Kenichi Katabami

Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality

INTRODUCTION Disseminated intravascular coagulation (DIC) with an antifibrinolytic phenotype is characterized by microvascular thrombosis leading to poor outcome at the late-stage of trauma. To test the hypothesis that DIC with a fibrinolytic phenotype at an early stage of trauma also contributes to a poor outcome due to severe bleeding, we conducted a retrospective, cohort study. MATERIALS AND METHODS The subjects included 314 consecutive severe trauma patients. A systematic review of medical records of the patients was conducted to provide the base line characteristics and DIC-related variables. The data of these variables were obtained at 4 time points within 24 hr after arrival to the emergency department (ED); Time Point 1, immediately after arrival to the ED to 4 hr after arrival; Time Point 2, 4 to 8 hr after arrival; Time Point 3, 8 to 16 hr after arrival; Time Point 4, 16 to 24 hr after arrival. RESULTS Nonsurvivors (87.3%, 48/55) met the Japanese Association for Acute Medicine (JAAM) DIC criteria showing lower fibrinogen levels, a prolonged prothrombin time, and higher fibrin/fibrinogen degradation products (FDP) and D-dimer levels in comparison to those of the 289 survivors. The FDP/D-dimer ratio and lactate level were significantly higher in the nonsurvivors than those of the survivors. Lower fibrinogen levels and higher FDP/D-dimer ratio suggest fibrinogenolysis in DIC of the nonsurvivors. Furthermore a stepwise logistic regression analysis showed that the JAAM DIC score, levels of fibrinogen, FDP and lactate at Time Point 1 are independent predictors of death. Low levels of fibrinogen and high FDP but not D-dimer predict massive bleeding at an early stage of trauma. The optimal cutoff points for the prediction of death and massive bleeding were fibrinogen (1.90, 1.90 g/L) and FDP (35.2, 68.7 mg/L), respectively. CONCLUSIONS DIC with a fibrinolytic phenotype modified through fibrinogenolysis at an early phase of trauma contributes to poor prognosis due to massive bleeding. Tissue hypoperfusion may be involved in the pathogenesis of this type of DIC.

Sivelestat (Selective Neutrophil Elastase Inhibitor) Improves the Mortality Rate of Sepsis Associated With Both Acute Respiratory Distress Syndrome and Disseminated Intravascular Coagulation Patients

Neutrophil elastase plays an important role in the development of acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) in sepsis. Sivelestat is a selective neutrophil elastase inhibitor. It is possible that sivelestat improves the outcome of septic patients associated with ARDS and DIC. A retrospective data analysis of septic patients associated with ARDS and DIC was conducted to investigate the effects of sivelestat. Observational period was 5 days after admission to intensive care unit (ICU). The study included 167 septic patients associated with ARDS and DIC. Control group included 133 patients without sivelestat, and sivelestat group included 34 patients started to deadministered sivelestat on the admission to ICU. The lung injury scores and PaO2/FiO2 ratio of the sivelestat group were significantly more severe than those of the control group from days 1 to 4. On day 5, the lung injury score and PaO2/FiO2 ratio of the sivelestat group improved to the same levels of those of the control group. The DIC score of sivelestat group improved on day 3 in comparison to day 1, and those of control group remained unchanged until day 4. The length of ICU stay of the sivelestat group was significantly shorter than that of the control group. A stepwise multiple logistic-regression analysis showed the sivelestat administration to be an independent predictor of survival of the septic patients associated with both ARDS and DIC. The length of ICU stay of the sivelestat group was significantly shorter than that of the control group. In addition, sivelestat administration was found to be an independent predictor of survival of those patients.

Application of the Japanese Association for Acute Medicine disseminated intravascular coagulation diagnostic criteria for patients at an early phase of trauma

INTRODUCTION To validate the diagnostic criteria for disseminated intravascular coagulation (DIC) established by the Japanese Association for Acute Medicine (JAAM) at an early stage of trauma and to evaluate the hypothesis that the JAAM criteria can diagnose DIC with a higher sensitivity than the International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria. MATERIALS AND METHODS Based on a review of medical records, the data of 314 trauma patients were retrospectively obtained at 4 time points within 24 hr after arrival to the Emergency Department. RESULTS One hundred and forty-one JAAM DIC patients (44.9%) showed differences in the prevalence of massive bleeding and multiple organ dysfunction syndrome (MODS), and the outcome in comparison to the non-DIC patients. A stepwise logistic regression analysis showed that the maximum JAAM DIC scores independently predicted the patient death. All of the patients who developed ISTH overt DIC could be identified by the JAAM DIC criteria at early time points. The mortality rate and the incidence of massive bleeding and MODS of the patients with the ISTH overt DIC were higher than those only met the JAAM DIC criteria. Stepwise increases in the ISTH overt DIC scores and the incidence of the overt DIC were observed in accordance with the increases in the JAAM DIC scores. While the mortality rates were identical, there were marked differences in the incidence of MODS and Sequential Organ Failure Assessment scores between the DIC patients associated with trauma and sepsis. CONCLUSIONS The results show that the JAAM scoring system has acceptable validity for the DIC diagnosis at an early phase of trauma, and also that the scoring system can diagnose DIC with a higher sensitivity than the criteria of the ISTH overt DIC. Bleeding as well as MODS may affect the prognosis of the patients associated with DIC.

Invasive group A streptococcal infection in pregnancy

We conducted a literature review of 55 pregnancies with symptomatic Group A streptococcus (Streptococcus pyogenes) infection reported in English (20 cases), French (2 cases) and Japanese (33 cases) to seek ways of improving prognosis. Multiparous women (83% [39/47]) in the third trimester (90% [47/52]) were prone to infection from winter to spring (75% [21/28]). Onset was heralded by flu-like symptoms, such as high fever (94% [46/49]), with upper respiratory (40% [22/55]) and/or gastrointestinal symptoms (49% [27/55]). Characteristic findings were early onset of shock (91% [50/55]) and infection-induced strong uterine contraction (73% [40/55]) suggestive of placental abruption. The clinical course was too acute and severe to rescue the mother (58% [32/55] died) and/or infant (66% [39/59] died). However, outcome has improved over the last decade, with rescue of 68% (15/22) of the mothers since 2000, and early use of antibiotics (71% [22/31] survived) and use of intravenous immunoglobulin (91% [10/11] survived) were associated with favourable outcome. Early use of antibiotics and intravenous immunoglobulin may improve outcome of pregnant women suffering from flu-like symptoms, shock and strong uterine contractions suggestive of placental abruption.

Fibrin/fibrinogen degradation products (FDP) at hospital admission predict neurological outcomes in out-of-hospital cardiac arrest patients☆

OBJECTIVE This study aimed to test the hypothesis that coagulation, fibrinolytic markers and disseminated intravascular coagulation (DIC) score (International Society on Thrombosis and Haemostasis) at hospital admission of out-of-hospital cardiac arrest (OHCA) patients can predict neurological outcomes 1 month after cardiac arrest. METHODS In this retrospective, observational analysis, data were collected from the Sapporo Utstein Registry and medical records at Hokkaido University Hospital. We included patients who experienced OHCA with successful return of spontaneous circulation (ROSC) between 2006 and 2012 and were transferred to Hokkaido University Hospital. From medical records, we collected information about the following coagulation and fibrinolytic factors at hospital admission: platelet count; prothrombin time; activated partial thromboplastin time; plasma levels of fibrinogen, D-dimer, fibrin/fibrinogen degradation products (FDP), and antithrombin; and calculated DIC score. Favorable neurological outcomes were defined as a cerebral performance category 1-2. RESULTS We analyzed data for 315 patients. Except for fibrinogen level, all coagulation variables, fibrinolytic variables, and DIC score were associated with favorable neurological outcomes. In the receiver operating characteristic curve analysis, FDP level had the largest area under the curve (AUC; 0.795). In addition, the AUC of FDP level was larger than that of lactate level. CONCLUSIONS All of the coagulation and fibrinolytic markers, except for fibrinogen level, and DIC score at hospital admission, were associated with favorable neurological outcomes. Of all of the variables, FDP level was most closely associated with favorable neurological outcomes in OHCA patients who successfully achieved ROSC.

The response time threshold for predicting favourable neurological outcomes in patients with bystander-witnessed out-of-hospital cardiac arrest

OBJECTIVE It is well established that the period of time between a call being made to emergency medical services (EMS) and the time at which the EMS arrive at the scene (i.e. the response time) affects survival outcomes in patients who experience out-of-hospital cardiac arrest (OHCA). However, the relationship between the response time and favourable neurological outcomes remains unclear. We therefore aimed to determine a response time threshold in patients with bystander-witnessed OHCA that is associated with positive neurological outcomes and to assess the relationship between the response time and neurological outcomes in patients with OHCA. METHODS This study was a retrospective, observational analysis of data from 204,277 episodes of bystander-witnessed OHCA between 2006 and 2012 in Japan. We used classification and regression trees (CARTs) and receiver operating characteristic (ROC) curve analyses to determine the threshold of response time associated with favourable neurological outcomes (Cerebral Performance Category 1 or 2) 1 month after cardiac arrest. RESULTS Both CARTs and ROC analyses indicated that a threshold of 6.5min was associated with improved neurological outcomes in all bystander-witnessed OHCA events of cardiac origin. Furthermore, bystander cardiopulmonary resuscitation (CPR) prolonged the threshold of response time by 1min (up to 7.5min). The adjusted odds ratio for favourable neurological outcomes in patients with OHCA who received care within ≤6.5min was 1.935 (95% confidential interval: 1.834-2.041, P<0.001). CONCLUSIONS A response time of ≤6.5min was closely associated with favourable neurological outcomes in all bystander-witnessed patients with OHCA. Bystander CPR prolonged the response time threshold by 1min.

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.

Improved detection of heat stroke-induced brain injury by high b-value diffusion-weighted imaging.

We report a case of heat stroke in which detection of brain injury was improved by high b-value diffusion-weighted imaging (DWI). High b-value DWI revealed moderate to marked hyperintensity at/around bilateral dentate nuclei and part of thalami. Apparent diffusion coefficient maps revealed apparent diffusion coefficient decrease of the dentate lesions. Routine DWI showed only mild hyperintensity of part of dentate lesions. High b-value DWI could be valuable for improved detection of heat stroke-induced brain injury.

Severe methemoglobinemia due to sodium nitrite poisoning

Case. We report a case of severe methemoglobinemia due to sodium nitrite poisoning. A 28-year-old man was brought to our emergency department because of transient loss of consciousness and cyanosis. He was immediately intubated and ventilated with 100% oxygen. A blood test revealed a methemoglobin level of 92.5%. Outcome. We treated the patient with gastric lavage, activated charcoal, and methylene blue (2 mg/kg) administered intravenously. Soon after receiving methylene blue, his cyanosis resolved and the methemoglobin level began to decrease. After relocation to the intensive care unit, his consciousness improved and he could recall ingesting approximately 15 g sodium nitrite about 1 hour before he was brought to our hospital. The patient was discharged on day 7 without neurologic impairment. Conclusion. Severe methemoglobinemia may be fatal. Therefore, accurate diagnosis of methemoglobinemia is very important so that treatment can be started as soon as possible.

Should laryngeal tubes or masks be used for out-of-hospital cardiac arrest patients?

OBJECTIVE Few studies have compared airway management via laryngeal masks (LM) or laryngeal tubes (LT) in patients with out-of-hospital cardiac arrest (OHCA). This study evaluated whether LT insertion by emergency medical service (EMS) personnel affected ventilation and outcomes in OHCA patients (vs. the standard LM treatment). METHODS This prospective, cluster-randomized, and open-label study evaluated data that were collected by the Sapporo Fire Department between June 2012 and January 2013. We selected the 14 EMS teams that treated the greatest number of OHCA patients in Sapporo, Japan during 2011, and randomized the teams into Groups A and B. In the first study period (June 2012 to September 2012), Group A treated OHCA patients via LT and Group B treated OHCA patients via LM. In the second period (October 2012 to January 2013), Group A treated OHCA patients via LM and Group B treated OHCA patients via LT. If necessary, both groups were allowed to use an esophageal obturator airway (EOA) kit. The primary endpoints were time from cardiopulmonary resuscitation to device insertion and the rate of successful pre-hospital ventilation. The secondary endpoints were return of spontaneous circulation and survival and favorable neurological outcomes at 1 month after cardiac arrest. RESULTS LT was used in 148 OHCA patients and LM was used in 165 OHCA patients. Our intention-to-treat analyses revealed no significant differences in the primary and secondary outcomes of the LT- and LM-treated groups. CONCLUSION Prehospital advanced airway management via LT provides similar outcomes to those of LM in OHCA patients.