Hemodialysis was applied for renal failure patients as the first blood purification modality. Apheresis using membrane filters, adsorption columns were consecutively developed for acute blood purification of liver failure, acute pancreatitis, multiple organ failure (MOF). Membrane blood purification, however, is incomplete because of loss of metabolic function. Bioartificial tubule devices (BTD) consisting of tubular epithelial cells and artificial membrane has been developed in order to improve survival rates of MOF patients, by which not only removal of toxins but metabolic function can be added. 24 male goats were injected lethal dose of lipopolysaccharide (LPS) at 48 hours after bilaterally nephrectomy, and were divided into 3 treatment groups (8 each); continuous hemofiltration (CHF) with cell-free BTD (sham group), CHF with BTD (BTD group) and non-treatment group. Plasma IL-6 levels, and mRNA expression of IL-1β, IL-6, IL-10, TNFα, and interferonγin peripheral blood mononuclear cells (PBMC) using RT-PCR were determined before and during the treatment in these goats. Survival time of BTD group was significantly longer than those of sham BTD and non-treatment (p＜0.01). Plasma IL-6 levels in BTD group were significantly lower than in sham group (p＜0.01). Expressions of cytokine mRNA in PBMC were stimulated after LPS injection, and suppressed thereafter in BTD group, although the expression were stimulated continuously in sham group. It is suggested that suppressed expression of mRNA of cytokines was main cause of lowered cytokine levels, and that longer survival time was brought from lowered cytokine levels in BTD group.

The basics of the earthquake disaster medical management consist of (1) recognition of specific injuries, (2) limited primary treatment in the affected area, (3) importance of immediate evacuation, and (4) urgent dispatch of medical teams from the non-affected area. Crush syndrome at the Hanshin Awaji great earthquake disaster (January, 1995) and economy-class syndrome at the Chuetsu earthquake (October, 2004) are widely recognized as the earthquake disaster specific concerns of the patient. Usefulness of the acute blood purification therapy in the large-scale natural disaster has been widely recognized. The medical cooperation in the neighbor of the chronic dialysis patient was carried out at the Chuetsu offing earthquake (July, 2007), thereafter the large-area mass evacuation and the cooperation to continue the dialysis medical care in the remote place for the evacuation, were carried out at the East Japan great earthquake disaster (March 11, 2011) more afterwards. The possible primary care including acute blood purification in the affected area must be limited. On the other hand, the early advance system to the affected area of DMAT has been already established in Japan, and it’s activity is expected. However, the stable chronic dialysis patient is unlikely to become a target of DMAT. From this reason, it is necessary to prepare for downsizing of the dialysis medical care in the affected area from the early days of the disaster.

【Introduction】 We compared the life times of polysulfone (following PS) membrane hemofilter with cellulose triacetate (following, CTA) membrane hemofilter for continuous hemodiafiltraion (CHDF) under renal indication. 【Method】 We performed a retrospective observational study for patients who underwent CHDF for renal indication from August, 2011 to July, 2012 for filter life time analysis using trans membrane pressure (TMP) increasing rate. 【Result】 The number of PS membrane enrolled was 107, and the number of CTA membrane was 113. The average increasing rate of TMP for PS and CTA membranes at the time of membrane exchange were 0.52±0.54 and 0.83±0.71 (p=0.002), respectively. 【Consideration】 The life times were equivalent for PS and CTA membranes, while PS membrane showed a significantly lower increasing rate of TMP. 【Conclusion】 The PS membrane may have superior life time when assessed by TMP increasing rate.

The settings and devices for use in artificial liver support (ALS) of pediatric acute liver failure have not yet been standardized. As a strategy for rapid deployment of ALS for children (5〜30kg), we have devised protocol that we introduced in May 2009. The simple plasma exchange (PE) in acute liver failure is important by not only the removal of the disease create substances but also the supplement of the coagulation factors. We began by examining the prescribed replacement plasma volume (100〜150mL/kg) for simple plasma exchange (PE) in this protocol. We compared the PT-INR and PT activity of seven cases (6.4〜19.3kg) of acute liver failure coma, before and after the first PE. The PT-INR and PT activity in six of the seven cases (86%) showed an improvement by more than 1.5 times and less than 40%, respectively. And no hemorrhagic complication was observed in all cases. The prescribed replacement plasma volume of PE used in this protocol reached a sufficient therapeutic dose for the supplement of the coagulation factors.

We report our study of continuous blood purification therapy (CBP) carried out for the purpose of fluid management in severe acute pancreatitis (SAP). We retrospectively examined 28 cases of SAP treated with CBP in our institution between April 1, 2005 and April 1, 2012. A comparison of the survivor and non-survivor groups shows that there was no significant difference in the pancreatitis disease severity score; however, the average APACHE Ⅱ score for time of onset of CBP and SOFA score were significantly higher in the non-survivor group. Among the survivors, despite early large-dose transfusions, central venous pressure and PaO₂/F_IO₂ ratio were maintained appropriately throughout, with no aggravation of respiratory status or overhydration. In the non-survivors, central venous pressure rose and gradually became in-over, so that the maintenance of blood pressure became difficult, and the volume of fluid drained was small. In treatment of the SAP, CBP is an important treatment modality for fluid management to control water and solutes or electrolytes.

【Objective】 The study aimed to examine the relationship between recombinant thrombomodulin (rTM) and obstruction of continuous blood purification (CBP) circuit in disseminated intravascular coagulation (DIC) cases. 【Method】 We compared the CBP circuit obstructive (within 24h) and non-obstructive group. and examined the relationship between the type of CBP circuit obstruction, patient characteristics, outcomes, and duration of patient’s stay in an ICU. 【Results】 The type of CBP circuit obstruction and patient characteristics or outcome did not significantly differ. Furthermore, the non-obstructive group required a significantly shorter period in the ICU than the obstructive group. The frequency of obstruction was intentionally low only with rTM use for a short. Moreover the difference was accepted by the rTM use existence without the patient characteristics and the duration of patient stay in the ICU. 【Conclusion】 Our result has suggested that rTM reduces the CBP circuit obstruction without changing the effect.

While prognoses are worsened by the development of cardiac surgery-associated acute kidney injury (CSA-AKI) following cardiac surgery, it has been reported that prognoses can improve if continuous renal replacement therapy (CRRT) is conducted at an early stage of within 3 days of the surgery. However, indications for this procedure and mechanisms underlying the improved prognosis remain unclear. The present study retrospectively assessed the efficacy of high flow-volume CHDF in 8 cases of circulatory failure following cardiac surgery under cardiopulmonary bypass complicated with CSA-AKI. Improvements were noted in various hemodynamic parameters following initiation of high flow-volume CHDF, and the catecholamine index (CAI) significantly decreased. Concentrations of serum lactate and serum IL-6 and body temperature also significantly decreased while urine volume significantly increased following high flow-volume CHDF. Details regarding the procedure were as follows: days to CRRT initiation following surgery, 1.6 days; duration of high flow-volume CHDF, 2.3 days; total number of days of CRRT, 8.6 days; ICU stay, 13.1 days; transition to maintenance dialysis, 0％; 28day survival, 100％; and in-hospital survival rate, 87.5%. Our findings suggest that early initiation of high flow-volume CHDF in cases of circulatory failure following cardiac surgery under cardiopulmonary bypass complicated with CSA-AKI is effective, as reflected by improved hemodynamic parameters and renal function.

Acute blood purification therapy is widely applied in emergency medicine. In particular, therapeutic plasma exchange (PE) or double filtration plasmapheresis (DFPP) is the treatment of choice for acute exacerbation episodes of autoimmune diseases. When PE and DFPP using albumin solution as replacement fluid are compared, in order to remove 65% of serum IgG, it is necessary to exchange 0.9 plasma volumes (PV) in PE and 1.15 PV in DFPP. On the other hand, removal of fibrinogen is 64% in PE and 75% in DFPP. PE using albumin as replacement solution requires less amount of patient plasma volume to be exchanged with smaller loss of fibrinogen compared to DFPP. Taking account of its relatively simple maneuver, PE using albumin as replacement solution is a considerable option of treatment for pathogenic antigen removal.

The accidental disconnection of venous circulation during CBP (Continuous blood purification therapy) is a life-threatening medical condition. Therefore, I investigated the implementation of an appropriate venous pressure lower limit alarm to detect the accidental disconnection of blood circulation. The experiment used a bypass model that simulated venous pressure during CBP and a model that simulated a deviation in the normal blood circuit (i.e., venous pressure decrease). I manipulated the conditions of blood flow quantity and Hct levels, as well as the stabilization of the blood circuit. I examined a venous pressure lower limit warning derived from the venous pressure differential between the bypass and the circuit solution models. The venous pressure changed relative to blood flow quantity and Hct levels, as did the circuit stabilization in each model, The change in blood flow quantity most greatly influenced venous pressure, and changes in the differential pressure increased in conjunction with blood flow quantity. Therefore, I determined a minimum for the differential pressure identified as the experiment’s lower limit alarm level. It became clear that the lower limit alarm level was higher than the venous pressure when blood circulation decreased under all conditions. It was determined that a machine’s sensitivity to a drop in venous pressure of less than 37mmHg was most appropriate for the purpose of the alarm.

The number of blood purification therapy (BPT) procedures performed in pediatric patients has been increasing in Japan despite BPT being technically difficult to perform in children. We report a clinical review of 112 pediatric cases treated with BPT in our hospital. The patient age ranged from 0 days to 25 years (median, 3 months) . The body weight ranged from 0.4 to 70kg (median, 3.8kg). Present illnesses included cardiogenic acute kidney injury (AKI) in 38 patients, septic AKI in 30, other AKI in 13, chronic kidney disease in 11, and others in 20. Underlying diseases included mature and premature neonates in 46 patients, cardiac disease in 30, renal disease in 8, others in 11, and none in 17. Eighty-six patients were treated with mechanical respirators, and 24 were treated with artificial heart-lung machines. BPT methods included peritoneal dialysis (PD) in 35 patients, continuous hemodiafiltration (CHDF) in 45, direct hemoperfusion using polymyxin B-immobilized fiber (PMX) in 17, plasma exchange (PE) in 12, hemoabsorption (HA) in 2, and hemodialysis (HD) in 1. The predicted mortality rates were as follows：overall, 64%; PD, 54%; CHDF, 77%; PMX, 91%; PE, 23%; and HA/HD, 1%. The mortality rates after 3 months were as follows: overall, 35%; PD, 40%; CHDF, 42%; PMX, 29%; PE, 8%; and HA/HD, 0%. No serious adverse events were noted. All 37 patients died of their primary diseases. Our results present that BPT can be performed safely in pediatric patients and might reduce the mortality rate in children.

There are many generic drugs of nafamostate mesilate (NM) in Japan, while only a few studies have compared the anticoagulant action of filter and/or circuit patency between the original and generic NMs. So, in this study, we retrospectively reviewed the medical records of maintenance hemodialysis (HD) patients who had been undergone open cardiovascular surgery. We examined the initial survival time of CHDF filter and circuit in patients who had administered either original NM (Fusan^®, Torii Pharmaceuticals Co., Ltd, Tokyo, Japan) (n=22) or generic NM (Coahibitor^®, Ajinomoto Pharmaceuticals Co., Ltd, Tokyo, Japan) (n=21). No difference was found in clinical parameters at the beginning of CHDF between the two groups. Mean filter and/or circuit lifespan was also identical between the both groups (1,390±433 vs. 1,225±434 min, p=0.219). The findings suggest that the generic drug has a comparable anticoagulant action to the original one in hemodialysis patients who had started CHDF treatment following open heart surgery. Additional studies will be needed whether the other generic NMs may afford an acceptable hemodiafilter lifespan in patients at a higher risk of filter and/or circuit coagulation.

In continuous renal replacement therapy, hemofilters gradually become clogged as a result of blood clotting and have to be replaced. In clinical use, the degree of clotting in these filters is usually determined by examining the pressure at both the filter inlet and the transmembrane. In this study, we investigated how the filters became clogged by examining the clotting distribution patterns within the hollow fibers of the membrane. For our study, we utilized hemofilters with a polysulfone membrane from two manufactures (Toray SHG-1.0 filters；Asahi Kasei Medical AEF-10 filters). Using bovine blood, we examined the blood clotting distribution patterns within the hollow fibers in two ways：the cross section clotting distribution and the lengthwise clotting distribution. The overall results for both filters showed no conclusive clotting distribution patterns in the cross section analysis, meaning the clotting patterns were varied and non-uniform. The lengthwise distribution did show some minor patterns occurring in the middle position. However, all the filters from both makers showed a lower probability of clotting taking place in the center of the inlet cross section. Additionally, all the filters also showed a higher probability of blood coagulation in the middle section of the lengthwise direction.

We treated 30 pediatric cases aged ＜15 years over the 10-year period from January 2003 through December 2012 for whom we devised countermeasures to safely conduct pediatric blood purification therapy. These countermeasures involved minimizing fluctuations in hemodynamics by initiating treatment after washing blood in the continuous hemodialysis (CHD) mode while transfusing blood and using albumin in the transfusion solution during the acute phase. In cases requiring plasma exchange(PE), PE ＋ continuous renal replacement therapy (CRRT) with the series–parallel method was used to correct electrolyte imbalances such as hypocalcemia caused by fresh frozen plasma (FFP) transfusion. Removal of impurities was also simplified by applying a series–parallel dedicated circuit. Incorporating a CRRT circuit into an extracorporeal membrane oxygenation (ECMO) circuit in cases requiring ECMO was useful for those in which vascular access was difficult. Pediatric blood purification therapy must be conducted safely using various measures that take into account the peculiarities of pediatric blood purification such as the ratio of circulating blood volume to the amount of filling solution and securing of vascular access.

The patient was a 40-year old woman who saw a doctor regularly for manic-depressive psychosis. She took in too much medicine for suicide attempt sometimes. She ingested a total of 119 tablets, including 44 lithium carbonate tablets. She took in for suicide attempt April in 2012 year. She was brought to our hospital 3 hr later. When she arrived, she was not able to talk well, she was drowsy and her Lithium concentration was 2.89mEq/L. We conducted hemodialysis to remove lithium for 4 hours. She recovered consciousness and she was able to talk well soon. The next day we conducted additional hemodialysis for lithium rebound-phenomenon. Two times hemodialysis has done and her condition has improved uneventfully.

A 14-day-old newborn with acute kidney injury associated with systemic herpes simplex virus infection was treated successfully with sustained low efficiency dialysis (SLED). The patient had developed multiple organ failure including kidney failure, liver failure, and bleeding disorders. To perform neonatal SLED, we used a common continuous renal replacement therapy machine designed for adult treatment (KM-8900; Kawasumi Laboratories, Inc., Japan); a hemofilter designed for pediatric use(EXCELFLO AEF03; Asahikasei Medical Co., Ltd., Japan); and a pediatric blood circuit with a priming volume of 70mL. For the vascular access needed for dialysis, indwelling needles were inserted into arterial (24-gauge) and venous vessels (22-gauge). The blood flow rate was 15～20mL/min, and the dialysate flow rate was 250mL/h. The treatment time was up to 11 h. At the start of dialysis, the blood circuit was filled with red cell concentrate and fresh frozen plasma. Continuous renal replacement therapy is generally the main modality for children; however, we selected SLED to avoid continuous use of anticoagulates and to save time for other therapeutic procedures. Six sessions of SLED were completed successfully without affecting the patient’s vital signs. The patient’s condition improved, including kidney failure recovery, and the patient was discharged on day 66 of the hospital stay. In conclusion, SLED can be performed safely in newborns and has several advantages, such as reducing the risk of bleeding and saving time for other procedures.

Acquired factor V inhibitor often presents with life-threatening bleeding and it is difficult to determine the operable condition. Immunosuppressive therapy and plasma exchange (PE) are the recommended treatment, but the results remain unclear. Case: An 81 year-old man with severe burns (burn index 35) was operated on on day 7 for debridement and split thickness skin grafting. After the surgery, the international normalized ratio（INR）and the activated partial thromboplastin time (APTT) were elevated. We postponed the planned second skin graft because supplementation of vitamin K and fresh frozen plasma was unable to stop the coagulation disturbance. The inhibitor pattern on the cross mixing test and the coagulation factor V activity (＜3%) made us suspect the existence of factor 5 inhibitors. From day 19 we performed PE to remove the inhibitors. INR and APTT showed only a temporary improvement so on day 21 we administered prednisolone (PSL). Some days later, we received word that a test on day 18 had proved positive for FV inhibitor, thus giving us our definitive diagnosis. After the PSL dosage, INR and APTT improved only a little so we repeated the treatment. This time, the INR and APTT improved only temporarily. Conclusion: PE is not a curative therapy, so it is necessary to give careful attention to the indications and timing of PE therapy.

[Background] Sodium bromate intoxication causes acute kidney injury and hearing loss, and often leads to chronic renal failure. We report a patient who developed acute kidney injury and hearing loss due to intoxication with sodium bromate solution. She was successfully treated with continuous renal replacement therapy (CRRT) and intermittent hemodialysis (IHD). [Case] A 68-year-old female ingested a cold wave neutralizer containing sodium bromate in a suicide attempt. At admission to our ICU, her circulation and respiratory status were stable, with normal laboratory data. However, she developed rapid hearing impairment and anuria on the first hospital day, and high flow-volume CRRT was performed. On the third hospital day, the amount of blood purification was further increased, and IHD was performed. Her renal function gradually recovered, allowing the discontinuation of renal replacement therapy. Her hearing ability improved day by day. She was transferred to another hospital on the 20th hospital day. [Conclusion] Rapid removal of bromate by early induction of blood purification therapy is important to prevent severe organ dysfunction.

The patient was a 4-year-old girl brought to our department with chief complaints of fever and clonic convulsions affecting the left side of her body. She had acute encephalopathy with febrile convulsive status epilepticus accompanied by concurrent hypercytokinemia (serum IL-6 36,100pg/mL, cerebrospinal fluid IL-6 2,460pg/mL) and multi-organ failure. We estimated her prognosis was poor. Although we started to treat her with steroids pulse therapy and high-dose gamma globulin, her condition was getting worse with multiple organ failure. However, her life could be saved by a multidisciplinary therapeutic approach including plasma exchange and continuous hemodiafiltration using a cytokine removal filter. As diffusion-weighted magnetic resonance imaging of the head showed high signals in the subcortical white matter of the right cerebral hemisphere, hemiconvulsion-hemiplegia syndrome was diagnosed. Although left hemiparesis remained, she recovered the ability to walk by herself and was discharged about 2.5 months after her admission. Blood purification can remove cytokine effectively and is listed as a special therapy in the influenza-associated encephalopathy treatment guidelines. In acute encephalopathy and encephalitis, cytokine removal by blood purification therapy may contribute to improving both survival and neurological prognosis by rapidly improving hypercytokinemia and inhibiting the progression of tissue damage.

One of the frequent problems leading to cessation of continuous renal replacement therapy (CRRT) is coagulation of the blood circuit attached to the dialysis machine. Also, the close association between coagulation of the blood circuit and filter materials is well known. The aim of this retrospective study was to analyze the lifetimes of 4 different types of filters -- polymethylmethacrylate acetate (PMMA) (n=16), polysulfon (PS) (n=91), polyethersulfone (PES) (n=39) and cellulose triacetate(CTA) (n=25)-- in patients who received CRRT from October 2009 year to January 2013 years (n means a number of sessions of CRRT). The average lifetime of the (PMMA) filter (n=16) was the shortest among the 4 filters. Besides, elevation of transmembrane pressure (TMP) was the second highest cause of discontinuing CRRT. Among the 4 types of filters, elevation of TMP was found more frequently in CTA and PMMA than in PES and PS. From these findings, it appears that filter materials are closely associated with the lifetime of filters in CRRT.

The efficacy of recombinant thrombomodulin (rTM) for treating disseminated intravascular coagulation (DIC)with septic shock has already been shown. However, adequate data on the action of rTM are not available. This retrospective study examined the sites of infection that rTM acted upon in treating septic DIC. The subjects were 19 septic DIC patients who were administered rTM and seen between July 2012 and July 2013. The evaluation items were SIRS, DIC, and SOFA scores. Also, subjects were divided into two groups: 10 patients treated with PMX-DHP and 9 not treated with PMX-DHP for whom the same evaluation items were investigated. The sites of infection were pneumonia 7, pyelonephritis 4, cellulitis 3, enterocolitis 3, catheter related infection 2, pleuritis 1, arthritis 1, cholangitis 1, discitis 1 (including overlapped). The mean initial dose was 7,009.0±2,680.7 U/day, mean days of administration were 5.9±2.1 days. The results before and after administration of rTM were: SIRS, from 2.95±0.91 to 0.68±1.06; DIC, from 4.21±1.96 to 2.35±1.54; SOFA, from 7.53±3.57 to 5.47±3.31. In SOFA score: respiratory, 1.32±1.38 to 0.68±1.25; coagulation, from 1.95±1.31 to 1.11±0.94; cardiovascular, from 1.42±1.64 to 0.68±1.29. All results were significant reductions. The 28-days survival rate of the PMX-DHP and non-PMX-DHP groups were 90.0% and 66.7% respectively, according to the Kaplan-Meier method. While there were only a small number of such cases, the results suggest administration of rTM protects organs from the effects of DIC.

Acute blood purification is performed in the intensive care unit and several different staff members are involved in the associated patient care. A team approach to health care is mandatory due to the wide range of specialists necessary for optimal care. The field of acute blood purification is no exception. We believe that problems occur because of a shortage of the necessary specialists, insufficient communication of information, and a lack of adequate cooperation. For optimal patient care, it is necessary to address these problems. Most importantly, a team approach in the management of acute blood purification must include all team members involved in patient care and all must be active participants.

Hemodiafiltration equipment is essential in the field of emergency and intensive care medicine for managing patients with various serious conditions. Multidisciplinary care for acute hemodiafiltration typically involves doctors, nurses, and clinical engineers; however, there are concerns regarding the risk of pitfalls arising due to “gaps” between each discipline. The present study investigated cases at our hospital and revealed that pitfalls occur due to insufficient communication during multidisciplinary care. As a result, efforts are now being made to prevent similar cases from occurring by establishing measures based on the details of the present investigations. Ideally, in order to prevent pitfalls, staff involved in multidisciplinary care should be constantly sharing information and providing mutual support.