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Obesity has been hypothesized to attenuate muscle wasting in critically ill patients due to increased ketogenesis. This study examined the associations between fat mass volume, ketone bodies, and muscle wasting in critically ill patients. We conducted a prospective study in an emergency intensive care unit (ICU) from November 2021 to October 2023, enrolling adult patients with an expected ICU stay of ≥ 7 days and abdominal computed tomography (CT) performed within 24 h of admission. Patients were classified as adipose or lean based on fat area measured via CT. The primary outcome was severe muscle wasting, defined as a > 10% decrease in the rectus femoris cross-sectional area measured by ultrasonography from day 1 to day 7. Among 134 enrolled patients, 108 were evaluable (57% male, median age 73 years). Severe muscle wasting was more frequent in the adipose group (48%) than in the lean group (27%, p = 0.023). Multivariate analysis confirmed a higher risk of muscle wasting in the adipose group (adjusted OR 2.52, p = 0.034). BHB levels were inversely correlated with fat area and associated with a reduced risk of muscle wasting. Contrary to our hypothesis, obesity increased the risk of muscle wasting, potentially due to decreased ketogenesis. 200/200 words

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.

The purpose of this study was to examine whether the temperature difference between the jugular bulb and pulmonary artery (ΔTjb-pa) is associated with the neurological outcome of patients with severe traumatic brain injury (TBI). We conducted a post hoc analysis of a multicenter randomized controlled trial of mild therapeutic hypothermia (TH, 32.0-34.0°C) or fever control (FC, 35.5-37.0°C) for the patients with severe TBI. ΔTjb-pa averaged every 12 h and the variation in ΔTjb-pa were compared between patients with favorable (n = 39) and unfavorable (n = 37) neurological outcomes. These values were also compared in the TH and FC subgroups. The average ΔTjb-pa values in patients with favorable and unfavorable outcomes were 0.24 ± 0.23 and 0.06 ± 0.36°C, respectively (P < 0.001). ΔTjb-pa trended significantly higher in the favorable outcome patients than in the unfavorable outcome patients throughout the 120 h after onset of severe TBI (P < 0.001). The variation in ΔTjb-pa from 0 to 72 h was significantly lower in the favorable outcome patients than in the unfavorable outcome patients (0.8 ± 0.8 vs 1.8 ± 2.5°C, respectively, P = 0.013). From 72 to 120 h, there was no significant difference in the variation in ΔTjb-pa. Significant differences between patients with favorable and unfavorable outcomes in ΔTjb-pa and the variation in ΔTjb-pa were similar in the TH subgroup, but not evident in the FC subgroup. A reduction in ΔTjb-pa and greater variation in ΔTjb-pa were associated with an unfavorable outcome in patients with severe TBI, especially those treated with TH. When treating severe TBI patients, it is important to understand that there will be differences in temperature reflecting the brain environment and the systemic temperature, depending on the severity and outcome of TBI during TH.

Guideline‐based management approaches for pain, agitation, and delirium (PAD) in critically ill adult patients are widely believed to result in good outcomes. However, there are some differences in the recommendations and evidence levels among the management guidelines established for PAD. To identify and compare the current management guidelines, we used the PubMed database. The PAD guidelines and Federación Panamericana e Ibérica de Sociedades de Medicina Crítica y Terapia Intensiva (FEPIMCTI) guidelines were identified from our search. We compared the main aspects of these two guidelines as well as the Japanese guidelines for the management of PAD (J‐PAD guidelines). The PAD, FEPIMCTI, and J‐PAD guidelines contained a total of 4, 12, and 5 sections, having 32, 138, and 37 recommendations, respectively, pertaining to routine monitoring of pain in adult patients in the intensive care unit. Intravenous opioids were recommended as the first‐line drug of choice for treating pain. Sedative titrated to maintain a light, rather than deep, level of sedation can be given unless clinically contraindicated. Although neither the PAD nor J‐PAD guidelines recommend use of a pharmacologic delirium prevention protocol or treatment with any pharmacological agent to reduce the duration of delirium, the FEPIMCTI guidelines provide such recommendations. The FEPIMCTI guidelines provide suggestions on which analgesics to use for several different cases and present algorithms for sedation and analgesia. The outlines of the three guidelines are similar, and all reinforce the management of PAD to improve patient outcomes. The outlines of the three guidelines are similar, and all reinforce the management of PAD to improve patient outcomes.

Aim To describe the registry design of the Japanese Association for Acute Medicine – out‐of‐hospital cardiac arrest (JAAM‐OHCA) Registry as well as its profile on hospital information, patient and emergency medical service characteristics, and in‐hospital procedures and outcomes among patients with OHCA who were transported to the participating institutions. Methods The special committee aiming to improve the survival after OHCA by providing evidence‐based therapeutic strategies and emergency medical systems from the JAAM has launched a multicenter, prospective registry that enrolled OHCA patients who were transported to critical care medical centers or hospitals with an emergency care department. The primary outcome was a favorable neurological status 1 month after OHCA. Results Between June 2014 and December 2015, a total of 12,024 eligible patients with OHCA were registered in 73 participating institutions. The mean age of the patients was 69.2 years, and 61.0% of them were male. The first documented shockable rhythm on arrival of emergency medical services was 9.0%. After hospital arrival, 9.4% underwent defibrillation, 68.9% tracheal intubation, 3.7% extracorporeal cardiopulmonary resuscitation, 3.0% intra‐aortic balloon pumping, 6.4% coronary angiography, 3.0% percutaneous coronary intervention, 6.4% targeted temperature management, and 81.1% adrenaline administration. The proportion of cerebral performance category 1 or 2 at 1 month after OHCA was 3.9% among adult patients and 5.5% among pediatric patients. Conclusions The special committee of the JAAM launched the JAAM‐OHCA Registry in June 2014 and continuously gathers data on OHCA patients. This registry can provide valuable information to establish appropriate therapeutic strategies for OHCA patients in the near future. The special committee of the JAAM has launched a multicenter, prospective registry (the JAAM‐OHCA Registry) that focused on OHCA patients who were transported by EMS personnel to the participating institutions since June 2014. This report described this registry's profile and briefly presented the characteristics of 12,024 OHCA patients between June 2014 and December 2015.

The purpose of this study was to clarify the practical clinical treatment for acute carbon monoxide (CO) poisoning in Japan and to investigate the efficacy of hyperbaric oxygen (HBO.sub.2) therapy in preventing delayed neurological sequelae (DNS) in the acute phase of CO poisoning. We conducted a multicenter, prospective, observational study of acute CO poisoning in Japan. Patients with acute CO poisoning were enrolled and their treatment details were recorded. The primary endpoint was the onset of DNS within 2 months of CO exposure. Factors associated with DNS were assessed with logistic regression analysis. A total of 311 patients from 57 institutions were registered and 255 were analyzed: 171 received HBO.sub.2 therapy (HBO.sub.2 group) and 84 did not (normobaric oxygen [NBO.sub.2 ] group). HBO.sub.2 therapy was performed zero, once, twice, or three times within the first 24 h in 1.8%, 55.9%, 30.9%, and 11.3% of the HBO.sub.2 group, respectively. The treatment pressure in the first HBO.sub.2 session was 2.8 ATA (47.9% of the HBO.sub.2 group), 2.0 ATA (41.8%), 2.5 ATA (7.9%), or another pressure (2.4%). The incidence of DNS was 13/171 (7.6%) in the HBO.sub.2 group and 3/84 (3.6%) in the NBO.sub.2 group (P = 0.212). The number of HBO.sub.2 sessions in the first 24 h was one of the factors associated with the incidence of DNS (odds ratio, 2.082; 95% confidence interval, 1.101-3.937; P = 0.024). The practical clinical treatment for acute CO poisoning, including HBO.sub.2 therapy, varied among the institutions participating in Japan. HBO.sub.2 therapy with inconsistent protocols showed no advantage over NBO.sub.2 therapy in preventing DNS. Multiple HBO.sub.2 sessions was associated with the incidence of DNS.

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.

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.

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. 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. 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. 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.

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. 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. 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. 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.