Nobuya Kitamura

Japanese guidelines for the management of acute pancreatitis: Japanese Guidelines 2015.

Japanese (JPN) guidelines for the management of acute pancreatitis were published in 2006. The severity assessment criteria for acute pancreatitis were later revised by the Japanese Ministry of Health, Labour and Welfare (MHLW) in 2008, leading to their publication as the JPN Guidelines 2010. Following the 2012 revision of the Atlanta Classifications of Acute Pancreatitis, in which the classifications of regional complications of pancreatitis were revised, the development of a minimally invasive method for local complications of pancreatitis spread, and emerging evidence was gathered and revised into the JPN Guidelines.

Blood Purification for Prevention and Treatment of Multiple Organ Failure

Abstract. Blood purification has been applied conventionally as an artificial kidney or artificial liver in the management of patients with multiple organ failure (MOF), and most blood purifications have been performed intermittently. Recent advances in medical engineering made it possible to perform such blood purifications continuously (i.e., 24 hours a day, 7 days a week if necessary) even in critically ill patients. This modality is referred to as continuous renal replacement therapy (CRRT) or continuous blood purification (CBP). Among many kinds of CBP, continuous hemodiafiltration (CHDF) is most useful for management of MOF, as it can be performed without serious or hazardous side effects, and improvement can be expected with it. Recently, CHDF and polymyxin B immobilized endotoxin adsorption columns were used for the prevention or treatment of MOF, with the expectation that such therapy can be effective as a countermeasure against the pathophysiologic causes of MOF. Our data and that of others clearly indicate that continuous blood purification, such as with CHDF and endotoxin adsorption, can remove or decrease the blood levels of humoral mediators, including proinflammatory cytokines, and can improve tissue oxygenation, especially oxygen consumption (VO 2 ) among critically ill patients including those with MOF. Blood purification is also useful in the careful management of fluid, electrolytes, and acid-base balance and for the removal of metabolic wastes. Blood purification is now considered to be one of the basic therapeutic tools of critical care, equal to nutritional support with total parenteral nutrition and respiratory support without a ventilator.

Usefulness of plasma exchange plus continuous hemodiafiltration to reduce adverse effects associated with plasma exchange in patients with acute liver failure.

ObjectiveTo efficiently remove middle-molecular-weight substances such as hepatic toxins and minimize adverse effects associated with plasma exchange implementation, we have performed plasma exchange slowly in combination with continuous hemodiafiltration. This study was designed to determine the usefulness of plasma exchange with continuous hemodiafiltration in reducing the adverse effects associated with implementation of plasma exchange alone. DesignA retrospective clinical study. SettingUniversity teaching hospital. PatientsThe study involved 90 patients with liver failure who had been treated with plasma exchange in our department over the past 12 yrs. We examined these patients by dividing them into two groups (48 patients treated with plasma exchange alone and 42 patients treated with plasma exchange plus continuous hemodiafiltration at the time of plasma exchange implementation). Measurements and Main Results Baseline blood Na+ concentration, HCO3− concentration, and colloid osmotic pressure were followed after implementation of plasma exchange to compare the frequency of development of three adverse effects (hypernatremia, metabolic alkalosis, and sharp decrease in colloid osmotic pressure) in the two groups. Hypernatremia was found in 26.7% of treatments in the group with plasma exchange alone and 3.3% in the group of plasma exchange plus continuous hemodiafiltration, and metabolic alkalosis was found in 30.6% of treatments in the group with plasma exchange alone and 4.9% in the group of plasma exchange plus continuous hemodiafiltration; both percentages were significantly higher in the group with plasma exchange alone (p < .001). A sharp decrease in colloid osmotic pressure occurred in 13.3% of treatments in the group with plasma exchange alone but was not observed at all in the patients treated with plasma exchange plus continuous hemodiafiltration. ConclusionsWe conclude that adverse effects associated with plasma exchange for artificial liver support for liver failure can be alleviated with use of plasma exchange plus continuous hemodiafiltration instead of plasma exchange alone.

Autophagy-Related IRGM Polymorphism Is Associated with Mortality of Patients with Severe Sepsis

Objective Autophagy is the regulated catabolic process for recycling damaged or unnecessary organelles, which plays crucial roles in cell survival during nutrient deficiency, and innate immune defense against pathogenic microorganisms. Autophagy has been also reported to be involved in various conditions including inflammatory diseases. IRGM (human immunity-related GTPase) has an important function in eliminating Mycobacterium tuberculosis from host cells via autophagy. We examined the association between genetic polymorphism and clinical course/outcome in severely septic patients. Methods The study included 125 patients with severe sepsis/septic shock (SS) and 104 non-sepsis patients who were admitted to the intensive care unit (ICU) of Chiba University Hospital between October 2001 and September 2008 (discovery cohort) and 268 SS patients and 454 non-sepsis patients who were admitted to ICUs of five Japanese institutions including Chiba University Hospital between October 2008 and September 2012 (multi-center validation cohort). Three hundred forty seven healthy volunteers who consented to this study were also included. Genotyping was performed for a single-nucleotide polymorphism (SNP) within the coding region of IRGM, IRGM(+313) (rs10065172). Lipopolysaccharide challenge of whole blood from randomly selected healthy volunteers (n = 70) was performed for comparison of IRGM mRNA expression among different genotypes. Results No significant difference in genotypic distributions (CC/CT/TT) at the IRGM(+313) locus was observed among the three subject groups (SS, non-sepsis, and healthy volunteers) in either cohort. When mortality were compared, no significant difference was observed in the non-sepsis group, while TT homozygotes exhibited a significantly higher mortality than the CC+CT genotype category in the SS group for both cohorts (P = 0.043, 0.037). Lipopolysaccharide challenge to whole blood showed a significant suppression of IRGM mRNA expression in TT compared with the CC+CT genotype category (P = 0.019). Conclusions The data suggest that the IRGM(+313), an autophagy-related polymorphic locus, influences outcome in severely septic patients, with the possible involvement of autophagy in sepsis exacerbation.

Continuous Hemodiafiltration with a Cytokine-Adsorbing Hemofilter in Patients with Septic Shock: A Preliminary Report

Background/Aim: We investigated the clinical efficacy of continuous hemodiafiltration (CHDF) with AN69ST hemofilter (AN69ST-CHDF) in patients with septic shock. Materials and Methods: A prospective, multicenter, single-arm study was conducted. Patients with sepsis and shock defined by hyperlactemia were enrolled. The patients were treated with CHDF and in accordance with the Surviving Sepsis Campaign guidelines (SSCG). Results: Thirty-four patients were enrolled. On ICU admission, the mean blood IL-6 level was 44,800 ± 77,700 pg/ml, and the mean blood lactate level was 69.0 ± 49.4 mg/dl. Both the mean blood IL-6 and lactate levels had significantly decreased to normal ranges after 72 h of AN69ST-CHDF. Though the mean APACHE II score was 32.7 ± 9.8, 28-day survival was 73.5%. Conclusion: The current study suggested that adding AN69ST-CHDF to the treatments outlined in the SSCG might lead to good outcomes for patients with septic shock, probably via the removal of cytokines from the bloodstream.

Subsequent shock deliveries are associated with increased favorable neurological outcomes in cardiac arrest patients who had initially non-shockable rhythms.

IntroductionPrevious studies evaluating whether subsequent conversion to shockable rhythms in patients who had initially non-shockable rhythms was associated with altered clinical outcome reported inconsistent results. Therefore, we hypothesized that subsequent shock delivery by emergency medical service (EMS) providers altered clinical outcomes in patients with initially non-shockable rhythms.MethodsWe tested for an association between subsequent shock delivery in EMS resuscitation and clinical outcomes in patients with initially non-shockable rhythms (n = 11,481) through a survey of patients after out-of-hospital cardiac arrest in the Kanto region (SOS-KANTO) 2012 study cohort, Japan. The primary investigated outcome was 1-month survival with favorable neurological functions. The secondary outcome variable was the presence of subsequent shock delivery. We further evaluated the association of interval from initiation of cardiopulmonary resuscitation to shock with clinical outcomes.ResultsIn the univariate analysis of initially non-shockable rhythms, patients who received subsequent shock delivery had significantly increased frequency of return of spontaneous circulation, 24-hour survival, 1-month survival, and favorable neurological outcomes compared to the subsequent not shocked group (P <0.0001). In the multivariate logistic regression analysis, subsequent shock was significantly associated with favorable neurological outcomes (vs. not shocked; adjusted P = 0.0020, odds ratio, 2.78; 95 % confidence interval, 1.45–5.30). Younger age, witnessed arrest, initial pulseless electrical activity rhythms, and cardiac etiology were significantly associated with the presence of subsequent shock in patients with initially non-shockable rhythms.ConclusionsIn this study of cardiac arrest patients with initially non-shockable rhythms, patients who received early defibrillation by EMS providers had increased 1-month favorable neurological outcomes.

Modulation of Polymorphonuclear Leukocyte Apoptosis in the Critically Ill by Removal of Cytokines with Continuous Hemodiafiltration

Delay of polymorphonuclear leukocyte (PMN) apoptosis caused by hypercytokinemia is considered to be a potential cause of tissue damage and resultant organ failure. We evaluated whether continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF), which can remove cytokines in the circulating blood, can modulate apoptosis in peripheral blood neutrophils and thereby reduce tissue damage and organ dysfunction in 25 critically ill patients. Following the completion of a 3-day PMMA-CHDF session, serum cytokine levels were significantly decreased and the percentage of apoptotic PMNs was significantly increased. A significant correlation was observed between the PMMA-CHDF-induced increase in the percentage of apoptotic PMNs and the degree of decrease in the serum interleukin-6 level. A significant correlation was also found between the increase in the percentage of apoptotic PMNs and improvement in sequential organ failure assessment score following PMMA-CHDF. These results suggest that PMMA-CHDF in critically ill patients with hypercytokinemia and concomitant delay in apoptosis of PMNs can alleviate the delay of PMN apoptosis through the removal of serum cytokines and thus may result in avoidance of organ dysfunction.

Efficacy of continuous hemodiafiltration for patients with congestive heart failure.

Background/Aims: The basic principle of treatment of congestive heart failure is achieving adequate control of preload and afterload through enhancement of cardiac contractility. In severe cases, however, we have usually applied continuous hemodiafiltration (CHDF) as a type of mechanical support. In this study, we investigated hemodynamic changes caused by CHDF in patients with congestive heart failure. Methods: We treated seven patients with congestive heart failure complicated by multiple organ failure by CHDF over 72 h, during which we measured hemodynamic parameters to determine their changes. Results: Implementation of CHDF resulted in a significant decrease in pulmonary artery occluded pressure and significant increases in cardiac index and left ventricular stroke work index. In addition, 72-hour cumulative water balance was found to be –1,791 ± 2,119 ml, and systemic vascular resistance index decreased significantly. Conclusion: Hemodynamics of patients were improved with CHDF through strict control of preload and consequently tissue oxygen metabolism was improved.

Efficacy and Bleeding Risk of Antithrombin Supplementation in Patients With Septic Disseminated Intravascular Coagulation A Third Survey

Introduction: Although recent studies have reported the efficacy of antithrombin (AT) supplementation for sepsis-associated disseminated intravascular coagulation (DIC), the factors that influence AT’s effect have not been sufficiently studied. The purpose of this survey was to identify factors that modulate the effects and the adverse effects of AT. Methods: We performed a multi-institutional survey. The data from 159 patients with septic DIC with AT ≤70% and who had undergone AT supplementation were analyzed. The patients’ demographic characteristics, including the infection site, baseline sepsis-related organ failure assessment (SOFA) score, baseline DIC score, and baseline AT activity, were analyzed in relation to the 28-day mortality. Bleeding-related adverse events were also examined. Results: Overall, 116 patients survived and 43 did not (28-day mortality: 27.0%). A logistic regression analysis revealed that the baseline SOFA score (odds ratio [OR]: 0.816, P = .001), coadministration of recombinant thrombomodulin (rTM; OR: 3.989, P = .006), and respiratory tract infection (OR: 0.129, P = .000) were significantly associated with the survival. Survivors exhibited a higher peak AT activity than nonsurvivors (85.1% vs 65.0%, P = .027). Bleeding events were observed in 4.13% (major bleeding: 1.65%) of the patients, and the coadministration of rTM did not increase the risk of bleeding (with rTM: 4.11% vs without rTM: 4.17%). Heparin was concomitantly used in 22 (18.2%) cases, and its use nonsignificantly increased the bleeding risk (with heparins: 9.09% vs without heparins: 3.03%; P = .224). Conclusion: The coadministration of rTM may improve survival without increasing the risk of bleeding in patients with sepsis-associated DIC treated with AT.

Nutritional Support for the Patient with Multiple Organ Failure in Gastroenterological Surgery.

消化器外科領域の多臓器不全 (multiple organ failure;MOF) 70例を対象に, いかにして代謝動態を把握し, いかなる栄養管理を施行すればよいかを検討した.代謝動態の把握には, indirect calorimetryによるエネルギ-消費量, respiratory quotient, %FAT, 動脈血中ケトン体比 (arterial ketone body ratio; AKBR) およびケトン体量, 血中乳酸値などが有効であった.MOF患者はhypermetabolicで, 基礎エネルギー消費量の140～150%を消費しており, AKBRの低下している肝不全合併MOF症例では, エネルギー基質の利用制限や蛋白代謝の低下が観察された.全症例に対して中心静脈栄養法を施行した.消費エネルギー量相当のエネルギ-量の投与は肝不全合併MOFおよび腎不全合併MOFで困難であったが, 前者ではATP-Mgやplasma exchangeの併用が, 後者では持続的血液濾過や持続的血液濾過透析の併用が有効であった.また分枝鎖アミノ酸を多量に含む製剤は有用であった.