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Abstract Background Venous air trap chamber designs vary considerably to suit specific continuous renal replacement therapy circuits, with key variables including inflow design and filter presence. Nevertheless, intrachamber flow irregularities do occur and can promote blood coagulation. Therefore, this study employed computational fluid dynamics (CFD) simulations to better understand how venous air trap chamber designs affect flow. Methods The flow within a venous air trap chamber was analyzed through numerical calculations based on CFD, utilizing large eddy simulation. The working fluid was a 33% glycerin solution, and the flow rate was set at 150 ml/min. A model of a venous air trap chamber with a volume of 15 ml served as the computational domain. Calculations were performed for four conditions: horizontal inflow with and without a filter, and vertical inflow with and without a filter. Streamline plots and velocity contour plots were generated to visualize the flow. Results In the horizontal inflow chamber, irrespective of filter presence, ultimately the working fluid exhibited a downstream vortex flow along the chamber walls, dissipating as it progressed, and being faster near the walls than in the chamber center. In the presence of a filter, the working fluid flowed uniformly toward the outlet, while in the absence of a filter the flow became turbulent before reaching the outlet. These observations indicate a streamlining effect of the filter. In the vertical inflow chamber, irrespective of filter presence, the working fluid flowed vertically from the inlet into the main flow direction. Part of the working fluid bounced back at the chamber bottom, underwent upward and downward movements, and eventually flowed out through the outlet. Stagnation was observed at the top of the chamber. Without a filter, more working fluid bounced back from the bottom of the chamber. Conclusions CFD analysis estimated that the flow in a venous air trap chamber is affected by inflow method and filter presence. The “horizontal inflow chamber with filter” was identified as the design creating a smooth and uninterrupted flow throughout the chamber.

Abstract Background Sepsis 3 definitions have shifted the focus from nonspecific inflammation to sepsis as an organ dysfunction caused by a dysregulated host response to infection. Neutrophils have become therapeutic targets because of their intimate but complex involvement in sepsis. We conducted ex vivo and animal experiments to apply a granulocyte and monocyte adsorption column, which is clinically used for inflammatory bowel disease, in sepsis. In this study, the biocompatibility was evaluated in sepsis-like hypercytokinemia. Methods Six female outbred pigs were anesthetized. Extracorporeal direct hemoperfusion (DHP) with an Adacolumn or a sham column was initiated after lipopolysaccharide (LPS) administration. The DHP was performed for 2 h at a blood flow rate (QB) of 30 or 60 mL/min. Blood samples were collected before and during the DHP (30, 60, 90, and 120 min). The percentage change in white blood cell count, platelet count, and cytokine concentration was compared between the Adacolumn and sham columns. Results The percentage change in white blood cells were 96 (95–98)% and 106 (101–108)% in the Adacolumn and sham groups, respectively, at QB = 60 mL/min (p

Abstract Background During continuous kidney replacement therapy (CKRT) in patients with sepsis and critical conditions, circuit coagulation can occur, often for unclear reasons. In this study, we investigate how the structure of the venous air trap chamber may contribute to venous air trap chamber coagulation. Clinical data were evaluated and experiments were performed. Methods The clinical evaluation involved patients who underwent continuous hemofiltration (CHF) using an acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) hemofilter (AN69ST-CHF) and either an ACH-Σ or Prismaflex CKRT machine in our ICU from April to July 2019. The patient data were divided into two groups based on CKRT machine and the percentage of CHF procedures that could continuously be performed for 22 h (CHF target achievement rate), and coagulation sites were evaluated. Statistical analysis was performed by the Mann–Whitney U test and Pearson’s chi-square test. For in vitro experiments, a system was constructed to circulate a 33% glycerol solution at a flow rate of 150 ml/min. In a venous air trap chamber, fluid dye disappearance times and fluid movements were visually evaluated. Results The clinical evaluation included 22 procedures (8 patients) in the ACH-Σ group and 22 procedures (11 patients) in the Prismaflex group, without significant differences in patient backgrounds between the groups. The CHF target achievement rate was 72.7% (16/22) in the ACH-Σ group and 77.3% (17/22) in the Prismaflex group, revealing no significant difference (p = 0.73). However, significantly fewer venous air trap chamber coagulations were observed in the Prismaflex group (1/5) than in the ACH-Σ group (5/6) (p

Abstract Background Tumor lysis syndrome is an oncological emergency triggered by the rapid release of intracellular materials from lysed malignant cells. Intensive chemotherapy is challenging for patients with severe renal dysfunction and a high risk of tumor lysis syndrome. Sustained high-efficiency daily diafiltration using a mediator-adsorbing membrane (SHEDD-fA) could work not only as a renal replacement therapy, but also as a novel method to control intracellular materials, including cytokines and damage-associated molecular patterns. We aimed to describe two cases of patients with Burkitt’s lymphoma with a very high risk of tumor lysis syndrome who were successfully treated with a combination of chemotherapy and SHEDD-fA. Case presentation The first case was of a 67-year-old man who was admitted to the intensive care unit for respiratory failure and diagnosed with Burkitt’s lymphoma. Extremely high lactate dehydrogenase levels and anuria, indicating severe acute kidney injury, are considered to be associated with a very high risk of tumor lysis syndrome. SHEDD-fA was initiated prophylactically to prevent exacerbation of tumor lysis syndrome. To ensure the blood concentration of antitumor drugs, SHEDD-fA was stopped temporarily and restarted 6 h after the completion of chemotherapy. No tumor lysis syndrome-related complications were observed. The second case involved a 68-year-old man who was admitted to the intensive care unit due to exacerbation of Burkitt’s lymphoma complicated by severe pneumonia and disseminated intravascular coagulation. The patient exhibited metabolic acidosis, hyperkalemia, hyperuricemia, and anuria. SHEDD-fA was performed immediately. As in the first case, we temporarily discontinued SHEDD-fA before chemotherapy and restarted it 6 h after the completion of chemotherapy. No tumor lysis syndrome-associated complications were observed and renal function recovered. Interleukin-6, interleukin-8, and high-mobility group box-1 protein levels in the blood were lower on the outlet side than on the inlet side. Conclusions SHEDD-fA allows safe and effective administration of chemotherapy in patients with severe renal dysfunction and a very high risk of tumor lysis syndrome. Our findings indicate that blood purification modality may need to be selected according to tumor lysis syndrome severity.

Objective: Sivelestat sodium hydrate (Siv) is expected to be an effective therapy for acute respiratory distress syndrome, although its mechanism of action is not understood. In this study, we investigated which myeloid cells-derived cytokines were suppressed by Siv. Methods: Continuous hemofiltration was performed by circulating fresh porcine blood through a semi-closed circuit. To ensure that leukocytes survived for 360 min, 5% glucose, heparin, and air were continuously injected. The control group received continuous administration of lipopolysaccharide (LPS) only, whereas the Siv group received LPS and Siv. Complete blood count, levels of various cytokines, and other variables were compared between the groups. Results: Interleukin (IL)-1β level was significantly suppressed in the Siv group compared with that in the control group (p

Abstract Background We examined whether high lactate level in septic patients was associated with 90-day mortality based on the patients’ disseminated intravascular coagulation (DIC) status. Methods We conducted a multicenter, retrospective, observational study of patients admitted to the intensive care unit (ICU) with a suspicion of severe infection and diagnosed with sepsis. Regression analyses were performed to estimate the interaction effect between DIC status and the lactate level. Then, the association between the lactate level and 90-day mortality was assessed in the DIC and non-DIC subgroups. Results The data of 415 patients were analyzed. We found a significant interaction between DIC status and the lactate level for predicting 90-day mortality (p interaction = 0.04). Therefore, we performed a subgroup analysis and found that high lactate concentration was significantly associated with 90-day mortality in the DIC group (odds ratio = 2.31, p = 0.039) but not in the non-DIC group. Conclusions In patients with DIC, a high lactate level significantly predicted 90-day mortality; no such association was found in the non-DIC group. Thus, DIC status may serve as a possible effect modifier of lactate level in predicting mortality in patients with sepsis.

Blood purification is performed to control cytokines in critically ill patients. The relationship between the clearance (CL) and the membrane area during adsorption is not clear. We hypothesized that the CL increases with the hydrophobic area when hydrophobic binding contributes to cytokine adsorption. We investigated the relationship between the hemofilter membrane area and the CL of the high mobility group box 1 protein (HMGB-1) and interleukin-6 (IL-6). We performed experimental hemofiltration in vitro using polymethyl methacrylate membranes CH-1.8W (1.8 m2) and CH-1.0N (1.0 m2), as well as polysulfone membrane NV-18X (1.8 m2). After adding 100 mg of HMGB1 or 10 μg of IL-6 into the test solution, experimental hemofiltration was conducted for 360 min in a closed-loop circulation system, and the same amount of HMGB1 and IL-6 was added after 180 min. With CH-1.8W and CH-1.0N, both HMGB-1 and IL-6 showed a rapid concentration decrease of more than 70% at 180 min and 360 min after the re-addition. At 15 min, the CL of HMGB-1 was CH-1.8W: 28.4 and CH-1.0N: 19.8, and that of IL-6 was CH-1.8W: 41.1 and CH-1.0N: 25.4. CH-1.8W and CH-1.0N removed HMGB1 and IL-6 by adsorption and CH-1.8W was superior in CL, which increased with a greater membrane area.

Objective: Previous studies have suggested that transpulmonary thermodilution (TPTD) measurements are influenced by extracorporeal circulation methods, such as blood purification. Using pigs, we investigated the effect of extracorporeal circulation on hemodynamic measurements at two sites of cold saline injection. Methods: Six female outbred pigs were included in the study. A vascular access site was made in the left external jugular vein. Cold saline was injected in the right external jugular vein or the right femoral vein. Hemodynamic monitoring was performed using TPTD (EV1000). Cardiac output (CO), global end-diastolic volume (GEDV), and extravascular lung water (EVLW) values were compared between extracorporeal circulation and no extracorporeal circulation. All data are expressed as median values. Results: The following data were obtained when cold saline was injected into the jugular vein (circulation on vs. circulation off): CO, 2.7 vs. 2.9 L/min (P = 0.04); GEDV, 403 vs. 438 ml (P = 0.04); and EVLW, 310 vs. 306 ml (P = 0.92). The following data were obtained when cold saline was injected into the femoral vein (circulation on vs. circulation off): CO, 2.6 vs. 2.8 L/min (P = 0.18); GEDV, 497 vs. 500 ml (P = 0.18); and EVLW, 341 vs. 345 ml (P = 0.44). Conclusions: Extracorporeal circulation has an effect on the accuracy of measurement of TPTD injection through the jugular vein. In contrast, no effect of extracorporeal circulation was observed when the femoral vein was used.

ABO blood groups have been implicated as potential risk factors for various diseases. However, no study has investigated the association between sepsis mortality and ABO blood types. We aimed to evaluate the impact of these blood types on mortality in patients with sepsis and septic shock. This retrospective observational study was conducted at two general hospitals in Japan. Patients diagnosed with sepsis or septic shock were included and divided into four groups based on blood type (O, A, B, and AB). The association between type O vs. other types and 28- and 90-day mortalities was evaluated using multivariate logistic regression analysis adjusted for age, sex, and Sequential (Sepsis-related) Organ Failure Assessment score. This study included 415 patients, of whom 131 (31.6%), 171 (41.2%), 81 (19.5%), and 32 (7.7%) had type O, A, B, and AB, respectively. Blood type O was not associated with 28-day (odds ratio: 1.7 p = 0.08) or 90-day mortality (odds ratio: 1.53, p = 0.091). However, type O was significantly associated with higher 90-day mortality (odds ratio: 3.26, p = 0.009) in patients with septic shock. The role of ABO blood type in risk stratification for septic shock and the mechanisms that potentially affect the prognosis of sepsis patients need further investigation.