中田 孝明

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.

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.

Background: The IL10 family of genes includes crucial immune regulators. We tested the hypothesis that single nucleotide polymorphisms (SNPs) in IL10, IL19, IL20, and IL24 of the IL10 family gene cluster alter the clinical outcome of septic shock. Methods: Patients with septic shock (n = 1,193) were genotyped for 13 tag SNPs of IL10, IL19, IL20, and IL24. IL20 gene expression was measured in genotyped lymphoblastoid cells in vitro. Cardiac surgical ICU patients (n = 981) were genotyped for IL20 rs2981573 A/G. The primary outcome variable was 28-day mortality. Results: Patients with the G allele of IL20 rs2981573 had a significantly increased hazard of death over the 28-day period compared to patients with the A allele in the septic shock cohort (adjusted hazard ratio 1.27 95% confidence interval 1.10-1.47 p = 8.0 × 10-4). Patients with the GG genotype had more organ dysfunction (p &lt 0.05). The GG genotype was associated with increased IL20 gene expression in stimulated lymphoblastoid cells in vitro (p &lt 0.05). The cardiac surgical ICU patients with the GG genotype had an increased length of ICU stay (p = 0.032). Conclusions: The GG genotype of IL20 rs2981573 SNP was associated with increased IL20 gene expression and increased adverse outcomes in patients with septic shock and following cardiac surgery.

重症腹部感染症患者に対し抗菌薬の適切な投与方法を評価するためには、感染巣の制御の有無によらず抗菌薬治療が転帰に与える影響を検討する必要があるが、報告は依然少ない。そこでわれわれは2013年4月から2016年3月の3年間に当ICUに入室し、腹部感染症と診断された86症例を対象として、患者背景、各種培養結果、抗菌薬治療および転帰について診療録をもとに後方視的に調査した。単変量解析の結果、28日死亡群は生存群に比して、初回に抗菌薬が単剤より複数剤投与されている割合が高く、総抗菌薬投与期間が長く、耐性菌の検出率が高かった。さらにこれらの中で多変量解析でも抗菌薬複数剤投与および耐性菌の検出は28日死亡と有意に関連していた。複数剤投与による影響や、どのような耐性機序が死亡と関連するのか、今後さらに症例を集積して検討する必要があると考えられる。(著者抄録)

Near-infrared spectroscopy (NIRS) is a noninvasive method for monitoring tissue oxygen saturation (StO2). Many commercial NIRS devices are presently available. However, the precision of those devices is relatively poor because they are using the reflectance-model with which it is difficult to obtain the blood volume and other unchanged components of the tissue. Human webbing is a thin part of the hand and suitable to measure spectral transmittance. In this paper, we present a method for measuring StO2 of human webbing from a transmissive continuous-wave nearinfrared spectroscopy (CW-NIRS) data. The method is based on the modified Beer-Lambert law (MBL) and it consists of two steps. In the first step, we give a pressure to the upstream region of the measurement point to perturb the concentration of deoxy-And oxy-hemoglobin as remaining the other components and measure the spectral signals. From the measured data, spectral absorbance due to the components other than hemoglobin is calculated. In the second step, spectral measurement is performed at arbitrary time instance and the spectral absorbance obtained in the step 1 is subtracted from the measured absorbance. The tissue oxygen saturation (StO2) is estimated from the remained data. The method was evaluated on an arterial occlusion test (AOT) and a venous occlusion test (VOT). In the evaluation experiment, we confirmed that reasonable values of StO2 were obtained by the proposed method.