中田 孝明

BACKGROUND:  Anticoagulant therapy has seldom been achieved in randomized trials targeting nonspecific overall sepsis patients. Although the key components to identify the appropriate target in sepsis may be disseminated intravascular coagulation (DIC) and high disease severity, the interaction and relation of these two components for the effectiveness of therapy remain unknown. OBJECTIVE:  This article identifies the optimal target of anticoagulant therapy in sepsis. METHODS:  We used a prospective nationwide cohort targeting consecutive adult severe sepsis patients in 59 intensive care units in Japan to assess associations between anticoagulant therapy and in-hospital mortality according to DIC (International Society on Thrombosis and Haemostasis [ISTH] overt and Japanese Association for Acute Medicine DIC scores) and disease severity (Acute Physiology and Chronic Health Evaluation II [APACHE II] and Sequential Organ Failure Assessment scores). Multivariable Cox proportional hazard regression analysis with nonlinear restricted cubic spline including a two-way interaction term (treatment × each score) and three-way interaction term (treatment × ISTH overt DIC score × APACHE II score) was performed. RESULTS:  The final study cohort comprised 1,178 sepsis patients (371 received anticoagulants and 768 did not). The regression model including the two-way interaction term showed significant interaction between intervention and disease severity as indicated by the ISTH overt DIC score and APACHE II score (p = 0.046 and p = 0.101, respectively). Three-way interaction analysis revealed that risk hazard was suppressed in the anticoagulant group compared with the control group in the most severe subset of both scores. CONCLUSION:  Anticoagulant therapy was associated with better outcome according to the deterioration of both DIC and disease severity, suggesting that anticoagulant therapy should be restricted to patients having DIC and high disease severity simultaneously.

肺コンプライアンスが低下した急性呼吸不全症例に対する侵襲的な人工呼吸管理はVentilator-Induced Lung Injury(VILI)を引き起こす。人工呼吸管理以外の二酸化炭素除去の方法として、低流量で脱血した血液を人工肺に通すExtracorporeal CO2 Removal(ECCO2R)が開発された。ARDSやCOPDを中心にその効果を示す研究結果が発表されているが、導入の適応や施行条件に関する明確な基準はなく、大規模な研究も行われていないことからその使用は限定的である。また、より低侵襲かつ効率的な二酸化炭素除去を目指したECCO2Rの改良が行われており、その代表的なものとして酸を投与することで溶存二酸化炭素を増加させ人工肺で除去するという酸塩基平衡を利用した方法が提案されている。動物実験ではその有効性が示されているが、構成が複雑であり、安全性の確保が臨床応用化に向けた課題である。エビデンスが集積されればECCO2Rは将来的にLung Protective Strategyを実践するうえで重要な手段として確立するであろう。(著者抄録)

Our analysis showed that improved compliance with sepsis bundles was associated with lower in-hospital mortality over a 7-year period in Japan, confirming that the SSC has been executed correctly in our country.

BACKGROUND: The beneficial effect of epinephrine during resuscitation from out-of-hospital cardiac arrest (OHCA) has been inconclusive, and potential harm has been suggested, particularly in trauma victims. Although no significant improvement in neurological outcomes has been found among resuscitated patients using epinephrine, including trauma patients, the use of epinephrine is recommended in the Advanced Trauma Life Support protocol. Given that the use of vasopressors was reported to be associated with increased mortality in patients with massive bleeding, the undesirable effects of epinephrine during the resuscitation of traumatic OHCA should be elucidated. We hypothesised that resuscitation with epinephrine would increase mortality in patients with OHCA following trauma. METHODS: This study is a post-hoc analysis of a prospective, multicentre, observational study on patients with OHCA between January 2012 and March 2013. We included adult patients with traumatic OHCA who were aged ≥15 years and excluded those with missing survival data. Patient data were divided into epinephrine or no-epinephrine groups based on the use of epinephrine during resuscitation at the hospital. Propensity scores were developed to estimate the probability of being assigned to the epinephrine group using multivariate logistic regression analyses adjusted for known survival predictors. The primary outcome was survival 7 days after injury, which was compared among the two groups after propensity score matching. RESULTS: Of the 1125 adults with traumatic OHCA during the study period, 1030 patients were included in this study. Among them, 822 (79.8%) were resuscitated using epinephrine, and 1.1% (9/822) in the epinephrine group and 5.3% (11/208) in the no-epinephrine group survived 7 days after injury. The use of epinephrine was significantly associated with decreased 7-day survival (odds ratio = 0.20; 95% CI = 0.08-0.48; P < 0.01), and this result was confirmed by propensity score-matching analysis, in which 178 matched pairs were examined (adjusted odds ratio = 0.11; 95% CI = 0.01-0.85; P = 0.02). CONCLUSIONS: The relationship between the use of epinephrine during resuscitation and decreased 7-day survival was found in patients with OHCA following trauma, and the propensity score-matched analyses validated the results. Resuscitation without epinephrine in traumatic OHCA should be further studied in a randomised controlled trial.

PURPOSE: Hospital services are reduced during off-hour such as nighttime or weekend. Investigations of the off-hour effect on initial management and outcomes in sepsis are very limited. Thus, we tested the hypothesis that patients who were diagnosed with severe sepsis during the nighttime or on non-business days had altered initial management and clinical outcomes. MATERIALS AND METHODS: Patients with severe sepsis from 59 ICUs between 2016 and 2017 were enrolled. The patients were categorized according to the diagnosis time or day and were then compared. The primary outcome was in-hospital mortality. RESULTS: One thousand one hundred and forty-eight patients were analyzed; 769 daytime patients, vs. 379 nighttime patients, and 791 business day patients vs. 357 non-business day patients. There were no significant differences in in-hospital mortality between either daytime and nighttime (24.4% vs. 21.4%, P = .27; nighttime, adjusted odds ratio [OR] 1.17, 95% confidence interval [CI], 0.87-1.59, P = .30) or between business and non-business days (22.9% vs. 24.6%, P = .55; non-business day, adjusted OR 0.85, 95% CI 0.60-1.22, P = .85). Time to antibiotics was significantly shorter in the nighttime (114 vs. 89 min, P = .0055). CONCLUSIONS: Nighttime and weekends were not associated with increased in-hospital mortality of severe sepsis.

BACKGROUND: Disseminated intravascular coagulation (DIC) associated with multiple organ dysfunction syndrome (MODS) plays pivotal roles in severe sepsis. OBJECTIVES: We performed a multicenter, prospective data collection study and retrospectively analyzed the data to confirm the role of DIC in severe sepsis. METHODS: Eligible patients were ICU patients who met the definitions of severe sepsis, and 1013 patients were included. DIC scores as well as disease severity and the development of MODS on the day of the diagnosis of severe sepsis (day 0) and at day 3 were evaluated. The primary outcome was hospital mortality, and MODS on days 0 and 3 was the secondary outcomes. RESULTS: The overall mortality rate of severe sepsis was 21.5%, and the prevalence of DIC was 50.9% (516/1013). DIC patients were more seriously ill and exhibited a higher prevalence of MODS (32.0% vs. 13.1%) on day 0 and worse mortality rate (24,8% vs. 17.5%) than non-DIC patients. DIC patients also showed a lower survival probability than non-DIC patients (Log rank p = 0.028). Logistic regression analyses after propensity score adjustment for potential confounders confirmed a significant association between DIC and MODS and hospital death in the patients with severe sepsis. The new development of DIC and persistent DIC from days 0 to 3 were associated with a high incidence of MODS and low survival probability. CONCLUSIONS: The mortality rate of severe sepsis has been improved; however, DIC is still associated with the poor prognosis of these patients. Evaluating the dynamic changes in the DIC status may improve the prediction capability.

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.

敗血症は感染によって臓器障害を呈した状態である。敗血症の診断後は早期の抗菌薬投与が求められるが、一方で耐性菌の増加も問題となっており、適切な抗菌薬治療は敗血症診療の要である。そのために、敗血症診療では感染巣を評価し、原因となりうる起炎菌を想定しempiric therapyとして適切な広域抗菌薬を選択する必要がある。また、抗菌薬は投与可能最大量を投与し、起炎菌が判明した場合には速やかにde-escalationすることも重要である。(著者抄録)

第45回日本集中治療医学会学術集会にて行われたシンポジウム「一歩進んだワーク・ライフ・バランスを考える」に先立ち、本学会員を対象にワーク・ライフ・バランスに関するwebアンケート調査を行った。その結果、本学会員において、理想とするワーク・ライフ・バランスは実現していないことが示され、本学会員にとってワーク・ライフ・バランスは解決が必要な課題と考えられた。未来を担う集中治療従事者に魅力的な働き方を提示できることを目指し、さらなる取り組みを行う必要があると考えられる。(著者抄録)

Background: Accurate and early identification of infection sites might help to drive crucial decisions regarding the treatment of sepsis. We aimed to determine the clinical and etiological features of infection according to sites among patients with severe sepsis in Japan. Methods: This secondary analysis of a multicenter, prospective cohort study included 59 intensive care units (ICU) and proceeded between January 2016 and March 2017. The study cohort comprised 1184 adults (≥ 16 years) who were admitted to an ICU with severe sepsis and septic shock diagnosed according to the sepsis-2 criteria. Sites of infection diagnosed by physicians in charge at the time of arrival comprised the lung, abdomen, urinary tract, soft tissue, bloodstream, central nervous system (CNS), and undifferentiated infections. The primary outcome was in-hospital mortality. Results: The most common sites of infection were the lungs (31.0%), followed by intra-abdominal sites (26.3%), the urinary tract (18.4%), and soft tissue (10.9%). The characteristics of the patients with severe sepsis across seven major suspected infection sites were heterogeneous. Septic shock was more frequent among patients with intra-abdominal (72.2%) and urinary tract (70.2%) infections than other sites. The in-hospital mortality rate due to severe sepsis and septic shock of a pooled sample was 23.4% (range, 11.9% [urinary tract infection] to 47.6% [CNS infection]). After adjusting for clinical background, sepsis severity, and stratification according to the presence or absence of shock, variations in hospital mortality across seven major sites of infection remained essentially unchanged from those for crude in-hospital mortality; adjusted in-hospital mortality rates ranged from 7.7% (95%CI, - 0.3 to 15.8) for urinary tract infection without shock to 58.3% (95%CI, 21.0-95.7) for CNS infection with shock in a generalized estimating equation model. Intra-abdominal and urinary tract infections were statistically associated with less in-hospital mortality than pneumonia. Infections of the CNS were statistically associated with higher in-hospital mortality rates than pneumonia in a logistic regression model, but not in the generalized estimating equation model. Conclusions: In-hospital mortality and clinical features of patients with severe sepsis and septic shock were heterogeneous according to sites of infection.