Safety and efficacy of the Seraph® 100 Microbind® Affinity Blood Filter to remove bacteria from the blood stream: results of the first in human study.

BACKGROUND: Bacterial burden as well as duration of bacteremia influence the outcome of patients with bloodstream infections. Promptly decreasing bacterial load in the blood by using extracorporeal devices in addition to anti-infective therapy has recently been explored. Preclinical studies with the Seraph® 100 Microbind® Affinity Blood Filter (Seraph® 100), which consists of heparin that is covalently bound to polymer beads, have demonstrated an effective binding of bacteria and viruses. Pathogens adhere to the heparin coated polymer beads in the adsorber as they would normally do to heparan sulfate on cell surfaces. Using this biomimetic principle, the Seraph® 100 could help to decrease bacterial burden in vivo. METHODS: This first in human, prospective, multicenter, non-randomized interventional study included patients with blood culture positive bloodstream infection and the need for kidney replacement therapy as an adjunctive treatment for bloodstream infections. We performed a single four-hour hemoperfusion treatment with the Seraph® 100 in conjunction with a dialysis procedure. Post procedure follow up was 14 days. RESULTS: Fifteen hemodialysis patients (3F/12 M, age 74.0 [68.0-78.5] years, dialysis vintage 28.0 [11.0-45.0] months) were enrolled. Seraph® 100 treatment started 66.4 [45.7-80.6] hours after the initial positive blood culture was drawn. During the treatment with the Seraph® 100 with a median blood flow of 285 [225-300] ml/min no device or treatment related adverse events were reported. Blood pressure and heart rate remained stable while peripheral oxygen saturation improved during the treatment from 98.0 [92.5-98.0] to 99.0 [98.0-99.5] %; p = 0.0184. Four patients still had positive blood culture at the start of Seraph® 100 treatment. In one patient blood cultures turned negative during treatment. The time to positivity (TTP) was increased between inflow and outflow blood cultures by 36 [- 7.2 to 96.3] minutes. However, overall TTP increase was not statistical significant. CONCLUSIONS: Seraph® 100 treatment was well tolerated. Adding Seraph® 100 to antibiotics early in the course of bacteremia might result in a faster resolution of bloodstream infections, which has to be evaluated in further studies. TRAIL REGISTRATION: ClinicalTrials.gov Identifier: NCT02914132 , first posted September 26, 2016.

Fosfomycin single- and multiple-dose pharmacokinetics in patients undergoing prolonged intermittent renal replacement therapy.

BACKGROUND: Fosfomycin is used increasingly in the treatment of MDR bacteria. It is eliminated by renal excretion, but data regarding dosing recommendations for patients undergoing modern means of renal replacement therapies are scarce. OBJECTIVES: Evaluation of the pharmacokinetics (PK) of fosfomycin in patients undergoing prolonged intermittent renal replacement therapy (PIRRT) to guide dosing recommendations. METHODS: Fosfomycin was given in 11 (7 female) patients with severe infections undergoing PIRRT. Plasma levels were measured at several timepoints on the first day of fosfomycin therapy, as well as 5-6 days into therapy, before and after the dialyser, to calculate its clearance. Fosfomycin was measured in the collected spent dialysate. RESULTS: The median (IQR) plasma dialyser clearance for fosfomycin was 183.4 (156.9-214.9) mL/min, eliminating a total amount of 8834 (4556-10 440) mg of fosfomycin, i.e. 73.9% (45.3%-93.5%) of the initial dose. During PIRRT, the fosfomycin half-life was 2.5 (2.2-3.4) h. Data from multiple-dose PK showed an increase in fosfomycin Cmax from 266.8 (166.3-438.1) to 926.1 (446.8-1168.0) mg/L and AUC0-14 from 2540.5 (1815.2-3644.3) to 6714 (4060.6-10612.6) mg·h/L. Dialysis intensity during the study was 1.5 L/h. T>MIC was 100% in all patients. CONCLUSIONS: Patients undergoing PIRRT experience significant fosfomycin elimination, requiring a dose of 5 g/8 h to reach adequate plasma levels. However, drug accumulation may occur, depending on dialysis frequency and intensity.

Population pharmacokinetics of vancomycin in critically ill patients receiving prolonged intermittent renal replacement therapy.

OBJECTIVES: The aim of this study was to describe the population pharmacokinetics of vancomycin during prolonged intermittent renal replacement therapy (PIRRT) in critically ill patients with acute kidney injury. METHODS: Critically ill patients prescribed vancomycin across two sites had blood samples collected during one to three dosing intervals during which PIRRT was performed. Plasma samples were assayed with a validated immunoassay method. Population pharmacokinetic analysis and Monte Carlo simulations were performed using Pmetrics®. The target vancomycin exposures were the area under the concentration-time curve within a 24-h period (AUC0-24)/minimum inhibitory concentration (MIC) ratio of 400 for efficacy and AUC0-24 700 for toxicity. RESULTS: Eleven critically ill patients (seven male) were enrolled and contributed 192 plasma samples. The patient's mean ± standard deviation (SD) age, weight and body mass index (BMI) were 57 ± 13 years, 98 ± 43 kg and 31 ± 9 kg/m2, respectively. A two-compartment linear model adequately described the data. The mean ± SD population pharmacokinetic parameter estimates were PIRRT clearance (CL) 3.47 ± 1.99 L/h, non-PIRRT CL 2.15 ± 2.07 L/h, volume of distribution of the central compartment (Vc) 41.85 ± 24.33 L, distribution rate constant from central to peripheral compartment 5.97 ± 7.93 per h and from peripheral to central compartment 5.29 ± 6.65 per h. Assuming a MIC of 1 mg/L, vancomycin doses of 25 mg/kg per day are suggested to be efficacious, whilst minimising toxic, exposures. CONCLUSIONS: This is the first population pharmacokinetic study of vancomycin in patients receiving PIRRT and we observed large pharmacokinetic variability. Empirically, weight-based doses that are appropriate for the duration of PIRRT, should be selected and supplemented with therapeutic drug monitoring.

Enhanced elimination of cyclophosphamide by high cut-off haemodialysis: single-dose pharmacokinetics in a patient with cast nephropathy.

High cut-off (HCO) haemodialysis removes free light chains in patients with multiple myeloma. This is possible as HCO dialysers allow clearance of molecules up to a molecular weight of 65 kDa. In contrast, high-flux dialysers, which are used in routine haemodialysis, only remove molecules up to a molecular weight of 20 kDa. Even though patients with advanced myeloma frequently need dialysis and alkylating agents, drug dosing recommendations in this patient population are scarce at best or absent as for cyclophosphamide dosing in patients with myeloma undergoing HCO dialysis. Therefore, we aimed to determine pharmacokinetics of cyclophosphamide in a 52-year-old man (height 172 cm, weight 80 kg) with cast nephropathy. Intermittent 4-hour haemodialysis was started ~6 hours after the end of a 70 min cyclophosphamide infusion containing 1700 mg of this drug. Blood/dialysate flow rates were 300/500 mL/hour, respectively. Peak concentration of cyclophosphamide was 24.7 mg/L. Using HCO dialysis, plasma concentration of cyclophosphamide decreased from 10.8 mg/L to 3.7 mg/L during the treatment. The calculated whole blood dialyser clearance was 166 mL/min. HCO dialysis led to a marked decrease of cyclophosphamide resulting in a a 50% reduction in half-life as compared with the half-life before dialysis. This removal has to be accounted for in dosing cyclophosphamide.

Therapeutic plasma exchange in a tertiary care center: 185 patients undergoing 912 treatments - a one-year retrospective analysis.

BACKGROUND: Therapeutic plasma exchange (TPE) is increasingly used throughout the world. Although the procedure itself is fairly standardized, it is yet unknown how the underlying disease entities influence the key coordinates of the treatment. METHODS: Retrospective chart review. The treatment indications were clustered into four categories. Data are presented as median and interquartile (25-75%) range [IQR]. RESULTS: Within 1 year, 912 TPE treatments were performed in 185 patients (90 female, 48.6%). The distribution of the treatment numbers to the pre-specified disease categories were as follows: transplantation (35.7%), neurology (31.9%), vasculitis and immunological disease (17.3%), and others including thrombotic microangiopathy (8.1%), critical care related diseases (5.4%), hematology [multiple myeloma] (1.1%), and endocrine disorders (0.5%). The calculated plasma volume was significantly higher in patients with vasculitis and immunological diseases (3984 [3433-4439] ml) as compared to patients treated for transplant related indications (3194 [2545-3658] ml; p = 0.0003) and neurological diseases (3058 [2533-3359] ml; p < 0.0001). This was mainly due to the differences in the hematocrit which was 30.5 [27.0-33.6] % in the vasculitis/immunological disease patients and 40.2 [37.5-42.9] % in the neurological patients; p < 0.0001. Interestingly, treatment time using a membrane based technology was significantly longer than TPE using a centrifugal device 135.0 [125.0-140.0] min vs. 120.0 [112.5-135.0] min. Furthermore, the relative exchanged plasma volume was significantly lower in the treatment of vasculitis and immunological diseases as compared to treatments of transplant related indications and neurological diseases. CONCLUSION: Patients with low hematocrit and high body weight do not receive the minimum recommended dose of exchange volume. Centrifugal TPE allowed faster plasma exchange than membrane TPE.

Pro: High dose of therapeutic plasma exchange-mind the gap!

'Mind the gap' is a recorded warning phrase used in the London Tube since 1969. The following article is meant to be a warning of an increasing knowing-doing gap in routine practice of therapeutic plasma exchange (TPE), a treatment method that is used more and more throughout the world. The American Society of Apheresis recommendations, including the most recent ones from 2016, suggest using a TPE volume of 1.0-1.5 times the actual calculated plasma volume of the patient. There are only a few exceptions to that rule, such as the recommnded exchange volume in vasculitis or mushroom poisoning. The published literature suggests that in routine clinical practice in many institutions in several countries the exchanged volume might in fact be lower than recommended by the guidelines. In the following article we argue for a high dose of exchanged plasma volume, yet sketch different scenarios on how this time-averaged high dose can be delivered in various ways depending on the underlying disease, refuting a one-size-fits-all strategy that might facilitate the procedure but may result in 'underpheresis' in many patients. Further, the objectives underlying the use of smaller exchange volumes, especially the gap between the cost of blood products and the reimbursement of TPE are discussed. Lastly, the knowing-guiding gap is described, which can only be overcome by collecting high-quality data and conducting prospective clinical trials in the field of TPE.

Health status, renal function, and quality of life after multiorgan failure and acute kidney injury requiring renal replacement therapy.

BACKGROUND: Critically ill patients with acute kidney injury (AKI) in need of renal replacement therapy (RRT) may have a protracted and often incomplete rehabilitation. Their long-term outcome has rarely been investigated. STUDY DESIGN: Survivors of the HANnover Dialysis OUTcome (HANDOUT) study were evaluated after 5 years for survival, health status, renal function, and quality of life (QoL). The HANDOUT study had examinded mortality and renal recovery of patients with AKI receiving either standard extendend or intensified dialysis after multi organ failure. RESULTS: One hundred fifty-six former HANDOUT participants were analyzed. In-hospital mortality was 56.4%. Five-year survival after AKI/RRT was 40.1% (86.5% if discharged from hospital). Main causes of death were cardiovascular complications and sepsis. A total of 19 survivors presented to the outpatient department of our clinic and had good renal recovery (mean estimated glomerular filtration rate 72.5±30 mL/min/1.73 m(2); mean proteinuria 89±84 mg/d). One person required maintenance dialysis. Seventy-nine percent of the patients had a pathological kidney sonomorphology. The Charlson comorbidity score was 2.2±1.4 and adjusted for age 3.3±2.1 years. Numbers of comorbid conditions averaged 2.38±1.72 per patient (heart failure [52%] > chronic kidney disease/myocardial infarction [each 29%]). Median 36-item short form health survey (SF-36™) index was 0.657 (0.69 physical health/0.66 mental health). Quality-adjusted life-years after 5 years were 3.365. CONCLUSION: Mortality after severe AKI is higher than short-term prospective studies show, and morbidity is significant. Kidney recovery as well as general health remains incomplete. Reduction of QoL is minor, and social rehabilitation is very good. Affectivity is heterogeneous, but most patients experience emotional well-being. In summary, AKI in critically ill patients leads to incomplete rehabilitation but acceptable QoL after 5 years.

Ultrasound findings in EHEC-associated hemolytic-uremic syndrome and their clinical relevance.

PURPOSE: Hemolytic-uremic syndrome (HUS) and acute kidney injury (AKI) after infection with Shiga toxin-producing E. coli (EHEC) are clinically important complications. We present a retrospective analysis of abdominal ultrasound findings in patients with HUS caused by EHEC O104:H4 (n = 41). METHODS: We assessed intrarenal resistance indices and quantitated kidney parenchymal density by the kidney/liver intensity ratio using computer-based image analysis. Findings in EHEC-HUS were compared to those in AKI due to other reasons (n = 60) and 19 healthy volunteers. RESULTS: Kidneys in EHEC-HUS patients showed severe morphologic changes with striking parenchymal echogenicity. Renal resistance index was increased in HUS (0.80 ± 0.08) compared to patients with AKI due to glomerulopathy (0.69 ± 0.08, p < 0.001) or patients with other causes of AKI (0.74 ± 0.10, p < 0.01). Parenchymal density was increased in EHEC-HUS (1.39 ± 0.35) compared to AKI due to glomerulopathy (1.18 ± 0.20, p < 0.05), other causes of AKI (1.12 ± 0.21, p < 0.001) and healthy controls (0.86 ± 0.16, p < 0.001). Patients with atypical HUS showed increased parenchymal density (1.43 ± 0.37), similar to those with EHEC-HUS. EHEC-HUS patients who required dialysis treatment had higher parenchymal density (1.58 ± 0.08) compared to those without dialysis (1.14 ± 0.05, p = 0.0004). Extrarenal findings in EHEC-HUS included hepatomegaly (45%), splenomegaly (39%), ascites (84%) and pleural effusions (84%). CONCLUSIONS: Patients with EHEC-HUS had a characteristic constellation of morphologic abnormalities on ultrasound examination, indicating that the effects of HUS are not limited to the kidney but include multiple organs, possibly mediated through systemic capillary leakage. Assessment of parenchymal echogenicity contributes to the differential diagnosis of AKI. Parameters reflecting renal perfusion correlated with severity of disease and thus may have prognostic value in future patient evaluation.

Membrane versus centrifuge-based therapeutic plasma exchange: a randomized prospective crossover study.

BACKGROUND: Therapeutic plasma exchange (TPE) is either performed using a highly permeable filter with standard multifunctional renal replacement equipment (mTPE) or a centrifugation device (cTPE). Although both techniques are well established in clinical practice, performance of these two modes of TPE was never compared in a prospective randomized fashion. Thus we aimed to compare two commercially available therapeutic apheresis systems: mTPE (Octonova with Plasmaflo filter) and cTPE (Spectra Optia apheresis system). METHODS: Twenty-one patients (age 51.6 ± 13.5 years; 10 F/11 M; BMI 25.1 ± 5.0 kg/m(2)) were enrolled in this randomized, prospective, paired, crossover study performed in the Hannover Medical School, Germany. First treatment (either mTPE or cTPE) was chosen by an online randomization list. The primary endpoints were plasma removal efficiency with 1.2× of the total plasma volume exchanged. Secondary endpoints were total amount of plasma substances removed, such as IgG and fibrinogen. Further, the treatment effect on platelet count and complications were evaluated. RESULTS: Despite a comparable volume of the processed plasma, mTPE treatment time was 10.5 % longer than cTPE treatment time (p < 0.05), resulting in a 10 % lower plasma removal rate of the mTPE treatment. Both treatments were comparable in terms of decrease in median (IQR) IgG [pre-mTPE 5.34 (3.48-8.37), post-mTPE 1.96 (1.43-2.84) g/L; pre-cTPE 5.88 (3.42-8.84), post-cTPE 1.89 (1.21-3.52) g/L]. Also the median (IQR) amount of IgG removed in mTPE [13.14 (7.42-16.10) g] was not different from the cTPE treatment [9.30 (6.26-15.69) g]. This was also true for IgM removal. Platelet loss during mTPE was nearly twice as much as with cTPE (15 ± 9 versus 7 ± 9 %, p < 0.05). CONCLUSION: Although the centrifugal procedures were conducted using flow rates that could easily be obtained using peripheral access, plasma removal efficiency was significantly higher and treatment time was significantly lower in cTPE as compared to mTPE. Despite this lower treatment time, the decline in markers of procedure efficacy was comparable. Especially in centers performing many procedures per year, cTPE in contrast to mTPE can reduce treatment time without compromising treatment efficacy.

Effect of therapeutic plasma exchange on plasma levels and total removal of adipokines and inflammatory markers.

BACKGROUND: Aside from well-established inflammatory mediators adipokines have recently been found to play an important role in a variety of immunologic diseases. Therapeutic plasma exchange (TPE) is an established treatment modality for the acute removal of pathophysiological relevant disease mediators. The aim of this study was to determine adipokine removal during TPE therapy. METHODS: 21 Caucasian patients (10 females, 11 males) with an indication for TPE using albumin as exchange fluid received two consecutive TPE sessions. Blood samples for measurement of resistin, leptin, sICAM-1, sCD40L, MCP-1, and sTNF-R were drawn before and at the end of each TPE session. Samples from the total removed plasma were collected at the end of every treatment. RESULTS: We found a significant reduction in pre- vs. post-TPE plasma concentrations for sICAM-1 (517 ± 246 vs. 260 ± 159 ng/ml, p < 0.0001), sTNF-R (8.1 ± 6.4 vs. 5.7 ± 3.9 ng/ml, p < 0.05), and resistin plasma levels (14.3 ± 6.9 vs. 9.5 ± 4.7 ng/ml, p < 0.001). Solely sICAM-1 reduction persisted for 25 ± 5 h between the first and second TPE treatment, while the other investigated mediators increased to baseline levels. Substantial amounts of all measured mediators could be recovered from the removed plasma. CONCLUSIONS: TPE provides a persistent reduction in sICAM-1 levels and temporarily affects several adipokine and cytokine plasma levels. Our findings are of importance not only for the interpretation of blood levels of cytokines in patients undergoing TPE but provide solid evidence that TPE markedly decreases sICAM-1.

Circulating long noncoding RNATapSaki is a predictor of mortality in critically ill patients with acute kidney injury.

BACKGROUND: Long noncoding RNAs (lncRNAs) are novel intracellular noncoding ribonucleotides regulating gene expression. Intriguingly, these RNA transcripts are detectable and stable in the blood of patients with cancer and cardiovascular disease. We tested whether circulating lncRNAs in plasma of critically ill patients with acute kidney injury (AKI) at inception of renal replacement therapy were deregulated and might predict survival. METHODS: We performed a global lncRNA expression analysis using RNA isolated from plasma of patients with AKI, healthy controls, and ischemic disease controls. This global screen revealed several deregulated lncRNAs in plasma samples of patients with AKI. lncRNA-array-based alterations were confirmed in kidney biopsies of patients as well as in plasma of 109 patients with AKI, 30 age-matched healthy controls, and 30 disease controls by quantitative real-time PCR. RESULTS: Circulating concentrations of the novel intronic antisense lncRNA TrAnscript Predicting Survival in AKI (TapSAKI) (P < 0.0001) were detectable in kidney biopsies and upregulated in plasma of patients with AKI. Cox regression and Kaplan-Meier curve analysis revealed TapSAKI as an independent predictor of 28-day survival (P < 0.01). TapSAKI was enriched in tubular epithelial cells subjected to ATP depletion (P = 0.03). CONCLUSIONS: The alteration of circulating concentrations of lncRNAs in patients with AKI supports TapSAKI as a predictor of mortality in this patient cohort.

Therapeutic plasma exchange as rescue therapy in severe sepsis and septic shock: retrospective observational single-centre study of 23 patients.

BACKGROUND: Several case series and small randomized controlled trials suggest that therapeutic plasma exchange (TPE) improves coagulation, hemodynamics and possibly survival in severe sepsis. However, the exact role of TPE in modern sepsis therapy remains unclear. METHODS: We performed a retrospective observational single-centre study on the use of TPE as rescue therapy in 23 consecutive patients with severe sepsis or septic shock from 2005 to 2012. Main surrogate markers of multiple organ failure (MOF) before, during and after TPE as well as survival rates are reported. RESULTS: At baseline, mean SOFA score was 13 (standard deviation [SD] 4) and median number of failed organ-systems was 5 (interquartile range [IQR] 4-5). TPEs were performed 3 days (IQR 2-10) after symptom onset and 1 day (IQR 0-8) after ICU admission. The median total exchange volume was 3750 ml (IQR 2500-6000), which corresponded to a mean of 1.5 times (SD 0.9) the individual plasma volume. Fresh frozen plasma was used in all but one treatments as replacement fluid. Net fluid balance decreased significantly within 12 hrs following the first TPE procedure by a median of 720 mL (p = 0.002), irrespective of outcome. Reductions of norepinephrine dose and improvement in cardiac index were observed in individual survivors, but this was not significant for the overall cohort (p = 0.574). Platelet counts decreased irrespective of outcome between days 0 and 2 (p < 0.003), and increased thereafter in many survivors. There was a non-significant trend towards younger age and higher procalcitonin levels among survivors. Nine out of 23 TPE treated patients (39%) survived until ICU discharge (among them 3 patients with baseline SOFA scores of 15, 17, and 20). CONCLUSIONS: Our data suggest that some patients with severe sepsis and septic shock may experience hemodynamic stabilisation by early TPE therapy.

Removal characteristics and total dialysate content of glutamine and other amino acids in critically ill patients with acute kidney injury undergoing extended dialysis.

BACKGROUND: Acute kidney injury in critically ill patients is associated with the activation of protein catabolism and a negative nitrogen balance. Renal replacement therapy (RRT) aggravates this problem by eliminating a substantial amount of amino acids. However, there is scarce data on the removal characteristics of modern dialysis membranes in extended dialysis. METHODS: This is a prospective study in 10 extended dialysis sessions using a 1.8-m(2) polysulfone membrane (EMiC2 dialyzer or AV 1000S; FMC, Germany). Blood samples for 19 amino acids were drawn before, during, and after 10 h of extended dialysis (blood/dialysate flow 150 ml/min). In addition, samples for the calculation of dialyzer clearance and samples from the total spent dialysate were measured using a Biochrom 30 amino acid analyzer. RESULTS: Despite no significant difference in pre- and postdialysis plasma amino acid levels, we found an impressive amount of amino acids in collected spent dialysate, i.e. 10.5 g/10 h of treatment. The dialyzer clearance ranged from 67.6 ml/min for phenylalanine to 140.0 ml/min for valine. The total eliminated masses of the measured amino acids had equal values for both membranes. There was a significant difference between the dialyzer clearance of the investigated membranes for glutamine (AV 1000S: 83.3 ml/min vs. EMiC2: 92.0 ml/min, p = 0.02) and serine (88.8 ml/min vs. 91.8 ml/min, p = 0.005). DISCUSSION: Our data indicate that the modern forms of RRT eliminate amino acids to an extent that has not been met by our nutritional support standards. Especially the removal of glutamine, important for immune function and cell regeneration, might have detrimental effects on the recovery of critically ill patients.

Tissue concentration of paraquat on day 32 after intoxication and failed bridge to transplantation by extracorporeal membrane oxygenation therapy.

BACKGROUND: Paraquat is a highly toxic herbicide, which not only leads to acute organ damage, but also to pulmonary fibrosis. There are only anecdotal reports of rescue lung transplantation, as paraquat is stored and only slowly released from different tissues. Bridging the time to complete depletion of paraquat from the body could render this exceptional therapy strategy possible, but not much is known on the time interval after which transplantation can safely be performed. CASE PRESENTATION: We report on a case of accidental paraquat poisoning in a 23 years old Caucasian man, who developed respiratory failure due to pulmonary fibrosis. The patient was listed for high urgency lung transplantion, and extracorporeal membrane oxygenation was implemented to bridge the time to transplantation. The patient died 32 days after paraquat ingestion, before a suitable donor organ was found. In postmortem tissue specimen, no paraquat was detectable anymore. CONCLUSION: This case report indicates that complete elimination of paraquat after oral ingestion of a lethal dose is achievable. The determined time frame for this complete elimination might be relevant for patients, in which lung transplantation is considered.

Effect of isovolemic, isothermic hemodialysis on cerebral perfusion and vascular stiffness using contrast computed tomography and pulse wave velocity.

BACKGROUND: Patients undergoing hemodialysis treatment have a six-fold increased risk for stroke relative to the general population. However, the effect of hemodialysis on cerebral blood flow is poorly studied and confounding factors like blood pressure and ultrafiltration as well as temperature changes have rarely been accounted for. The aim of our study was to use state-of-the-art technology to evaluate the effect of a single dialysis session on cerebral perfusion as well as on vascular stiffness. METHODS: Chronic hemodialysis patients (7 male/3 female, mean age 58 years) were recruited. Cerebral blood flow and arterial pulse wave velocity were measured before and immediately after a hemodialysis session. To exclude effects of volume changes we kept ultrafiltration to a minimum, allowing no change in body weight. Isothermic conditions were maintained by using the GENIUS single-pass batch-dialysis system with a high-flux polysulfone dialyser. Cerebral blood flow was measured by contrast-enhanced computed tomography. Pulse wave velocity was measured using the SphygmoCor (AtCor Medical, USA) device by a single operator. RESULTS: This study shows for the first time that isovolemic, isothermic hemodialysis neither affected blood pressure or heart rate, nor total or regional cerebral perfusion. There was also no change in pulse wave velocity. CONCLUSIONS: Mechanisms other than the dialysis procedure itself might be causative for the high incidence of ischemic strokes in this patient population. Moreover, the sole removal of uremic toxins does not lead to short-term effects on vascular stiffness, underlying the importance of volume control in this patient population.

Renal function and survival in 200 patients undergoing ECMO therapy.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used in the intensive care unit (ICU) setting to improve gas exchange in patients with acute respiratory distress syndrome as well as in patients pre- and post-heart and lung transplantation. In this clinical setting, acute kidney injury (AKI) is frequently observed. So far, it is unknown how AKI affects the survival of critically ill patients receiving ECMO support and whether veno-veno and veno-arterial ECMO have different effects on kidney function. METHODS: This is a retrospective analysis of patients undergoing ECMO treatment in medical and surgical ICUs in a tertiary care centre. We evaluated all patients undergoing ECMO treatment at our centre between 1 January 2005 and 31 December 2010. Data from all 200 patients (83F/117M), median age 45 (17-83) years, were obtained by chart review. Follow-up data were obtained for up to 3 months. RESULTS: Three-month survival of all patients was 31%. Of the 200 patients undergoing ECMO treatment, 60% (120/200) required renal replacement therapy (RRT) for AKI. While patients without RRT showed a 3-month survival of 53%, the survival of patients with AKI requiring RRT was 17% (P = 0.001). Longer duration of RRT was associated with a higher mortality. CONCLUSIONS: AKI requiring RRT therapy in patients undergoing ECMO treatment increases mortality in ICU patients. Future studies have to clarify whether it is possible to identify patients who benefit from the combination of ECMO and RRT.

New high-cutoff dialyzer allows improved middle molecule clearance without an increase in albumin loss: a clinical crossover comparison in extended dialysis.

BACKGROUND: Accumulation of middle molecules is thought to have adverse effects in patients with acute kidney injury (AKI). Elimination of middle molecules by non-convective means, i.e. hemodialysis, remains difficult. The aim of the study was to investigate the removal characteristics of a new high permeability membrane in AKI patients undergoing extended dialysis (ED). PATIENTS AND METHODS: We performed a prospective, crossover study comparing the EMiC2 dialyzer (1.8 m(2), FMC, Germany) and AV 1000S (1.8 m(2), FMC) in 11 critically ill patients with AKI. ß2-Microglobulin, cystatin c, creatinine, and urea were measured before and after 0.5, 5.0 and 10 h of ED. Serum reduction ratios, dialyzer clearances, and mass in the total collected dialysate were determined. RESULTS: Dialyzer clearance of ß2-microglobulin (EMiC2: 52 ± 1.7 ml/min, AV 1000S: 41.7 ± 1.5 ml/min, p = 0.0002) and cystatin c (EMiC2: 47.2 ± 1.2 ml/min, AV 1000S: 34.2 ± 2.3 ml/min, p < 0.0001) was markedly different, as was the reduction of serum levels of ß2-microglobulin (EMiC2: 54.3 ± 3.6%, AV 1000S: 39.1 ± 4.5%, p = 0.025) and cystatin c (EMiC2: 38.9 ± 2.6%, AV 1000S: 28.0 ± 3.9%, p = 0.043). Additionally, we observed a higher total amount of these substances in the collected dialysate. There was no significant difference in the total amount of albumin eliminated per treatment. CONCLUSION: The new EMiC2 dialyzer enhances removal of middle molecules without an increase in albumin loss. The clinical relevance of this finding needs to be determined.

Best supportive care and therapeutic plasma exchange with or without eculizumab in Shiga-toxin-producing E. coli O104:H4 induced haemolytic-uraemic syndrome: an analysis of the German STEC-HUS registry.

BACKGROUND: May 22nd marks the beginning of a Shiga-toxin-producing Escherichia coli (STEC) O104:H4 outbreak in Northern Germany. By its end on 27 July, it had claimed 53 deaths among 2987 STEC and 855 confirmed haemolytic-uraemic syndrome (HUS) cases. METHODS: To describe short-term effectiveness of best supportive care (BSC), therapeutic plasma exchange (TPE) and TPE with eculizumab (TPE-Ecu) in 631 patients with suspected HUS treated in 84 hospitals in Germany, Sweden and the Netherlands using the web-based registry of the DGfN (online since 27 May). RESULTS: Of 631 entries, 491 fulfilled the definition of HUS (median age 46 years; 71% females). The median (inter-quartile range) hospital stay was 22 (14-31) days. Two hundred and eighty-one (57%) patients underwent dialysis and 114 (23%) mechanical ventilation. Fifty-seven patients received BSC, 241 TPE and 193 TPE-Ecu. Treatment strategy was dependent on disease severity (laboratory signs of haemolysis, thrombocytopenia, peak creatinine level, need for dialysis, neurological symptoms, frequency of seizures) which was lower in BSC than in TPE and TPE-Ecu patients. At study endpoint (hospital discharge or death), the median creatinine was lower in BSC [1.1 mg/dL (0.9-1.3)] than in TPE [1.2 mg/dL (1.0-1.5), P < 0.05] and TPE-Ecu [1.4 mg/dL (1.0-2.2), P < 0.001], while need for dialysis was not different between BSC (0.0%, n = 0), TPE (3.7%; n = 9) and TPE-Ecu (4.7%, n = 9). Seizures were absent in BSC and rare in TPE (0.4%; n = 1) and TPE-Ecu (2.6%; n = 5) patients. Total hospital mortality in HUS patients was 4.1% (n = 20) and did not differ significantly between the TPE and TPE-Ecu groups. CONCLUSIONS: Despite frequent renal impairment, advanced neurological disorders and severe respiratory failure, short-term outcome was better than expected when compared with previous reports. Within the limitations of a retrospective registry analysis, our data do not support the notion of a short-term benefit of Ecu in comparison to TPE alone in the treatment of STEC-HUS. A randomized trial comparing BSC, TPE and Ecu seems to be prudent and necessary prior to establishing new treatment guidelines for STEC-HUS.