the covariates suggested no association between PMX-HP therapy and improved mortality overall. Effect modification of PMX-HP by APACHE II score was statistically significant (P for interaction = 0.189) but non-significant for SOFA score (P for interaction = 0.413). Three-way interaction analysis revealed suppressed risk hazard in the PMX-HP group versus control group only in septic shock patients with high age and in the most severe subset of both scores, whereas increased risk hazard was observed in those with high age but in the lower severity subset of both scores. CONCLUSIONS: Our results suggested that although PMX-HP did not reduce in-hospital mortality among overall septic shock patients, it may benefit a limited population with high age and higher disease severity.

Clinical manifestations of sepsis differ between patients with and without diabetes mellitus (DM), and these differences could influence the clinical behaviors of medical staff. Therefore, we aimed to investigate whether pre-existing DM was associated with the time to antibiotics or sepsis care protocols.This was a retrospective cohort study.It conducted at 53 intensive care units (ICUs) in Japan.Consecutive adult patients with severe sepsis admitted directly to ICUs form emergency departments from January 2016 to March 2017 were included.The primary outcome was time to antibiotics.Of the 619 eligible patients, 142 had DM and 477 did not have DM. The median times (interquartile ranges) to antibiotics in patients with and without DM were 103 minutes (60-180 minutes) and 86 minutes (45-155 minutes), respectively (P = .05). There were no significant differences in the rates of compliance with sepsis protocols or with patient-centred outcomes such as in-hospital mortality. The mortality rates of patients with and without DM were 23.9% and 21.6%, respectively (P = .55). Comparing patients with and without DM, the gamma generalized linear model-adjusted relative difference indicated that patients with DM had a delay to starting antibiotics of 26.5% (95% confidence intervals (95%CI): 4.6-52.8, P = .02). The gamma generalized linear model-adjusted relative difference with multiple imputation for missing data of sequential organ failure assessment was 19.9% (95%CI: 1.0-42.3, P = .04). The linear regression model-adjusted beta coefficient indicated that patients with DM had a delay to starting antibiotics of 29.2 minutes (95%CI: 6.8-51.7, P = .01). Logistic regression modelling showed that pre-existing DM was not associated with in-hospital mortality (odds ratio, 1.26; 95%CI: 0.72-2.19, P = .42).Pre-existing DM was associated with delayed antibiotic administration among patients with severe sepsis or septic shock; however, patient-centred outcomes and compliance with sepsis care protocols were comparable.

The clinical implications of bacteremia among septic patients remain unclear, although a vast amount of data have been accumulated on sepsis. We aimed to compare the clinical characteristics and outcomes of severe sepsis patients with and without bacteremia. This secondary analysis of a multicenter, prospective cohort study included 59 intensive care units (ICUs) in Japan between January 2016 and March 2017. The study cohort comprised 1,184 adults (aged ≥ 16 years) who were admitted to an ICU with severe sepsis and diagnosed according to the Sepsis-2 criteria. Of 1,167 patients included in the analysis, 636 (54.5%) had bacteremia. Those with bacteremia had significantly higher rates of septic shock (66.4% vs. 58.9%, p = 0.01) and higher sepsis severity scores, including the Acute Physiology and Chronic Health Evaluation (APACHE) II and the Sequential Organ Failure Assessment (SOFA). No significant difference in in-hospital mortality was seen between patients with and without bacteremia (25.6% vs. 21.0%, p = 0.08). In conclusion, half of severe sepsis patients in ICUs have bacteremia. Although patients with bacteremia had more severe state, between-group differences in patient-centered outcomes, such as in-hospital mortality, have not been fully elucidated.

Traumatic brain injury (TBI) in the form of diffuse axonal injury (DAI) is difficult to diagnose in the early phase of the injury. Early diagnosis of DAI may provide opportunity for developing treatment and management strategies. Tau protein has been demonstrated to increase in the early phase of TBI with high diagnostic accuracy in patients with DAI. We tested the biological plausibility of tau protein using a rat DAI model by evaluating the association between serum tau levels and the severity of brain injury. DAI was induced in animals using the Marmarou model. After a survival of 60 minutes, rats were anesthetized and sacrificed after obtaining blood samples (5ml) from the heart. Eighteen rats were employed in the present study and were randomly subjected to sham-operated control (n=4), mild DAI (n=7), and severe DAI (n=7). Of seven severe DAI rats, two rats that had focal injury caused by skull fracture were excluded in the measurement of tau protein level. The serum levels of tau protein in the rat DAI model were found to increase significantly and consistently according to the severity of the injury. Rats with DAI showed significantly higher serum levels of tau protein compared to sham rats; the severe DAI rats had higher levels of tau than moderate DAI and sham rats (sham vs. mild,  P=0.02; mild vs. severe,  P=0.02). In conclusion, serum tau protein levels may be useful as a biomarker for diagnosing and estimating the severity of DAI in the early phase.

Introduction: Quality improvement in the administration of extracorporeal cardiopulmonary resuscitation (ECPR) over time and its association with low-flow duration (LFD) and outcomes of cardiac arrest (CA) have been insufficiently investigated. In this study, we hypothesized that quality improvement in efforts to shorten the duration of initiating ECPR had decreased LFD over the last 15 years of experience at an academic tertiary care hospital, which in turn improved the outcomes of in-hospital CA (IHCA). Methods: This was a single-center retrospective observational study of ECPR patients between January 2003 and December 2017. A rapid response system (RRS) and an extracorporeal membrane oxygenation (ECMO) program were initiated in 2011 and 2013. First, the association of LFD per minute with the 90-day mortality and neurological outcome was analyzed using multiple logistic regression analysis. Then, the temporal changes in LFD were investigated. Results: Of 175 study subjects who received ECPR, 117 had IHCA. In the multivariate logistic regression, IHCA patients with shorter LFD experienced significantly increased 90-day survival and favorable neurological outcomes (LFD per minute, 90-day survival: odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.94-1.00, P = 0.032; 90-day favorable neurological outcome: OR = 0.97, 95% CI = 0.94-1.00, P = 0.049). In the study period, LFD significantly decreased over time (slope - 5.39 [min/3 years], P < 0.0001). Conclusion: A shorter LFD was associated with increased 90-day survival and favorable neurological outcomes of IHCA patients who received ECPR. The quality improvement in administering ECPR over time, including the RRS program and the ECMO program, appeared to ameliorate clinical outcomes.

Background: Diagnosing sepsis remains difficult because it is not a single disease but a syndrome with various pathogen- and host factor-associated symptoms. Sepsis-3 was established to improve risk stratification among patients with infection based on organ failures, but it has been still controversial compared with previous definitions. Therefore, we aimed to describe characteristics of patients who met sepsis-2 (severe sepsis) and sepsis-3 definitions. Methods: This was a multicenter, prospective cohort study conducted by 22 intensive care units (ICUs) in Japan. Adult patients (≥ 16 years) with newly suspected infection from December 2017 to May 2018 were included. Those without infection at final diagnosis were excluded. Patient's characteristics and outcomes were described according to whether they met each definition or not. Results: In total, 618 patients with suspected infection were admitted to 22 ICUs during the study, of whom 530 (85.8%) met the sepsis-2 definition and 569 (92.1%) met the sepsis-3 definition. The two groups comprised different individuals, and 501 (81.1%) patients met both definitions. In-hospital mortality of study population was 19.1%. In-hospital mortality among patients with sepsis-2 and sepsis-3 patients was comparable (21.7% and 19.8%, respectively). Patients exclusively identified with sepsis-2 or sepsis-3 had a lower mortality (17.2% vs. 4.4%, respectively). No patients died if they did not meet any definitions. Patients who met sepsis-3 shock definition had higher in-hospital mortality than those who met sepsis-2 shock definition. Conclusions: Most patients with infection admitted to ICU meet sepsis-2 and sepsis-3 criteria. However, in-hospital mortality did not occur if patients did not meet any criteria. Better criteria might be developed by better selection and combination of elements in both definitions. Trial registration: UMIN000027452.

Background: Predisposing conditions and risk modifiers instead of causes and risk factors have recently been used as alternatives to identify patients at a risk of acute respiratory distress syndrome (ARDS). However, data regarding risk modifiers among patients with non-pulmonary sepsis is rare. Methods: We conducted a secondary analysis of the multicenter, prospective, Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) cohort study that was conducted in 59 intensive care units (ICUs) in Japan during January 2016-March 2017. Adult patients with severe sepsis caused by non-pulmonary infection were included, and the primary outcome was having ARDS, defined as meeting the Berlin definition on the first or fourth day of screening. Multivariate logistic regression modeling was used to identify risk modifiers associated with ARDS, and odds ratios (ORs) and their 95% confidence intervals were reported. The following explanatory variables were then assessed: age, sex, admission source, body mass index, smoking status, congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, steroid use, statin use, infection site, septic shock, and acute physiology and chronic health evaluation (APACHE) II score. Results: After applying inclusion and exclusion criteria, 594 patients with non-pulmonary sepsis were enrolled, among whom 85 (14.3%) had ARDS. Septic shock was diagnosed in 80% of patients with ARDS and 66% of those without ARDS (p = 0.01). APACHE II scores were higher in patients with ARDS [26 (22-33)] than in those without ARDS [21 (16-28), p < 0.01]. In the multivariate logistic regression model, the following were independently associated with ARDS: ICU admission source [OR, 1.89 (1.06-3.40) for emergency department compared with hospital wards], smoking status [OR, 0.18 (0.06-0.59) for current smoking compared with never smoked], infection site [OR, 2.39 (1.04-5.40) for soft tissue infection compared with abdominal infection], and APACHE II score [OR, 1.08 (1.05-1.12) for higher compared with lower score]. Conclusions: Soft tissue infection, ICU admission from an emergency department, and a higher APACHE II score appear to be the risk modifiers of ARDS in patients with non-pulmonary sepsis.

BACKGROUND: Dysglycemia is frequently observed in patients with sepsis. However, the relationship between dysglycemia and outcome is inconsistent. We evaluate the clinical characteristics, glycemic abnormalities, and the relationship between the initial glucose level and mortality in patients with sepsis. METHODS: This is a retrospective sub-analysis of a multicenter, prospective cohort study. Adult patients with severe sepsis (Sepsis-2) were divided into groups based on blood glucose categories (<70 (hypoglycemia), 70-139, 140-179, and ≥180 mg/dL), according to the admission values. In-hospital mortality and the relationship between pre-existing diabetes and septic shock were evaluated. RESULTS: Of 1158 patients, 69, 543, 233, and 313 patients were categorized as glucose levels <70, 70-139, 140-179, ≥180 mg/dL, respectively. Both the Acute Physiological and Chronic Health Evaluation II and Sequential Organ Failure Assessment (SOFA) scores on the day of enrollment were higher in the hypoglycemic patients than in those with 70-179 mg/dL. The hepatic SOFA scores were also higher in hypoglycemic patients. In-hospital mortality rates were higher in hypoglycemic patients than in those with 70-139 mg/dL (26/68, 38.2% vs 43/221, 19.5%). A significant relationship between mortality and hypoglycemia was demonstrated only in patients without known diabetes. Mortality in patients with both hypoglycemia and septic shock was 2.5-times higher than that in patients without hypoglycemia and septic shock. CONCLUSIONS: Hypoglycemia may be related to increased severity and high mortality in patients with severe sepsis. These relationships were evident only in patients without known diabetes. Patients with both hypoglycemia and septic shock had an associated increased mortality rate.

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.

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.