ABCD approach at the #7119 center, telephone triage system in Tokyo, Japan; a retrospective cohort study.

BACKGROUND: The algorithm and protocol of the #7119 telephone triage in Tokyo, Japan, had been originally established and consists of three steps. In this study, we investigated the outcome of patients treated with physiological abnormality (ABCD approach: A, airway; B, breathing; C, circulation, and D, dysfunction of central nervous system) in step 2 during the #7119 telephone triage and clarified the meaning of evaluation of this approach. METHODS: We retrospectively reviewed data from the Tokyo Fire Department from January 2016 to December 2017. Almost all the patients triaged using the ABCD approach were transferred to the hospital by ambulance and assigned severity by a physician. We divided patients into groups with combinations of 15 patterns including A, B, C, D, AB, AC, AD, BC, BD, CD, ABC, ABD, ACD, BCD, and ABCD. We compared the proportion of severe cases in each group using a Fisher's exact test, followed by residual analysis. RESULTS: We analyzed 13,793 cases triaged using the ABCD approach. In this analysis, 31% of total cases were assessed as severe cases. Groupwise analysis showed that the proportion of severe cases was significantly higher in the AD, BC, CD, ABD, and ABCD groups, while it was significantly less in the C and AB groups than in the total cases. CONCLUSION: At the #7119 telephone triage, we can pick up the severe cases by the ABCD approach. This may contribute to the prompt transportation of severe patients to hospitals by dispatching ambulance cars using the #7119 telephone triage methods.

A simulation study of high-flow versus normal-flow three-way stopcock for rapid fluid administration in emergency situations: A randomised crossover design.

BACKGROUND: Initial fluid resuscitation is presumed to be important for treating shock in the resuscitation phase. However, little is known how quickly and easily a physician could perform a rapid infusion with a syringe. OBJECTIVES: We hypothesised that using a high-flow three-way stopcock (HTS) makes initial fluid resuscitation faster and easier than using a normal-flow three-way stopcock (NTS). METHODS: This was a simulation study with a prospective, nonblinded randomised crossover design. Twenty physicians were randomly assigned into two groups. Each participant used six peripheral intravenous infusion circuits, three with the HTS and the others with the NTS, and three cannulae, 22, 20, and 18 gauge (G). The first group started with the HTS first, while the other started with the NTS first. They were asked to inject the fluid as quick as possible. We compared the time until the participants finished rapid infusions of 500 ml of 0.9% saline and the practitioner's effort. RESULTS: In infusion circuits attached with the 22G cannula, the mean difference using the HTS and the NTS (95% confidence interval [CI]) was 16.30 ml/min (7.65-24.94) (p < 0.01). In those attached with the 20G cannula, the mean difference (95% CI) was 23.47 (12.43-34.51) (p < 0.01). In those attached with the 18G cannula, the mean difference (95% CI) was 42.53 (28.68-56.38) (p < 0.01). CONCLUSIONS: This study revealed that the push-and-pull technique using the HTS was faster, easier, and less tiresome than using the NTS, with a statistically significant difference. In the resuscitation phase, initial and faster infusion is important. If only a single physician or other staff member such as a nurse is attending or does not have accessibility to any other devices in such an environment where medical resources are scarce, performing the push-and-pull technique using the HTS could help a physician to perform fluid resuscitation faster. By setting up the HTS instead of the NTS from the beginning, we would be able to begin fluid resuscitation immediately while preparing other devices.

Evaluation of Autonomous Actions on Bystander-Initiated Cardiopulmonary Resuscitation and Public Access Defibrillation in Tokyo.

The frequencies of autonomous bystander-initiated cardiopulmonary resuscitation (CPR) and public access defibrillation have not yet been clarified. We aimed to evaluate the frequency of autonomous actions by citizens not having a duty to act.This retrospective observational study included patients who suffered an out-of-hospital cardiac arrest (OHCA) in Tokyo between January 1, 2013 and December 31, 2017. The Delphi method with a panel of 11 experts classified the locations of OHCA resuscitations into 3 categories as follows; autonomous, non autonomous, and undetermined. The locations determined as autonomous were further divided into 2 groups; home and other locations. Bystander-initiated CPR and application of an automated external defibrillator (AED) pad were evaluated in 43,460 patients with OHCA.Group A (non autonomous), group B (autonomous, not home), and group C (home), consisted of 7,352, 3,193, and 32,915 patients, respectively. Compared with group A, group B and group C had significantly lower rates of bystander-initiated CPR (group A, B, C; 68.3% versus 38.6% versus 23.9%) and AED pad application (groups A, B, C; 26.8% versus 15.1% versus 0.6%). In addition, multivariate analysis demonstrated that an autonomous location of resuscitation was independently associated with the frequencies of bystander-initiated CPR and AED pad application, even after adjusting for age, sex, and witness status.Autonomous actions by citizens were unacceptably infrequent. Therefore, the education and training of citizens is necessary to further enhance autonomous CPR.

Pulse oximetry-based capillary refilling evaluation predicts postoperative outcomes in liver transplantation: a prospective observational cohort study.

BACKGROUND: Capillary refill time (CRT) is a non-invasive technique to evaluate tissue perfusion, and quantitative CRT (Q-CRT) adapted to pulse oximetry was developed with patients with sepsis and compared to blood lactate and sepsis scores. In post liver transplantation, large amounts of fluid administration are necessary for maintaining tissue perfusion to grafted liver against intravascular hypovolemia. This study aimed to evaluate whether Q-CRT can predict poor outcomes by detecting peripheral tissue perfusion abnormality in patients with liver transplantations who were treated with massive fluid administration. METHODS: In this single-center prospective cohort study, we enrolled adult patients with liver transplantations between June 2018 and July 2019. Measurement of Q-CRT was conducted at intensive care units (ICU) admission and postoperative day 1 (POD1). RESULTS: A total of 33 patients with liver transplantations were enrolled. Significant correlations of Q-CRT and ΔAb, a tissue oxygen delivery parameter calculated by pulse oximetry data, at ICU admission with the postoperative outcomes such as length of ICU and hospital stay and total amount of ascitic fluid discharge were observed. Quantitative CRT and ΔAb at ICU admission were significantly associated with these postoperative outcomes, even after adjusting preoperative and operative factors (MELD score and bleeding volume, respectively). However, quantitative CRT and ΔAb at POD1 and changes from ICU admission to POD1 failed to show significant associations. CONCLUSIONS: Q-CRT values were significantly associated with postoperative outcomes in liver transplantation. Although the mechanisms of this association need to be clarified further, Q-CRT may enable identification of high-risk patients that need intensive postoperative managements.

Validation of age-specific survival prediction in pediatric patients with blunt trauma using trauma and injury severity score methodology: a ten-year Nationwide observational study.

BACKGROUND: In-hospital mortality in trauma patients has decreased recently owing to improved trauma injury prevention systems. However, no study has evaluated the validity of the Trauma and Injury Severity Score (TRISS) in pediatric patients by a detailed classification of patients' age and injury severity in Japan. This retrospective nationwide study evaluated the validity of TRISS in predicting survival in Japanese pediatric patients with blunt trauma by age and injury severity. METHODS: Data were obtained from the Japan Trauma Data Bank during 2009-2018. The outcomes were as follows: (1) patients' characteristics and mortality by age groups (neonates/infants aged 0 years, preschool children aged 1-5 years, schoolchildren aged 6-11 years, and adolescents aged 12-18 years), (2) validity of survival probability (Ps) assessed using the TRISS methodology by the four age groups and six Ps-interval groups (0.00-0.25, 0.26-0.50, 0.51-0.75, 0.76-0.90, 0.91-0.95, and 0.96-1.00), and (3) the observed/expected survivor ratio by age- and Ps-interval groups. The validity of TRISS was evaluated by the predictive ability of the TRISS method using the receiver operating characteristic (ROC) curves that present the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, area under the receiver operator characteristic curve (AUC) of TRISS. RESULTS: In all the age categories considered, the AUC for TRISS demonstrated high performance (0.935, 0.981, 0.979, and 0.977). The AUC for TRISS was 0.865, 0.585, 0.614, 0.585, 0.591, and 0.600 in Ps-interval groups (0.96-1.00), (0.91-0.95), (0.76. - 0.90), (0.51-0.75), (0.26-0.50), and (0.00-0.25), respectively. In all the age categories considered, the observed survivors among patients with Ps interval (0.00-0.25) were 1.5 times or more than the expected survivors calculated using the TRISS method. CONCLUSIONS: The TRISS methodology appears to predict survival accurately in Japanese pediatric patients with blunt trauma; however, there were several problems in adopting the TRISS methodology for younger blunt trauma patients with higher injury severity. In the next step, it may be necessary to develop a simple, high-quality prediction model that is more suitable for pediatric trauma patients than the current TRISS model.

Recombinant Thrombomodulin on Neutrophil Extracellular Traps in Murine Intestinal Ischemia-Reperfusion.

BACKGROUND: In multiple-organ dysfunction, an injury affecting one organ remotely impacts others, and the injured organs synergistically worsen outcomes. Recently, several mediators, including extracellular histones and neutrophil extracellular traps, were identified as contributors to distant organ damage. This study aimed to elucidate whether these mediators play a crucial role in remote organ damage induced by intestinal ischemia-reperfusion. This study also aimed to evaluate the protective effects of recombinant thrombomodulin, which has been reported to neutralize extracellular histones, on multiple-organ dysfunction after intestinal ischemia-reperfusion. METHODS: Intestinal ischemia was induced in male C57BL/6J mice via clamping of the superior mesenteric artery. Recombinant thrombomodulin (10 mg/kg) was administered intraperitoneally with the initiation of reperfusion. The mice were subjected to a survival analysis, histologic injury scoring, quantitative polymerase chain reaction analysis of tumor necrosis factor-α and keratinocyte-derived chemokine expression, Evans blue dye vascular permeability assay, and enzyme-linked immunosorbent assay analysis of histones in the jejunum, liver, lung, and kidney after 30- or 45-min ischemia. Neutrophil extracellular trap formation was evaluated by immunofluorescence staining. RESULTS: Recombinant thrombomodulin yielded statistically significant improvements in survival after 45-min ischemia (ischemia-reperfusion without vs. with 10 mg/kg recombinant thrombomodulin: 0% vs. 33%, n = 21 per group, P = 0.001). Recombinant thrombomodulin reduced the histologic injury score, expression of tumor necrosis factor-α and keratinocyte-derived chemokine, and extravasation of Evans blue dye, which were augmented by 30-min ischemia-reperfusion, in the liver, but not in the intestine. Accumulated histones and neutrophil extracellular traps were found in the livers and intestines of 30-min ischemia-reperfusion-injured mice. Recombinant thrombomodulin reduced these accumulations only in the liver. CONCLUSIONS: Recombinant thrombomodulin improved the survival of male mice with intestinal ischemia-reperfusion injury. These findings suggest that histone and neutrophil extracellular trap accumulation exacerbate remote liver injury after intestinal ischemia-reperfusion. Recombinant thrombomodulin may suppress these accumulations and attenuate liver injury.

Patients With Refractory Out-of-Cardiac Arrest and Sustained Ventricular Fibrillation as Candidates for Extracorporeal Cardiopulmonary Resuscitation　- Prospective Multi-Center Observational Study.

BACKGROUND: We investigated whether patients with out-of-hospital cardiac arrest (OHCA) and sustained ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT) or conversion to pulseless electrical activity/asystole (PEA/asystole) benefit more from extracorporeal cardiopulmonary resuscitation (ECPR). Methods and Results: We analyzed data from the Study of Advanced Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan, which was a prospective, multicenter, observational study with 22 institutions in the ECPR group and 17 institutions in the conventional CPR (CCPR) group. Patients were divided into 4 groups by cardiac rhythm and CPR group. The primary endpoint was favorable neurological outcome, defined as Cerebral Performance Category 1 or 2 at 6 months. A total of 407 patients had refractory OHCA with VF/pVT on initial electrocardiogram. The proportion of ECPR patients with favorable neurological outcome was significantly higher in the sustained VF/pVT group than in the conversion to PEA/asystole group (20%, 25/126 vs. 3%, 4/122, P<0.001). Stratifying by cardiac rhythm, on multivariable mixed logistic regression analysis an ECPR strategy significantly increased the proportion of patients with favorable neurological outcome at 6 months in the patients with sustained VF/pVT (OR, 7.35; 95% CI: 1.58-34.09), but these associations were not observed in patients with conversion to PEA/asystole. CONCLUSIONS: OHCA patients with sustained VF/pVT may be the most promising ECPR candidates (UMIN000001403).

Organ system network analysis and biological stability in critically ill patients.

BACKGROUND: Continuous coordination among organ systems is necessary to maintain biological stability in humans. Organ system network analysis in addition to organ-oriented medicine is expected to improve patient outcomes. However, organ system networks remain beyond clinical application with little evidence for their importance on homeostatic mechanisms. This proof-of-concept study examined the impact of organ system networks on systemic stability in severely ill patients. METHODS: Patients admitted to the intensive care unit of the University of Tokyo Hospital with one representative variable reflecting the condition of each of the respiratory, cardiovascular, renal, hepatic, coagulation, and inflammatory systems were enrolled. Relationships among the condition of individual organ systems, inter-organ connections, and systemic stability were evaluated between non-survivors and survivors whose organ system conditions were matched to those of the non-survivors (matched survivors) as well as between non-survivors and all survivors. We clustered these six organ systems using principal component analysis and compared the dispersion of the principal component scores of each cluster using the Ansari-Bradley test to evaluate systemic stability involving multiple organ systems. Inter-organ connections were evaluated using Spearman's rank test. RESULTS: Among a total of 570 enrolled patients, 91 patients died. The principal component analysis yielded the respiratory-renal-inflammatory and cardiovascular-hepatic-coagulation system clusters. In the respiratory-renal-inflammatory cluster, organ systems were connected in both the survivors and the non-survivors. The principal component scores of the respiratory-renal-inflammatory cluster were dispersed similarly (stable cluster) in the non-survivors, the matched survivors, and the total survivors irrespective of the severity of individual organ system dysfunction. Conversely, in the cardiovascular-hepatic-coagulation cluster, organ systems were connected only in the survivors, and the principal component scores of the cluster were significantly dispersed (unstable cluster) in the non-survivors compared to the total survivors (P = 0.002) and the matched survivors (P = 0.004). CONCLUSIONS: This study demonstrated that systemic instability was closely associated with network disruption among organ systems irrespective of their dysfunction severity. Organ system network analysis is necessary to improve outcomes in severely ill patients.

Kinetic estimated glomerular filtration rate as a predictor of successful continuous renal replacement therapy discontinuation.

AIM: No standardized criteria for continuous renal replacement therapy (CRRT) discontinuation have been established. Kinetic estimated glomerular filtration rate (eGFR) is a newly developed estimation method based on dynamic changes of serum creatinine expected to reflect the true GFR. This study aimed to evaluate the predictive role of kinetic eGFR for CRRT discontinuation. METHODS: A retrospective single-centre cohort study was conducted. Acute kidney injury (AKI) patients who received CRRT between May 2015 and April 2016 were enrolled. Successful CRRT discontinuation was defined as neither resuming CRRT for the next 48 h nor receiving intermittent haemodialysis 7 days from the CRRT discontinuation. Clinical factors associated with CRRT discontinuation were evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Of 52 AKI patients treated with CRRT, 38 could discontinue CRRT while 14 could not. Urine volume, regular and kinetic eGFR of days 0 (day of CRRT discontinuation) and 1 were all good predictive parameters (area under the ROC curve (AUC) > 0.7). Kinetic eGFR of day 1 showed the AUC of 0.87 [95% confidence interval 0.73-0.94]). Combining kinetic eGFR of day 1 and urine volume of day 0 gave a high AUC of 0.93 [95% confidence interval 0.82-0.97]. The combination was significantly greater than urine volume of day 0 (P = 0.008). CONCLUSION: Kinetic eGFR combined with urine volume was a better predictor for CRRT discontinuation. Evaluation of kinetic eGFR utility in other clinical settings will be necessary.

Association of the time to first epinephrine administration and outcomes in out-of-hospital cardiac arrest: SOS-KANTO 2012 study.

OBJECTIVE: This study assessed the association between the timing of first epinephrine administration (EA) and the neurological outcomes following out-of-hospital cardiac arrests (OHCAs) with both initial shockable and non-shockable rhythms. METHODS: This was a post-hoc analysis of a multicenter prospective cohort study (SOS-KANTO 2012), which registered OHCA patients in the Kanto region of Japan from January 2012 to March 2013. We included consecutive adult OHCA patients who received epinephrine. The primary result included 1-month favorable neurological outcomes defined as cerebral performance category (CPC) 1 or 2. Secondary results included 1-month survival and return of spontaneous circulation (ROSC) after arrival at the hospital. Multivariable logistic regression analysis determined the association between delay per minute of the time from call to first EA in both pre- or in-hospital settings and outcomes. RESULTS: Of the 16,452 patients, 9344 were eligible for our analyses. In univariable analysis, the delay in EA was associated with decreased favorable neurological outcomes only when the initial rhythm was a non-shockable rhythm. In multivariable analyses, delay in EA was associated with decreased ROSC (adjusted odds ratio [OR] for one minute delay, 0.97; 95% confidence interval [CI], 0.96-0.98) and 1-month survival (adjusted OR, 0.95; 95% CI, 0.92-0.97) when the initial rhythm was a non-shockable rhythm, whereas during a shockable rhythm, delay in EA was not associated with decreased ROSC and 1-month survival. CONCLUSIONS: While assessing the effectiveness of epinephrine for OHCA, we should consider the time-limited effects of epinephrine. Additionally, consideration of early EA based on the pathophysiology is needed.

Association Between Therapeutic Hypothermia and Outcomes in Patients with Non-shockable Out-of-Hospital Cardiac Arrest Developed After Emergency Medical Service Arrival (SOS-KANTO 2012 Analysis Report).

BACKGROUND/OBJECTIVE: The outcomes of patients with non-shockable out-of-hospital cardiac arrest (non-shockable OHCA) are poorer than those of patients with shockable out-of-hospital cardiac arrest (shockable OHCA). In this retrospective study, we selected patients from the SOS-KANTO 2012 study with non-shockable OHCA that developed after emergency medical service (EMS) arrival and analyzed the effect of therapeutic hypothermia (TH) on non-shockable OHCA patients. METHODS: Of 16,452 patients who have definitive data on the 3-month outcome in the SOS-KANTO 2012 study, we selected 241 patients who met the following criteria: age ≥ 18 years, normal spontaneous respiration or palpable pulse upon emergency medical services arrival, no ventricular fibrillation or pulseless ventricular tachycardia before hospital arrival, and achievement of spontaneous circulation without cardiopulmonary bypass. Patients were divided into two groups based on the presence or absence of TH and were analyzed. RESULTS: Of the 241 patients, 49 underwent TH. Univariate analysis showed that the 1-/3-month survival rates and favorable 3-month cerebral function outcome rates in the TH group were significantly better than the non-TH group (46% vs 19%, respectively, P < 0.001, 35% vs 12%, respectively, P < 0.001, 20% vs 7%, respectively, P = 0.01). Multivariate logistic regression analysis showed that TH was a significant, independent prognostic factor for cerebral function outcome. CONCLUSIONS: In this study, TH was an independent prognostic factor for the 3-month cerebral function outcome. Even in patients with non-shockable OHCA, TH may improve outcome if the interval from the onset of cardiopulmonary arrest is relatively short, and adequate cardiopulmonary resuscitation is initiated immediately after onset.

Confirmed cardiac output on emergency medical services arrival as confounding by indication: an observational study of prehospital airway management in patients with out-of-hospital cardiac arrest.

OBJECTIVES: Many registry studies on patients with out-of-hospital cardiac arrest (OHCA) have reported that conventional bag-valve-mask (BVM) ventilation is independently associated with favourable outcomes. This study aimed to compare the data of patients with OCHA with confirmed cardiac output on emergency medical services (EMS) arrival and consider the confounding factors in prehospital airway management studies. METHODS: This was a cohort study using the registry data for survivors after out-of hospital cardiac arrest in the Kanto region at 2012 in Japan (SOS-KANTO 2012). Survivors who received advanced airway management (AAM) group and a BVM group were compared for confirmed cardiac output on EMS arrival and neurolgical outcome at 1 month. Favourable neurological outcome was defined as a score of one or two on the Cerebral Performance Categories Scale. Multivariable logistic regression was used to adjust the neurological outcome by age, gender, cardiac aetiology, witnessed arrest, shockable rhythm, cardiopulmonary resuscitation performed by a bystander, BVM at prehospital ventilation and presence of confirmed cardiac output on EMS arrival. RESULTS: A total of 16 452 patients were enrolled in the SOS-KANTO 2012 study, and of those data 12 867 were analysed; 5893 patients comprised the AAM group and 6974 comprised the BVM group. Of the study participants, 386 (2.9%) had confirmed cardiac output on EMS arrival; 340 (2.6%) of the entire study group had a favourable neurological outcome. The proportion of patients with confirmed cardiac output on EMS arrival was significantly higher in the BVM group (272: 3.9%) than in the AAM group (114: 1.9%) (95% CI: 1.65 to 2.25). The proportion of patients with favourable neurological outcomes was 30% (117/386) in those with cardiac output on EMS arrival compared with 1.8% (223/12481) in those without. The OR for a good neurological outcome with BVM decreased from 3.24 (2.49 to 4.20) to 2.60 (1.97 to 3.44) when confirmed cardiac output on EMS arrival was added to the multivariable model analysis. CONCLUSION: Confirmed cardiac output on EMS arrival should be considered as confounding by indication in observational studies of prehospital airway management.

Pectin-containing liquid enteral nutrition for critical care: a historical control and propensity score matched study.

BACKGROUND AND OBJECTIVES: Pectin-containing liquid enteral nutrition (PCLEN) contains pectin, which becomes solid in the stomach and therefore mitigates vomiting and diarrhea. Its efficacy for use in critical care medicine was evaluated. METHODS AND STUDY DESIGN: We used liquid enteral nutrition (LEN) (traditional LEN (TLEN)) as the primary LEN at the emergency and critical care center. We adopted PCLEN as the primary LEN from 2014. During 2012-2016, 954 patients admitted to intensive care units and emergency wards were given PCLEN or TLEN. We conducted propensity score matching for 693 eligible patients for age, sex, and organ dysfunctions for six organs. RESULTS: We included 199 PCLEN patients and 199 TLEN patients. Severity was higher in the PCLEN group. The enteral nutrition failure rate was significantly lower for PCLEN than for TLEN. The diarrhea incidence rates were 28.1% vs 38.2% (p=0.033), and the incidence rates of nosocomial pneumonia were 4.5% and 9.6% (p=0.048). For PCLEN, the enteral nutrition failure rates were not different for patients with gastric acid inhibitors and without them. CONCLUSIONS: PCLEN can be used effectively for critically ill patients irrespective of the use of gastric acid inhibitors. It can decrease the incidence of enteral nutrition failure and diarrhea.

IFN-ß Improves Sepsis-related Alveolar Macrophage Dysfunction and Postseptic Acute Respiratory Distress Syndrome-related Mortality.

IFN-ß is reported to improve survival in patients with acute respiratory distress syndrome (ARDS), possibly by preventing sepsis-induced immunosuppression, but its therapeutic nature in ARDS pathogenesis is poorly understood. We investigated the therapeutic effects of IFN-ß for postseptic ARDS to better understand its pathogenesis in mice. Postseptic ARDS was reproduced in mice by cecal ligation and puncture to induce sepsis, followed 4 days later by intratracheal instillation of Pseudomonas aeruginosa to cause pneumonia with or without subcutaneous administration of IFN-ß 1 day earlier. Sepsis induced prolonged increases in alveolar TNF-α and IL-10 concentrations and innate immune reprogramming; specifically, it reduced alveolar macrophage (AM) phagocytosis and KC (CXCL1) secretion. Ex vivo AM exposure to TNF-α or IL-10 duplicated cytokine release impairment. Compared with sepsis or pneumonia alone, pneumonia after sepsis was associated with blunted alveolar KC responses and reduced neutrophil recruitment into alveoli despite increased neutrophil burden in lungs (i.e., "incomplete alveolar neutrophil recruitment"), reduced bacterial clearance, increased lung injury, and markedly increased mortality. Importantly, IFN-ß reversed the TNF-α/IL-10-mediated impairment of AM cytokine secretion in vitro, restored alveolar innate immune responsiveness in vivo, improved alveolar neutrophil recruitment and bacterial clearance, and consequently reduced the odds ratio for 7-day mortality by 85% (odds ratio, 0.15; 95% confidence interval, 0.03-0.82; P = 0.045). This mouse model of sequential sepsis → pneumonia infection revealed incomplete alveolar neutrophil recruitment as a novel pathogenic mechanism for postseptic ARDS, and systemic IFN-ß improved survival by restoring the impaired function of AMs, mainly by recruiting neutrophils to alveoli.

Renal Function and Outcome of Out-of-Hospital Cardiac Arrest　- Multicenter Prospective Study (SOS-KANTO 2012 Study).

BACKGROUND: Renal dysfunction is associated with increased cardiovascular-related mortality, but its impact on outcome of out-of-hospital cardiac arrest (OHCA) remains unclear. We assessed whether post-OHCA outcome correlated with renal function early after OHCA. Methods and Results: Of the 16,452 registered patients in the SOS-KANTO 2012 Study, 5,112 cardiogenic OHCA adults with creatinine measurement (mean age, 72 years; male, 64%) were examined. First-obtained creatinine was used to assess eGFR. Associations between eGFR groups, ≥60 (n=997), 45-59 (n=1,311), 30-44 (n=1,441), and <30 mL/min/1.73 m2(n=1,363), and 3-month survival and neurological outcomes were examined. Favorable neurological outcome was defined as cerebral performance categories 1 or 2. Survival rate (15.1%, 9.7%, 3.9%, and 2.9%; P<0.001) and proportion of favorable neurological outcome (12.3%, 7.4%, 2.6%, and 2.2%; P<0.001) were determined for eGFR groups ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively. The survival rate decreased with eGFR (<60 mL/min/1.73 m2), and survival adjusted OR were 0.74 (95% CI: 0.54-1.03), 0.42 (95% CI: 0.28-0.62), and 0.43 (95% CI: 0.28-0.68) for eGFR 45-59, 30-44, and <30 mL/min/1.73 m2, respectively. The adjusted OR for favorable neurological outcome also decreased with eGFR: 0.74 (95% CI: 0.52-1.06), 0.40 (95% CI: 0.25-0.64), and 0.48 (95% CI: 0.29-0.81), respectively. CONCLUSIONS: An independent and graded association was observed between decreased eGFR and 3-month survival and proportion of favorable neurological outcome in cardiogenic OHCA patients.

Early Lactate Clearance Is Associated With Improved Outcomes in Patients With Postcardiac Arrest Syndrome: A Prospective, Multicenter Observational Study (SOS-KANTO 2012 Study).

OBJECTIVES: To determine whether early lactate reduction is associated with improved survival and good neurologic outcome in patients with out-of-hospital cardiac arrest. DESIGN: Ad hoc data analysis of a prospective, multicenter observational study. SETTING: Out-of-hospital cardiac arrest patients at 67 emergency hospitals in Kanto, Japan between January 2012 and March 2013. PATIENTS: Adult patients with out-of-hospital cardiac arrest admitted to the hospital after successful resuscitation were identified. INTERVENTIONS: Blood lactate concentrations were measured at hospital admission and 6 h after hospital admission. Early lactate clearance was defined as the percent change in lactate level 6 h after a baseline measurement. MEASUREMENTS AND MAIN RESULTS: The 543 patients (mean age, 65 ± 16 yr; 72.6% male) had a mean lactate clearance of 42.4% ± 53.7%. Overall 30-day survival and good neurologic outcome were 47.1% and 27.4%, respectively. The survival proportion increased with increasing lactate clearance (quartile 1, 29.4%; quartile 2, 42.6%; quartile 3, 51.5%; quartile 4, 65.2%; p < 0.001). Multivariate logistic regression analysis showed that lactate clearance quartile was an independent predictor of the 30-day survival and good neurologic outcome. In the Cox proportional hazards model, the frequency of mortality during 30 days was significantly higher for patients with lactate clearance in quartile 1 (hazard ratio, 3.12; 95% CI, 2.14-4.53), quartile 2 (hazard ratio, 2.13; 95% CI, 1.46-3.11), and quartile 3 (hazard ratio, 1.49; 95% CI, 1.01-2.19) than those with lactate clearance in quartile 4. Furthermore, multivariate logistic regression analysis revealed that lactate clearance was a significant predictor of good neurologic outcome at 30 days after hospital admission. CONCLUSIONS: Effective lactate reduction over the first 6 hours of postcardiac arrest care was associated with survival and good neurologic outcome independently of the initial lactate level.

Hyperfibrinolysis in severe isolated traumatic brain injury may occur without tissue hypoperfusion: a retrospective observational multicentre study.

BACKGROUND: Hyperfibrinolysis is a critical complication in severe trauma. Hyperfibrinolysis is traditionally diagnosed via elevated D-dimer or fibrin/fibrinogen degradation product levels, and recently, using thromboelastometry. Although hyperfibrinolysis is observed in patients with severe isolated traumatic brain injury (TBI) on arrival at the emergency department (ED), it is unclear which factors induce hyperfibrinolysis. The present study aimed to investigate the factors associated with hyperfibrinolysis in patients with isolated severe TBI. METHODS: We conducted a multicentre retrospective review of data for adult trauma patients with an injury severity score ≥ 16, and selected patients with isolated TBI (TBI group) and extra-cranial trauma (non-TBI group). The TBI group included patients with an abbreviated injury score (AIS) for the head ≥ 4 and an extra-cranial AIS < 2. The non-TBI group included patients with an extra-cranial AIS ≥ 3 and head AIS < 2. Hyperfibrinolysis was defined as a D-dimer level ≥ 38 mg/L on arrival at the ED. We evaluated the relationships between hyperfibrinolysis and injury severity/tissue injury/tissue perfusion in TBI patients by comparing them with non-TBI patients. RESULTS: We enrolled 111 patients in the TBI group and 126 in the non-TBI group. In both groups, patients with hyperfibrinolysis had more severe injuries and received transfusion more frequently than patients without hyperfibrinolysis. Tissue injury, evaluated on the basis of lactate dehydrogenase and creatine kinase levels, was associated with hyperfibrinolysis in both groups. Among patients with TBI, the mortality rate was higher in those with hyperfibrinolysis than in those without hyperfibrinolysis. Tissue hypoperfusion, evaluated on the basis of lactate level, was associated with hyperfibrinolysis in only the non-TBI group. Although the increase in lactate level was correlated with the deterioration of coagulofibrinolytic variables (prolonged prothrombin time and activated partial thromboplastin time, decreased fibrinogen levels, and increased D-dimer levels) in the non-TBI group, no such correlation was observed in the TBI group. CONCLUSIONS: Hyperfibrinolysis is associated with tissue injury and trauma severity in TBI and non-TBI patients. However, tissue hypoperfusion is associated with hyperfibrinolysis in non-TBI patients, but not in TBI patients. Tissue hypoperfusion may not be a prerequisite for the occurrence of hyperfibrinolysis in patients with isolated TBI.

Effectiveness of Prehospital Epinephrine Administration in Improving Long-term Outcomes of Witnessed Out-of-hospital Cardiac Arrest Patients with Initial Non-shockable Rhythms.

OBJECTIVE: We evaluated the association between prehospital epinephrine administration by emergency medical services (EMS) and the long-term outcomes of out-of-hospital cardiac arrest (OHCA) with initial pulseless electrical activity (PEA) or asystole. METHODS: We conducted a controlled, propensity-matched, retrospective cohort study by using Japan's nationwide OHCA registry database. We studied 110,239 bystander-witnessed OHCA patients aged 15-94 years with initial non-shockable rhythms registered between January 2008 and December 2012. We created 1-1 matched pairs of patients with or without epinephrine by using sequential risk set matching based on time-dependent propensity scores to balance the patients' severity and characteristics. We compared overall and neurologically intact survival 1 month after OHCA between cases and controls using conditional logistic regression models by category of the initial rhythm. RESULTS: Propensity matching created 7,431 pairs in patients with PEA and 8,906 pairs in those with asystole. Epinephrine administration was associated with higher overall survival (4.49% vs. 2.96%; odds ratio [OR], 1.55; 95% confidence interval [CI], 1.30-1.85) but not with neurologically intact survival (0.98% vs. 0.78%; OR, 1.26; 95% CI, 0.89-1.78) in patients with PEA, and with higher overall survival (2.38% vs. 1.04%; OR, 2.34; 95% CI, 1.82-3.00) and neurologically intact survival (0.48% vs. 0.22%; OR, 2.28; 95% CI, 1.31-3.96) in those with asystole. CONCLUSIONS: Prehospital epinephrine administration by EMS is favorably associated with long-term neurological outcomes in patients with initial asystole and with long-term survival outcomes in those with PEA.

Does the number of emergency medical technicians affect the neurological outcome of patients with out-of-hospital cardiac arrest?

BACKGROUND: It is unclear whether the number of paramedics in an ambulance improves the outcome of patients with out-of-hospital cardiac arrest (OHCA) or not. METHODS AND RESULTS: This study was a prospective, observational study conducted on patients with OHCA. Patients were divided into the One-paramedic group (Group O) and the Two-or-more-paramedic group (Group T) and we analyzed the differences. Patients who were treated with only basic life support during transportation, and whose cause of cardiac arrest were extrinsic cause such as trauma and poisoning were excluded. Good neurological outcome was defined as cerebral performance category (CPC) 1 or 2. In Group O, there were 1516 patients (male/female, 922/594). In Group T, there were 2932 patients (male/female, 1798/1134). Return of spontaneous circulation (ROSC) was obtained in 528 patients (34.8%) in Group O and 1058 patients (36.1%) in Group T (p=0.589). 320 patients (21.1%) in Group O and 656 patients (22.4%) in Group T were admitted to hospital after ROSC (p=0.461). At 90days, there were 57 survivors (3.8%) in Group O and 114 survivors (3.9%) in Group T (p=0.873). At 90days, 14 patients (0.9%) in Group T had a CPC of 1 or 2, while 30 patients (1.0%) in Group T did so (p=0.87). From the results of logistic regression analysis, age [odds ratio (OR): 0.983, 95% confidence interval (CI): 0.952-0.993], witnessed OHCA (OR: 4.583, 95% CI: 1.587-13.234), and shockable rhythm as first documented (OR: 19.67, 95% CI: 9.181-42.13) were associated with good outcome. CONCLUSION: The number of paramedics in an ambulance did not affect the outcome in OHCA patients.

Association between cardiopulmonary resuscitation duration and one-month neurological outcomes for out-of-hospital cardiac arrest: a prospective cohort study.

BACKGROUND: The duration of cardiopulmonary resuscitation (CPR) is an important factor associated with the outcomes for an out-of-hospital cardiac arrest. However, the appropriate CPR duration remains unclear considering pre- and in-hospital settings. The present study aimed to evaluate the relationship between the CPR duration (including both the pre- and in-hospital duration) and neurologically favorable outcomes 1-month after cardiac arrest. METHODS: Data were utilized from a prospective multi-center cohort study of out-of-hospital cardiac arrest patients transported to 67 emergency hospitals between January 2012 and March 2013 in the Kanto area of Japan. A total of 3,353 patients with out-of-hospital cardiac arrest (age ≥18 years) who underwent CPR by emergency medical service personnel and achieved the return of spontaneous circulation in a pre- or in-hospital setting were analyzed. The primary outcome was a 1-month favorable neurological outcome. Logistic regression analysis was performed to estimate the influence of cardiopulmonary resuscitation duration. The CPR duration that achieved a cumulative proportion >99% of cases with a 1-month neurologically favorable outcome was determined. RESULTS: Of the 3,353 eligible cases, pre-hospital return of spontaneous circulation was obtained in 1,692 cases (50.5%). A total of 279 (8.3%) cases had a 1-month neurologically favorable outcome. The CPR duration was significantly and inversely associated with 1-month neurologically favorable outcomes with adjustment for pre- and in-hospital confounders (adjusted odds ratio: 0.911, per minute, 95% CI: 0.892-0.929, p < 0.001). After 30 min of CPR, the probability of a 1-month neurologically favorable outcome decreased from 8.3 to 0.7%. At 45 min of CPR, the cumulative proportion for a 1-month neurologically favorable outcome reached >99%. CONCLUSIONS: The CPR duration was independently and inversely associated with 1-month neurologically favorable outcomes after out-of-hospital cardiac arrest. The CPR duration required to achieve return of spontaneous circulation in >99% of out-of-hospital cardiac arrest patients with a 1-month favorable neurological outcome was 45 min, considering both pre- and in-hospital settings.