Continuous renal replacement therapy (CRRT), which is performed in the critical care or intensive care fields, is a lengthy treatment for patients with hemodynamic instability and impaired renal function. The clotting of blood is a frequent problem during CRRT, because the treatment uses the extracorporeal circulation. To minimize the clotting problem, users need to know the characteristics of the various treatment devices, and to pursue the conditions to avoid blood clotting in the extracorporeal circuit. In this work, we compared the influence of different materials in various extracorporeal circuits for CRRT and examined the conditions for safety and long-term use. To decrease the fill ration of blood and minimize the contact area of air and blood by reducing the size of an artery, a side air trap chamber was found to be effective for a long term use of the extracorporeal circuit.

Toray is marketing “HEMOFEEL CH” consisting of PMMA membrane and “HEMOFEEL SHG” consisting of polysulfone (PS) membrane as materials of hollow fiber membranes built in continuous hemofiltration devices. PMMA membrane in a uniform symmetrical structure has a unique characteristic of adsorbing proteins such as cytokines, which is not provided in PS membrane. The structure of PMMA membrane is designed optimally to improve adsorbability of cytokines and, it was demonstrated in in vitro circulation study that saturation adsorption does not occur even after 24 hours. PS membrane is blended with polyvinylpyrrolidone (PVP), which is a hydrophilic polymer, to prevent adhesion of blood components. We have shown that uniformity of surface distribution of PVP and mobility of hydrophilic polymer are largely responsible for adhesion of platelets. We succeeded in development of “HEMOFEEL SHG” with dramatically reduced platelet adhesion compared to existing products.

Initiation of acute blood purification is frequently determined by individual clinical judgment based on renal dysfunction and failure of other organs. This study, which retrospectively analyzed 26 AKI patients requiring dialysis, was undertaken to evaluate the new AKI biomarker’s association with acute blood purification initiation. The early initiation group, who needed blood purification during the first day of ICU admission (n=12), showed significantly higher urinary biomarker levels of L-FABP, NAG, and albumin at ICU admission than patients for whom blood purification was performed on day 2 or thereafter (n=14). Adding urinary L-FABP, NAG, and albumin to the clinical model including age, gender, serum creatinine, and APACHE Ⅱ score improved the prediction of early initiation. Although this study was performed retrospectively, these data suggest the potential of these new AKI biomarkers for determining the start of acute blood purification.

Teicoplanin has been considered to be non-dialyzable and non-filterable due to its high protein binding. This study was performed to evaluate the pharmacokinetics of teicoplanin during continuous blood purification therapy using polysulfone (PS) and polymethylmethacrylate (PMMA) membrane. As a result, Teicoplanin was cleared much more rapidly from the blood by adsorption of PS and PMMA membrane. We recommend obligatory drug monitoring to achieve therapeutic plasma concentrations.

In the field of emergency and intensive care medicine, continuous hemodiafiltration (CHDF) is the major treatment modality for acute blood purification. In most cases, nafamostat mesilate (NM) is used as an anticoagulant to prevent dialyzer clotting during CHDF. However, mixed results have been obtained in terms of prevention of clotting by NM. So far, there are few reports concerning how to adjust NM dosage by checking the activated clotting time (ACT) of the dialyzer circuit. In this study, we examined the ACT of the arterial inflow line and the venous return line simultaneously during CHDF using NM. Among cases in which clotting did not occur, the optimal ACT was checked. The ACT of the arterial inflow line and the venous return line were as follows: in the group in which the dialyzer was exchanged at 24 hours, 170 seconds and 444 seconds, respectively; in the group in which the dialyzer was exchanged at 48 hours, 176 seconds and 470 seconds, respectively; in the group in which clotting did not occur over 72 hours, 190 seconds and 443 seconds, respectively. The ACT of the venous return line showed no significant differences between all groups. However, in the group in which clotting did not occur over 72 hours, the ACT of the arterial inflow line was significantly prolonged. No bleeding complication was seen in all cases. Based on these results, we recommend controlling the ACT of the arterial side around 170 seconds to prevent dialyzer clotting over 24 hours during CHDF using NM.

Performing direct hemoperfusion using polymyxin B-immobilized fiber (PMX-DHP) for low-body-weight children is not common. Because acute blood purification is technically difficult to perform and there are no appropriate tools for these children. We report our experience of PMX-DHP in children under 10kg with unstable circulatory dynamics and the efficacy of PMX-DHP in these children. We performed PMX-DHP nine children (age, 0 days-7 months; body weight, 1.2 to 6.6 kg) diagnosed septic shock. We evaluated the following parameters before and after treatment: mean arterial pressure (MAP), catecholamine index (CAI), ratio of the arterial partial pressure of oxygen to the fraction of inspired oxygen (P/F ratio), serum creatinine, urine volume, pediatric logistic organ dysfunction (PELOD) score, and predicted mortality rate. There were some complications, namely, hypothermia, intracircuit clot formation, and decrease in platelet count. No PMX-related deaths occurred. MAP values elevated from 34.9±12.2 mmHg to 47.4±8.5 mmHg within 2h. The PELOD score and predicted mortality rate significantly decreased from 43.2±10.9 to 24.8±6.1 and from 90.4%±22.9% to 37.7%±22.2%, respectively. The prognosis at 28 days was as follows: alive, 6 patients and dead, 3 patients. PMX was safely performed in low-body-weight children. PMX could elevate their body pressure and improve their prognosis. PMX-DHP might help in elevating the survival rate of low-blood-weight children with poor prognosis.

Background: It has been reported that a PMMA membrane hemofilter (hemofeel^®CH-1.0N) provides intense adsorptive removal capacity for interleukin 6 (IL-6). We assessed in vitro the ability of hemofeel^®CH-1.0N to adsorb the high concentration of IL-6 (477,000pg/mL) from human waste plasma, by CHD or CHF. Methods: Under the plasma flow rate of 80mL/min, the body fluid removal rate of 0mL/hr, and the dialysate/filtration flow rate of 400mL/hr, we assessed using ELISA method for the IL-6 concentrations, IL-6 clearance, IL-6 SC, IL-6 removal rate, total amount of removed IL-6, and assessed TMP in the waste plasma collected from the inlet and the outlet of the hemofilter, and from the filtered solution. Results: The IL-6 concentrations on the inlet side, at 0.5, 6, 18 and 48 hrs after the initiation of CHD/CHF, were 186,000/161,000, 11,600/6,650, 1,440/564, 1,040/546 respectively. The IL-6 clearances, at 0.5 and 18 hr after initiation of CHD/CHF, were 31/36 and 2/2 mL/min, respectively. IL-6 was removed at a rate of approximately 97% from the plasma within 6 hrs. Conclusions: The total amount of IL-6 removed was 4 hundred million pg for both CHD and CHF. To ascertain the limits of the adsorption capacity, it is necessary to perform the spiked blank recovery test.

Acute pulmonary edema (PE) is a frequent complication in emergency settings among hemodialysis patients. Frequently, emergency hemodialysis (HD) with ultrafiltration is effective for treating such patients. However, we occasionally encounter atypical PE that is nonresponsive to emergency HD. We tried to identify the clinical findings of and develop treatments for nonresponsive PE using a retrospective cohort study. Between April 1, 2008 and March 31, 2011, 93 hemodialysis patients with acute PE underwent emergency HD in the intensive care unit of our hospital. Clinical symptoms of 29 patients did not improve or became worse following emergency HD. We compared the clinical data on admission between the 64 patients who showed improvement (responder group) and the 29 patients whose respiratory failure did not improved with emergency HD (nonresponder group). Higher body temperature, lower arterial oxygen pressure, higher levels of C-reactive protein, and significantly higher lactate levels were observed in the nonresponder group. The cutoff level for the lactate was calculated as 1.90mmol/L with a sensitivity of 88.2% and a specificity of 96.8％ for differentiation of nonresponsive PE patients from others. We found that combination therapy of HD treatment with a polymethylmethacrylate (PMMA) dialyzer and administration of methylprednisolone is effective for nonresponsive PE. In conclusion, lactate levels proved to be an appropriate predictor for nonresponsive PE, and a combination therapy comprising HD with a PMMA dialyzer and short-term administration of methylprednisolone would be an acceptable treatment.

Ensuring safety is an important aspect during acute blood purification therapy. Our hospital has had many years of experience in maintenance dialysis therapy and has conducted different types of inspections to enhance safety while administering continuous hemodiafiltration (CHDF). From these inspections, 1 inspection is performed before administering CHDF, when priming is completed, treatment conditions are appropriate, and all items are available. At our hospital, our clinical engineers have always implemented this inspection since the introduction of the CHDF device at our institution in 2000. When the data obtained on abnormal incidents discovered and corrected through the inspection were accumulated, the result showed that the number of abnormal incidents caused by human errors, such as setting mistakes, surpassed the number of abnormal incidents caused by device failures. Thus, the results suggest that inspections effective ensure safety while performing acute blood purification therapy.

In order to ensure safety during blood purification by the percutaneous cardiopulmonary support (PCPS) circuit, we measured the flow rate in the side branches of a mock blood infusion/ removal circuit for different rates of blood removal and infusion; in addition, we measured the pressure in each of the three-gang three-way stopcocks installed in the shunt part of the circuit. In PCPS, the pressure in the blood removal circuit is always negative, and therefore, any error in the circuit-opening operation may lead to influx of a large amount of air. If air flows into the centrifugal pump, centrifugal force in the pump will be reduced to zero, causing the circulation to stop, or the air bubbles will be broken into finer ones and sent to all parts of the body via the blood infusion circuit. In this study, we confirmed that the positive pressure changed to negative in the three-gang three-way stopcocks when the negative pressure in the blood removal circuit was increased. This finding is expected to help in enhancing the safety of the blood purification process.

Objective：The usefulness of the Risk, Injury, Failure, Loss of Kidney Function, End-stage Kidney Disease (RIFLE) and Acute Kidney Injury Network (AKIN) classifications was compared in the patients admitted to the intensive care unit (ICU). Methods：In all, 442 patients who were admitted for more than 48 hours in the ICU of our hospital over the last 3 years were retrospectively evaluated. The grades of difference in the acute physiology and chronic health evaluation (APACHE) Ⅱ score and ICU mortality rate were compared between the 2 classifications. Results：The APACHEⅡscore and ICU mortality rate were not significantly different between the 2 classifications. Only 6 patients were classified as stage 1 according to the AKIN classification, but classified as having no acute kidney injury in RIFLE (an acute change in serum creatinine level：＞0.3mg/dL). A total of 86 patients undergoing renal replacement therapy (RRT) were classified in stage 3 in AKIN, but not classified as Failure in RIFLE. Conclusions：Compared to the RIFLE classification, the AKIN classification does not provide improved ability to predict mortality in ICU patients. There has been no standard to determine when patients need to undergo RRT；therefore, using the RIFLE classification seems more appropriate at this moment for discussing the effective prevention and treatment of AKI.

Escherichia coli O111 is a verotoxin-producing enterohemorrhagic E coli (EHEC) as is E coli O157 serotype. Verotoxin may cause bloody diarrhea and abdominal pain, hemolytic uremic syndrome (HUS), as well as fatal acute encephalitis. We report the case of a 2-year-old boy who was healthy until the day of admission. The boy experienced vomiting and diarrhea and passed bloody stools. Because of rapid progression of acute kidney injury (AKI), continuous renal replacement therapy (CRRT) was administered the next day, the dialysis flow rate was kept low because he experienced convulsions and also to prevent an increase in intracranial pressure (ICP). His renal function improved after consecutive attempts of CRRT for 6 days, followed by peritoneal dialysis for another 2 weeks. He was discharged without sequelae. E coli O111 infection, similar to E coli O157 infection, is likely to progress to a more severe disease in the case of infants. CRRT is indicated when young infants present with severe HUS and show progression to a stage of AKI. If encephalopathy is suspected, a low dialysis flow rate should be considered to prevent the increase in ICP.

A 68-year-old man presented to our hospital with acute respiratory failure that had worsed rapidly over the last month. On chest roentgenogram and CT, he showed diffuse ground-glass opacites in bilateral his lung fields. We interpreted heart failure through echocardiography and pulmonary infectious disease through bronchoalveolar lavage. Therefore, we diagnosed the patient with acute respiratory failure due to interstitial pneumonia induced by the chest roentgenogram, the high KL-6 blood concentration, and other findings. We immediately initiated treatment with elastase inhibitors and anticoagulant agents along with methylprednisolone pulse therapy and mechanical ventilation. However, the patient’s condition worsened. Therefore, we performed blood purification therapy with a combination of the sustained high-efficacy daily diafiltration using a mediator-adsorbing membrane (SHEDD-fA) and the direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP); this therapy was performed over 2 days. Consequently, his respiratory failure was greatly improved and the acute phase of this disorder was alleviated.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening generalized disorder. Most of the patients with TTP achieve remission following plasma exchange (PE). This report presents the case of a patient with refractory TTP that was successfully treated with PE and rituximab. A 47-year-old female was referred to our hospital due to general fatigue and slurred speech. She had a slight fever at the time of admission (37.2℃) without any change in consciousness. Her blood examination showed a hemoglobin concentration of 7.0g/dL, platelet counts of 0.7×104/μL, LDH level of 1,555 IU/μL, serum creatinine level of 0.78mg/dL, plasma ADAMTS13 activity of＜0.5％, and anti-ADAMTS13 inhibitor level of 4.8 Bethesda unit/ml. Her platelet counts and ADAMTS13 activity were increased by PE on day 3. However, her platelet counts and ADAMTS13 activity decreased again with an elevation of anti-ADAMTS13 inhibitor on day 7. Therefore, she was treated with PE and rituximab. She achieved clinical remission following the administration three courses of rituximab. These results indicated that daily measurement of ADAMTS13 activity and its inhibitor level were useful to identify patients that require administration of rituximab to reduce the times of PE and improve the prognosis of patients with TTP.

In our hospital, continuous hemodiafiltration (CHDF) is performed in an annual mean of more than 600 patients, and hypercalcemia is sometimes observed during long-term CHDF. We encountered 2 patients on maintenance hemodialysis (HD) who developed hypercalcemia during long-term CHDF after cardiovascular surgery, and evaluated the background of hypercalcemia and preventive measures. Long-term CHDF was performed in HD patients (HD group) and patients not receiving HD (non-HD group), and 2 patients in the HD group developed hypercalcemia during CHDF. Long-term CHDF was defined as CHDF for more than 10 days, while hypercalcemia was defined as corrected Ca levels10.5mg/dL. Using these definitions, changes in the Ca level during long-term CHDF were evaluated in the HD and non-HD groups. As a result, the Ca level elevated with an increase in the treatment days, showing a correlation, in the HD group. In the non-HD group, the Ca level also gradually increased, but the rise was slow compared with that in the HD group, and presented few clinical problems. In the HD group, the cause of hypercalcemia observed in the 2 patients during long-term CHDF could not be identified, but the possible causes included the influences of the Ca load in Sublood^®, total parenteral nutrition solutions, various cytokines associated with multiple organ dysfunction, and disruption of the 1-25D3 metabolic pathway. To prevent these, regular measurement of Ca and consultation with physicians about changes or adjustments of CHDF fluids/dialysates may be important. In the future, careful attention should be paid to the possible development of hypercalcemia during long-term CHDF in HD patients, and blood analysis and appropriate adjustments of fluids and dialysates may be necessary.

The prognosis of neonatal hyperammonemia due to an inborn error of metabolism is poor, and as irreversible brain damage occurs within a short period of time, it is necessary to rapidly reduce the blood ammonia level. While exchange transfusion and peritoneal dialysis have been performed to remove blood ammonia, their effectiveness has often been insufficient, and hemodialysis is necessary for rapid and reliable removal of ammonia. To remove ammonia by hemodialysis, it is important to maximize the blood flow rate (Qb) and set the dialysate flow rate (Qd) at a level sufficient for the maximized Qb. We treated a neonate with ornithine transcarbamylase deficiency by continuous hemodialysis. The Qb was set at 25mL/min, and the Qd was increased to 3,000mL/hr (50mL/min), at which the Qd/Qb was 2.0, and then appropriately adjusted. This case is presented because a favorable outcome could be obtained by setting the Qb and Qd at levels higher than were previously reported.

A 80 years-old male who had interstitial pneumonia and a chronic obstructive pulmonary disease. He was diagnosed with acute exacerbation of interstitial pneumonia acuteness and admitted to ICU. He suffered in respiratory distress and was needed Biphasic positive airway pressure (BIPAP). We treated with Polymyxin-B Immobilized Fiber (PMX-DHP), Steroid Pulse Therapy and multi-Antibiotic. The patient’s condition improved following PMX-DHP and BIPAP was removed. We report a case in which PMX-DHP was effective for improving acute exacerbation of interstitial pneumonia acuteness. Futher study of the PMX-DHP in acute exacerbation of interstitial pneumonia acuteness will be necessary.

Due to the Tohoku earthquake and resulting tsunami, the supply of dialysate and substitution fluid used for continuous hemodiafiltration (CHDF) in our hospital has become unstable. Therefore, online HDF substitution fluid was used as the CHDF dialysate. We herein report on the investigation carried out in order to reconfirm safety. Dialysis patient monitoring equipment was used to collect dialysate in a bag for transfusion using a fluid replacement pump. The presence of ET, cultivation study, change in composition, and calcium carbonate deposition was confirmed. The pH value increased compared to when it was prepared, exceeding pH7.4 after approximately 18 hours. The PCO2 showed a tendency to decrease over time. Calcium carbonate was not observed upon visual inspection. ET/viable cells were not detected. In this study, it was suggested that online substitution fluid may be successfully used as the dialysate of CHDF.