Takeyuki Kiguchi

Recombinant human soluble thrombomodulin improves mortality and respiratory dysfunction in patients with severe sepsis.

BACKGROUND: Respiratory dysfunction associated with severe sepsis is a serious condition leading to poor prognosis. Activation of coagulation is a consequence of and contributor to ongoing lung injury in severe sepsis. The purpose of this study was to examine the efficacy of recombinant human soluble thrombomodulin (rhTM), a novel anticoagulant agent, for treating patients with sepsis-induced disseminated intravascular coagulation (DIC) in terms of mortality and respiratory dysfunction. METHODS: This study comprised 86 consecutive patients with sepsis-induced DIC who required ventilator management. The initial 45 patients were treated without rhTM (control group), and the following 41 patients were given rhTM (0.06 mg/kg/d) for 6 days (rhTM group). Patients were followed up for 90 days after study entry. Sequential Organ Failure Assessment (SOFA) score and lung injury score were recorded until 7 days after entry. RESULTS: The baseline characteristic of severity of illness was significantly higher in the rhTM group than in the control group. Nevertheless, 90-day mortality rate in the rhTM group was significantly lower than that in the control group (37% vs. 58%, p = 0.038). There was a significant difference in the serial change of SOFA score from baseline to day 7 between the two groups (p = 0.009). Both the respiratory component of the SOFA score and the lung injury score in the rhTM group were significantly lower compared with the control group (p = 0.034 and p < 0.001, respectively). CONCLUSIONS: rhTM may have a significant beneficial effect on mortality and respiratory dysfunction in patients with sepsis-induced DIC. LEVEL OF EVIDENCE: III, therapeutic study.

Impact on survival of whole-body computed tomography before emergency bleeding control in patients with severe blunt trauma

IntroductionWhole-body computed tomography (CT) has gained importance in the early diagnostic phase of trauma care. However, the diagnostic value of CT for seriously injured patients is not thoroughly clarified. This study assessed whether preoperative CT beneficially affected survival of patients with blunt trauma who required emergency bleeding control.MethodsThis retrospective study was conducted from January 2004 to December 2010 in two tertiary trauma centers in Japan. The primary inclusion criterion was patients with blunt trauma who required emergency bleeding control (surgery or transcatheter arterial embolization). CT before emergency bleeding control was performed at the attending physicians discretion based on individual patient condition (for example, hemodynamic stability or certain abnormalities in the primary survey). We assessed covariates associated with 28-day mortality with multivariate logistic regression analysis and evaluated standardized mortality ratio (SMR, ratio of observed to predicted mortality by Trauma and Injury Severity Score (TRISS) method) in two subgroups of patients who did or did not undergo CT.ResultsThe inclusion criterion was fulfilled by 152 patients with a median Injury Severity Score of 35.3. During the early resuscitation phase, 132 (87%) patients underwent CT and 20 (13%) did not. Severity of injury was significantly higher in the non-CT versus CT group patients. Observed mortality rate was significantly lower in the CT versus non-CT group (18% vs. 80%, P <0.001). Multivariate adjustment for the probability of survival (Ps) by TRISS method confirmed CT as an independent predictor for 28-day mortality (adjusted OR, 7.22; 95% CI, 1.76 to 29.60; P = 0.006). In the subgroup with less severe trauma (TRISS Ps ≥50%), SMR in the CT group was 0.63 (95% CI, 0.23 to 1.03; P = 0.066), indicating no significant difference between observed and predicted mortality in the CT group. In contrast, in the subgroup with more severe trauma (TRISS Ps <50%), SMR was 0.65 (95% CI, 0.41 to 0.90; P = 0.004) only in the CT group, whereas the difference between observed and predicted mortality was not significant in the non-CT group, suggesting a possible beneficial effect of CT on survival only in trauma patients at high risk of death.ConclusionCT performed before emergency bleeding control might be associated with improved survival, especially in severe trauma patients with TRISS Ps of <50%.

Maximal Chemiluminescent Intensity in Response to Lipopolysaccharide Assessed by Endotoxin Activity Assay on Admission Day Predicts Mortality in Patients With Sepsis

Objective:Sepsis is the leading cause of death among critically ill patients. There are, however, few appropriate biomarkers to predict mortality in patients with sepsis. We focused on maximal chemiluminescent intensity in response to lipopolysaccharide assessed by endotoxin activity assay and evaluated the diagnostic value of maximal chemiluminescent intensity on admission day as a predictor of mortality in patients with sepsis. Design:Prospective, observational study. Setting:ICU. Patients:One hundred and thirty-two patients with sepsis. Interventions:None. Measurements and Main Results:Within 12 hours after admission, a whole-blood sample was collected, and variables assessed by endotoxin activity assay were measured in each patient. Severity of illness was assessed simultaneously by Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score. The primary outcome was 28-day mortality. One hundred and fifteen patients survived and 17 died. maximal chemiluminescent intensity values were significantly lower in the nonsurvivors than in the survivors (p <0.05). We investigated maximal chemiluminescent intensity, APACHE II score, and SOFA score as predictors of 28-day mortality. Receiver operating characteristic analysis showed that area under the curve for maximal chemiluminescent intensity was 0.902, which was superior to the area under the curves for APACHE II score (0.836) and SOFA score (0.807). At the optimal cutoff value for maximal chemiluminescent intensity, 21,000 RLU/s, the sensitivity for correct prediction of 28-day mortality was 82.4% and the specificity was 92.2%. Kaplan-Meier analysis showed that low maximal chemiluminescent intensity (<21,000 RLU/s) closely correlated with poor overall patient survival compared with high maximal chemiluminescent intensity (>21,000 RLU/s) (p <0.001 by log-rank test). After adjusting for APACHE II score by Cox regression analysis, maximal chemiluminescent intensity was identified as an independent predictor for the probability of 28-day mortality. Conclusion:Maximal chemiluminescent intensity level measured on admission day appears to have high predictive value for mortality in patients with sepsis.

Design and Evaluation of New Unified Criteria for Disseminated Intravascular Coagulation Based on the Japanese Association for Acute Medicine Criteria

Background: Current disseminated intravascular coagulation (DIC) criteria are insufficient for predicting mortality. Hemostatic endothelial molecular markers are useful for DIC diagnoses. We aimed to design new DIC criteria involving these markers based on the recently published Japanese Association for Acute Medicine (JAAM) DIC criteria, which exhibit higher sensitivity for mortality. Materials and Methods: Patients with severe sepsis or septic shock admitted to a tertiary referral hospital in Japan between September 2009 and November 2011 were included. Clinical data, including hemostatic endothelial molecular markers, were measured within 12 hours after admission. Receiver operating characteristic analyses were conducted for 8 candidate variables to identify the mortality-related markers. Then, we designed new unified criteria based on the JAAM DIC criteria and involving the identified optimal markers. Results: Of the 79 patients, 66 (83.5%) survived and 13 (16.5%) died. Protein C activity correlated best with mortality with a very high prognostic value (area under the curves [AUCs] = 0.850; P < .001), followed by plasminogen activator inhibitor 1 (AUC = 0.828; P < .001). The unified criteria, consisting of the JAAM DIC criteria plus these 2 markers, exhibited greater prognostic value for mortality (sensitivity, 84.6%; specificity, 80.3%). Moreover, DIC-positive patients using the unified criteria had significantly higher disease severity, as indicated by the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. Conclusion: Our unified criteria involving hemostatic endothelial molecular markers reflected not only mortality but also the severity of illness in patients with severe sepsis.

Timing of advanced airway management by emergency medical services personnel following out-of-hospital cardiac arrest: A population-based cohort study

BACKGROUND Early prehospital advanced airway management (AAM) by emergency medical services (EMS) personnel has been intended to improve patient outcomes from out-of-hospital cardiac arrest (OHCA). However, few studies examine the effectiveness of early prehospital AAM. We investigated whether early prehospital AAM was associated with functionally favourable survival after adult OHCA. METHODS We conducted a population-based cohort study of OHCA in Osaka, Japan, between 2005 and 2012. We included all consecutive, non-traumatic adult OHCA in which EMS personnel performed cardiopulmonary resuscitation (CPR) and AAM. Main exposure was time from CPR to AAM. Primary outcome was functionally favourable survival at one-month. As the primary analysis, we estimated adjusted odds ratio (OR) of time from CPR to AAM using multivariable logistic regression in the original cohort. In the secondary analysis, we divided the time from CPR to AAM into early (0-4 min) and late (5-29 min). We calculated propensity scores (PS) for early AAM and performed PS-matching. RESULTS We included 27,471 patients who received prehospital AAM by EMS personnel. In this original cohort, time from CPR to AAM was inversely associated with functionally favourable survival (adjusted OR 0.90 for one-increment of minute, 95% confidence interval [CI] 0.87-0.94). In the PS-matched cohort of 17,022 patients, early AAM, compared to late AAM, was associated with functionally favourable survival: 2.2% vs 1.4%; adjusted OR 1.58 (95% CI 1.24-2.02). CONCLUSIONS Earlier prehospital AAM by EMS personnel was associated with functionally better survival among adult patients who received AAM.

Effect of Serum Albumin Concentration on Neurological Outcome After Out-of-Hospital Cardiac Arrest (from the CRITICAL [Comprehensive Registry of Intensive Cares for OHCA Survival] Study in Osaka, Japan)

The aim of this study was to assess whether serum albumin concentration upon hospital arrival had prognostic indications on out-of-hospital cardiac arrest (OHCA). This prospective, multicenter observational study conducted in Osaka, Japan (the CRITICAL [Comprehensive Registry of Intensive Cares for OHCA Survival] study), enrolled all patients with consecutive OHCA transported to 14 participating institutions. We included adult patients aged ≥18 years with nontraumatic OHCA who achieved return of spontaneous circulation and whose serum albumin concentration was available from July 2012 to December 2014. Based on the serum albumin concentration upon hospital arrival, patients were divided into quartiles (Q1 to Q4), namely, Q1 (<2.7 g/dl), Q2 (2.7 to 3.1 g/dl), Q3 (3.1 to 3.6 g/dl), and Q4 (≥3.6 g/dl). The primary outcome was 1-month survival with favorable neurological outcome (cerebral performance category scale 1 or 2). During the study period, a total of 1,269 patients with OHCA were eligible for our analyses. The highest proportion of favorable neurological outcome was 33.5% (109 of 325) in the Q4 group, followed by 13.2% (48 of 365), 5.0% (13 of 261), and 3.5% (11 of 318) in the Q3, Q2, and Q1 groups, respectively. In the multivariable logistic regression analysis, the proportion of favorable neurological outcome in the Q4 group was significantly higher, compared with that in the Q1 group (adjusted odds ratio 8.61; 95% confidence interval 4.28 to 17.33). The adjusted proportion of favorable neurological outcome increased in a stepwise manner across increasing quartiles (p for trend <0.001). Higher serum albumin concentration was significantly and independently associated with favorable neurological outcome in a dose-dependent manner.

Out-of-hospital cardiac arrests during exercise among urban inhabitants in Japan: Insights from a population-based registry of Osaka City

BACKGROUND The patient characteristics, pre-hospital interventions, and outcomes of out-of-hospital cardiac arrests (OHCA) occurring during exercise, have not been sufficiently investigated among the general population. METHODS OHCA data from 2009 to 2015 were obtained from the population-based OHCA registry in Osaka City, Japan. Patients who suffered OHCA, which occurred during exercise before the arrival of emergency medical service personnel, were included. The primary endpoint was one-month survival with a favourable neurological outcome after OHCA, defined using the Glasgow-Pittsburgh cerebral performance category scale 1 or 2. RESULTS During the 7-year study period, 16,278 OHCAs were observed, and 52 (0.3%) occurred during exercise (male, n=41 [79%]; median age, 62 years). These incidents occurred mainly during running activities (n=14), followed by swimming (n=8), dance/social dance (n=6), tennis (n=4), and weight training (n=3). Within these exercise-related OHCAs, 47 (90%) were of cardiac origin, 45 (87%) were bystander-witnessed cardiac arrests, 49 (94%) received bystander-initiated cardiopulmonary resuscitation, and 30 (57%) received public-access defibrillation (PAD). Overall, 56% (29/52) had one-month survival with a favourable neurological outcome after OHCA, which was significantly higher among OHCAs of cardiac origin with PAD (77%, 23/30) than among those of cardiac origin without PAD (35%, 6/17) and among those of non-cardiac origin (0%, 0/5) (p<0.001). CONCLUSION In Osaka, OHCAs during exercise represented a small subset of the overall OHCA burden, but occurred during a wide variety of exercise activities. Patients with OHCA of cardiac origin had a good prognosis, and PAD played an important role in improving patient outcomes.

The possibility of the treatment for long-acting injectable antipsychotics induced severe side effects

We present the case of a 47-year-old man with schizophrenia who developed acute and persistent circulatory failure after receiving injections of paliperidone palmitate. We measured blood concentrations of paliperidone and performed resection of hip tissues, where paliperidone palmitate was suspected to be present, in order to reduce the side effects. Unfortunately, the resection could not save the patient from prolonged and severe side effects and he died of multiple organ failure. We suggest that resection of the tissues suspected of containing paliperidone palmitate can help reduce its severe side effects. However, identifying the site of injection is essential.

High-rise buildings and neurologically favorable outcome after out-of-hospital cardiac arrest.

BACKGROUND The number of people living in high-rise buildings has recently been increasing in Japan, and delayed transport time by emergency-medical-service (EMS) personnel from higher floors could lead to lower survival after out-of-hospital cardiac arrest (OHCA). However, there are no clinical studies assessing the association between the floor where patients reside and neurologically favorable outcome after OHCA. METHODS This was a prospective, population-based study conducted in Osaka City, Japan that enrolled adults aged >=18years suffering an OHCA of cardiac origin before EMS arrival between 2013 and 2014. The primary outcome measure was one-month survival with neurologically favorable outcome. We divided OHCA patients into the following groups: those residing on >=3 floors (the high floor group) and <3 floors (the low floor group). Multiple logistic regression analysis was used to assess factors associated with neurologically favorable outcome. RESULTS A total of 2979 patients were eligible for analysis. Of them, 1885 (62.3%) occurred below the third floor and 1094 (37.4%) occurred at or above the third floor. The proportion of neurologically favorable outcome after OHCA was significantly lower in the high floor group than in the low floor group (2.7% [30/1094] versus 4.8% [91/1885], P=0.005). In a multivariate analysis, neurologically favorable outcome after OHCA was significantly lower in the high floor group than in the low floor group (adjusted odds ratio, 0.59 [95% confidence interval, 0.37-0.96]). CONCLUSIONS In this population, one-month survival with neurologically favorable outcome from OHCA was lower in the high floor group than in the low floor group.

Exercise‐Related Out‐of‐Hospital Cardiac Arrest Among the General Population in the Era of Public‐Access Defibrillation: A Population‐Based Observation in Japan

Background Exercise can trigger sudden cardiac arrest. Early initiation of cardiopulmonary resuscitation and automated external defibrillator use by laypersons could maximize the survival rate following exercise‐related out‐of‐hospital cardiac arrest (OHCA). Methods and Results OHCA data between 2005 and 2012 were obtained from a prospective population‐based OHCA registry in Osaka Prefecture. Patients with OHCA of presumed cardiac origin and occurring before emergency medical service personnel arrival were included. The incidence trends of exercise‐related OHCA over the 8‐year study period were assessed. Among patients with bystander‐witnessed, exercise‐related OHCA, the trends in the initiation of bystander cardiopulmonary resuscitation, public‐access defibrillation, and outcome were evaluated. The primary outcome was 1‐month survival with favorable neurological outcome, defined as cerebral performance category 1 or 2. During the study period, 0.7% of OHCAs of cardiac origin (222/31 030) were exercise related. The incidence of exercise‐related OHCA increased from 1.8 (per million population per year) in 2005 to 4.3 in 2012. Of these, 83.8% (186/222) were witnessed by bystanders. Among the patients with bystander‐witnessed, exercise‐related OHCA, the proportion that received bystander cardiopulmonary resuscitation (50.0% in 2005 and 86.2% in 2012) and public‐access defibrillation (7.1% in 2005 and 62.1% in 2012) significantly increased during the study period. Furthermore, the rate of 1‐month survival with favorable neurological outcome among these patients significantly improved (from 28.6% in 2005 to 58.6% in 2012). Conclusions The incidence rate of exercise‐related OHCA was low in the study population. The increase in bystander cardiopulmonary resuscitation and public‐access defibrillation rates were associated with improved outcome among patients with bystander‐witnessed, exercise‐related OHCA.