Cytokines and various mediators play pivotal roles in the pathophysiology of severe sepsis/septic shock. Continuous hemodiafiltration (CHDF) using a polymethylmethacrylate (PMMA) membrane hemofilter (PMMA-CHDF) removes cytokines efficiently and continuously mainly through adsorption onto a hemofilter membrane, thereby giving a favorable outcome. Further, we have occasionally encountered cases of refractory septic shock, and we have reported that “enhanced intensity PMMA-CHDF” may contribute to improved hemodynamics and intensive care unit (ICU) survival rate by enhancing cytokine removal. We reviewed various modalities of acute blood purification for controlling mediators, and we believe that the clinical efficacy and usefulness of PMMA-CHDF is higher than that of other modalities. Earlier introduction of enhancing intensity of acute blood purification may improve the outcome in cases of toxic shock-like syndrome and presence of genetic high-risk haplotypes and refractory septic shock.

Polymyxin B immobilized fiber cartridge (PMX) has been used clinically in some countries in Europe and Asia outside Japan with good safety results. Sustained septic shock after surgery due to abdominal infection is a good indication for PMX, and a similar clinical improvement has been reported in these countries as in Japan. A biomarker to direct PMX treatment is urgently needed not only to give a rational for PMX use, but also for a rapid diagnosis of endotoxemia. A FDA approved blood endotoxin measurement method (EAA) has been used in some countries to diagnose endotoxemia and select an appropriate patient who are most likely to benefit from PMX treatment. Two multicenter randomized controlled studies, EUPHRATES trial in North America and ABDO-MIX in France are currently recruiting patients. These two studies are being expected to give a definitive answer for the effectiveness of PMX in reducing mortality and improving clinical parameters. While the complete mechanism of action of PMX is still not fully understood, regulation of inflammatory mediators as a result of endotoxin removal and the immunomodulatory effect associated with the removal of immune cells, such as monocytes and neutrophils with PMX have been proposed. To proceed from a phenomenological observation to an essential explanation for the complete mechanism of action of PMX treatment, further study is still needed to clarify the role of PMX and the other associated biochemical alterations in the clinical settings.

Blood purification therapy in pediatric critical care was performed for 35 children from December 2007, when instruments were introduced as a center hospital for children, to September 2011. Its methods for children in our hospital have been standardized. A 6Fr catheter was inserted into the right internal jugular vein in neonates under general anesthesia, and a 7Fr catheter in infants to children. In children weighting less than 10kg, a circuit was filled with albumin (neonates: 10% albumin, infants to children: 5% albumin）. In neonates, after starting circuit circulation, rapid blood transfusion was performed with body fluid removal. The blood flow rate (Qb) was established at 25mL/min in neonates and 50mL/min in infants to children. In continuous hemodialysis, the dialysis flow rate (Qd) was established at 500mL/hr for acute renal failure, while it was started at a Qd/Qb ratio of 1.0 for acute liver failure/inborn error of metabolism. In plasmapheresis, 5% albumin or fresh frozen plasma- leukocytes reduced was employed as substitution fluid. The degree of substitution was 80mL/kg. Standardization/simple procedures have facilitated prompt introduction of blood purification therapy in pediatric critical care, and the survival rate of children with blood purification may be improved.

Pharmacokinetics of meropenem (MEPM) in patients undergoing continuous hemodiafiltrarion (CHDF) has not been fully elucidated in Japan. Therefore, we evaluated the pharmacokinetics of MEPM to obtain optimal dose and times of MEPM infusion under CHDF therapy. Eight patients with multiple organ failure and anuria due to sepsis who needed CHDF treatment were injected 0.5 gram of MEPM twice daily. Among 8 patients, 4 patients used polysulfone (PS) membrane and 4 patients used polymethyl methacrylate (PMMA) membrane, and blood concentrations of MEPM were sequentially evaluated. Time above MIC (%T＞MIC) of MEPM more than 40～50% is usually thought to be effective and sufficient to sterilize bacteria. In our study, drip infusion of MEPM 0.5 gram twice daily under CHDF(blood flow 100mL/minute, dialysate flow 300mL/hour, replacement flow 300 mL/hour)could achieve effective therapeutic dose (%T＞MIC more than 50%) if the MIC of bacteria against MEPM was below 4µg/mL. Blood concentration of MEPM did not differ between PS and PMMA group. In critically ill patients with severe infection, adequate administration of antibiotics is crucial. Therefore, evidence of antibiotic pharmacokinetics under CHDF therapy should be accumulated to obtain optimal effect for such patients.

Background: Minimum changes in serum creatinine (SCr) concentration affect the prognosis of patients with acute kidney injury (AKI). AKI backgrounds vary widely, therefore , all cases cannot be compared from the same perspective. Postoperative patients with AKI admitted to the intensive care unit (ICU) were examined. Materials and Methods：Twenty-seven patients diagnosed with AKI were admitted to our ICU from January to August in 2009. These patients were divided into group R, in which the patients underwent renal replacement therapy (RRT), and group NR, in which did not. The duration of ICU stay, mechanical ventilation, sequential organ failure assessment(SOFA)scores, and postoperative death within 1 year (PDWY) were further divided into groups A and D based on whether there was PDWY. Postoperative SCr-concentrations, its increasing rate, and SOFA scores were compared between the 2 groups. Univariate regression analysis was conducted for the SOFA index and RRT to PDWY. Results: Group R showed higher SOFA scores, and a longer duration of ICU stay and mechanical ventilation. Postoperative SCr-concentration and SOFA scores at postoperative day 2 were higher in group D than in group A. Univariate regression analysis revealed that RRT to PDWY was statistically significant with odds ratio of 7.5; however, the SOFA index to PDWY was not significant. Discussion: Because the SOFA score was not sufficiently useful to predict PDWY, long-term prognosis, an early detectable marker for AKI is necessary for the early intervention of patients with AKI and multiple organ dysfunction syndrome (MODS).

When blood purification is needed after early stage of hematopoietic stem cell transplantation, it is performed in clean room (CR) because of protection from infectious diseases. We examined the contamination test for console in clean room after transporting from outside. After cleaning console by two kind of disinfectant detergent, the surface hygiene test with relative light unit (RLU) was measured with Adenosine Triphosphate and Adenosine Monophosphate. A permissible range of them is from 200 to 500 RLU. Even though just after disinfecting some data were exceeded over the permissible range, the RLU after 15hours were within the permissible range in all of the places and disinfectant detergent. It is considered that we can control CR atmosphere in the permissible range, cleaning console by disinfectant detergent just before transporting into CR, and infectious risk for the patient in CR would be decreased.

We investigated whether risk factors of coagulation in the circuit during continuous purification therapy (CBP) can be predicted from laboratory data. The subjects were 96 patients who underwent CBP at our hospital between November 2009 and August 2011. Coagulation in the circuit occurred within 24 hours on 7-day or longer treatment in an ER-ICU in 15 of the 96 patients. The total duration of treatment in 15 patients was 285 days. The daily data during the treatment period were subjected to multivariate analysis, and the risk factors influencing circuit coagulation were identified. The following 3 items were risk factors necessitating emergency exchange of the blood circuit: 25％ or lower Hct (HR: 3.189, 95％ CI: 1.606～6.335, P=0.0009), 350mg/dL or higher Fbg (HR: 4.266, 95％ CI: 1.082～16.826, P=0.0382), and 30μg/dL or higher FDP (HR: 3.077, 95％ CI: 1.275～7.425, P=0.011). The risk factors of coagulation in the circuit are increasing Fbg and FDP values and a lower Hct representing hypercoagulation. Circuit coagulation may occur in patients with a 25％ or lower Hct, 350mg/dL or higher Fbg, and 30μg/dL or higher FDP, for whom investigation of anticoagulants and consideration of the timing of circuit exchange are necessary.

【Objective】We analyzed the current status of acute blood purification therapy in children in Japan. 【Method】The subjects were 50 children (neonates and infants) weighing 20kg or less who received acute blood purification (ABP) therapy at 15 centers between July 2007 and July 2008. Therapeutic conditions for ABP and 28-day survival rates were investigated. 【Results】There was a high incidence of sepsis, inborn errors of metabolism, and acute renal failure. A 6- to 9-Fr. double-lumen catheter in the internal jugular vein was used for vascular access. A module of 0.3m2 was generally used. Nafamostat mesilate was administered as an anticoagulant in 86％ of the cases. Packed red cells were added to the priming solution in children weighing 9kg or less. The volume of blood to be purified was adjusted appropriately for children’s weight and disease condition. The 28-day survival was 80％. 【Conclusion】This study showed that ABP therapy is performed in almost the same way. In the future, standardization of ABP therapy is required in children, for example by defining optimal therapeutic conditions for each disease condition.

A few cases of blood purification (BP) performed in newborns have been reported in Japan. BP for newborns involves some specific issues, such as priming volume, vascular access, and the effect on hemodynamics. We report on two cases of successful BP in newborns with hyperammonemia. In general, for newborns, the priming volume must be decreased, and we have been using an original circuit specifically designed for newborn BP. The circuit has certain disadvantages, however, such as an uncoordinated alarm system and blood pump. Patient 1 was treated using the original circuit, while a BP system and a circuit of the same manufacturer were used in Patient 2. In the latter case, treatment safety improved with the automated priming, decreased priming volume, and the coordinated alarm system and blood pump. Clinical engineering technologists should further evaluate the safety of BP to increase its use in more newborn patients.

Instead of “Acute Renal Failure (ARF),” a new concept of “Acute Kidney Injury (AKI)” including pre-kidney failure has been widely spreading in recent years. As the new concept is known, it can be possible to make a definite and early diagnosis of AKI. It is also expected the improvement rate and the survival rate to improve. In this paper, we would like to introduce our approach in the field of CRRT.

In Japan, the supply of replacement substitution from the A company had temporally stopped by the tsunami disaster due to the Great East Japan Earthquake on March 11, 2011. So, we urgently used the bicarbonate Ringer solution as a replacement filtrate solution in the 2 ICU patients who had been on continuous hemodiafiltration (CHDF). The main differences of fluid composition between bicarbonate Ringer solution and the conventional substitution were as follows; a higher potassium (4mEq/L) and no glucose in the bicarbonate Ringer solution. We conducted CHDF therapy for the both patients during 21 and 26 days respectively. During the treatment, serum potassium levels were stable with lower potassium supplementation. In 1 case, serum glucose level was transiently decreased to below 100mg/dL, while it easily recovered with glucose administration. Thus, when urgently use the bicarbonate Ringer solution as a replacement substitution, it is relatively safe to control serum potassium and glucose during CHDF treatment.