The Relationship Between Acute-Phase Circuit Occlusion and Blood Calcium Concentration in an Ex Vivo Continuous Renal Replacement Therapy Model.

Background and objective Continuous renal replacement therapy (CRRT) is a blood purification therapy modality for the treatment of renal failure in critically ill hospitalized patients with multiorgan dysfunction, effectively preventing uremia and multiple organ failure while improving renal function. However, the perfusion of patient blood through extracorporeal circulation often results in unexpected early occlusion of the CRRT circuit or hemofilter, leading to frequent interruptions in CRRT and wastage of medical resources. Moreover, clinical research on such circuit occlusions is limited. In Japan, CRRT circuits require long-term perfusion, often lasting 24 hours or more, indicating the need for a model capable of inducing occlusion at any arbitrary time; this model can evaluate various aspects, including causes and underlying mechanisms, and contribute to the development of an occlusion prediction method. Hence, we hypothesized the need for a model for inducing occlusion at arbitrary time points. Consequently, we strove to develop an ex vivo circuit occlusion model involving the injection of calcium into circulating citrated animal blood to evaluate the relationship between the amount of calcium chloride injected, circuit occlusion time, and changes in circuit pressure over time. Methods We developed a circuit occlusion model using a commercially available CRRT circuit, polysulfone membrane hemofilter, heating extension tube, and thermostatic water bath, along with commercially available citrated bovine whole blood. The circuit was filled with blood over a 10-min duration using a roller pump and was occluded after a specific period by varying the flow rate of calcium injected into bovine whole blood. Additionally, continuous injection of 1 mEq/mL calcium chloride into the circuit was maintained while bovine whole blood circulated. Measurements were performed at each calcium injection flow rate (2, 3, and 4 mL/h), with each measurement performed five times. The group that did not receive calcium injection was used as the control (0 mL/h: Con), and the experiment was performed three times. Groups were defined as "0, 2, 3, and 4" for each calcium injection flow rate. The relationship among the amount of calcium chloride injected, circuit occlusion time, and changes in circuit pressure over time was evaluated. Furthermore, blood tests and blood viscoelastic tests were performed at arbitrary times. Results The circuit occlusion time varied with each calcium injection flow rate, and a significant difference was observed between each group (p<0.05). Circuit pressure gradually changed at four min before occlusion when calcium was injected at 2, 3, and 4 mL/h, with a more rapid change at one min before occlusion. We measured circuit pressure at four and one min before occlusion (-4 min, and -1 min, respectively), and at the time of circuit occlusion (0 min) in the Con and 4 mL/h groups. Significant differences were observed in AP between -4 min and 0 min and -1 min and 0 min at a calcium flow rate of 4 mL/h. Additionally, significant differences were seen in prefilter and return pressures between -4 min and 0 min, -4 min and -1 min, and -1 min and 0 min at a calcium flow rate of 4 mL/h (p<0.05). Conclusions Our proposed model accurately estimated the occlusion time based on changes in circuit pressure. This model can be used to create various experimental systems depending on the desired occlusion time.

Effects of physician-present prehospital care in patients with out-of-hospital cardiac arrest on return of spontaneous circulation: A retrospective, observational study in Saga, Japan.

Background and Aims: Emergency medical services for out-of-hospital cardiac arrest (OHCA) vary according to region and country, and patient prognosis differs accordingly. In Japan, physicians may provide prehospital care. However, the effect of physician-present prehospital care on achieving return of spontaneous circulation (ROSC) in patients with cardiac arrest is not clear. Here, we aimed to examine the effect of physician-present prehospital care on the prognosis of patients with OHCA at our hospital compared with physician-absent care. Methods: In this retrospective, observational study, patients aged ≥18 years with non-traumatic OHCA from a single center in Saga City, Japan, between April 2011 and December 2019, were included. Patients were divided into two groups, based on prehospital physician presence or absence. Logistic regression analysis was used to determine the association between physician-present prehospital care and ROSC. Results: Of 820 patients with OHCA, 151 had a physician present and 669 did not. Logistic regression analysis with no adjustment showed that the odds ratio (OR) of physician-present prehospital care for an increased ROSC rate was 1.74 (95% confidence interval [CI]: 1.22-2.48, p = 0.002). Logistic-regression analysis adjusted for ROSC-related factors indicated an OR of 1.05 (95% CI: 0.47-2.34, p = 0.914) for physician-present prehospital care to ROSC. Conclusion: Physician-present prehospital care may not necessarily lead to increased ROSC rates. However, insufficient data limited our study findings. Further studies involving larger sample sizes are warranted.

Efficacy of antithrombin administration for patients with sepsis: A systematic review, meta-analysis, and meta-regression.

Aims: There have been inconsistent reports regarding the effect of antithrombin on sepsis; furthermore, there are limited reports on how dosage affects therapeutic efficacy. Thus, we aimed to perform a systematic review and meta-analysis of the use of antithrombin for sepsis and a meta-regression analysis of antithrombin dosage. Methods: We included randomized controlled trials (RCTs) and observational studies of adult patients with sepsis who received antithrombin. Outcomes included all-cause mortality and serious bleeding complications. Statistical analyses and data synthesis were performed using a random-effects model; further, meta-regression and funnel plots were used to explore heterogeneity and biases. Results: Seven RCTs and six observational studies were included. Most patients in the RCTs and observational studies had severe sepsis and septic-disseminated intravascular coagulation (DIC), respectively. A meta-analysis using RCTs showed no significant differences in mortality between the antithrombin and control groups. However, the meta-analysis of observational studies indicated a trend of decreasing mortality rates with antithrombin administration (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.68-0.92; p = 0.002). Bleeding complications were significantly higher in the antithrombin group than in the control group in both study types (OR, 1.90; 95% CI, 1.52-2.37; p < 0.01). The meta-regression analysis showed no correlation between antithrombin dosage and mortality. Conclusion: A meta-analysis of RCTs confirmed no survival benefit of antithrombin, whereas that of observational studies, which mostly focused on septic DIC, showed a significant beneficial effect on improving outcomes. Indications of antithrombin should be considered based on its beneficial and harmful effects.

Thromboelastometric Analysis of the Correlation Between Burn-Induced Coagulopathy and Severity of Burn Injury.

Background In this study, we aimed to analyze the association between the burn index (BI) and burn-induced coagulopathy. Methods Adult burn patients transported to our emergency department who underwent rotational thromboelastometry (ROTEM) between April 1, 2013, and December 31, 2021, were enrolled in this study. The patients were categorized into two groups based on burn severity. Severe burns were defined as BI scores of > 15. Patient demographics, clinical variables of burns, standard laboratory test data, ROTEM data, and clinical outcomes of both groups were evaluated. In addition, the correlation between severe burns and significant variables was evaluated using a univariate analysis. Results Seven patients were enrolled and categorized into the severe (n = 2) and control (n = 5) groups. The severe group had a significantly worse consciousness level and higher mortality rate and showed higher tendencies of burn severity and clinical severity scores. Disseminated intravascular coagulation was confirmed in one patient. All ROTEM variables in the severe group regarding clot firmness in the extrinsic coagulation cascade (EXTEM) and fibrinogen-specific coagulation cascade (FIBTEM) showed a decreasing tendency as compared to those in the control group. Moreover, correlation analyses revealed strong correlations between the BI and clot firmness (rho = -0.946 to -0.721). Conclusions Severe BI was strongly associated with decreased blood clot firmness in EXTEM, FIBTEM, and ROTEM. Future research using viscoelastic devices may provide new possibilities for the treatment of severe burns.

Effects of combination therapy of antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a systematic review and meta-analysis.

BACKGROUND: Disseminated intravascular coagulation (DIC) syndrome is a highly lethal condition characterized by the complication of multiple organ damage. Although the effects of combined antithrombin (AT) and recombinant thrombomodulin (rTM) on DIC syndrome have previously been examined, the results are inconsistent and inconclusive. Therefore, we conducted a systematic review on the combined administration of AT and rTM for the treatment of septic DIC to investigate the superiority of the combination therapy over either AT or rTM monotherapy using a random-effects analysis model. METHOD: We searched electronic databases, including Medline, Cochrane Central Register of Controlled Trials, Scopus, and Igaku-Chuo Zasshi (ICHU-SHI) Japanese Central Review of Medicine Web from inception to January 2022. Studies assessing the efficacy of combined AT and rTM were included. The primary outcome was all-cause mortality, and the secondary outcome was occurrence of serious bleeding complications compared to monotherapy. We presented the pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI) depending on reporting results in each primary study. RESULTS: We analyzed seven enrolled clinical trials, all of which were observational studies. Combination therapy had a non-significant favorable association with lower 28-day mortality compared to monotherapy (HR 0.67 [0.43-1.05], OR 0.73 [0.45-1.18]). The I2 values were 60% and 72%, respectively, suggesting high heterogeneity. As a secondary outcome, bleeding complications were similar between the two groups (pooled OR 1.11 [0.55-2.23], I2 value 55%). CONCLUSIONS: Although the findings in this analysis could not confirm a statistically significant effect of AT and rTM combination therapy for septic DIC, it showed a promising effect in terms of improving mortality. The incidence of bleeding was low and clinically feasible. Further research is warranted to draw more conclusive results. TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: 000049820).

Fibrinogen Fragment X Mediates Endothelial Barrier Disruption via Suppression of VE-Cadherin.

INTRODUCTION: Major traumatic injury is associated with early hemorrhage-related and late-stage deaths due to multiple organ failure (MOF). While improvements to hemostatic resuscitation have significantly reduced hemorrhage-related deaths, the incidence of MOF among trauma patients remains high. Dysregulation of vascular endothelial cell (EC) barrier function is a central mechanism in the development of MOF; however, the mechanistic triggers remain unknown. Accelerated fibrinolysis occurs in a majority of trauma patients, resulting in high circulating levels of fibrin(ogen) degradation products, such as fragment X. To date, the relationship between fragment X and EC dysregulation and barrier disruption is unknown. The goal of this study was to determine the effects of fragment X on EC barrier integrity and expression of paracellular junctional proteins that regulate barrier function. METHODS: Human lung microvascular endothelial cells (HLMVECs) were treated with increasing concentrations of fragment X (1, 10, and 100 µg/mL), and barrier function was monitored using the xCELLigence live-cell monitoring system. Quantitative PCR (qPCR) was performed to measure changes in EC expression of 84 genes. Immunofluorescent (IF) cytostaining was performed to validate qPCR findings. RESULTS: Fragment X treatment significantly increased endothelial permeability over time (P < 0.05). There was also a significant reduction in VE-cadherin mRNA expression in fragment X-treated HLMVECs compared to control (P = 0.01), which was confirmed by IF staining. CONCLUSIONS: Fragment X may induce EC hyperpermeability by reducing VE-cadherin expression. This suggests that a targeted approach to disrupting EC-fragment X interactions could mitigate EC barrier disruption, organ edema, and MOF associated with major trauma.

Bayesian network predicted variables for good neurological outcomes in patients with out-of-hospital cardiac arrest.

Out-of-hospital cardiac arrest (OHCA) is linked to a poor prognosis and remains a public health concern. Several studies have predicted good neurological outcomes of OHCA. In this study, we used the Bayesian network to identify variables closely associated with good neurological survival outcomes in patients with OHCA. This was a retrospective observational study using the Japan Association for Acute Medicine OHCA registry. Fifteen explanatory variables were used, and the outcome was one-month survival with Glasgow-Pittsburgh cerebral performance category (CPC) 1-2. The 2014-2018 dataset was used as training data. The variables selected were identified and a sensitivity analysis was performed. The 2019 dataset was used for the validation analysis. Four variables were identified, including the motor response component of the Glasgow Coma Scale (GCS M), initial rhythm, age, and absence of epinephrine. Estimated probabilities were increased in the following order: GCS M score: 2-6; epinephrine: non-administered; initial rhythm: spontaneous rhythm and shockable; and age: <58 and 59-70 years. The validation showed a sensitivity of 75.4% and a specificity of 95.4%. We identified GCS M score of 2-6, initial rhythm (spontaneous rhythm and shockable), younger age, and absence of epinephrine as variables associated with one-month survival with CPC 1-2. These variables may help clinicians in the decision-making process while treating patients with OHCA.

Evaluation of the delirium preventive effect of dual orexin receptor antagonist (DORA) in critically ill adult patients requiring ventilation with tracheal intubation at an advanced emergency center: A single-center, retrospective, observational study.

OBJECTIVE: ICU delirium reportedly contributes to increased mortality attributed to underlying diseases, long-term cognitive decline, and increased healthcare costs. Dual orexin receptor antagonists (DORAs), suvorexant and lemborexant, have been suggested for preventing ICU delirium. Although ventilator management is a risk factor for delirium, no study has examined the efficacy of suvorexant and lemborexant in preventing delirium in critically ill patients requiring ventilation. Thus, we retrospectively evaluated the efficacy of DORA in preventing delirium in critically ill adult patients requiring ventilatory management in the emergency room. METHOD: This retrospective study included patients aged ≥18 years who were admitted to the emergency room and received ventilator support between January 2015 and April 2022. The HR (95% CI) for delirium development in patients taking DORA was estimated using a Cox proportional hazards model, which was adjusted for the patient background and concomitant medications. HRs were calculated for patients taking suvorexant and those taking lemborexant using a stratified analysis. RESULTS: Of the 297 patients included in the study, 67 were in the DORA group; 50 were on suvorexant and 17 were on lemborexant. The DORA group had a lower incidence of delirium than the control group (p < 0.0001). The risk of delirium was lower in the DORA group compared the control group (HR, 0.22; 95% CI 0.12-0.40).The risk of developing delirium was lower with suvorexant (HR 0.22; 95% CI 0.11-0.41) and lemborexant (HR 0.25; 95% CI 0.08-0.81). CONCLUSION: DORA is a promising drug that could have the potential to prevent delirium, and its efficacy in preventing delirium should be tested in randomized controlled trials in the future.

Prediction of return of spontaneous circulation in out-of-hospital cardiac arrest with non-shockable initial rhythm using point-of-care testing: a retrospective observational study.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a public health concern, and many studies have been conducted on return of spontaneous circulation (ROSC) and its prognostic factors. Rotational thromboelastometry (ROTEM®), a point-of-care testing (POCT) method, has been useful for predicting ROSC in patients with OHCA, but very few studies have focused on patients with non-shockable rhythm. We examined whether the parameters of POCT could predict ROSC in patients with OHCA and accompanying non-shockable rhythm. METHODS: This is a single-center, retrospective observational study. Complete blood count, blood gas, and ROTEM POCT measurements were used. This study included patients with non-traumatic OHCA aged 18 years or older who were transported to the emergency department and evaluated using POCT between January 2013 and December 2021. The patients were divided into the ROSC and non-ROSC groups. Prehospital information and POCT parameters were compared using receiver operating characteristic (ROC) curve analysis, and further logistic regression analysis was performed. RESULTS: Sixty-seven and 135 patients were in the ROSC and non-ROSC groups, respectively. The ROC curves showed a high area under the curve (AUC) for K+ of 0.77 (95% confidence interval [CI]: 0.71-0.83) and EXTEM amplitude 5 min after clotting time (A5) of 0.70 (95%CI: 0.62-0.77). The odds ratios for ROSC were as follows: female sex 3.67 (95%CI: 1.67-8.04); K+ 0.64 (95%CI: 0.48-0.84); and EXTEM A5 1.03 (95%CI: 1.01-1.06). CONCLUSION: In OHCA patients with non-shockable rhythm, K+ level and the ROTEM parameter EXTEM A5 may be useful in predicting ROSC.

Investigation of differences in coagulation characteristics between hospitalized patients with SARS-CoV-2 Alpha, Delta, and Omicron variant infection using rotational thromboelastometry (ROTEM): A single-center, retrospective, observational study.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 Omicron variant has a low rate of serious illness, is highly contagious, and has spread rapidly since January 2022. The number of severe cases and deaths remains problematic. Here, we aimed to elucidate the coagulation pathology of Omicron-infected patients using rotational thromboelastometry. METHODS: Patients with coronavirus disease 2019, hospitalized and treated from January 2021 to April 2022, were included. The Alpha-Delta and Omicron groups were defined during admission. Blood tests, clinical course, and rotational thromboelastometry measurements were compared using a propensity score-matched cohort. RESULTS: Both groups had 21 patients each. Lactate dehydrogenase (Alpha-Delta group [interquartile range] vs. Omicron group [interquartile range]; 449 [368-518] U/L vs. 241 [196-398] U/L, p = 0.01) and ferritin (1428 [1145-3061] ng/dl vs. 481 [188-881] ng/dl, p = 0.0002) levels were significantly lower in the Omicron group. In rotational thromboelastometry, the thrombus hardness indexes FIBTEM A5 (29 [23-34] mm vs. 23 [18-28] mm, p = 0.034) and maximum clot firmness (34 [27-40] mm vs. 26 [21-33] mm, p = 0.021) were significantly lower in the Omicron group, whereas the fibrinolysis index FIBTEM LI60 (98 [92-100] % vs. 100 [100-100] %, p = 0.0082) was higher. CONCLUSION: Severe coagulation abnormalities may be less likely in Omicron-infected patients than in those infected with the previous Alpha and Delta variants.

Gastrointestinal Perforation Complicated by Continuous Opioids Administration for Intrahepatic Cystic Hemorrhage Pain Management.

Intracystic hemorrhage is a rare complication of multiple hepatic cysts and can lead to hemorrhagic shock. Hence, measures should be taken to prevent the rupture of cysts. The incidence of intestinal perforation is high in patients undergoing hemodialysis. The diagnosis can be difficult in a patient without typical symptoms. We report the case of a woman in her late 60s with multiple renal and hepatic cysts, which caused chronic renal failure managed with dialysis. She presented with abdominal pain and was diagnosed with intrahepatic cystic bleeding. Continuous intravenous fentanyl was administered for pain management, which temporarily alleviated pain, but abdominal pain recurred with increased intensity when she resumed feeding. Subsequently, a contrast-enhanced computed tomography revealed perforation of the lower gastrointestinal tract. Therefore, in cases of intrahepatic cystic hemorrhage that require administration of analgesics, the complications of other diseases that may also cause acute abdominal pain should also be considered.

Coagulation Influencing Liberation from Respiratory Support in Patients with Coronavirus Disease 2019: A Retrospective, Observational Study.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) occasionally develop respiratory failure and coagulopathy. We aimed to determine whether coagulation abnormalities at admission and during the course of hospitalization can predict the liberation from respiratory support in critically ill patients with COVID-19 by combining the results of rotational thromboelastometry (ROTEM) with standard laboratory tests. METHODS: This single-center, retrospective, observational study included 31 consecutive adult patients with COVID-19 who were admitted to the intensive care unit (ICU) and who required respiratory support between April 2021 and August 2021. We divided the patients into two groups according to the liberation from respiratory support and analyzed the differences between the groups. RESULTS: There were 20 patients in the liberation group and 11 in the non-liberation group. There were no significant differences in the overt disseminated intravascular coagulation scores or abnormal counts in the ROTEM parameters at admission between groups, although there was a significant difference in the highest score in the ICU. The Sequential Organ Failure Assessment and sepsis-induced coagulopathy scores were significantly different between both groups at admission and at the time when the highest values were reported during the ICU stay. CONCLUSIONS: High sepsis-induced coagulopathy scores at admission to the ICU were found to be useful predictors of difficulties in the liberation from respiratory support in patients with severe COVID-19. However, increased overt disseminated intravascular coagulation scores and abnormal counts in the ROTEM parameters during the ICU stay were associated with difficulties in the liberation from respiratory support.

Investigation of predictors of bleeding complications in COVID-19 using rotational thromboelastometry (ROTEMⓇ): A retrospective study.

Background: Hemorrhagic complications in patients with coronavirus 19 disease (COVID-19) are infrequent but associated with a prognosis. This study aimed to elucidate the risk factors for bleeding complications in patients with COVID-19 using rotational thromboelastometry (ROTEM) parameters and blood tests performed at admission. Methods: In total, 31 patients with severe COVID-19 treated intensively at Saga University Hospital were included in this study. Patients were divided into two groups according to the presence or absence of hemorrhagic complications. Results from the blood tests performed at admission and during hospitalization, and ROTEM values acquired upon admission, were compared between the two groups. Results: There were significant differences in ROTEM values upon admission between the bleeding and non-bleeding groups. Receiver operating curve analysis showed that the area under the curve for prothrombin time international normalized ratio (PT-INR) and extrinsically-activated test with tissue factor (EXTEM) amplitude at 10 min (A10) were 0.82 (0.52-0.92) and 0.81 (0.58-0.93), respectively. Logistic regression analysis with PT-INR and EXTEM A10 as factors calculated an odds ratio of 1.94 (1.04-3.62) and EXTEM A10 0.86 (0.71-1.05) for bleeding complications occurrence. Conclusion: ROTEM may be a sensitive predictor for bleeding complications in patients with COVID-19.

Development of a delirium predictive model for adult trauma patients in an emergency and critical care center: a retrospective study.

BACKGROUND: Delirium has been shown to prolong the length of intensive care unit stay, hospitalization, and duration of ventilatory control, in addition to increasing the use of sedatives and increasing the medical costs. Although there have been a number of reports referring to risk factors for the development of delirium, no model has been developed to predict delirium in trauma patients at the time of admission. This study aimed to create a scoring system that predicts delirium in trauma patients. METHODS: In this single-center, retrospective, observational study, trauma patients aged 18 years and older requiring hospitalization more than 48 hours were included and divided into the development and validation cohorts. Univariate analysis was performed in the development cohort to identify factors significantly associated with prediction of delirium. The final scoring system for predicting delirium was developed using multivariate analysis and internal validation was performed. RESULTS: Of the 308 patients in the development cohort, 91 developed delirium. Clinical Frailty Score, fibrin/fibrinogen degradation products, low body mass index, lactate level, and Glasgow Coma Scale score were independently associated with the development of delirium. We developed a scoring system using these factors and calculated the delirium predictive score, which had an area under the curve of 0.85. In the validation cohort, 46 of 206 patients developed delirium. The area under the curve for the validation cohort was 0.86, and the calibration plot analysis revealed the scoring system was well calibrated in the validation cohort. DISCUSSION: This scoring system for predicting delirium in trauma patients consists of only five risk factors. Delirium prediction at the time of admission may be useful in clinical practice. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III.

Planned Versus On-Demand Relaparotomy Strategy in Initial Surgery for Non-occlusive Mesenteric Ischemia.

BACKGROUND: There has been insufficient evidence regarding a treatment strategy for patients with non-occlusive mesenteric ischemia (NOMI) due to the lack of large-scale studies. We aimed to evaluate the clinical benefit of strategic planned relaparotomy in patients with NOMI using detailed perioperative information. METHODS: We conducted a multicenter retrospective cohort study that included NOMI patients who underwent laparotomy. In-hospital mortality, 28-day mortality, incidence of total adverse events, ventilator-free days, and intensive care unit (ICU)-free days were compared between groups experiencing the planned and on-demand relaparotomy strategies. Analyses were performed using a multivariate mixed effects model and a propensity score matching model after adjusting for pre-operative, intra-operative, and hospital-related confounders. RESULTS: A total of 181 patients from 17 hospitals were included, of whom 107 (59.1%) were treated using the planned relaparotomy strategy. The multivariate mixed effects regression model indicated no significant differences for in-hospital mortality (61 patients [57.0%] in the planned relaparotomy group vs. 28 patients [37.8%] in the on-demand relaparotomy group; adjusted odds ratio [95% confidence interval] = 1.94 [0.78-4.80]), as well as in 28-day mortality, adverse events, and ICU-free days. Significant reduction in ventilator-free days was observed in the planned relaparotomy group. Propensity score matching analysis of 61 matched pairs with comparable patient severity did not show superiority of the planned relaparotomy strategy. CONCLUSIONS: The planned relaparotomy strategy, compared with on-demand relaparotomy strategy, did not show clinical benefits after the initial surgery of patients with NOMI. Further studies estimating potential subpopulations who may benefit from this strategy are required.

High-dose Factor XIII administration induces effective hemostasis for trauma-associated coagulopathy (TAC) both in vitro and in rat hemorrhagic shock in vivo models.

BACKGROUND: Trauma-associated coagulopathy (TAC) is an early and primary complication in severe trauma patients. Factor XIII (FXIII) is reported to stabilize a clot in the late phase of the coagulation cascade. The goal of this study was to investigate whether the administration of FXIII improves the condition of TAC both in vitro and in vivo. METHODS: We evaluated the effects of different doses, including a very high dose of FXIII (3.6-32.4 IU/mL) on tissue-plasminogen activator-induced hyperfibrinolysis and the combined condition of dilutional coagulopathy and tissue-plasminogen activator-induced hyperfibrinolysis in vitro. The coagulation status was analyzed by rotational thromboelastometry (ROTEM) and Sonoclot. Then, we evaluated the effect of high-dose FXIII (300 IU/kg) for severe coagulopathy in vivo using a rat liver trauma model in which coagulopathy similar to TAC was observed. Survival time and the amount of intra-abdominal bleeding of rats were measured, and a coagulation test was also performed. Histologic evaluations of rats' lung and kidney after FXIII administration were completed. RESULTS: High-dose FXIII significantly improved clot strength as well as increased resistance to hyperfibrinolysis in vitro which was confirmed by ROTEM. Platelet function on Sonoclot was significantly increased by FXIII in a dose-dependent manner. Factor XIII significantly decreased the total amount of bleeding and prolonged the survival time compared to control (control vs FXIII: 108.9 ± 11.4 vs 32.6 ± 5.5 mL/kg; p < 0.001; 26.0 ± 8.8 vs 120 minutes, p < 0.001) in a rat model. Rotational thromboelastometry parameters and platelet function on Sonoclot were significantly improved in the FXIII (+) group compared to control. No adverse effects of FXIII were detected histologically. CONCLUSION: Factor XIII not only generated stable clot resistance to hyperfibrinolysis but also enhanced platelet function by facilitating clot retraction. High-dose FXIII administration therapy has significant clinical impact for severe trauma accompanied with TAC. STUDY TYPE: Human in vitro and rat in vivo experimental study.

Sepsis-Induced Coagulopathy and Japanese Association for Acute Medicine DIC in Coagulopathic Patients with Decreased Antithrombin and Treated by Antithrombin.

Disseminated intravascular coagulation (DIC) in patients with sepsis represents a critical condition. Thus, a simple and rapid diagnosis is required. The purpose of this study was to compare the performances of a recently developed Sepsis-Induced Coagulopathy (SIC) with the Japanese Association for Acute Medicine (JAAM) DIC. Four hundred nine patients with sepsis having coagulopathy and antithrombin activity of less than 70% and treated with antithrombin were retrospectively analyzed, and the SIC and JAAM-DIC criteria on days 1 (before treatment), 2, 4, and 7 were compared. The prevalence of JAAM-DIC on day 1 was significantly higher than that of SIC (91.4% vs 81.8%, P = .003), but there were no differences on days 2, 4, and 7. The mortality rates in the SIC and JAAM-DIC groups were both 23.3%. The specificity to 28-day mortality on day 1 was higher in the SIC group (15.8% vs 9.2%, P = .013). There were no differences in sensitivity on days 1, 2, 4, and 7. Mortality was significantly different between SIC-positive and SIC-negative groups on days 2, 4, and 7 ( P < .01, respectively), while significant differences were seen between JAAM-DIC-positive and JAAM-DIC-negative groups only on days 4 and 7 ( P < .05, .01, respectively). In summary, the SIC characteristics were similar to the JAAM-DIC group, and the classifications were comparable in terms of mortality prediction. The SIC scoring system is simple, easy to use, and adaptable to the new sepsis definitions and offers an important approach to evaluating patients in emergency and critical care settings.

Sphingosine-1-Phosphate (S1P) Is a Feasible Biomarker in Predicting the Efficacy of Polymyxin B-Immobilized Fiber Direct Hemoperfusion (PMX-DHP) in Patients with Septic Shock.

PURPOSE: The aim of this study was to identify a useful biomarker to predict the efficacy of polymyxin B-immobilized fiber direct hemoperfusion (PMX-DHP) in patients with septic shock. METHODS: The 44 patients included in this study were divided into two groups. Group A had an increase in systolic blood pressure (SBP) over 30 mmHg after PMX-DHP treatment. Group B had an increase in SBP less than 30 mmHg after PMX-DHP treatment. We evaluated the clinical characteristics and demographics of both groups. We also assessed whether the cause of sepsis affected the efficacy of PMX-DHP and compared the prognosis of both groups. Finally, we investigated whether there were any significant differences in the levels of sepsis-related biomarkers, including sphingosine-1-phosphate (S1P), between both groups before PMX-DHP in an effort to identify a biomarker that could predict the efficacy of PMX-DHP. RESULTS: PMX-DHP significantly increased SBP regardless of the cause of sepsis. Although there was some tendency, PMX-DHP did not significantly improve the prognosis of effective cases in comparison with non-effective cases, probably because of the limited number of patients included. Among the sepsis-related biomarkers, only S1P values were significantly different between the two groups before PMX-DHP, and S1P levels were significantly increased after treatment in the effective cases. CONCLUSION: S1P levels prior to PMX-DHP can be used to predict its efficacy. In addition, continuous monitoring of S1P levels can indicate the effectiveness of PMX-DHP in patients with septic shock.

The efficacy and associated bleeding complications of recombinant antithrombin supplementation among intensive care unit patients.

INTRODUCTION: The aim of this study was to evaluate the efficacy and complications of recombinant antithrombin (rAT) supplementation for adult patients with disseminated intravascular coagulation (DIC) compared with conventional plasma derived AT (pAT) treatment in the intensive care unit. MATERIALS AND METHODS: This study was performed in a single national university hospital in Japan. Adult patients from April 2015 to March 2016 with DIC were divided into two groups based on the type of AT agent used: the pAT group (n=24) and the rAT group (n=21). Patient demographics, medical history, diagnosis, blood tests, various clinical scores, AT activity, complications, and clinical outcome were collected and analyzed retrospectively. RESULTS: Significantly higher SIRS and APACHEII scores were confirmed in the rAT group than the pAT group. The initial dose of AT was significantly higher in the rAT group than in the pAT group. ATIII values before and after initial supplementation and during their ten-day clinical course were statistically similar between two groups. During the same period, 10 bleeding adverse events were found and there was no significant difference between both groups. Significantly more cases of the rAT group were administered with recombinant thrombomodulin concomitantly than those of the pAT group. Despite significantly more severe patients in rAT group, the clinical outcomes were the same in each group. CONCLUSIONS: Compared with pAT, the supplementation of rAT indicates clinical effectiveness without increasing the risk of bleeding complications in adult DIC patients with low AT activity.