Polymyxin B-immobilized fiber hemoperfusion in a patient with active ulcerative colitis

A case involving a 31-year-old woman with active ulcerative colitis is described. She suffered symptoms of infraumbilical abdominal pain, severe diarrhea, and low-grade fever that did not improve with conventional treatment, including antidiarrheal drugs and antibiotics. Ulcerative colitis was diagnosed according to endoscopic and histologic findings. She was treated with prednisolone and sulfasalazine, and her symptoms disappeared after 1 month. Sulfasalazine therapy was continued for 3 months, and the patient's condition remained stable for 4 years. Recently, she was admitted with abdominal pain, severe diarrhea, and melena. She was again treated with prednisolone and intravenous hyperalimentation, but her symptoms did not improve. Colonoscopy showed multiple ulcers with bleeding and polyposis and severe edema in the colon. In addition, she had a high blood endotoxin concentration (38.0 pg/ml; normal < 9.8 pg/ml). She underwent polymyxin B-immobilized fiber (PMX-F) hemoperfusion therapy twice. After 2 weeks, her symptoms resolved completely, colonoscopy showed disappearance of the edema, revascularization of the mucosa, and improvement of the ulcers, and blood endotoxin concentration decreased to 5.0 pg/ml. These results suggest that PMX-F treatment may be beneficial for the management of ulcerative colitis with endotoxemia.     

Polymyxin B-immobilized fiber hemoperfusion in a high school football player with septic shock caused by osteitis pubis

A 17-year-old male high school football player treated by polymyxin B-immobilized fiber (PMX-F) hemoperfusion for mild-moderate septic shock caused by osteitis pubis is described in this study. He was admitted for inguinal pain, gait disturbance, and high fever (40.6°C). His white blood cell (WBC) count and C-reactive protein (CRP), endotoxin, and procalcitonin (PCT) levels were significantly elevated. His blood pressure was 76/46 mm Hg. Magnetic resonance imaging showed bone and muscle injury at the pubic symphysis. Septic shock with high blood endotoxin and PCT concentrations was diagnosed, and the patient was treated with antibiotics, γ-globulin, and dopamine on the admission day. However, the septic shock did not improve. On day 3, we performed direct hemoperfusion twice using a PMX-F column. After the second PMX-F treatment, the patient's temperature decreased to 37.0°C, and his WBC count, CRP levels, blood endotoxin, and PCT levels decreased. The inguinal pain diminished, and the patient's blood pressure increased to 112/76 mm Hg. He was discharged on day 10 after admission. This case reflects association of PMX-F with decreased endotoxin, PCT, and CRP, suggesting the association of PMX-F with clinical improvement in mild-moderate sepsis in a young athlete.     

Polymyxin B-immobilized fiber hemoperfusion attenuates increased plasma atrial natriuretic peptide and brain natriuretic Peptide levels in patients with septic shock

Polymyxin B-immobilized fiber (PMX-F) hemoperfusion is reported to be safe and effective in septic shock patients. Because atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) may have pathophysiologic significance in the cardiac dysfunction of septic shock patients, we conducted a study to determine whether PMX-F treatment affects plasma ANP and BNP levels in patients with septic shock. Fifty septic shock patients (34 men and 16 women; mean age 60.0 years) and 30 healthy volunteers (18 men and 12 women; mean age 56.0 years) were included in this study. Polymyxin B-immobilized fiber treatment was performed twice, separated by an interval of 24 hours. Blood endotoxin, interleukin (IL)-6, ANP, and BNP levels were measured before, immediately after the second PMX-F treatment, and the following day. In comparing patients with septic shock with healthy control subjects, we found significant increases in plasma endotoxin (p < 0.001), IL-6 (p < 0.001), ANP (p < 0.001), and BNP (p < 0.001). After the second PMX-F treatment, plasma levels of endotoxin (p < 0.01), IL-6 (p < 0.01), ANP (p < 0.01), and BNP (p < 0.01) were reduced significantly. Values decreased further the following day. Both plasma ANP and BNP levels are increased in septic shock patients and PMX-F treatment is effective in reducing these natriuretic peptide levels.     

Clinical responses and improvement of some laboratory parameters following polymyxin B-immobilized fiber treatment in septic shock

Direct hemoperfusion using a polymyxin B-immobilized fiber column (PMX; Toray Industries Inc., Tokyo, Japan) was first developed in 1994 and has since been used for the treatment of septic shock. Positive clinical data, such as an increase in systolic blood pressure (SBP) and an improved Pao2/Fio2 ratio, have also been reported. We treated 27 septic shock patients using DHP-PMX. The patients were separated into two groups for analysis: those whose Pao2/Fio2 ratio increased after DHP-PMX (9 cases) and those whose Pao2/Fio2 ratio did not increase after DHP-PMX (18 cases). The patients were also separated into two other groups for analysis: those whose SBP increased by more than 30 mm Hg immediately after DHP-PMX (15 cases) and those whose SBP did not increase by more than 30 mm Hg after DHP-PMX (12 cases). The Pao2/Fio2 ratio increased significantly after DHP-PMX in the groups showing improved 2AG and PAI-1 levels (p = 0.0040). The SBP increased significantly in the group showing improved HMGB-1 levels (p < 0.0001). We observed a relationship between hemodynamic improvement and increase of the serum HMGB-1 levels and between improvement of respiratory functions and increase of the serum 2-AG and PAI-1 levels in septic shock patients treated with DHP-PMX.     

Relationship between effect of polymyxin B-immobilized fiber and high-mobility group box-1 protein in septic shock patients

Direct hemoperfusion (DHP) using a polymyxin B (PMX)-immobilized fiber column has been used for treatment of endotoxemia-induced septic shock in Japan since 1994 and is now an accepted therapy for reducing serum endotoxin levels. Although a reduction in inflammatory cytokines has been reported, the detailed mechanism of DHP-PMX is not known. We investigated the high-mobility group box-1 (HMGB-1) level in septic shock patients treated with DHP-PMX. Subjects (n = 20) were separated into two group: those whose systolic blood pressure increased to more than 30 mm Hg immediately after DHP-PMX (effective [E] group: nine cases) and those whose systolic blood pressure did not increase to more than 30 mm Hg (noneffective [N-E] group: 11 cases). The interleukin-6, plasminogen activator inhibitor-1, and HMGB-1 levels were measured in each group. The Pao2/Fio2 ratio and the Sepsis-Related Organ Failure Assessment (SOFA) score were also evaluated. Pretreatment interleukin-6, plasminogen activator inhibitor-1, and HMGB-1 levels were similar in the E and N-E groups, but mortality rate was significantly higher in the N-E group. Furthermore, posttreatment SOFA score was significantly lower in the E group. In the E group, only the HMGB-1 levels improved significantly after DHP-PMX. Present data suggest that the circulation dynamics of septic shock patients can be improved by reducing HMGB-1 levels by using DHP-PMX.     

Effectiveness of continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter after polymyxin B-immobilized fiber column therapy of septic shock

Septic shock is a condition associated with diffuse coagulopathy and multiple organ failure, and frequently ends in death. Direct hemoperfusion using a polymyxin B-immobilized fiber column (DHP-PMX) was first developed in Japan in 1994 and has since been used for the treatment of septic shock. On the other hand, the effectiveness of continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA- CHDF) for critically ill patients has also been reported. We treated 27 septic shock patients by DHP-PMX. The patients, except for the nine in whom CHDF was not performed after DHP-PMX, were divided into two groups: namely, a group in which PMMA-CHDF therapy was added after DHP-PMX (11 cases), and a group in which continuous hemodiafiltration using a polyacrylonitrile membrane hemofilter (PAN-CHDF) therapy was added after DHP-PMX (7 cases). The outcomes in the two groups were compared. The average Acute Physiology and Chronic Health Evaluation (APACHE) II score and the average sepsis-related organ failure assessment (SOFA) score were not significantly different between the two groups. The PMMA-CHDF group showed significantly better outcomes, with significant improvements of the serum PAI-1, protein C, IL-6 and N-arachidonoylethanolamine (AEA) levels. We conclude that PMMA-CHDF may be more effective than PAN-CHDF in the management of septic shock.     

Effects of hemoperfusion on serum cardiac troponin T concentrations using polymyxin B-immobilized fibers in septic patients undergoing hemodialysis

We investigated whether serum cardiac troponin T levels are altered in septic patients undergoing hemodialysis and whether polyinyxin B-immobilized fiber (PMX-F) treatment affects these levels. Fourteen heinodialysis patients with sepsis, 14 hemodialysis patients without sepsis, and 12 age matched healthy controls were included in this study. Cardiac troponin T levels in hemodialysis patients with sepsis (0.56+/-0.28 microg/L) were higher than levels in hemodialysis patients without sepsis (0.16+/-0.06 microg/L, p < 0.01) and healthy control subjects (0.03+/-0.01 microg/L, p < 0.001). The 14 hemodialysis patients with sepsis were randomly assigned to one of two treatment approaches: PMX-F treatment (n = 7) or conventional treatment (n = 7). Plasma endotoxin levels were significantly reduced from 46.6+/-17.8 pg/mI to 8.2+/-2.4 pg/ml, p < 0.01, in patients treated with PMX-F, and serum cardiac troponin T levels were also reduced from 0.62+/-0.30 microg/L to 0.26 = 0.12 microg/L, p < 0.05. Cardiac troponin T levels were unchanged in patients under conventional treatment. These data suggest that cardiac troponin T is indeed elevated in septic patients undergoing hemodialysis and niay reflect subclinical myocardial cell damage. PMX-F is effective in reducing myocardial damage, in part, due to reducing plasma endotoxin levels.     

Effectiveness of early start of direct hemoperfusion with polymyxin B-immobilized fiber columns judging from stabilization in circulatory dynamics in surgical treatment patients

Background:

Septic shock remains a major cause of multiple organ failure and is associated with a high mortality rate. In 1994, direct hemoperfusion using a polymyxin B-immobilized fiber column (PMX; Toray Industries Inc., Tokyo Japan) was developed in Japan and has since been used for the treatment of septic shock arising from endotoxemia.

Materials and Method:

We treated 36 patients with septic shock using direct hemoperfusion with PMX. The patients were analyzed in two groups based on whether they had undergone surgery prior to DHP-PMX treatment (surgical group: surgical treatment before DHP-PMX, medical group: no surgical treatment). In surgical group, DHP-PMX was started within three hours after the surgical treatment. Various factors were measured before and after DHP-PMX.

Results:

The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 27.4 ± 8.8, and the mean sepsis-related organ failure assessment (SOFA) score was 11.8 ± 4.9 before DHP-PMX. The SOFA score was significantly higher (P = 0.0091) and the PaO2/FiO2 ratio (P/F ratio) was significantly lower (P = 0.0037) in medical group than in surgical group prior to DHP-PMX. A chi-square test showed that the survival rate in surgical group was significantly better than in medical group (P = 0.0027). The survival rate of surgical group (84.2%) was judged to be very good because the predicated survival rate based on the APACHE II score (25.0) was only 46.5%. On the other hand, the survival rate of medical group (35.3%) was almost equal to that predicted by the APACHE II score (30.6; predicted survival rate, 27.4%).

Conclusion:

The results of this study suggest the utility of early DHP-PMX in surgical group.     

Successful treatment of septic shock with purpura fulminans caused by Trichosporon asahii in an immunocompetent patient

Trichosporon asahii is an emerging mycosis characterized by high mortality rate in immunologically compromised patients. Only a few cases have been reported in immunocompetent subjects. We report a 46-yr-old man who had been healthy and who presented with septic shock and purpura fulminans caused by Trichosporon asahii. He responded well to antifungal therapy with amphotericin B and voriconazole.     

Selection of hemoperfusion therapy for patients with septic shock on the basis of the primary disease

The objective of this study was to analyze retrospectively the efficacy of polymyxin-B immobilized fiber (PMX-F) alone and in combination with continuous venovenous hemofiltration (CHF) on the prognosis of critically ill patients with sepsis using a retrospective chart review in a university hospital in Japan. A cohort of 246 patients meeting the criteria of sepsis, septic shock, or both, according to the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/ACCM) Consensus Conference, were examined in this study. From these patients, 48 were selected who were found to have definitive causative bacteria and whose primary diseases were clearly identified. According to the charts, two major primary diseases were identified: one related to cardiovascular disease and the other to gastrointestinal disease. Other diseases were excluded from this study because of the small numbers of patients in categories such as malignant, hematological, genitourinary, and other diseases. Furthermore, patients who had levels of serum creatinine above 2.0mg/dl were excluded. The prevalence of diabetes mellitus (up to 63%) was very high in both groups. There were no significant differences between the two groups in age or the Apache II scores at the start of hemoperfusion treatment; however, the gender ratio varied: 72% of the cardiovascular group were male, compared to 46% of the gastrointestinal group. The causative bacteria were markedly different between the two groups. For half of the gastrointestinal group the causative bacterium was Escherichia coli, while for half of the cardiovascular group the causative bacterium was Pseudomonas aeruginosa.The survival rate differed significantly between the two groups. The patients in the cardiovascular group survived longer than those in the gastrointestinal group. Moreover, for the patients with cardiovascular disease, there was no significant difference in the survival rate between treatment with PMX-F alone and with PMX-F and CHF in combination. In contrast, for the patients with gastrointestinal disease, there was a significant difference between treatment with PMX-F alone and with PMX-F and CHF in combination. When a patient with sepsis or septic shock is treated with hemoperfusion, the decision as to whether PMX-F should be given alone or in combination with CHF might be determined on the basis of the primary disease of the patient.     

Risk factors for mortality in patients with low lactate level and septic shock

BackgroundAccording to the new definition of septic shock, vasopressor therapy and hyperlactatemia are essential for diagnosis. However, there is controversy regarding the cutoff value for lactate, and prognostic factors in patients with septic shock and hypolactatemia. This study evaluated the prognostic significance of the cutoff value for lactate level in septic shock patients.MethodsThe retrospective observational cohort study enrolled 1043 patients aged ≥18 years who meet the revised definition of septic shock. Clinical outcomes of patients with hyperlactatemia were compared with hypolactatemia.ResultsOf the 1022 eligible patients, 369 had an arterial lactate level ≤2 mmol/L. More patients in the high lactate group had poor prognosis than in the low lactate group. A high Sequential Organ Failure Assessment score (SOFA) score group was significant (p < 0.001) in predicting lactate levels. On the subgroup analysis of risk factors affecting mortality in the low lactate group, high Acute Physiology And Chronic Health Evaluation Ⅱ (APACHEⅡ) score (p = 0.003), high C-reactive protein (p = 0.034), and chronic heart failure (p = 0.001) were independently associated with 28-day mortality.ConclusionArterial lactate is a very reliable diagnostic and prognostic predictor of septic shock. However, despite low arterial lactate, patients with a high APACHEⅡ score, high C-reactive protein levels, and chronic heart failure had a poorer prognosis.     

Morphology of cardiac muscle in septic shock. Observations with a porcine septic shock model

The morphology of cardiac muscle was investigated in a porcine model of septic shock, created by intermitted application of Escherichia coli-endotoxin. The earliest lesions, found after 18 h of septic shock, were endothelial cell swelling, marked leucostasis and slight ischaemic alterations of the muscle fibres. At the end point of the experiments, after 48 h, some fibrin thrombi were found associated with more pronounced ischaemic alterations of cardiac muscle cells and some necrotic fibres. Comparing these findings with the severe endothelial and muscle fibre lesions found in skeletal muscle, the endothelial cells of the heart microvasculature, are clearly more resistant to the attack of the endotoxins and mediators liberated in septic shock.     

Effect of direct hemoperfusion with a polymyxin B immobilized fiber column on high mobility group box-1 (HMGB-1) in severe septic shock: report of a case

Because of the many difficult aspects in the treatment of septic shock and poor outcome of this condition, establishing the most appropriate therapeutic strategy is problematic. Recently, high mobility group box-1 (HMGB-1) has been shown to activate inflammatory responses and to be a late mediator in endotoxemia and sepsis. Therefore, we considered that it might be worthwhile to investigate the therapeutic potential of HMGB-1 blockade in cases of septic shock.Herein, we describe the case of a patient with septic shock with hepatic portal venous gas caused by intestinal obstruction. Hepatic portal venous gas is a rare condition associated with significant radiographic findings and a fatal outcome. Our patient, however, recovered from severe septic shock and was saved by the use of direct hemoperfusion with a polymyxin B immobilized fiber column (DHP-PMX). This treatment resulted in a decrease in the serum levels of endotoxin, interleukin-6 (IL-6), and HMGB-1.     

Early induction of direct hemoperfusion with a polymyxin-B immobilized column is associated with amelioration of hemodynamic derangement and mortality in patients with septic shock

This study was conducted to clarify the effectiveness of induction timing of direct hemoperfusion with a polymyxin-B immobilized column (PMX-DHP) for amelioration of hemodynamic derangement and outcome in patients with septic shock. Suspected Gram-negative septic shock patients who received PMX-DHP therapy from January 2010 to December 2014 in our ICU were enrolled in this study. The patients were divided into two groups that received PMX-DHP therapy within 8 h (early group) and more than 8 h (late group) from catecholamine administration. Changes in catecholamine dose [catecholamine index (CAI)], catecholamine dose/mean arterial pressure [catecholamine index pressure (CAIP)], PaO₂/FiO₂ and PEEP level were determined at the start of and 24 h after the start of PMX-DHP therapy. Ventilator-free days (VFD), ICU-free days (IFD), 28-day and hospital mortality were also determined. There were no significant differences in patients’ characteristics between the two groups. CAI and CAIP were significantly decreased in the early group. PaO₂/FiO₂ was not changed whereas PEEP level in the early group was significantly decreased during PMX-DHP therapy. IFD and VFD were not different in the two groups. Mortality at 28 days was significantly improved in the early group. Endotoxin acts as an early mediator in sepsis patients with suspected Gram-negative infection. Earlier induction of PMX-DHP therapy as in our study is closely associated with earlier weaning from hemodynamic derangement and with improvement of mortality. Therefore, early induction of PMX-DHP therapy is recommended for the treatment of septic shock in patients with presumed Gram-negative infection.     

Knowledge-based approach to septic shock patient data using a neural network with trapezoidal activation functions

In this contribution we present an application of a knowledge-based neural network technique in the domain of medical research. We consider the crucial problem of intensive care patients developing a septic shock during their stay at the intensive care unit. Septic shock is of prime importance in intensive care medicine due to its high mortality rate. Our analysis of the patient data is embedded in a medical data analysis cycle, including preprocessing, classification, rule generation and interpretation. For classification and rule generation we chose an improved architecture based on a growing trapezoidal basis function network for our metric variables. Our results extend those of a black box classification and give a deeper insight in our patient data. We evaluate our results with classification and rule performance measures. For feature selection we introduce a new importance measure.     

Emphysematous cystitis in an elderly patient with ulcerative colitis

Emphysematous cystitis is a rare complication of lower urinary tract infections. The disease is characterized by air within the bladder wall and lumen and commonly occurs in middle-aged diabetic women. Intramural bladder gas seen on imaging is pathognomonic for this condition. The severity of the illness varies widely from cases diagnosed incidentally to patients presenting with life-threatening sepsis. We report the case of an 80-year-old non-diabetic man presenting with emphysematous cystitis after a total colectomy for ulcerative colitis.     

Plasmablastic lymphoma in an elderly immunocompetent patient

Plasmablastic lymphoma (PBL) is a distinct type of diffuse B cell lymphoma that typically occurs in the oral cavity of patients with HIV infection or immunodeficiency status. PBL is characterized by its plasmablastic morphology and an immunophenotype indicative of a plasma cell differentiation. We present a case of a 75-year-old HIV-negative and Epstein-Barr virus (EBV)-negative patient presenting with an isolated oral cavity mass. The tumor consisted of a monotonous proliferation of undifferentiated large cells with relatively abundant cytoplasm, eccentrically located round nuclei with prominent nucleoli and numerous mitoses. Immunohistochemically, these cells were negative for CD45 and B cell antigens, while they showed diffuse positivity of CD138 and focal staining for epithelial membrane antigen (EMA), indicating plasma cell differentiation. Based on these histopathological and immunohistochemical characteristics, we diagnosed it as PBL. The patient received chemotherapy and is alive with locally persistent disease 3 years after diagnosis. To date, only several cases of oral PBL have been reported in HIV-negative, EBV-negative and immunocompetent patients. PBL should be included in the differential diagnosis of oral mass lesions and careful evaluation of the morphology and awareness of the existence of this uncommon type of lymphoma can lead to a correct diagnosis.