Background This study aimed to compare and validate the out-of-hospital cardiac arrest (OHCA); cardiac arrest hospital prognosis (CAHP); non-shockable rhythm, unwitnessed arrest, long no-flow or long low-flow period, blood pH < 7.2, lactate > 7.0 mmol/L, end-stage chronic kidney disease, age ≥ 85 years, still resuscitation, and extracardiac cause (NULL-PLEASE) clinical; post-cardiac arrest syndrome for therapeutic hypothermia (CAST); and revised CAST (rCAST) scores in OHCA patients treated with recent cardiopulmonary resuscitation strategies. Methods We retrospectively collected data on adult OHCA patients admitted to our emergency department between February 2015 and July 2018. OHCA, CAHP, NULL-PLEASE clinical, CAST, and rCAST scores were calculated based on the data collected. The predictive abilities of each score were tested using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Results We identified 236 OHCA patients from computer-based medical records and analyzed 189 without missing data. In OHCA patients without bystander witnesses, CAHP and OHCA scores were not calculated. Although the predictive abilities of the scores were not significantly different, the NULL-PLEASE score had a large AUC of ROC curve in various OHCA patients. Furthermore, in patients with bystander-witnessed OHCA, the NULL-PLEASE score had large partial AUCs of ROC from sensitivity 0.8–1.0 and specificity 0.8–1.0. Conclusions The NULL-PLEASE score had a high, comprehensive predictive ability in various OHCA patients. Furthermore, the NULL-PLEASE score had a high predictive ability for good and poor neurological outcomes in patients with bystander-witnessed OHCA.

Background: In recent years, the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with cardiopulmonary arrest who do not respond to conventional resuscitation, has increased. However, despite the development of VA-ECMO, the outcomes of resuscitated patients remain poor. The poor prognosis may be attributed to deterioration owing to the post-cardiac arrest syndrome (PCAS); this includes the systemic inflammatory response and coagulation activation caused by the extracorporeal circulation (VA-ECMO circuit) itself. This study aimed to evaluate the coagulofibrinolytic changes caused by VA-ECMO and to identify predictive factors of poor prognosis.Methods: We analyzed 151 cases of PCAS with witnessed cardiac arrest. As biomarkers, platelet counts, prothrombin time ratio, fibrin/fibrinogen degradation products, fibrinogen, antithrombin, and lactate were recorded from blood samples from the time of delivery to the third day of hospitalization. The maximum (max) and minimum (min) values of each factor during the study period were calculated. To evaluate the impact of VA-ECMO on patients with PCAS, we performed propensity score matching between the patients who received and did not receive VA-ECMO. Sub-analysis was performed for the group with VA-ECMO.Results: There were significant differences in all baseline characteristics and demographics except the time from detection to hospital arrival, percentage of cardiopulmonary resuscitations (CPR) by witnesses, and the initial rhythm between the groups. Propensity score matching adjusted for prehospital factors demonstrated that the patients who received VA-ECMO developed significantly severe coagulation disorders. In a sub-analysis, significant differences were noted in the prothrombin time ratio min, fibrinogen max, antithrombin max, and lactate min between survivors and non-survivors. In particular, the prothrombin time ratio min and antithrombin max were strongly correlated with poor outcome.Conclusion: In the present study, significant coagulopathy was observed in patients who received VA-ECMO for CPR. In particular, in patients receiving VA-ECMO, the minimum prothrombin time ratio and maximum antithrombin by day 3 of hospitalization were strongly correlated with poor outcomes. These results suggest that VA-ECMO-induced coagulopathy can be a promising therapeutic target for patients resuscitated by VA-ECMO.

BackgroundVarious animal models of sepsis have been developed to optimize sepsis treatment. However, therapeutic agents that were successful in animal models were rarely effective in human clinical trials. The cecal ligation and puncture (CLP) model is currently the gold standard for sepsis studies. However, its limitations include the high variability among researchers and the difficulty in comparing animals with different cecum shapes and sizes. In this study, we established a protocol for the creation of a simple and accessible sepsis rodent model using fecal suspensions that minimized differences in technical effects among researchers and individual differences in animals.MethodsA mouse model of sepsis using fecal suspension intraperitoneal injection (FSI) was created using fresh stool excreted within 24 h. The collected fresh stool was dissolved in saline solution and filtered. The obtained fecal suspension was injected intraperitoneally into the mice. Moreover, fecal suspensions with different concentrations were prepared, and the survival rates were compared among the fecal suspensions for each concentration. To assess the validity of the FSI as a sepsis model, CLP and FSI with similar mortality rates were compared pathologically, physiologically, immunologically, and bacteriologically. Histopathological comparison was evaluated by hematoxylin-eosin and Gram staining of the parenchymal organs. Physiological evaluation was performed by comparing the respiratory rate, body temperature, and blood gas analysis results. Immunological assessment was performed using multiplex analysis. Bacteriological comparisons were performed by culturing ascites fluid.ResultsThe FSI model increased mortality in proportion to the fecal suspension concentration. The mortality rate was reduced with antibiotic administration. In various comparative experiments conducted using the FSI and CLP models, both models showed findings consistent with sepsis. Furthermore, the FSI model showed less variability among the individuals in each test.ConclusionThis is the first detailed and accurate report of a protocol for creating a sepsis model using fecal suspension. The FSI model is a minimally invasive and accessible sepsis rodent model. Its clinical validity as a sepsis model was proven via histological, physiological, microbiological, and immunological evaluation methods. The FSI model minimizes individual differences between mice and helps to conduct accurate studies after the onset of sepsis.

Background Supplementation with antithrombin (AT) concentrates is now common in the treatment of congenital and acquired AT deficiency. However, there is no established consensus on the target and timing of supplementation. We aimed to elucidate the effects of AT deficiency on the balance between coagulation activation and inhibition using a thrombin generation assay as in vitro global assay. Methods Samples were prepared by admixing commercially acquired AT-deficient plasma with < 1% AT activity with pooled normal plasma. The AT activity in each sample was adjusted to 100, 90, 70, 50, 40, 30, 10, 5, and < 1%. A thrombin generation assay was performed in each sample. AT concentrate-spiked samples were also prepared by adjusting the AT activities in four types of the concentrates: one recombinant and three plasma-derived AT concentrates. The final targeted AT activities in the samples were adjusted to 100, 50, 30, and 5% by spiking each concentrate into the AT-deficient plasma. We also prepared samples with five levels of prothrombin time (PT) % in coagulation factors with the AT activity fixed at 30% by dilution by mixing AT-deficient plasma and normal plasma with Owren’s veronal buffer to adjust the coagulation factor activities in several proportions. The theoretical target PT% values were 100, 66, 50, 40, and 30%. A thrombin generation assay was performed on all samples. Results The ability to generate thrombin depended on the AT activity, and the amount of thrombin generation was increased as AT was decreased. Additionally, the amount of thrombin generation was changed significantly when AT activity was ≤ 50%, indicating that AT suppressed thrombin generation. In particular, thrombin generation was remarkable when AT activity was < 30%, and it can be assumed that the prognosis is poor due to organ failure from thrombotic tendency. Conclusions The results presented in this basic research were found to be consistent with the clinical findings to date. The mechanism by which 30–50% of AT activity is set as the clinical boundary was elucidated by the thrombin generation assay.

In severe trauma, excessive fibrinolytic activation is associated with an increase in the transfusion volume and mortality rate. However, in the first several hours after a blunt trauma, changes in fibrinolytic activation, suppression, and activation–suppression balance have not yet been elucidated, which the present study aimed to clarify. Anesthetized 9-week-old male Wistar S/T rats experienced severe blunt trauma while being placed inside the Noble–Collip drum. Rats were randomly divided into four groups of seven. The no-trauma group was not exposed to any trauma; the remaining groups were analysed 0, 60, and 180 min after trauma. Immediately following trauma, total tissue-plasminogen activator (tPA) levels significantly increased in the plasma, and the balance of active tPA and active plasminogen activator inhibitor-1 (PAI-1) significantly tipped toward fibrinolytic activation. After trauma, both tPA and PAI-1 levels increased gradually in various organs and active and total PAI-1 levels increased exponentially in the plasma. Total plasma tPA levels 60 min after trauma returned quickly to levels comparable to those in the no-trauma group. In conclusion, fibrinolytic activation was observed only immediately following trauma. Therefore, immediately after trauma, the fibrinolytic system was activated; however, its activation was quickly and intensely suppressed.