Long-Term Neurological Outcome of Extracorporeal Cardiopulmonary Resuscitation for Out-of-Hospital Cardiac Arrest Patients With Nonshockable Rhythms: A Single-Center, Consecutive, Retrospective Observational Study.

BACKGROUND: Data on extracorporeal cardiopulmonary resuscitation (ECPR) in patients with out-of-hospital cardiac arrest (OHCA) and initially nonshockable rhythms are limited. OBJECTIVE: This study aimed to evaluate the long-term neurological outcomes of ECPR for patients with OHCA and initially nonshockable rhythms. METHODS: In this single-center, consecutive, retrospective, observational study, patients with OHCA and initially nonshockable rhythms who underwent ECPR between January 2012 and December 2017 were included. All patients with refractory cardiopulmonary arrest were transported while undergoing conventional CPR and received ECPR on arrival in the emergency department. We retrospectively collected characteristics at admission and neurological outcomes at the last visit or telephone interview. Cerebral performance category (CPC) scales 1 and 2 were defined as good neurological outcomes and CPC scales 3, 4, and 5 were defined as poor neurological outcomes. RESULTS: Of the 39 patients included in this study, 32 died in the hospital and only 7 survived. There were 4, 0, 0, 3, and 32 patients with CPC 1, 2, 3, 4, and 5, respectively. The proportion of good neurological outcomes for all patients was 10.3% (95% CI 2.9-24.2%) and 14.3% (95% CI 4.0-32.7%) for patients with pulseless electrical activity. No patients with asystole had a good neurological outcome. Median follow-up period was 1052 days (interquartile range 116-1589 days) for those who survived to discharge. CONCLUSIONS: Approximately 10% of initially nonshockable patients with OHCA, generally considered to be a poor prognosis, could acquire good neurological outcomes when they underwent ECPR with our indications.

Extracorporeal cardiopulmonary resuscitation in adult patients with out-of-hospital cardiac arrest: a retrospective large cohort multicenter study in Japan.

BACKGROUND: The prevalence of extracorporeal cardiopulmonary resuscitation (ECPR) in patients with out-of-hospital cardiac arrest (OHCA) has been increasing rapidly worldwide. However, guidelines or clinical studies do not provide sufficient data on ECPR practice. The aim of this study was to provide real-world data on ECPR for patients with OHCA, including details of complications. METHODS: We did a retrospective database analysis of observational multicenter cohort study in Japan. Adult patients with OHCA of presumed cardiac etiology who received ECPR between 2013 and 2018 were included. The primary outcome was favorable neurological outcome at hospital discharge, defined as a cerebral performance category of 1 or 2. RESULTS: A total of 1644 patients with OHCA were included in this study. The patient age was 18-93 years (median: 60 years). Shockable rhythm in the initial cardiac rhythm at the scene was 69.4%. The median estimated low flow time was 55 min (interquartile range: 45-66 min). Favorable neurological outcome at hospital discharge was observed in 14.1% of patients, and the rate of survival to hospital discharge was 27.2%. The proportions of favorable neurological outcome at hospital discharge in terms of shockable rhythm, pulseless electrical activity, and asystole were 16.7%, 9.2%, and 3.9%, respectively. Complications were observed during ECPR in 32.7% of patients, and the most common complication was bleeding, with the rates of cannulation site bleeding and other types of hemorrhage at 16.4% and 8.5%, respectively. CONCLUSIONS: In this large cohort, data on the ECPR of 1644 patients with OHCA show that the proportion of favorable neurological outcomes at hospital discharge was 14.1%, survival rate at hospital discharge was 27.2%, and complications were observed during ECPR in 32.7%.

Microthrombosis as a cause of fulminant myocarditis-like presentation with COVID-19 proven by endomyocardial biopsy.

Myocardial injury has been reported as a complication of COVID-19. Although several mechanisms have been proposed as its cause, they are mostly based on autopsy studies, We report a 49-year-old male with COVID-19-associated myocardial injury presented like fulminant myocarditis. We performed endomyocardial biopsy on day 2 and we confirmed the presence of microthrombosis histologically. He died on day 5 due to cardiogenic shock.

Time-Series Change of Serum Soluble T-Cadherin Concentrations and Its Association with Creatine Kinase-MB Levels in ST-Segment Elevation Myocardial Infarction.

AIMS: T-cadherin (T-cad) is a specific binding partner of adiponectin (APN), adipocyte-specific secretory protein. APN exhibits organ protection via the T-cad-dependent accumulation onto several tissues such as the aorta, heart, and muscle. Recently, for the first time, we showed that three forms (130, 100, and 30 kDa) of soluble T-cad existed in human serum and correlated with several clinical parameters in patients with type 2 diabetes. Nevertheless, the significance of soluble T-cad has not been elucidated in the acute stage of cardiovascular diseases. We herein examined soluble T-cad concentrations and investigated their clinical significance in patients with emergency hospital admission due to ST-segment elevation myocardial infarction (STEMI). METHODS: This observational study enrolled 47 patients with STEMI who were treated via primary percutaneous coronary intervention (PCI). Soluble T-cad and APN concentrations were measured by using an enzyme-linked immunosorbent assay. This study is registered with the University Hospital Medical Information Network (Number: UMIN 000014418). RESULTS: Serum concentrations of soluble 130 and 100 kDa T-cad rapidly and significantly decreased after hospitalization and reached the bottom at 72 h after admission (p＜0.001 and p＜0.001, respectively). The patients with high soluble T-cad and low APN concentrations on admission showed a significantly higher area under the curve of serum creatine kinase-MB (p＜0.01). CONCLUSION: Serum soluble T-cad concentration changed dramatically in patients with STEMI, and the high T-cad and low APN concentrations on admission were associated with the myocardial infarction size. Further study is needed to investigate the usefulness of categorizing patients with STEMI by serum T-cad and APN for the prediction of severe prognoses.

Impact of Induced Therapeutic Hypothermia by Intravenous Infusion of Ice-Cold Fluids After Hospital Arrival in Comatose Survivors of Out-of-Hospital Cardiac Arrest With Initial Shockable Rhythm.

BACKGROUND: The effect of in-hospital rapid cooling by intravenous ice-cold fluids for comatose survivors of out-of-hospital cardiac arrest (OHCA) is unclear.Methods and Results:From the J-PULSE-HYPO study registry, data for 248 comatose survivors with return of spontaneous circulation (ROSC) who were treated with therapeutic hypothermia (34℃ for 12-72 h) after witnessed shockable OHCA were extracted. Patients were divided into 2 groups by the median collapse-to-ROSC interval (18 min), and then into 2 groups by cooling method (rapid cooling by intravenous ice-cold fluids vs. standard cooling). The primary endpoint was favorable neurological outcome (Cerebral Performance Category of 1 or 2) at 30 days after OHCA. In the whole cohort, the shorter collapse-to-ROSC interval group had significantly higher favorable neurological outcome than the longer collapse-to-ROSC interval group (78.2% vs. 46.8%, P<0.001). In the shorter collapse-to-ROSC interval group, no significant difference was observed in favorable neurological outcome between the 2 cooling groups (rapid cooling group: 79.4% vs. standard cooling group: 77.0%, P=0.75). In the longer collapse-to-ROSC interval group, however, favorable neurological outcome was significant higher in the rapid cooling group than in the standard cooling group (60.7% vs. 33.3%, P<0.01) and the adjusted odds ratio after rapid cooling was 3.069 (95% confidence interval 1.423-6.616, P=0.004). CONCLUSIONS: In-hospital rapid cooling by intravenous ice-cold fluids improved neurologically intact survival in comatose survivors whose collapse-to-ROSC interval was delayed over 18 min after shockable OHCA.

Variability of extracorporeal cardiopulmonary resuscitation practice in patients with out-of-hospital cardiac arrest from the emergency department to intensive care unit in Japan.

AIM: A lack of known guidelines for the provision of extracorporeal cardiopulmonary resuscitation (ECPR) to patients with out-of-hospital cardiac arrest (OHCA) has led to variability in practice between hospitals even in the same country. Because variability in ECPR practice has not been completely examined, we aimed to describe the variability in ECPR practice in patients with OHCA from the emergency department (ED) to the intensive care units (ICU). METHODS: An anonymous online questionnaire to examine variability in ECPR practice was completed in January 2020 by 36 medical institutions who participated in the SAVE-J II study. Institutional demographics, inclusion and exclusion criteria, initial resuscitation management, extracorporeal membrane oxygenation (ECMO) initiation, initial ECMO management, intra-aortic balloon pumping/endotracheal intubation/management during coronary angiography, and computed tomography criteria were recorded. RESULTS: We received responses from all 36 institutions. Four institutions (11.1%) had a hybrid emergency room. Cardiovascular surgery was always involved throughout the entire ECMO process in only 14.7% of institutions; 60% of institutions had formal inclusion criteria and 50% had formal exclusion criteria. In two-thirds of institutions, emergency physicians carried out cannulation. Catheterization room was the leading location of cannulation (48.6%) followed by ED (31.4%). The presence of formal exclusion criteria significantly increased with increasing ECPR volume (P for trend <0.001). Intra-aortic balloon pumping was routinely initiated in only 25% of institutions. Computed tomography was routinely carried out before coronary angiography in 25% of institutions. CONCLUSIONS: We described the variability in ECPR practice in patients with OHCA from the ED to the ICU.

Impact of Enteral Nutrition Within 24 Hours Versus Between 24 and 48 Hours in Patients With Severe Acute Pancreatitis: A Multicenter Retrospective Study.

OBJECTIVES: In patients with severe acute pancreatitis (SAP), early enteral nutrition (EN) is recommended by major clinical practice guidelines, but the exact timing for the initiation of EN is unknown. METHODS: We conducted a post hoc analysis of the database for a multicenter (44 institutions) retrospective study of patients with SAP in Japan. The patients were classified into 3 groups according to the timing of EN initiation after the diagnosis of SAP: within 24 hours, between 24 and 48 hours, and more than 48 hours. The primary outcome was in-hospital mortality. RESULTS: Of the 1094 study patients, 176, 120, and 798 patients started EN within 24 hours, between 24 and 48 hours, and more than 48 hours after SAP diagnosis, respectively. On multivariable analysis, hospital mortality was significantly better with EN within 48 hours than with more than 48 hours (adjusted odds ratio, 0.49; 95% confidence interval, 0.29-0.83; P < 0.001) but did not significantly differ between the groups with EN starting within 24 hours and between 24 and 48 hours (P = 0.29). CONCLUSIONS: Enteral nutrition within 24 hours may not confer any additional benefit on clinical outcomes compared with EN between 24 and 48 hours.

Etiology and mortality in severe acute pancreatitis: A multicenter study in Japan.

BACKGROUND/OBJECTIVES: Severe acute pancreatitis (SAP) has a high mortality rate despite ongoing attempts to improve prognosis through a various therapeutic modalities. This study aimed to delineate etiology-based routes that may guide clinical decisions for the treatment of SAP. METHODS: Using data from a recent retrospective multicenter study in Japan, we analyzed the association between clinical outcomes, mainly in-hospital mortality and pancreatic infection, and various etiologies while considering confounding factors. We performed additional multivariate analyses and built decision tree models. RESULTS: The 1097 participating patients were classified into the following groups by etiology: alcohol (n = 436, 39.7%); cholelithiasis (n = 230, 21.0%); idiopathic (n = 227, 20.7%); and others (n = 204, 18.6%). Mortality at hospital discharge was 8.4%, 12.2%, 16.7%, and 16.2% in the alcohol, cholelithiasis, idiopathic, and others groups, respectively. According to multivariable analysis, early enteral nutrition (EN) was significantly associated with reduced in-hospital mortality only in the cholelithiasis group. However, there was a consistent association between age and the need for mechanical ventilation and increased mortality, regardless of etiology. Our decision tree models presented different contributing factors depending on the etiology and patient background. Interaction analysis showed that EN and the use of prophylactic antibiotics may influence these results differently according to etiology. CONCLUSIONS: No study has yet used comprehensive models to investigate etiology-related prognostic factors for SAP; our results can, therefore, be used as a reference for improving clinical decisions.

Optimal extracorporeal cardiopulmonary resuscitation inclusion criteria for favorable neurological outcomes: a single-center retrospective analysis.

AIM: Although age ≤75 years, witnessed arrest, shockable initial cardiac rhythm, and short cardiac arrest duration are commonly cited inclusion criteria for extracorporeal cardiopulmonary resuscitation (ECPR), these criteria are not well-established, and ECPR outcomes remain poor. We aimed to evaluate whether the aforementioned inclusion criteria are appropriate for ECPR, and estimate the improvements in prognoses associated with their fulfillment. METHODS: Between October 2009 and December 2017, we retrospectively examined consecutive out-of-hospital cardiac arrest patients who were admitted to our hospital and received ECPR. We established four ECPR inclusion criteria: age ≤75 years, witnessed arrest, shockable initial cardiac rhythm, and call-to-hospital arrival time ≤45 min, and also evaluated the relationship between these criteria and patient outcomes. RESULTS: During the study period, 1,677 out-of-hospital cardiac arrest patients were admitted to our hospital, and 156 (9%) with ECPR were examined. The proportion of favorable neurological outcomes was 15% (24/156). However, when the study population was limited to individuals who fulfilled all four criteria, 27% (15/55) had favorable neurological outcomes; only one patient had favorable outcomes when two or more criteria were fulfilled. There was a significant positive linear correlation between the proportion of cases with favorable neurological outcomes and fulfillment of the four criteria (P = 0.005, r = 0.975). CONCLUSION: Fulfillment of at least three of the aforementioned criteria could yield improved ECPR outcomes.

The Effect of an Invasive Strategy for Treating Pancreatic Necrosis on Mortality: a Retrospective Multicenter Cohort Study.

BACKGROUND: Infected acute necrotic collections (ANC) and walled-off necrosis (WON) of the pancreas are associated with high mortality. The difference in mortality between open necrosectomy and minimally invasive therapies in these patients remains unclear. METHODS: This retrospective multicenter cohort study was conducted among 44 institutions in Japan from 2009 to 2013. Patients who had undergone invasive treatment for suspected infected ANC/WON were enrolled and classified into open necrosectomy and minimally invasive treatment (laparoscopic, percutaneous, and endoscopic) groups. The association of each treatment with mortality was evaluated and compared. RESULTS: Of 1159 patients with severe acute pancreatitis, 122 with suspected infected ANC or WON underwent the following treatments: open necrosectomy (33) and minimally invasive treatment (89), (laparoscopic three, percutaneous 49, endoscopic 37). Although the open necrosectomy group had a significantly higher mortality on univariate analysis (p = 0.047), multivariate analysis showed no significant associations between open necrosectomy or Charlson index and mortality (p = 0.29, p = 0.19, respectively). However, age (for each additional 10 years, p = 0.012, odds ratio [OR] 1.50, 95% confidence interval [CI] 1.09-2.06) and revised Atlanta criteria-severe (p = 0.001, OR 7.84, 95% CI 2.40-25.6) were significantly associated with mortality. CONCLUSIONS: In patients with acute pancreatitis and infected ANC/WON, age and revised Atlanta criteria-severe classification are significantly associated with mortality whereas open necrosectomy is not. The mortality risk for patients undergoing open necrosectomy and minimally invasive treatment does not differ significantly. Although minimally invasive surgery is generally preferred for patients with infected ANC/WON, open necrosectomy may be considered if clinically indicated.

Association between rewarming duration and neurological outcome in out-of-hospital cardiac arrest patients receiving therapeutic hypothermia.

AIM: The European Resuscitation Council guidelines recommend a slow rate of rewarming of 0.25 °C/h-0.5 °C/h for out-of-hospital cardiac arrest (OHCA) patients receiving therapeutic hypothermia (TH). Conversely, a very slow rewarming of 1 °C/day is generally applied in Japan. The rewarming duration ranged from less than 24 h up to more than 50 h. No randomized control trials have examined the optimal rewarming speed for TH in OHCA patients. Therefore, we examined the association between the rewarming duration and neurological outcomes in OHCA patients who received TH. METHODS: This study was a secondary analysis of the Japanese Population-based Utstein-style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia (J-PULSE-HYPO) study registry, a multicenter prospective cohort study. Patients suffering from OHCA who received TH (target temperature, 34 °C) after the return of spontaneous circulation from 2005 to 2011 in 14 hospitals throughout Japan were enrolled. The rewarming duration was defined as the time from the beginning of rewarming at a target temperature of 34 °C until reaching 36 °C. The primary outcome was an unfavorable neurological outcome at hospital discharge, i.e., a cerebral performance category of 3-5. RESULTS: The J-PULSE-HYPO study enrolled 452 OHCA patients. Of these, 328 were analyzed; 79.9% survived to hospital discharge, of which 56.4% had a favorable neurological outcome. Multivariable logistic regression analysis revealed that the rewarming duration was independently associated with unfavorable neurological outcomes [odds ratio (per 5 h), 0.89; 95% confidence interval, 0.79-0.99; p =  0.032]. CONCLUSION: A longer rewarming duration was significantly associated with and was an independent predictor of favorable neurological outcomes in OHCA patients who received TH.

Continuous regional arterial infusion versus intravenous administration of the protease inhibitor nafamostat mesilate for predicted severe acute pancreatitis: a multicenter, randomized, open-label, phase 2 trial.

BACKGROUND: Continuous regional arterial infusion (CRAI) of protease inhibitor nafamostat mesilate (NM) is used in the context of predicted severe acute pancreatitis (SAP) to prevent the development of pancreatic necrosis. Although this therapy is well known in Japan, its efficacy and safety remain unclear. METHODS: This investigator-initiated and -driven, multicenter, open-label, randomized, controlled trial (UMIN000020868) enrolled 39 patients with predicted SAP and low enhancement of the pancreatic parenchyma on computed tomography (CT). Twenty patients were assigned to the CRAI group, while 19 served as controls and were administered NM at the same dose intravenously (IV group). The primary endpoint was the development of pancreatic necrosis as determined by CT on Day 14, judged by blinded central review. RESULTS: There was no difference between the CRAI and IV groups regarding the percentages of participants who developed pancreatic necrosis (more than 1/3 of the pancreas: 25.0%, range 8.7-49.1% vs. 15.8%, range 3.4-39.6%, respectively, P = 0.694; more than 2/3 of the pancreas: 20%, range 5.7-43.7% vs. 5.3%, range 0.1-26.0%, respectively, P = 0.341). The early analgesic effect was evaluated based on 24-h cumulative fentanyl consumption and additional administration by intravenous patient-controlled analgesia. The results showed that the CRAI group used significantly less analgesic. There were two adverse events related to CRAI, namely bleeding and splenic infarction. CONCLUSIONS: CRAI with NM did not inhibit the development of pancreatic necrosis although early analgesic effect of CRAI was superior to that of IV. Less-invasive IV therapy can be considered a viable alternative to CRAI therapy.

Impact of Antimicrobial Prophylaxis for Severe Acute Pancreatitis on the Development of Invasive Candidiasis: A Large Retrospective Multicenter Cohort Study.

OBJECTIVE: Antimicrobial prophylaxis is not generally recommended for patients with severe acute pancreatitis (SAP) owing to the limited clinical benefits. Nonetheless, it is frequently administered in actual practice given the patients' critical condition and the lack of solid evidence showing adverse effects of antimicrobial prophylaxis. We evaluated herein an association between antimicrobial prophylaxis and invasive pancreatic candidiasis as an adverse effect in patients with SAP. METHODS: This is a retrospective cohort study of all consecutive patients with SAP who were admitted to the study institutions (n = 44) between January 1, 2009, and December 31, 2013. We performed multivariable logistic regression analysis adjusting for the extent of pancreatic necrosis and surgical interventions for invasive pancreatic candidiasis. RESULTS: Of the 1097 patients with SAP, 850 (77.5%) received antimicrobial prophylaxis, and 21 (1.9%) had invasive pancreatic candidiasis. In multivariable logistic regression analysis, antimicrobial prophylaxis was significantly associated with the development of invasive pancreatic candidiasis (adjusted odds ratio, 4.23; 95% confidence interval, 1.14-27.6) (P = 0.029). CONCLUSIONS: The results suggest that antimicrobial prophylaxis may contribute to the development of invasive pancreatic candidiasis, and therefore, the routine use of antimicrobial prophylaxis for SAP may be discouraged.

Large Volume Fluid Resuscitation for Severe Acute Pancreatitis is Associated With Reduced Mortality: A Multicenter Retrospective Study.

BACKGROUND AND AIMS: Although fluid resuscitation is critical in acute pancreatitis, the optimal fluid volume is unknown. The aim of this study is to evaluate the association between the volume of fluid administered and clinical outcomes in patients with severe acute pancreatitis (SAP). METHODS: We conducted a multicenter retrospective study at 44 institutions in Japan. Inclusion criteria were age 18 years or older, and diagnosed with SAP from 2009 to 2013. Patients were stratified into 2 groups: administered fluid volume <6000 and ≥6000 mL in the first 24 hours. We evaluated the association between the 2 groups and clinical outcomes using multivariable logistic regression analysis. The primary outcome was in-hospital mortality. Secondary outcomes included the incidence of pancreatic infection and the need for surgical intervention. RESULTS: We analyzed 1097 patients, and the mean fluid volume administered was 5618±3018 mL (mean±SD), with 708 and 389 patients stratified into the fluid <6000 mL and fluid ≥6000 mL groups, respectively. Overall in-hospital mortality was 12.3%. The fluid ≥6000 mL group had significantly higher mortality than the fluid <6000 mL group (univariable analysis, 15.9% vs. 10.3%; P<0.05). In multivariable logistic regression analysis, administration of ≥6000 mL of fluid within the first 24 hours was significantly associated with reduced mortality (odds ratio, 0.58; P<0.05). No significant association was found between the administered fluid volume and pancreatic infection, or between the volume administered and the need for surgical intervention. CONCLUSIONS: In patients with SAP, administration of a large fluid volume within the first 24 hours is associated with decreased mortality.

Low-flow time is associated with a favorable neurological outcome in out-of-hospital cardiac arrest patients resuscitated with extracorporeal cardiopulmonary resuscitation.

PROPOSE: The aim of this retrospective study was to investigate the prognostic factors in extracorporeal cardiopulmonary resuscitation (ECPR) patients and to assess their accuracy as predictors of a favorable neurological outcome. MATERIALS AND METHODS: Between October 2009 and December 2017, we retrospectively analyzed witnessed out-of-hospital cardiac arrest patients who were admitted to our hospital and resuscitated with ECPR. We compared the baseline characteristics, pre-hospital clinical course, arrest causes, and blood samples on admission for the favorable and unfavorable outcome groups. RESULTS: Among the 135 patients included, 22 (16%) had a favorable neurological outcome. Low-flow time was shorter (median 38 vs. 48 min, p < 0.001) in the favorable neurological outcome group; in multiple logistic analyses, low-flow time was significantly associated with a favorable neurological outcome (odds ratio, 0.88; 95% confidence interval, 0.82-0.94). The area under the receiver-operating characteristic curve of low-flow time was 0.80 (95% confidence interval, 0.70-0.89), and the cut-off value of 58 min corresponded to a sensitivity of 0.25 and a specificity of 1.0. CONCLUSIONS: In ECPR patients, low-flow time was significantly associated with a favorable neurological outcome, and ECPR should be performed within 58 min of the low-flow time.

Impact of extracorporeal cardiopulmonary resuscitation on outcomes of elderly patients who had out-of-hospital cardiac arrests: a single-centre retrospective analysis.

OBJECTIVES: Little is known about the effectiveness of extracorporeal cardiopulmonary resuscitation (ECPR) for elderly patients who had out-of-hospital cardiac arrest (OHCA). The aim of this study was to examine the impact of age on outcomes among patients who had OHCA treated with ECPR. DESIGN: Single-centre retrospective cohort study. SETTING: A critical care centre that covers a population of approximately 1 million residents. PARTICIPANTS: Patients who had consecutive OHCA aged ≥18 years who underwent ECPR from 2005 to 2013. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were 1 month neurologically favourable outcomes and survival. To determine the association between advanced age and each outcome, we fitted multivariable logistic regression models using: (1) age as a continuous variable and (2) age as a categorical variable (<50 years, 50-59 years, 60-69 years and ≥70 years). RESULTS: Overall, 144 patients who had OHCA who underwent ECPR were eligible for our analyses. The proportion of neurologically favourable outcomes was 7%, while survival was 19% in patients who had OHCA. After the adjustment for potential confounders, while advanced age was non-significantly associated with neurologically favourable outcomes (adjusted OR 0.96 (95% CI 0.91 to 1.01), p=0.08), the association between advanced age and the poor survival rate was significant (adjusted OR 0.96 (95% CI 0.93 to 0.99), p=0.04). Additionally, compared with age <50 years, age ≥70 years was non-significantly associated with poor neurological outcomes (adjusted OR 0.08 (95% CI 0.01 to 1.00), p=0.051), whereas age ≥70 years was significantly associated with worse survival in the adjusted model (adjusted OR 0.14 (95% CI 0.03 to 0.80), p=0.03). CONCLUSIONS: In our analysis of consecutive OHCA data from a critical care hospital in an urban area of Japan, we found that advanced age was associated with the lower rate of 1-month survival in patients who had OHCA who underwent ECPR. Although larger studies are required to confirm these results, our findings suggest that ECPR may not be beneficial for patients who had OHCA aged ≥70 years.

The Impact of Heart Rate Response During 48-Hour Rewarming Phase of Therapeutic Hypothermia on Neurologic Outcomes in Out-of-Hospital Cardiac Arrest Patients.

OBJECTIVES: Bradycardia during therapeutic hypothermia has been reported to be a predictor of favorable neurologic outcomes in out-of-hospital cardiac arrests. However, bradycardia occurrence rate may be influenced by the target body temperature. During therapeutic hypothermia, as part of the normal physiologic response, heart rate decreases in the cooling phase and increases during the rewarming phase. We hypothesized that increased heart rate during the rewarming phase is another predictor of favorable neurologic outcomes. To address this hypothesis, the study aimed to examine the association between heart rate response during the rewarming phase and neurologic outcomes in patients having return of spontaneous circulation after out-of-hospital cardiac arrest. DESIGN: A secondary analysis of the Japanese Population-based Utstein style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia registry, which was a multicenter prospective cohort study. SETTING: Fourteen hospitals throughout Japan. PATIENTS: Patients suffering from out-of-hospital cardiac arrest who received therapeutic hypothermia after the return of spontaneous circulation from 2005 to 2011. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: This study enrolled 452 out-of-hospital cardiac arrest patients, of which 354 were analyzed, and 80.2% survived to hospital discharge, of which 57.3% had a good neurologic outcome. Heart rate response was calculated using heart rate data recorded during therapeutic hypothermia in the abovementioned registry. Heart rate response in the rewarming phase (heart rate response-rewarming) was calculated as follows: (heart rate [post rewarming]-heart rate [pre rewarming])/heart rate (pre rewarming) × 100. The primary outcome was an unfavorable neurologic outcome at hospital discharge, that is, a Cerebral Performance Category of 3-5. Multivariable logistic regression analysis was performed to determine the association between heart rate response-rewarming and unfavorable neurologic outcomes. Multivariable logistic regression analysis showed that heart rate response-rewarming was independently associated with unfavorable outcomes (odds ratio [per 10% change], 0.86; 95% CI, 0.78-0.96; p = 0.004). CONCLUSIONS: Increased heart rate in the approximately 48-hour rewarming phase during therapeutic hypothermia was significantly associated with and was an independent predictor of favorable neurologic outcomes during out-of-hospital cardiac arrest.

D-dimer predicts bleeding complication in out-of-hospital cardiac arrest resuscitated with ECMO.

PURPOSE: In out-of-hospital cardiac arrest (OHCA) patients resuscitated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO), known as extracorporeal cardiopulmonary resuscitation (ECPR), bleeding is a common complication. The purpose of this study was to assess the risk factors for bleeding complications in ECPR patients. METHODS: We retrospectively analyzed the data for OHCA patients admitted to our hospital and resuscitated with ECPR between October 2009 and December 2016. We compared patients with and without major bleeding (i.e. the Bleeding Academic Research Consortium class≥3 bleeding) within 24h of hospital admission. Patients, whose bleeding complication was not evaluated, were excluded. RESULTS: During the study period, 133 OHCA patients were resuscitated with ECPR, of whom 102 (77%) were included. In total, 71 (70%) patients experienced major bleeding. There were significant differences in age (median 65 vs. 50years, P<0.001), prior antiplatelet therapy (25% vs. 3%, P=0.008), hemoglobin (median 11.6 vs. 12.6g/dL, P=0.003), platelet count (median 125 vs. 155×103/µL, P=0.001), and D-dimer levels on admission (median 18.8 vs. 6.7µg/mL, P<0.001) among patients with and those without major bleeding. Multivariate analysis showed significant associations between major bleeding and D-dimer levels (odds ratio, 1.066; 95% confidence interval, 1.018-1.116). Area under receiver-operating characteristic curve, which describes the accuracy of D-dimer levels in predicting major bleeding, was 0.76 (95% confidence interval, 0.66-0.87). CONCLUSION: D-dimer levels may predict major bleeding in ECPR patients, suggesting that hyperfibrinolysis may be related to bleeding.

The Prognosis of Severe Acute Pancreatitis Varies According to the Segment Presenting With Low Enhanced Pancreatic Parenchyma on Early Contrast-Enhanced Computed Tomography: A Multicenter Cohort Study.

OBJECTIVE: The aim of this study was to investigate the outcomes of severe acute pancreatitis (SAP) according to the segment presenting with low enhanced pancreatic parenchyma (LEPP) on early contrast-enhanced computed tomography. METHODS: This was a post hoc analysis of a multicenter, retrospective study conducted at 44 institutions in Japan. Patients diagnosed as having SAP according to the Japanese Severity Score between January 2009 and December 2013 were included. We compared the effect of LEPP in each segment on mortality. RESULTS: A total of 1097 patients were assessed. The numbers of patients with LEPP in the pancreatic head (Ph), body (Pb), or tail (Pt) were 272, 273, and 204 (with some overlaps), respectively. In multivariate analysis, LEPP in Ph and Pt was significantly related to mortality (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.11-3.40 [P < 0.05], for LEPP in Ph; OR, 2.44; 95% CI, 1.27-4.67 [P < 0.05], for LEPP in Pt), but LEPP in Pb was unrelated to mortality (OR, 0.70; 95% CI, 0.35-1.37; P = 0.30). CONCLUSIONS: Presence of LEPP in Ph and Pt on early contrast-enhanced computed tomography was independently associated with increased mortality in SAP. These patients require close observation to ensure timely and adequate intervention.