Three cases of neutralization of factor Xa inhibitors with andexanet alfa under rotational thromboelastography monitoring.

Background: Factor Xa inhibitors are direct oral anticoagulants that are extremely useful in clinical applications, safe, and do not require dose adjustment. It is desirable to be able to monitor their effects in the event of hemorrhagic complications requiring neutralization. However, it is difficult to monitor their activity and neutralization using conventional coagulation tests. Case Presentation: We report three patients taking factor Xa inhibitors who underwent rotational thromboelastography (ROTEM) monitoring before and after neutralization with andexanet alfa. All three patients had hemorrhagic complications that required neutralization of their factor Xa inhibitors using andexanet alfa. One ROTEM parameter, the EXTEM clotting time (EXTEM-CT), was immediately shortened after andexanet alfa bolus administration, without subsequent extension of the EXTEM-CT assessed 4 h after the bolus dose. Conclusion: ROTEM parameters, particularly EXTEM-CT, might be useful for monitoring neutralization of factor Xa inhibitors.

Rapid rewarming rate associated with favorable neurological outcomes in patients with post-cardiac arrest syndrome patients treated with targeted temperature management.

Aim: To determine whether the rewarming rate is associated with neurological outcomes in patients with post-cardiac arrest syndrome treated with targeted temperature management (TTM) at 34°C. Methods: We conducted a retrospective analysis of a nationwide cohort study of out-of-hospital cardiac arrest in Japan. Adult patients who experienced a return of spontaneous circulation and completed TTM at 34°C between June 2014 and December 2019 were divided equally into three groups (slow, moderate, and rapid) according to their rewarming rates from 34°C to 36°C. The rates of favorable neurological outcomes (Cerebral Performance Category of 1-2 after 30 days) were compared among the groups, and the adjusted odds ratios for a favorable neurological outcome were calculated for the groups. Results: We analyzed 348, 357, and 358 patients in the slow, moderate, and rapid groups, respectively. The periods of rewarming from 34°C to 36°C were 41.9 ± 10.5, 22.4 ± 1.8, and 12.2 ± 3.6 h, respectively. The number of favorable neurological outcomes after 30 days was 121 (34.8%), 125 (35.0%), and 147 (41.1%), respectively, with no significant differences among the three groups (p = 0.145). Rapid rewarming was independently associated with a favorable neurological outcome compared with slow rewarming (adjusted odds ratio 1.57 [95% confidence interval 1.04-2.37]; p = 0.031). Conclusions: Rapid rewarming after TTM at 34°C was associated with a more favorable neurological outcome than slow rewarming.

Effects of cardiopulmonary resuscitation instructions on the outcomes of out-of-hospital cardiac arrest: An analysis of the JAAM-OHCA registry.

Aim: To determine whether dispatcher-provided cardiopulmonary resuscitation (CPR) instructions improve the outcomes of out-of-hospital cardiac arrest (OHCA). Methods: Cases registered in the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest (JAAM-OHCA) Registry between June 2014 and December 2019 were included. Cases in which the dispatcher provided CPR instructions to the bystander were included in the "Instructions" group", and cases without CPR instructions were included in the "No Instructions" group. The primary outcome was the proportion of patients with a favorable neurological outcome, defined as a Glasgow-Pittsburgh cerebral performance category scale of 1 to 2 at 1 month after OHCA. Results: Overall, 51,199 patients with OHCA were registered in the JAAM-OHCA Registry during the study period. Of these, 33,745 were eligible for the study, with 16,509 in the Instructions group and 17,236 in the No Instructions group. The proportion of patients with a favorable neurological outcome at 1 month after OHCA was inferior in the Instructions group than in the No Instructions group (2.3% versus 3.0%, p < 0.001). After adjustment for patient background characteristics, no association was found between CPR instructions provided by a dispatcher and favorable neurological outcomes at 1 month after OHCA (adjusted odds ratio, 1.000; 95% confidence interval, 0.869-1.151, p = 0.996). Conclusion: The present study found no clear clinical benefit of dispatcher-provided CPR instructions on the neurological outcomes of cases with OHCA.

Pathophysiology of Coagulopathy Induced by Traumatic Brain Injury Is Identical to That of Disseminated Intravascular Coagulation With Hyperfibrinolysis.

Background: Traumatic brain injury (TBI)-associated coagulopathy is a widely recognized risk factor for secondary brain damage and contributes to poor clinical outcomes. Various theories, including disseminated intravascular coagulation (DIC), have been proposed regarding its pathomechanisms; no consensus has been reached thus far. This study aimed to elucidate the pathophysiology of TBI-induced coagulopathy by comparing coagulofibrinolytic changes in isolated TBI (iTBI) to those in non-TBI, to determine the associated factors, and identify the clinical significance of DIC diagnosis in patients with iTBI. Methods: This secondary multicenter, prospective study assessed patients with severe trauma. iTBI was defined as Abbreviated Injury Scale (AIS) scores ≥4 in the head and neck, and ≤2 in other body parts. Non-TBI was defined as AIS scores ≥4 in single body parts other than the head and neck, and the absence of AIS scores ≥3 in any other trauma-affected parts. Specific biomarkers for thrombin and plasmin generation, anticoagulation, and fibrinolysis inhibition were measured at the presentation to the emergency department (0 h) and 3 h after arrival. Results: We analyzed 34 iTBI and 40 non-TBI patients. Baseline characteristics, transfusion requirements and in-hospital mortality did not significantly differ between groups. The changes in coagulation/fibrinolysis-related biomarkers were similar. Lactate levels in the iTBI group positively correlated with DIC scores (rho = -0.441, p = 0.017), but not with blood pressure (rho = -0.098, p = 0.614). Multiple logistic regression analyses revealed that the injury severity score was an independent predictor of DIC development in patients with iTBI (odds ratio = 1.237, p = 0.018). Patients with iTBI were further subdivided into two groups: DIC (n = 15) and non-DIC (n = 19) groups. Marked thrombin and plasmin generation were observed in all patients with iTBI, especially those with DIC. Patients with iTBI and DIC had higher requirements for massive transfusion and emergency surgery, and higher in-hospital mortality than those without DIC. Furthermore, DIC development significantly correlated with poor hospital survival; DIC scores at 0 h were predictive of in-hospital mortality. Conclusions: Coagulofibrinolytic changes in iTBI and non-TBI patients were identical, and consistent with the pathophysiology of DIC. DIC diagnosis in the early phase of TBI is key in predicting the outcomes of severe TBI.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020).

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

Hyperoxemia during resuscitation of trauma patients and increased intensive care unit length of stay: inverse probability of treatment weighting analysis.

BACKGROUND: Information on hyperoxemia among patients with trauma has been limited, other than traumatic brain injuries. This study aimed to elucidate whether hyperoxemia during resuscitation of patients with trauma was associated with unfavorable outcomes. METHODS: A post hoc analysis of a prospective observational study was carried out at 39 tertiary hospitals in 2016-2018 in adult patients with trauma and injury severity score (ISS) of > 15. Hyperoxemia during resuscitation was defined as PaO2 of ≥ 300 mmHg on hospital arrival and/or 3 h after arrival. Intensive care unit (ICU)-free days were compared between patients with and without hyperoxemia. An inverse probability of treatment weighting (IPW) analysis was conducted to adjust patient characteristics including age, injury mechanism, comorbidities, vital signs on presentation, chest injury severity, and ISS. Analyses were stratified with intubation status at the emergency department (ED). The association between biomarkers and ICU length of stay were then analyzed with multivariate models. RESULTS: Among 295 severely injured trauma patients registered, 240 were eligible for analysis. Patients in the hyperoxemia group (n = 58) had shorter ICU-free days than those in the non-hyperoxemia group [17 (10-21) vs 23 (16-26), p < 0.001]. IPW analysis revealed the association between hyperoxemia and prolonged ICU stay among patients not intubated at the ED [ICU-free days = 16 (12-22) vs 23 (19-26), p = 0.004], but not among those intubated at the ED [18 (9-20) vs 15 (8-23), p = 0.777]. In the hyperoxemia group, high inflammatory markers such as soluble RAGE and HMGB-1, as well as low lung-protective proteins such as surfactant protein D and Clara cell secretory protein, were associated with prolonged ICU stay. CONCLUSIONS: Hyperoxemia until 3 h after hospital arrival was associated with prolonged ICU stay among severely injured trauma patients not intubated at the ED. TRIAL REGISTRATION: UMIN-CTR, UMIN000019588 . Registered on November 15, 2015.

Association between low body mass index and increased 28-day mortality of severe sepsis in Japanese cohorts.

Current research regarding the association between body mass index (BMI) and altered clinical outcomes of sepsis in Asian populations is insufficient. We investigated the association between BMI and clinical outcomes using two Japanese cohorts of severe sepsis (derivation cohort, Chiba University Hospital, n = 614; validation cohort, multicenter cohort, n = 1561). Participants were categorized into the underweight (BMI < 18.5) and non-underweight (BMI ≥ 18.5) groups. The primary outcome was 28-day mortality. Univariate analysis of the derivation cohort indicated increased 28-day mortality trend in the underweight group compared to the non-underweight group (underweight 24.4% [20/82 cases] vs. non-underweight 16.0% [85/532 cases]; p = 0.060). In the primary analysis, multivariate analysis adjusted for baseline imbalance revealed that patients in the underweight group had a significantly increased 28-day mortality compared to those in the non-underweight group (p = 0.031, adjusted odds ratio [OR] 1.91, 95% confidence interval [CI] 1.06-3.46). In a repeated analysis using a multicenter validation cohort (underweight n = 343, non-underweight n = 1218), patients in the underweight group had a significantly increased 28-day mortality compared to those in the non-underweight group (p = 0.045, OR 1.40, 95% CI 1.00-1.97). In conclusion, patients with a BMI < 18.5 had a significantly increased 28-day mortality compared to those with a BMI ≥ 18.5 in Japanese cohorts with severe sepsis.

Clinical characteristics of patients with severe sepsis and septic shock in relation to bacterial virulence of beta-hemolytic Streptococcus and Streptococcus pneumoniae.

AIM: Combined detailed analysis of patient characteristics and treatment as well as bacterial virulence factors, which all play a central role in the cause of infections leading to severe illness, has not been reported. We aimed to describe the patient characteristics (Charlson comorbidity index [CCI]), treatment (3-h bundle), and outcomes in relation to bacterial virulence of Streptococcus pneumoniae and beta-hemolytic Streptococcus (BHS). METHODS: This sepsis primary study is part of the larger Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) study, a multicenter, prospective cohort study. We included patients diagnosed with S. pneumoniae and BHS sepsis and examined virulence, defining the high-virulence factor as follows: S. pneumoniae serotype 3, 31, 11A, 35F, and 17F; Streptococcus pyogenes, emm 1; Streptococcus agalactiae, III; and Streptococcus dysgalactiae ssp. equisimilis, emm typing pattern stG 6792. Included patients were divided into high and normal categories based on the virulence factor. RESULTS: Of 1,184 sepsis patients enrolled in the Japanese Association for Acute Medicine's FORECAST study, 62 were included in the current study (29 cases with S. pneumoniae sepsis and 33 with BHS). The CCI and completion of a 3-h bundle did not differ between normal and high virulence groups. Risk of 28-day mortality was significantly higher for high-virulence compared to normal-virulence when adjusted for CCI and completion of a 3-h bundle (Cox proportional hazards regression analysis, hazard ratio 3.848; 95% confidence interval, 1.108-13.370; P = 0.034). CONCLUSION: The risk of 28-day mortality was significantly higher for patients with high-virulence compared to normal-virulence bacteria.

Rapid Detection of Microbial Contamination in Intravenous Fluids by ATP-Based Monitoring System.

In this study, we investigated four clinical cases of microbial contamination of in-use intravenous infusion fluid, detected by measuring "Adenosine triphosphate (ATP) + adenosine monophosphate (AMP)" ("ATP+AMP") levels. High "ATP+AMP" values correlate with microbial contamination, and by utilizing these values as indicator for microbial contamination possibility, we were able to rapidly detect the contamination and recommend replacement of catheters and administration sets. In three out of four cases, changing the infusion fluid led to improvement in the condition of the patients. "ATP+AMP" levels can be used to confirm microbial contamination of in-use intravenous infusion fluids, as it is fast (several minites) and convenient to measure them.

Risk modifiers of acute respiratory distress syndrome in patients with non-pulmonary sepsis: a retrospective analysis of the FORECAST study.

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.

Comparison of high-flow nasal cannula oxygen therapy and non-invasive ventilation as first-line therapy in respiratory failure: a multicenter retrospective study.

AIM: To identify which subgroups of respiratory failure could benefit more from high-flow nasal cannula oxygen therapy (HFNC) or non-invasive ventilation (NIV). METHODS: We undertook a multicenter retrospective study of patients with acute respiratory failure (ARF) who received HFNC or NIV as first-line respiratory support between January 2012 and December 2017. The adjusted odds ratios (OR) with 95% confidence intervals (CI) for HFNC versus NIV were calculated for treatment failure and 30-day mortality in the overall cohort and in patient subgroups. RESULTS: High-flow nasal cannula oxygen therapy and NIV were used in 200 and 378 patients, and the treatment failure and 30-day mortality rates were 56% and 34% in the HFNC group and 41% and 39% in the NIV group, respectively. The risks of treatment failure and 30-day mortality were not significantly different between the two groups. In subgroup analyses, HFNC was associated with increased risk of treatment failure in patients with cardiogenic pulmonary edema (adjusted OR 6.26; 95% CI, 2.19-17.87; P < 0.01) and hypercapnia (adjusted OR 3.70; 95% CI, 1.34-10.25; P = 0.01), but the 30-day mortality was not significantly different in these subgroups. High-flow nasal cannula oxygen therapy was associated with lower risk of 30-day mortality in patients with pneumonia (adjusted OR 0.43; 95% CI, 0.19-0.94; P = 0.03) and in patients without hypercapnia (adjusted OR 0.51; 95% CI, 0.30-0.88; P = 0.02). CONCLUSION: High-flow nasal cannula oxygen therapy could be more beneficial than NIV in patients with pneumonia or non-hypercapnia, but not in patients with cardiogenic pulmonary edema or hypercapnia.

Impact of type of emergency department on the outcome of out-of-hospital cardiac arrest: a prospective cohort study.

AIM: To assess whether the outcomes of out-of-hospital cardiac arrest (OHCA) differ between patients treated at tertiary or secondary emergency medical facilities. METHODS: Data from the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest (JAAM-OHCA) registry between June 2014 and December 2015 were analyzed and compared between patients treated at tertiary (tertiary group) and secondary (secondary group) emergency medical facilities. The primary outcome of this study was a favorable neurological outcome at 1 and 3 months after OHCA, defined as a Glasgow-Pittsburgh cerebral performance category of 1 or 2. RESULTS: Between June 2014 and December 2015, a total of 13,491 patients with OHCA were registered in the JAAM-OHCA registry. Of these, 12,836 were eligible in the present analysis, with 11,583 in the tertiary group and 1,253 in the secondary group. The proportions of patients with favorable neurological outcomes in the tertiary group were significantly higher than those in the secondary group at 1 (4.7% versus 2.0%, P < 0.001) and 3 (3.5% versus 1.6%, P < 0.001) months after OHCA. Even after adjusting for baseline characteristics of patients, treatment at a tertiary emergency medical facility was independently associated with favorable neurological outcomes at 1 (odds ratio, 2.856, 95% confidence interval, 1.429-5.710; P = 0.003) and 3 (odds ratio, 2.462, 95% confidence interval, 1.203-5.042; P = 0.014) months after OHCA. CONCLUSION: The neurological outcomes of patients with OHCA treated at tertiary emergency medical facilities were better than those of patients treated at secondary emergency medical facilities.

Trends in sepsis care in Japan: comparison of two sepsis cohort studies conducted by the Japanese Association for Acute Medicine.

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.

Severe Fever with Thrombocytopenia Syndrome Complicated with Pseudomembranous Aspergillus Tracheobronchitis in a Patient without Apparent Risk Factors for Invasive Aspergillosis.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease. A 91-year-old woman was admitted to our intensive-care unit with SFTS, and she developed dyspnea with wheezes 5 days after admission. Bronchoscopy showed scattered white mold in her central airway. An airway tissue biopsy and culture of bronchial lavage fluid revealed fungal hyphae in the necrotic tissue, confirmed as Aspergillus fumigatus. She was thus diagnosed with pseudomembranous aspergillus tracheobronchitis. She had no common risk factors for invasive aspergillosis (IA). Patients with SFTS, even those without apparent risk factors for IA, may be at risk of developing IA.

Comparison of clinical practice guidelines for the management of pain, agitation, and delirium in critically ill adult patients.

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 profile of Japanese Association for Acute Medicine - out-of-hospital cardiac arrest registry in 2014-2015.

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.

Early evaluation of severity in patients with severe sepsis: a comparison with "septic shock" - subgroup analysis of the Japanese Association for Acute Medicine Sepsis Registry (JAAM-SR).

Aim: The purpose of this subgroup analysis of a Japanese multicenter registry, the Japanese Association for Acute Medicine Sepsis Registry Advanced (JAAM-SR-Advanced), was to identify early outcome indicators for severe sepsis that are useful and more objective than "septic shock." Methods: Among 624 patients with severe sepsis registered in JAAM-SR-Advanced, 554 with valid serum lactate data were retrospectively studied. Hypotension before and after fluid resuscitation and the highest lactate values over the initial 24 h were compared for their ability to predict in-hospital mortality. Results: Of the study group, 155 (28.0%) patients were non-survivors and had significantly lower systolic blood pressures and higher lactate peaks. The mortality of 364 patients with initial hypotension was higher than those patients without it (32.7% versus 19.1%, P < 0.01). Patients with the worst lactate values ≥4 mmol/L had much higher mortality than other patients (P < 0.001). In an attempt to predict outcomes, we combined initial hypotension and the worst lactate values. The patient group with initial hypotension and the worst lactate values ≥4 mmol/L (183 patients, 33.0%) had a significantly higher mortality rate of 48.6% than the other groups (P < 0.01). Conclusion: The novel combined criterion of initial hypotension and the worst lactate values ≥4 mmol/L within the initial 24 h is potentially useful as a single outcome predictor for severe sepsis.

Serum neutrophil gelatinase-associated lipocalin levels predict the neurological outcomes of out-of-hospital cardiac arrest victims.

BACKGROUND: Serum neutrophil gelatinase-associated lipocalin (NGAL) is a well-known biomarker of acute kidney injury. Serum NGAL was recently proposed as a potential predictor of mortality in post cardiac arrest syndrome (PCAS) patients following out-of-hospital cardiac arrest (OHCA). However, the potential predictive value of NGAL for neurological outcomes is unknown. Therefore, we assessed the potential predictive value of NGAL for neurological outcomes after OHCA. We also compared its predictive value with that of neuron-specific enolase (NSE) as an established biomarker. METHODS: Blood samples were prospectively collected from 43 PCAS patients following OHCA. Serum NGAL was measured on days 1 and 2, and NSE was measured on day 2. These biomarkers were compared between patients with favourable (cerebral performance category [CPC] 1-2) and unfavourable (CPC 3-5) outcomes. Receiver operating characteristic (ROC) curve analysis was performed. RESULTS: Serum NGAL and NSE on day 2 (both P < 0.001), but not NGAL on day 1 (P = 0.609), were significantly different between the favourable and unfavourable groups. In ROC curve analysis, the sensitivity and specificity were 83% and 85%, respectively, for NGAL (day 2) at a cutoff value of 204 ng/mL and were 84% and 100% for NSE (day 2) at a cutoff value of 28.8 ng/mL. The area under the ROC curve of NGAL (day 2) was equivalent to that of NSE (day 2) (0.830 vs. 0.918). Additionally, the area under the ROC curve in subgroup of estimated glomerular filtration rate (eGFR) > 20 mL/min/1.73 m2 (n = 38, 0.978 vs. 0.923) showed the potential of NGAL predictability. CONCLUSIONS: Serum NGAL might predict the neurological outcomes of PCAS patients, and its predictive value was equivalent to that of NSE.

Risk factors for late defecation and its association with the outcomes of critically ill patients: a retrospective observational study.

BACKGROUND: Late defecation was recently reported to be associated with worse clinical outcomes in critically ill patients. However, more research is needed to examine the causes and clinical significance of late defecation. The objectives of this study were to investigate the risk factors for late defecation and its association with the outcomes of intensive care unit (ICU) patients. METHODS: Patients in an ICU for ≥7 days between January and December 2011 were retrospectively assessed. Based on the time between admission and the first defecation, they were assigned to early (<6 days; n = 186) or late (≥6 days; n = 96) defecation groups. Changes in clinical variables between admission and ICU day 7 were assessed to investigate the effects of late defecation. The clinical outcomes were ICU mortality, length of ICU stay, and length of mechanical ventilation. RESULTS: Late enteral nutrition (odds ratio (OR) 3.42; 95 % confidence interval (CI) 1.88-6.22; P < 0.001), sedatives (OR 3.07; 95 % CI 1.71-5.52; P < 0.001), and surgery (OR 1.86; 95 % CI 1.01-3.42; P = 0.047) were the independent risk factors for late defecation. The median (interquartile) changes in body temperature (0.3 [-0.4 to 1.0] vs 0.7 [0.1 to 1.5] °C; P = 0.004), serum C-reactive protein concentration (1.6 [-0.5 to 6.6] vs 3.5 [0.7 to 8.5] mg/dL; P = 0.035), and Sequential Organ Failure Assessment score (-1 [-2 to 1] vs 0 [-1 to 2]; P = 0.008) between admission and ICU day 7 were significantly greater in the late defecation group than in the early defecation group. ICU stay was significantly longer in the late defecation group (12 [9 to 19] vs 16 [10 to 23] days; P = 0.021), whereas ICU mortality and the length of mechanical ventilation were similar in both groups. CONCLUSIONS: Late enteral nutrition, sedatives, and surgery were independent the risk factors for late defecation in critically ill patients. Late defecation was associated with prolonged ICU stay.

Splenic volume in severe sepsis is associated with disease severity and pneumococcal infection.

Aim: A small spleen, which is occasionally found in patients with pneumococcal sepsis, may increase pneumococcal susceptibility because of splenic malfunction. However, a small spleen may also originate from severe disease. We carried out a retrospective study to evaluate the association between splenic volume and severe pneumococcal sepsis or disease severity. Methods: We reviewed the medical records of 23 patients with severe pneumococcal sepsis treated at our institution between January 2004 and September 2015 (pneumococcal group) and 61 patients with severe non-pneumococcal bacteremia treated between April 2011 and September 2015 (control group). Splenic volume measured by abdominal computed tomography on admission was compared between the two groups. Correlations between Acute Physiology and Chronic Health Evaluation (APACHE) II scores and splenic volume on admission and the change in splenic volume from the non-septic state to admission were also determined. Results: Splenic volume on admission was significantly smaller (P = 0.001) and a small spleen was more frequent (P < 0.001) in the pneumococcal group. The APACHE II score was negatively correlated with splenic volume on admission (r = -0.46, P < 0.001) and the change in splenic volume (r = -0.44, P = 0.004). Pneumococcal infection (odds ratio 13.1, 95% confidence interval 2.6-65.7; P = 0.002) and APACHE II score (odds ratio 1.2, 95% confidence interval 1.1-1.3; P = 0.002) were independently associated with small spleen. Conclusion: Splenic volume decreased with increasing severity of severe sepsis. A small spleen was also associated with severe pneumococcal infection.