Lacosamide Intoxication-induced Wide QRS Tachycardia Successfully Treated with Veno-arterial Extracorporeal Membrane Oxygenation.

Lacosamide is an antiepileptic drug that acts on voltage-gated sodium channels and was approved as an antiepileptic by the Food and Drug Administration in 2008. Although the efficacy and safety of lacosamide have been established in many previous trials, some case reports have shown that it may lead to cardiovascular side effects, especially in patients with electrical conduction system disorders. We herein report a case of life-threatening cardiac arrhythmia caused by lacosamide intoxication that was successfully treated with veno-arterial extracorporeal membrane oxygenation.

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.

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.

Biomarker profiles of coagulopathy and alveolar epithelial injury in acute respiratory distress syndrome with idiopathic/immune-related disease or common direct risk factors.

BACKGROUND: Altered coagulation and alveolar injury are the hallmarks of acute respiratory distress syndrome (ARDS). However, whether the biomarkers that reflect pathophysiology differ depending on the etiology of ARDS has not been examined. This study aimed to investigate the biomarker profiles of coagulopathy and alveolar epithelial injury in two subtypes of ARDS: patients with direct common risk factors (dARDS) and those with idiopathic or immune-related diseases (iARDS), which are classified as "ARDS without common risk factors" based on the Berlin definition. METHODS: This retrospective, observational study included adult patients who were admitted to the intensive care unit (ICU) at a university hospital with a diagnosis of ARDS with no indirect risk factors. Plasma biomarkers (thrombin-antithrombin complex [TAT], plasminogen activator inhibitor [PAI]-1, protein C [PC] activity, procalcitonin [PCT], surfactant protein [SP]-D, and KL-6) were routinely measured during the first 5 days of the patient's ICU stay. RESULTS: Among 138 eligible patients with ARDS, 51 were excluded based on the exclusion criteria (n = 41) or other causes of ARDS (n = 10). Of the remaining 87 patients, 56 were identified as having dARDS and 31 as having iARDS. Among the iARDS patients, TAT (marker of thrombin generation) and PAI-1 (marker of inhibited fibrinolysis) were increased, and PC activity was above normal. In contrast, PC activity was significantly decreased, and TAT or PAI-1 was present at much higher levels in dARDS compared with iARDS patients. Significant differences were also observed in PCT, SP-D, and KL-6 between patients with dARDS and iARDS. The receiver operating characteristic (ROC) analysis showed that areas under the ROC curve for PC activity, PAI-1, PCT, SP-D, and KL-6 were similarly high for distinguishing between dARDS and iARDS (PC 0.86, P = 0.33; PAI-1 0.89, P = 0.95; PCT 0.89, P = 0.66; and SP-D 0.88, P = 0.16 vs. KL-6 0.90, respectively). CONCLUSIONS: Coagulopathy and alveolar epithelial injury were observed in both patients with dARDS and with iARDS. However, their biomarker profiles were significantly different between the two groups. The different patterns of PAI-1, PC activity, SP-D, and KL-6 may help in differentiating between these ARDS subtypes.

Influence of contrast media on renal function and outcomes in patients with sepsis-associated acute kidney injury: a propensity-matched cohort study.

BACKGROUND: Recent studies have suggested a low potential risk for contrast medium-induced kidney injury in patients with relatively normal renal function. However, whether contrast media cause additional deterioration of renal function in patients with acute kidney injury (AKI), including those with sepsis-associated AKI, remains unclear. This study aimed to evaluate the effect of contrast media on renal function and mortality in patients with sepsis who already had AKI. METHODS: We performed a propensity score-matched historical cohort study in the medico-surgical intensive care unit of Jichi Medical University Hospital. Adult patients who were diagnosed with sepsis and AKI were enrolled. Records from our sepsis database from 2011 to 2017 were examined. Septic patients with AKI who received contrast media within 24 h of admission (C group) were matched 1:1 with septic patients who did not receive contrast media (NC group). The primary outcome was deterioration of kidney function (DRF), which was defined as an elevation of serum creatinine levels (> 0.3 mg/dL or 1.5-fold from baseline) or induction of renal replacement therapy. RESULTS: A total of 339 septic patients with AKI were included. After propensity score adjustment, the DRF rate was similar between the C and NC groups (34.0% versus 35.0%; P = 1.00). The 7-day mortality (3.0% versus 6.0%; P = 0.50), 28-day mortality (9.2% versus 15.0%; P = 0.25), and 90-day mortality (25.8% versus 32.1%; P = 0.45) rates were comparable between the two groups. In propensity-adjusted subsets of a high-risk subset (AKI stages 2 and 3 on admission), the rate of DRF was also similar between the two groups. CONCLUSIONS: A single administration of contrast media was not associated with exacerbation of AKI or increased short/long-term mortality in patients with sepsis.

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.

Thrombomodulin, Plasminogen Activator Inhibitor-1 and Protein C Levels, and Organ Dysfunction in Sepsis.

Since endothelial function is closely related to organ dysfunction in sepsis and the relationship among endothelial injury, organ dysfunction, and other biomarkers remains unclear, we aimed to evaluate the correlation among endothelial injury, organ dysfunction, and several biomarkers in patients with sepsis. DESIGN: This was a retrospective observational study. SETTING: The study was conducted in a university hospital with 14 mixed ICU beds. PATIENTS: ICU patients with sepsis from June 2011 to December 2017 were enrolled in this study. INTERVENTIONS: Endothelial biomarkers (soluble thrombomodulin, plasminogen activator inhibitor-1, and protein C) and markers of inflammation and coagulation were evaluated during the ICU stay. Sequential Organ Failure Assessment scores were assessed for 7 days after ICU admission to determine organ dysfunction. Variables were compared among five stratified groups according to the Sequential Organ Failure Assessment score (0-2, 3-5, 6-8, 9-12, and 13-24). Regression analysis and 95% CIs were used to evaluate trends in biomarkers. MEASUREMENTS AND MAIN RESULTS: The patients were divided into five stratified groups (Sequential Organ Failure Assessment 0-2, n = 159 [20.5%]; Sequential Organ Failure Assessment 3-5, n = 296 [38.2%]; Sequential Organ Failure Assessment 6-8, n = 182 [23.5%]; Sequential Organ Failure Assessment 9-12, n = 75 [9.7%]; Sequential Organ Failure Assessment 13-24, n = 31 [4.0%]). Protein C activity was significantly correlated with the severity of organ dysfunction. It was lower on day 1, increased upon successful treatment, and was significantly higher in groups with lower Sequential Organ Failure Assessment scores. CONCLUSIONS: Trends and activity of protein C were superior in predicting organ dysfunction compared with other endothelial biomarkers. Monitoring the level of protein C activity is an ideal tool to monitor organ dysfunctions in patients with sepsis.

Transient hyperlactatemia during intravenous administration of glycerol: a prospective observational study.

BACKGROUND: Intravenous glycerol treatment, usually administered in the form of a 5% fructose solution, can be used to reduce intracranial pressure. The administered fructose theoretically influences blood lactate levels, although little is known regarding whether intravenous glycerol treatment causes transient hyperlactatemia. This study aimed to evaluate blood lactate levels in patients who received intravenous glycerol or mannitol. METHODS: This single-center prospective observational study was performed at a 14-bed general intensive care unit between August 2016 and January 2018. Patients were excluded if they were < 20 years old or had pre-existing hyperlactatemia (blood lactate > 2.0 mmol/L). The included patients received intravenous glycerol or mannitol to reduce intracranial pressure and provided blood samples for lactate testing before and after the drug infusion (before the infusion and after 15 min, 30 min, 45 min, 60 min, 90 min, 120 min, and 150 min). RESULTS: Among the 33 included patients, 13 patients received 200 mL of glycerol over 30 min, 13 patients received 200 mL of glycerol over 60 min, and 7 patients received 300 mL of mannitol over 60 min. Both groups of patients who received glycerol had significantly higher lactate levels than the mannitol group (2.8 mmol/L vs. 2.2 mmol/L vs. 1.6 mmol/L, P < 0.0001), with the magnitude of the increase in lactate levels corresponding to the glycerol infusion time. There were no significant inter-group differences in cardiac index, stroke volume, or stroke volume variation. In the group that received the 30-min glycerol infusion, blood lactate levels did not return to the normal range until after 120 min. CONCLUSIONS: Intravenous administration of glycerol leads to higher blood lactate levels that persist for up to 120 min. Although hyperlactatemia is an essential indicator of sepsis and/or impaired tissue perfusion, physicians should be aware of this phenomenon when assessing the blood lactate levels.

Body weight definitions for evaluating a urinary diagnosis of acute kidney injury in patients with sepsis.

BACKGROUND: We hypothesized that the use of actual body weight might lead to more frequent misdiagnosis of acute kidney injury (AKI) than when ideal body weight is used in underweight and/or obese patients. We examined which definition of body weight is most effective in establishing a urinary diagnosis of AKI in septic patients. METHODS: Consecutive patients aged ≥ 20 years admitted to the intensive care unit of a university hospital between June 2011 and December 2016 were analyzed. Sepsis was defined in accordance with the Sepsis-3 criteria. AKI was defined as a urinary output of < 0.5 mL/kg/6h during intensive care unit stay. Patients were divided into one of four body mass index-based classes. The severity of illness and 90-day mortality were compared across the body mass index subgroups in patients diagnosed using the actual body weight or ideal body weight. RESULTS: Of 5764 patients, 569 septic patients were analyzed. One hundred and fifty-three (26.9%) and 140 (24.6%) patients were diagnosed as having AKI using actual body weight and ideal body weight, respectively. There were no significant differences in the severity of illness among these groups. Also, 90-day mortality did not differ significantly among these groups. According to body mass index, 90-day mortality significantly differed in patients diagnosed using their actual body weights (underweight vs. normal vs. overweight vs. obese: 76.7% vs. 39.5% vs. 26.0% vs. 35.7%, P = 0.033). CONCLUSION: Generally, using actual body weight to calculate the weight-adjusted hourly urine output for diagnosing AKI increased the sensitivity compared to ideal body weight, irrespective of the severity of illness in septic patients. Delayed diagnosis, however, was more common among underweight patients in this situation, and clinicians should be cautious when diagnosing urinary AKI using actual body weight.

Time course of immature platelet count and its relation to thrombocytopenia and mortality in patients with sepsis.

INTRODUCTION: The pathogenesis of thrombocytopenia in patients with sepsis is not fully understood. The aims of this study were to investigate changes in thrombopoietic activity over time by using absolute immature platelet counts (AIPC) and to examine the impact of platelet production on thrombocytopenia and mortality in patients with sepsis. METHODS: This retrospective observational study included adult patients with sepsis admitted to the intensive care unit at a university hospital. Two hundred five consecutive sepsis patients were stratified into four groups according to nadir platelet count: severe (nadir ≤40×103/µL), moderate (41-80×103/µL), or mild thrombocytopenia (81-120×103/µL), or normal-increased platelet count (>120×103/µL). The development of thrombocytopenia was assessed during the first week; mortality was assessed at day 28. RESULT: Of the 205 patients included, 61 (29.8%) developed severe thrombocytopenia. On admission, AIPC did not differ among the four groups. In patients with severe thrombocytopenia, AIPC decreased significantly from days 2 to 7, but remained within or above the normal range in the other three groups (overall group comparison, P<0.0001). Multivariate analysis including coagulation biomarkers revealed that AIPC was independently associated with the development of severe thrombocytopenia (day 3 AIPC, odds ratio 0.49 [95% confidence interval (CI) 0.35-0.66], P<0.0001; day 5 AIPC, 0.59 [95% CI 0.45-0.75], P<0.0001). AIPC was a significant predictor of 28-day mortality in Cox hazard models adjusted for Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores (day 3 AIPC, hazard ratio 0.70 [95% CI 0.52-0.89], P = 0.0029; day 5 AIPC, 0.68 [95% CI 0.49-0.87], P = 0.0012). CONCLUSIONS: Thrombopoietic activity was generally maintained in the acute phase of sepsis. However, a decrease in AIPC after admission was independently associated with the development of severe thrombocytopenia and mortality, suggesting the importance of suppressed thrombopoiesis in the pathophysiology of sepsis-induced thrombocytopenia.

Markers of acute kidney injury in patients with sepsis: the role of soluble thrombomodulin.

BACKGROUND: Endothelial activation and damage occur early during sepsis, with activated coagulopathy and playing a major role in the pathophysiology of sepsis-induced acute kidney injury (AKI). The aim of this study was to compare the various biomarkers of endothelial injury with the biomarkers of coagulation and inflammation and to determine a significant predictor of AKI in patients with sepsis. METHODS: We conducted a single-center, retrospective, observational study on patients with sepsis fulfilling the Third International Consensus Definitions for Sepsis and Septic Shock criteria admitted to an adult intensive care unit (ICU) at a university hospital from June 2011 to December 2016. Levels of 13 biomarkers were measured on ICU admission, including markers of endothelial injury (soluble thrombomodulin [sTM], E-selectin, protein C, and plasminogen activator inhibitor-1 [PAI-1]) and markers of coagulation derangement (platelet count, fibrin degradation product [FDP], prothrombin time [PT], fibrinogen, α2-plasminogen inhibitor [α2-PI], antithrombin III [AT III], plasminogen, thrombin-antithrombin complex, and plasmin-α2-plasmin inhibitor complex). All patients with sepsis were reviewed, and the development of AKI was evaluated. Multivariate logistic regression analysis was performed to identify significant independent predictive factors for AKI. RESULTS: Of the 514 patients admitted with sepsis, 351 (68.3%) developed AKI. Compared with the non-AKI group, all the endothelial biomarkers were significantly different in the AKI group (sTM [23.6 vs. 15.6 U/ml, P < 0.0001], E-selectin [65.5 vs. 46.2 ng/ml, P = 0.0497], PAI-1 [180.4 vs. 75.3 ng/ml, P = 0.018], and protein C [45.9 vs. 58.7 ng/ml, P < 0.0001]). Biomarkers of coagulopathy and inflammation, platelet counts, FDP, PT, α2-PI, AT III, plasminogen, and C-reactive protein were significantly different between the two groups. Multivariable logistic regression analysis showed that sTM was an independent predictive factor of AKI, with an AUROC of 0.758 (P < 0.0001). CONCLUSIONS: Endothelial biomarkers were significantly changed in the sepsis patients with AKI. Particularly, sTM was an independent predictive biomarker for the development of AKI that outperformed other coagulation and inflammation biomarkers as well as organ function in patients with sepsis.

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.

Validation of the efficacy of the prognostic factor score in the Japanese severity criteria for severe acute pancreatitis: A large multicenter study.

BACKGROUND: The Japanese severity criteria for acute pancreatitis (AP), which consist of a prognostic factor score and contrast-enhanced computed tomography grade, have been widely used in Japan. OBJECTIVE: This large multicenter retrospective study was conducted to validate the predictive value of the prognostic factor score for mortality and complications in severe AP patients in comparison to the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. METHODS: Data of 1159 patients diagnosed with severe AP according to the Japanese severity criteria for AP were retrospectively collected in 44 institutions. RESULTS: The area under the curve (AUC) for the receiver-operating characteristic curve of the prognostic factor score for predicting mortality was 0.78 (95% confidence interval (CI), 0.74-0.82), whereas the AUC for the APACHE II score was 0.80 (95% CI, 0.76-0.83), respectively. There were no significant differences in the AUC for predicting mortality between two scoring systems. The AUCs of the prognostic factor scores for predicting the need for mechanical ventilation, the development of pancreatic infection, and severe AP according to the revised Atlanta classification were 0.84 (95% CI, 0.81-0.86), 0.73 (95% CI, 0.69-0.77), and 0.83 (95% CI, 0.81-0.86), respectively, which were significantly greater than the AUCs for the APACHE II score; 0.81 (95% CI, 0.78-0.83) for the need for mechanical ventilation (p = 0.03), 0.68 (95% CI, 0.63-0.72) for the development of pancreatic infection (p = 0.02), and 0.80 (95% CI, 0.77-0.82) for severe AP according to the revised Atlanta classification (p = 0.01). CONCLUSION: The prognostic factor score has an equivalent ability for predicting mortality compared with the APACHE II score. Regarding the ability for predicting the development of severe complications during the clinical course of AP, the prognostic factor score may be superior to the APACHE II score.

Continuous Regional Arterial Infusion of Protease Inhibitors Has No Efficacy in the Treatment of Severe Acute Pancreatitis: A Retrospective Multicenter Cohort Study.

OBJECTIVE: The aim of this study is to assess the effectiveness of continuous regional arterial infusion (CRAI) of protease inhibitors in patients with severe acute pancreatitis (SAP) including acute necrotizing pancreatitis. METHODS: This retrospective study was conducted among 44 institutions in Japan from 2009 to 2013. Patients 18 years or older diagnosed with SAP according to the criteria of the Japanese Ministry of Health, Labour and Welfare study group (2008) were consecutively enrolled. We evaluated the association between CRAI of protease inhibitors and mortality, incidence of infection, and the need for surgical intervention using multivariable logistic regression analysis. RESULTS: Of 1159 patients admitted, 1097 patients with all required data were included for analysis. Three hundred and seventy-four (34.1%) patients underwent CRAI of protease inhibitors and 723 (65.9%) did not. In multivariable analysis, CRAI of protease inhibitors was not associated with a reduction in mortality, infection rate, or need for surgical intervention (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.47-1.32, P = 0.36; OR 0.97, 95% CI 0.61-1.54, P = 0.89; OR 0.76, 95% CI 0.50-1.15, P = 0.19; respectively). CONCLUSIONS: Continuous regional arterial infusion of protease inhibitors was not efficacious in the treatment of patients with SAP.

Immature platelet fraction predicts coagulopathy-related platelet consumption and mortality in patients with sepsis.

INTRODUCTION: The diagnostic and prognostic value of immature platelet fraction (IPF) in sepsis has not been determined. This study aimed to assess whether IPF is an early predictor of platelet decline due to coagulopathy and is associated with mortality in patients with sepsis. MATERIALS AND METHODS: In total, 149 patients with a platelet count of ≥80×10(3)/µL on intensive care unit admission (101 with sepsis, 48 controls without sepsis) were prospectively evaluated. We measured IPF on admission and observed for development of subsequent platelet count decline (defined as a >30% decrease or <80×10(3)/µL) in 5days, and mortality at 28days. The absolute immature platelet count (AIPC) was calculated to evaluate thrombopoiesis. RESULTS: Forty-seven patients with sepsis subsequently developed a decrease in platelet count. The IPF was highest in patients whose platelet count decreased, followed by patients without a decrease in platelet count and controls (median, 4.3% [3.1%-8.1%] vs. 3.7% [2.6%-4.6%] vs. 2.1% [1.6%-3.5%], respectively; P<0.0001). The AIPC was similar in patients with and without a decrease in platelet count (7.6 [4.2-10.0] vs. 5.9 [4.2-8.7]×10(3)/µL, respectively; P=0.32). Coagulation derangement was more severe in patients who did than did not subsequently develop a decreased platelet count. Cox regression and receiver operator characteristic curve analysis revealed that IPF was a strong independent predictor of mortality, with accuracy similar to a standard prognostic scoring system. CONCLUSIONS: The admission IPF in septic patients predicts a subsequent decrease in platelet count, indicating platelet consumption with ongoing coagulopathy and risk of poor prognosis.

Combination of thrombin-antithrombin complex, plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study.

INTRODUCTION: Current criteria for early diagnosis of coagulopathy in sepsis are limited. We postulated that coagulopathy is already complicated with sepsis in the initial phase, and severe coagulopathy or disseminated intravascular coagulation (DIC) becomes overt after progressive consumption of platelet and coagulation factors. To determine early diagnostic markers for severe coagulopathy, we evaluated plasma biomarkers for association with subsequent development of overt DIC in patients with sepsis. METHODS: A single-center, prospective observational study was conducted in an adult ICU at a university hospital. Plasma samples were obtained from patients with sepsis at ICU admission. Fourteen biomarkers including global markers (platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen and fibrin degradation product (FDP)); markers of thrombin generation (thrombin-antithrombin complex (TAT) and soluble fibrin); markers of anticoagulants (protein C (PC) and antithrombin); markers of fibrinolysis (plasminogen, α2-plasmin inhibitor (PI), plasmin-α2-PI complex, and plasminogen activator inhibitor (PAI)-1); and a marker of endothelial activation (soluble E-selectin) were assayed. Patients who had overt DIC at baseline were excluded, and the remaining patients were followed for development of overt DIC in 5 days, and for mortality in 28 days. RESULTS: A total of 77 patients were enrolled, and 37 developed overt DIC within the following 5 days. Most patients demonstrated hemostatic abnormalities at baseline with 98.7% TAT, 97.4% FDP and 88.3% PC. Most hemostatic biomarkers at baseline were significantly associated with subsequent development of overt DIC. Notably, TAT, PAI-1 and PC discriminated well between patients with and without developing overt DIC (area under the receiver operating characteristic curve (AUROC), 0.77 (95% confidence interval, 0.64 to 0.86); 0.87 (0.78 to 0.92); 0.85 (0.76 to 0.91), respectively), and using the three together, significantly improved the AUROC up to 0.95 (vs. TAT, PAI-1, and PC). Among the significant diagnostic markers for overt DIC, TAT and PAI-1 were also good predictors of 28-day mortality (AUROC, 0.77 and 0.81, respectively). CONCLUSIONS: Severe coagulation and fibrinolytic abnormalities on ICU admission were associated with subsequent development of overt DIC. A single measurement of TAT, PAI-1, and PC activity could identify patients with ongoing severe coagulopathy, early in the course of sepsis.

Concurrent treatment with a tumor necrosis factor-alpha inhibitor and veno-venous extracorporeal membrane oxygenation in a post-hematopoietic stem cell transplant patient with idiopathic pneumonia syndrome: a case report.

Idiopathic pneumonia syndrome (IPS) is a fatal non-infectious respiratory complication that develops after hematopoietic stem cell transplantation (HSCT). Because of the poor prognosis of post-HSCT patients with IPS requiring mechanical ventilatory support, performing extracorporeal membrane oxygenation (ECMO) has been regarded as relatively contraindicated in these patients. A tumor necrosis factor-alpha inhibitor, etanercept, has been reported to be a promising treatment option for post-HSCT patients with IPS; however, the phase III clinical trial of etanercept has recently been terminated without definitive conclusion. If post-HSCT patients with IPS really benefit from etanercept, mechanical ventilation (MV)-dependent IPS patients might be worth receiving ECMO treatment in line with the protective lung strategy. We therefore performed veno-venous ECMO (VV-ECMO), which substantially acted as an extracorporeal carbon dioxide removal, on a 56-year-old post-HSCT male with severe MV-dependent IPS due to graft-versus-host disease. Although a serious bleeding complication due to post-HSCT thrombocytopenia occurred, the VV-ECMO was continued for 11 days. The patient successfully entered remission of the IPS and was finally extubated on the 12th MV day. However, the patient soon complained of dyspnea, probably due to cytomegalovirus infection and/or exacerbation of the IPS, and was reintubated after 3 days of extubation. The patient then rapidly developed irreversible type II respiratory failure despite the administration of etanercept and an anti-cytomegalovirus agent and died on the eighth re-MV day. The autopsy findings of the patient revealed diffuse alveolar damage and alveolar hemorrhage, accompanied with bronchitis obliterans in his lungs, as well as whole body cytomegalovirus infection, which were compatible with the clinical diagnosis of the patient. We think that the legitimacy of this treatment strategy is dependent on the overall prognosis of IPS, which is influenced by the complications induced by immunosuppressants and ECMO, especially infections and bleeding.