Epidemiology, microbiology, and diagnosis of infection in diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: A multicenter retrospective observational study.

AIMS: We investigated the characteristics of infection and the utility of inflammatory markers in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS). METHODS: A multicenter, retrospective observational study in 21 acute-care hospitals was conducted in Japan. This study included adult hospitalized patients with DKA and HHS. We analyzed the diagnostic accuracy of markers including C-reactive protein (CRP) and procalcitonin (PCT) for bacteremia. Multiple regression models were created for estimating bacteremia risk factors. RESULTS: A total of 771 patients, including 545 patients with DKA and 226 patients with HHS, were analyzed. The mean age was 58.2 (SD, 19.3) years. Of these, 70 tested positive for blood culture. The mortality rates of those with and without bacteremia were 14 % and 3.3 % (P-value < 0.001). The area under the curve (AUC) of CRP and PCT for diagnosis of bacteremia was 0.85 (95 %CI, 0.81-0.89) and 0.76 (95 %CI, 0.60-0.92), respectively. Logistic regression models identified older age, altered level of consciousness, hypotension, and higher CRP as risk factors for bacteremia. CONCLUSIONS: The mortality rate was higher in patients with bacteremia than patients without it. CRP, rather than PCT, may be valid for diagnosing bacteremia in hyperglycemic emergencies. TRIAL REGISTRATION: This study is registered in the UMIN clinical trial registration system (UMIN000025393, Registered December 23, 2016).

Association of initial lactate levels and red blood cell transfusion strategy with outcomes after severe trauma: a post hoc analysis of the RESTRIC trial.

BACKGROUND: The appropriateness of a restrictive transfusion strategy for those with active bleeding after traumatic injury remains uncertain. Given the association between tissue hypoxia and lactate levels, we hypothesized that the optimal transfusion strategy may differ based on lactate levels. This post hoc analysis of the RESTRIC trial sought to investigate the association between transfusion strategies and patient outcomes based on initial lactate levels. METHODS: We performed a post hoc analysis of the RESTRIC trial, a cluster-randomized, crossover, non-inferiority multicenter trials, comparing a restrictive and liberal red blood cell transfusion strategy for adult trauma patients at risk of major bleeding. This was conducted during the initial phase of trauma resuscitation; from emergency department arrival up to 7 days after hospital admission or intensive care unit (ICU) discharge. Patients were grouped by lactate levels at emergency department arrival: low (< 2.5 mmol/L), middle (≥ 2.5 and < 4.0 mmol/L), and high (≥ 4.0 mmol/L). We compared 28 days mortality and ICU-free and ventilator-free days using multiple linear regression among groups. RESULTS: Of the 422 RESTRIC trial participants, 396 were analyzed, with low (n = 131), middle (n = 113), and high (n = 152) lactate. Across all lactate groups, 28 days mortality was similar between strategies. However, in the low lactate group, the restrictive approach correlated with more ICU-free (ß coefficient 3.16; 95% CI 0.45 to 5.86) and ventilator-free days (ß coefficient 2.72; 95% CI 0.18 to 5.26) compared to the liberal strategy. These findings persisted even after excluding patients with severe traumatic brain injury. CONCLUSIONS: Our results suggest that restrictive transfusion strategy might not have a significant impact on 28-day survival rates, regardless of lactate levels. However, the liberal transfusion strategy may lead to shorter ICU- and ventilator-free days for patients with low initial blood lactate levels.

Net reclassification index in comparison of prognostic value of disseminated intravascular coagulation diagnostic criteria by Japanese Society on Thrombosis and Hemostasis and International Society on Thrombosis and Haemostasis: a multicenter prospective cohort study.

BACKGROUND: We compared the prognostic value of the Japanese Society on Thrombosis and Hemostasis (JSTH) disseminated intravascular coagulation (DIC) diagnostic criteria with that of the International Society on Thrombosis and Haemostasis (ISTH) DIC diagnostic criteria for 28-day in-hospital mortality. METHODS: We conducted a multicenter prospective cohort study involving two hematology departments, four emergency departments, and one general medicine department in Japan between August 2017 and July 2021. We assessed three ISTH DIC diagnostic criteria categories using low cutoff levels of D-dimer (low D-dimer), high cutoff levels of D-dimer (high D-dimer), and fibrinogen/fibrin degradation products (FDP) as fibrin-related markers. The main outcome was diagnosis-based category additive net reclassification index (NRI). RESULTS: A total of 222 patients were included: 82 with hematopoietic disorders, 86 with infections, and 54 with other diseases. The 28-day in-hospital mortality rate was 14% (n = 31). The DIC rates diagnosed by the JSTH, ISTH-low D-dimer, high D-dimer, and FDP DIC diagnosis were 52.7%, 47.3%, 42.8%, and 27.0%, respectively. The overall category additive NRI by JSTH DIC diagnosis vs. ISTH-low D-dimer, high D-dimer, and FDP DIC diagnosis were - 10 (95% confidence interval [CI]: -28 to 8, p = 0.282), - 7.8 (95% CI: -26 to 10, p = 0.401), and - 11 (95% CI: -26 to 3, p = 0.131), respectively. CONCLUSIONS: JSTH criterion showed the highest sensitivity for DIC diagnosis that did not improve but reflected the same prognostic value for mortality evaluated using ISTH DIC diagnosis criteria. This finding may help clinicians to use JSTH DIC criterion as an early intervention strategy in patients with coagulopathy.

Emergency administration of fibrinogen concentrate for haemorrhage: systematic review and meta-analysis.

INTRODUCTION: The occurrence of massive haemorrhages in various emergency situations increases the need for blood transfusions and increases the risk of mortality. Fibrinogen concentrate (FC) use may increase plasma fibrinogen levels more rapidly than fresh-frozen product or cryoprecipitate use. Previous several systematic reviews and meta-analyses have not effectively demonstrated FC efficacy in significantly improving the risk of mortality and reducing transfusion requirements. In this study, we investigated the use of FC for haemorrhages in emergency situations. METHODS AND ANALYSIS: In this systematic review and meta-analysis, we included controlled trials, but excluded randomized controlled trials (RCTs) in elective surgeries. The study population consisted of patients with haemorrhages in emergency situations, and the intervention was emergency supplementation of FC. The control group was administered with ordinal transfusion or placebo. The primary and secondary outcomes were in-hospital mortality and the amount of transfusion and thrombotic events, respectively. The electronic databases searched included MEDLINE (PubMed), Web of Science, and the Cochrane Central Register of Controlled Trials. RESULTS: Nine RCTs in the qualitative synthesis with a total of 701 patients were included. Results showed a slight increase in in-hospital mortality with FC treatment (RR 1.24, 95% CI 0.64-2.39, p = 0.52) with very low certainty of the evidence. There was no reduction in the use of red blood cells (RBC) transfusion in the first 24 h after admission with FC treatment (mean difference [MD] 0.0 Unit in the FC group, 95% CI - 0.99-0.98, p = 0.99) with very low certainty of the evidence. However, the use of fresh-frozen plasma (FFP) transfusion significantly increased in the first 24 h after admission with FC treatment (MD 2.61 Unit higher in the FC group, 95% CI 0.07-5.16, p = 0.04). The occurrence of thrombotic events did not significantly differ with FC treatment. CONCLUSIONS: The present study indicates that the use of FC may result in a slight increase in in-hospital mortality. While FC did not appear to reduce the use of RBC transfusion, it likely increased the use of FFP transfusion and may result in a large increase in platelet concentrate transfusion. However, the results should be interpreted cautiously due to the unbalanced severity in the patient population, high heterogeneity, and risk of bias.

Ductus arteriosus banding to regulate excessive pulmonary blood flow in a neonate with necrotizing enterocolitis and complex congenital heart disease, including pulmonary atresia and total anomalous pulmonary venous return: a case report.

BACKGROUND: Patients with right isomerism have accompanying complex congenital heart disease, which is characterized by pulmonary atresia and total anomalous pulmonary venous return. Balanced regulation of the systemic and pulmonary circulation is essential for successful management, especially for cases complicated with necrotizing enterocolitis (NEC). CASE PRESENTATION: A 6-day-old male neonate with a single ventricle, pulmonary atresia, patent ductus arteriosus (DA), and total anomalous pulmonary venous return associated with right isomerism was admitted because of dyspnea, cyanosis, and melena. The patient presented circulatory incompetence due to excessive pulmonary blood flow, resulting in NEC. The patient underwent DA banding and colectomy following continuous intravenous infusion of prostaglandin E1 at six days. Subsequently, his condition improved, reaching a systemic oxygen saturation of around 80%. He underwent a bidirectional Glenn procedure and closure of colectomy at the ages of 5 and 6 months, respectively. CONCLUSION: DA banding can be an alternative to placing an aortopulmonary shunt, which is conventional in patients with ductus-dependent pulmonary circulation, because DA banding is feasible without cardiopulmonary bypass.

Prognostic value of serum high mobility group box 1 protein and histone H3 levels in patients with disseminated intravascular coagulation: a multicenter prospective cohort study.

BACKGROUND: We compared the prognostic value of serum high mobility group box 1 protein (HMGB1) and histone H3 levels with the International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) scores for 28-day in-hospital mortality in patients with DIC caused by various underlying diseases. METHODS: We conducted a multicenter prospective cohort study including two hematology departments, four emergency departments, and one general medicine department in Japan, between August 2017 and July 2021. We included patients diagnosed with DIC by the ISTH DIC scoring system. RESULTS: Overall, 104 patients were included: 50 with hematopoietic disorders, 41 with infections, and 13 with the other diseases. The 28-day in-hospital mortality rate was 21%. The receiver operator characteristic (ROC) curve showed that a DIC score of 6 points, serum HMGB1 level of 8 ng/mL, and serum histone H3 level of 2 ng/mL were the optimal cutoff points. The odds ratios of more than these optimal cutoff points of the DIC score, serum HMGB1, and histone H3 levels were 1.58 (95% confidence interval [CI]: 0.60 to 4.17, p = 0.36), 5.47 (95% CI: 1.70 to 17.6, p = 0.004), and 9.07 (95% CI: 2.00 to 41.3, p = 0.004), respectively. The area under the ROC curve of HMGB1 (0.74, 95% CI: 0.63 to 0.85) was better than that of the ISTH DIC scores (0.55, 95% CI: 0.43 to 0.67, p = 0.03), whereas that of histone H3 was not (0.71, 95% CI: 0.60 to 0.82, p = 0.07). Calibration and net reclassification plots of HMGB1 identified some high-risk patients, whereas the ISTH DIC scores and histone H3 did not. The category-free net reclassification improvement of HMGB1 was 0.45 (95% CI: 0.01 to 0.90, p = 0.04) and that of histone H3 was 0.37 (95% CI: - 0.05 to 0.78, p = 0.08). CONCLUSIONS: Serum HMGB1 levels have a prognostic value for mortality in patients with DIC. This finding may help physicians develop treatment strategies.

Association of trauma severity with antibody seroconversion in heparin-induced thrombocytopenia: A multicenter, prospective, observational study.

BACKGROUND: Heparin administration can induce the production of anti-platelet factor 4 (PF4)/heparin antibodies with platelet-activating properties, causing heparin-induced thrombocytopenia (HIT). Previous studies have suggested that trauma severity influences HIT immune responses, but their relationship has not been fully explained. This study aimed to clarify this association by multicenter prospective observational study. METHODS: Trauma patients who met the criteria of age 18 years or older and Injury Severity Scores (ISSs) of ≥9 from March 2018 to February 2019 were included. Patients who did not receive any heparin and those who received it as flushes or for treatment were also included. Patients were divided into three groups based on trauma severity (to mild [ISS 9-15], moderate [ISS 16-24], and severe injury groups [ISS ≥25]) and were compared by the seroconversion time and rate, as well as the disappearance rate of antibodies on day 30. RESULTS: A total of 184 patients were included: 55, 62, and 67 patients were classified into the mild, moderate, and severe injury groups, respectively. Overall, the seroconversion rates of anti-PF4/heparin immunoglobulin G (IgG) and HIT antibodies by washed platelet activation assay were 26.6% and 16.3%, respectively. There was a significant difference in the seroconversion rates of anti-PF4/heparin IgG ( p = 0.016) and HIT antibodies ( p = 0.046) among the groups. Seroconversion rates in both assays increased with increasing trauma severity. The time required to achieve seroconversion was similar (between 5 and 10 days of trauma onset) regardless of heparin administration. Anti-PF4/heparin IgG and HIT antibodies were no longer detected on day 30 in 28.6% and 60.9% of seroconverted patients, respectively. CONCLUSION: Development of HIT antibodies was observed commonly in severely injured trauma patients. Heparin-induced thrombocytopenia antibody development may be related to trauma severity, with a high disappearance frequency on day 30. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Restrictive transfusion strategy for critically injured patients (RESTRIC) trial: a study protocol for a cluster-randomised, crossover non-inferiority trial.

INTRODUCTION: Resuscitation using blood products is critical during the acute postinjury period. However, the optimal target haemoglobin (Hb) levels have not been adequately investigated. With the restrictive transfusion strategy for critically injured patients (RESTRIC) trial, we aim to compare the restrictive and liberal red blood cell (RBC) transfusion strategies. METHODS AND ANALYSIS: This is a cluster-randomised, crossover, non-inferiority trial of patients with severe trauma at 22 hospitals that have been randomised in a 1:1 ratio based on the use of a restrictive or liberal transfusion strategy with target Hb levels of 70-90 or 100-120 g/L, respectively, during the first year. Subsequently, after 1-month washout period, another transfusion strategy will be applied for an additional year. RBC transfusion requirements are usually unclear on arrival at the emergency department. Therefore, patients with severe bleeding, which could lead to haemorrhagic shock, will be included in the trial based on the attending physician's judgement. Each RBC transfusion strategy will be applied until 7 days postadmission to the hospital or discharge from the intensive care unit. The outcomes measured will include the 28-day survival rate after arrival at the emergency department (primary), the cumulative amount of blood transfused, event-free days and frequency of transfusion-associated lung injury and organ failure (secondary). Demonstration of the non-inferiority of restrictive transfusion will emphasise its clinical advantages. ETHICS AND DISSEMINATION: The trial will be performed according to the Japanese and International Ethical guidelines. It has been approved by the Ethics Committee of each participating hospital and The Japanese Association for the Surgery of Trauma (JAST). Written informed consent will be obtained from all patients or their representatives. The results of the trial will be disseminated to the participating hospitals and board-certified educational institutions of JAST, submitted to peer-reviewed journals for publication, and presented at congresses. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry; UMIN000034405. Registered 8 October 2018.

Early administration of fibrinogen concentrate is associated with improved survival among severe trauma patients: a single-centre propensity score-matched analysis.

Background: Fibrinogen plays an important role in haemostasis during the early phase of trauma, and low fibrinogen levels after severe trauma are associated with haemostatic impairment, massive bleeding, and poor outcomes. Aggressive fibrinogen supplementation may improve haemostatic function, as fibrinogen levels deteriorate before other routine coagulation parameters in this setting. Therefore, we evaluated whether early administration of fibrinogen concentrate (FC) was associated with improved survival in severe trauma patients. Methods: This single-centre retrospective study evaluated patients with severe trauma (injury severity score ≥ 16) who were admitted to our emergency department between January 2010 and July 2018. The exclusion criteria included age < 18 years, cardiac arrest before emergency department arrival, cervical spinal cord injury not caused by a high-energy accident, and severe burn injuries. The FC and control groups included trauma patients who received and did not receive FC within 1 h after emergency department arrival, respectively. Propensity scores were used to balance the two groups based on the trauma and injury severity score (TRISS), heart rate at emergency department admission, and age. The primary outcome was the in-hospital survival rate. Results: The propensity scoring model had a c-statistic of 0.734, the Hosmer-Lemeshow chi-squared value was 7.036 (degrees of freedom = 8), and the non-significant p value of 0.533 indicated a good model fit. The propensity score matching created 31 matched pairs of patients, who had appropriately balanced characteristics. The FC group had a significantly higher in-hospital survival rate than the control group (log-rank p = 0.013). The FC group also used significantly higher amounts of red blood cells and fresh frozen plasma within 6 h after emergency department admission. However, the two groups had similar transfusion amounts between 6 and 24 h after emergency department admission. Conclusions: The present study revealed that early FC administration was associated with a favourable survival rate among severe trauma patients. Therefore, FC may be useful for the early management of trauma-induced coagulopathy and may improve outcomes in this setting.

Acute compartment syndrome of the lower leg causing cardiac arrest after resection of the right external iliac vein for autologous graft: a case report.

BACKGROUND: The right external iliac vein (REIV) is often used for portal vein reconstruction in patients undergoing pancreatoduodenectomy with portal-superior mesenteric vein resection. We report a case of cardiac arrest caused by acute lower leg compartment syndrome as a result of REIV resection. CASE PRESENTATION: A 53-year-old man underwent pancreatoduodenectomy with portal vein resection. Hyperkalemia progressed during surgery due to intestinal reperfusion injury, which caused recurrent ventricular arrhythmia required for cardio-pulmonary resuscitation. The surgery was discontinued after resuscitation, and portal vein reconstruction using the REIV was performed 2 days post-operatively. Acute compartment syndrome was diagnosed immediately following the surgery. Hyperkalemia progressed, causing pulseless ventricular tachycardia. Emergent fasciotomy was performed, but right leg dysfunction persisted after discharge. CONCLUSION: REIV resection can cause lower-extremity acute compartment syndrome. The status, including intracompartmental pressure, of the lower extremity should be carefully observed after REIV resection during and after surgery.

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.

A summary of the Japan septic disseminated intravascular coagulation study.

Over the past few decades, the large, international, randomized controlled trials of anticoagulant therapies for patients with sepsis have not yielded any improvement in mortality rates. However, in Japan, anticoagulant therapies are administered for sepsis patients with disseminated intravascular coagulation (DIC), but not for sepsis patients without DIC. Furthermore, epidemiological data regarding sepsis in Japan are scarce. Therefore, a nationwide multicenter retrospective observational study, the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study, was undertaken. The JSEPTIC DIC study enrolled 42 intensive care units and included 3,195 patients with sepsis. The results of the JSEPTIC DIC study indicated the following: (i) anticoagulant therapy may be effective in sepsis-induced DIC patients at high risk for death, (ii) recombinant human soluble thrombomodulin administration and antithrombin supplementation are associated with survival benefits in patients with sepsis-induced DIC.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016).

Background and Purpose: The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 in Japanese. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. Methods: Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ), and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (>66.6%) majority vote of each of the 19 committee members. Results: A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for 5 CQs. Conclusions: Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

Screening itself for disseminated intravascular coagulation may reduce mortality in sepsis: A nationwide multicenter registry in Japan.

OBJECTIVES: Screening of patients with sepsis for disseminated intravascular coagulation (DIC) has been recommended in several guidelines. However, DIC screening is still not widely accepted as an essential component of sepsis management, partly because of a lack of evidence that DIC screening has an effect on mortality. We investigated whether DIC screening was associated with a survival benefit in patients with sepsis. DESIGN: Post hoc analysis of a nationwide multicenter retrospective cohort study. SETTING: 42 intensive care units in Japan. PARTICIPANTS: 2663 adult patients diagnosed as having severe sepsis: 1893 (71.1%) patients were considered candidates for and 770 (28.9%) patients were not considered candidates for International Society of Thrombosis and Hemostasis (ISTH) overt DIC screening on ICU day 1. MAIN OUTCOME MEASURES: The primary outcome measure was all-cause in-hospital mortality. Patients were stratified according to whether DIC screening was performed at the time of ICU admission (day 1) to investigate the survival effect associated with DIC screening. We also evaluated survival benefit by classifying patients according to whether DIC screening was performed on day 1 and repeated on day 3. Effects of screening on mortality were assessed using Cox proportional hazards models adjusted by the inverse probability of treatment weighting (IPTW) method using propensity scoring. RESULTS: After adjustment for imbalances, ISTH overt DIC screening on day 1 was associated with significantly lower mortality (IPTW-adjusted HR: 0.836; 95% confidence interval [CI]: 0.711-0.984), and this association became even stronger when ISTH overt DIC screening was repeated on day 3 (IPTW-adjusted HR: 0.727; 95% CI: 0.597-0.884). Besides, we observed an almost comparable effect on mortality associated with DIC screening using the Japanese Association for Acute Medicine criteria. CONCLUSION: DIC screening was associated with a reduction in mortality in patients with sepsis. This association could be even stronger by repeating DIC screening.

Respiratory extracorporeal membrane oxygenation for severe sepsis and septic shock in adults: a propensity score analysis in a multicenter retrospective observational study.

Aim: This multicenter retrospective observational study aimed to evaluate the efficacy of extracorporeal membrane oxygenation (ECMO) support for septic patients with severe respiratory failure using propensity score analyses. Methods: The data of severe sepsis patients from 42 intensive care units between January 2011 and December 2013 were retrospectively collected. Propensity score matching analyses were undertaken for severe respiratory failure patients with/without veno-venous ECMO support. The main outcome was in-hospital all-cause mortality. Results: Of 3195 patients with severe sepsis, 570 had severe respiratory failure. Forty patients in the ECMO group were matched with 150 patients in the control group. A survival time analysis revealed no difference in the in-hospital survival (hazard ratio, 0.854; 95% confidence interval, 0.531-1.373; P = 0.515). Two-hundred and eighty-five patients had severe respiratory failure induced by lung infection. Twenty-five ECMO group patients were matched with 89 patients in the control group. In the ECMO group, the survival time was longer than in the control group (hazard ratio, 0.498; 95% confidence interval, 0.279-0.889; P = 0.018). The number of renal replacement therapy- and vasopressor-free days improved. The ECMO group received more red blood cells transfused than the control group, but there was no significant difference in the rate of severe bleeding complications between the groups. Conclusions: There was no difference in the in-hospital survival between the ECMO group and control group among overall septic patients with severe respiratory failure. However, in sepsis patients with severe respiratory failure induced by lung infection, ECMO support may improve their survival time.

Minocycline Prevents the Impairment of Hippocampal Long-Term Potentiation in the Septic Mouse.

Sepsis-associated encephalopathy is a major complication during sepsis, and an effective treatment remains unknown. Although minocycline (MINO) has neuroprotective effects and is an attractive candidate for treating sepsis-associated encephalopathy, the effect of MINO on synaptic plasticity during sepsis is still unclear. In the present study, we investigated the effects of MINO on long-term potentiation (LTP) in the hippocampus in a cecal ligation and puncture (CLP) mouse model. We divided mice into four groups; sham + vehicle, sham + MINO (60 mg/kg, i.p. for 3 consecutive days before slice preparation), CLP + vehicle, and CLP + MINO. We tested LTP in the CA1 region of the hippocampus, using slices taken 24 h after surgery. Because MINO is also anti-inflammatory, LTP was analyzed following 30 min of IL-1 receptor antagonist (IL-1ra) perfusion. The endotoxin level in the blood was increased at 24 h after CLP operations regardless of MINO administrations, and LTP in the CLP + vehicle group mice was severely impaired (P < 0.05). High doses of MINO prevented the LTP impairment during sepsis in the CLP + MINO group. Interleukin (IL)-1ra administration ameliorated LTP impairment only in the CLP + vehicle group (P < 0.05); it had no additional effects on LTP in the CLP + MINO group. In conclusion, we have provided the first evidence that MINO prevents impaired LTP related to sepsis-induced encephalopathy in the mouse hippocampus, and that mechanisms associated with IL-1 receptor activity may be involved.

Can Early Aggressive Administration of Fresh Frozen Plasma Improve Outcomes in Patients with Severe Blunt Trauma?--A Report by the Japanese Association for the Surgery of Trauma.

BACKGROUND: This study investigated the effect of a high ratio of fresh frozen plasma (FFP) to red blood cells (RBCs) within the first 6 and 24  h after admission on mortality in patients with severe, blunt trauma. METHODS: This retrospective observational study included 189 blunt trauma patients with an Injury Severity Score (ISS) ≥16 requiring RBC transfusions within the first 24  h. Receiver operating characteristic (ROC) curve analysis was performed to calculate cut-off values of the FFP/RBC ratio for outcome. The patients were then divided into two groups according to the cut-off value. Patient survival was compared between groups using propensity score matching (PSM). RESULTS: The area under the ROC curve was 0.57, and the FFP/RBC ratio was 1.0 at maximum sensitivity (0.57) and specificity (0.67). All patients were then divided into two groups (FFP/RBC ratio ≥1 or <1) and analyzed using PSM and inverse probability of treatment weighting (IPTW). The unadjusted hazard ratio (HR) was 0.44, and the adjusted HR was 0.29. The HR was 0.38 by PSM and 0.41 by IPTW. The survival rate was significantly higher in patients with an FFP/RBC ratio ≥1 within the first 6  h. CONCLUSIONS: Severe blunt trauma patients transfused with an FFP/RBC ratio ≥1 within the first 6  h had an HR of about 0.4. The transfusion of an FFP/RBC ratio ≥1 within the first 6  h was associated with the outcomes of blunt trauma patients with ISS ≥16 who need a transfusion within 24  h.

Pathophysiology of Trauma-Induced Coagulopathy and Management of Critical Bleeding Requiring Massive Transfusion.

Trauma-induced coagulopathy is caused by multiple factors, such as anemia, hemodilution, hypothermia, acidosis, shock, and serious trauma itself, which affects patient outcomes due to critical bleeding requiring massive transfusion. Disseminated intravascular coagulation (DIC) with the fibrinolytic phenotype directly caused by trauma and/or traumatic shock has been considered to be the primary pathophysiology of trauma-induced coagulopathy. The key to controlling DIC is vigorous treatment of the underlying disorder, that is, trauma itself and hemorrhagic shock. Damage control resuscitation, consisting of damage control surgery, permissive hypotension, and hemostatic resuscitation, aims to control severe trauma and critical bleeding, which is equivalent to managing the underlying disorder of DIC. At present, however, evidence-based practices for damage control resuscitation are lacking. A robust prospective outcome study for damage control resuscitation that considers DIC with the fibrinolytic phenotype as the main pathological condition of trauma-induced coagulopathy affecting patient outcome is essential for improving therapeutic strategies.

Rapid evaluation of fibrinogen levels using the CG02N whole blood coagulation analyzer.

Rapid evaluation of fibrinogen (Fbg) levels is essential for maintaining homeostasis in patients with massive bleeding during severe trauma and major surgery. This study evaluated the accuracy of fibrinogen levels measured by the CG02N whole blood coagulation analyzer (A&T Corporation, Kanagawa, Japan) using heparinized blood drawn for blood gas analysis (whole blood-Fbg). A total of 100 matched pairs of heparinized blood samples and citrated blood samples were simultaneously collected from patients in the intensive care unit. Whole blood-Fbg results were compared with those of citrated plasma (standard-Fbg). The whole blood coagulation analyzer measured fibrinogen levels within 2 minutes. Strong correlations between standard-Fbg and whole blood-Fbg were observed (ρ = 0.91, p < 0.001). Error grid analysis showed that 88% of the values were clinically acceptable, and 12% were in a range with possible effects on clinical decision-making; none were in a clinically dangerous range without appropriate treatment. Using a fibrinogen cutoff value of 1.5 g/L for standard-Fbg, the area under the receiver operating characteristic curve of whole blood-Fbg was 0.980 (95% confidence interval 0.951-1.000, p < 0.001). The whole blood coagulation analyzer can rapidly measure fibrinogen levels in heparinized blood and could be useful in critical care settings where excessive bleeding is a concern.