Bernd Haditsch

Effect of extracorporeal liver support by MARS and Prometheus on serum cytokines in acute-on-chronic liver failure

IntroductionCytokines are believed to play an important role in acute-on-chronic liver failure (ACLF). Extracorporeal liver support systems may exert beneficial effects in ACLF via removal of cytokines. At present, two systems are commercially available, the Molecular Adsorbent Recirculating System (MARS™) and Fractionated Plasma Separation, Adsorption and Dialysis (Prometheus™). The aim of this study was to compare the effects of MARS and Prometheus treatments on serum cytokine levels and their clearances.MethodsEight patients with ACLF underwent alternating treatments with either MARS or Prometheus in a randomized cross-over design. Thirty-four treatments (17 MARS, 17 Prometheus) were available for analysis. Serum cytokines were measured before and after each treatment, and cytokine clearance was calculated from paired arterial and venous samples and effective plasma flow one hour after the start of treatment.ResultsBaseline serum levels of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α), and soluble TNF-α receptor 1 were significantly elevated in patients with ACLF. Measurable plasma clearances were detected for all cytokines tested, but no significant changes in serum levels of any cytokine were found after treatments with MARS or Prometheus. In MARS treatments, IL-10 was cleared from plasma more efficiently than IL-6. Clearance of IL-10 was higher in Prometheus than in MARS treatments.ConclusionCytokines are cleared from plasma by both MARS and Prometheus, but neither system is able to change serum cytokine levels. This discrepancy is probably due to a high rate of cytokine production in patients with ACLF.

Removal of bile acids by two different extracorporeal liver support systems in acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is accompanied by marked intrahepatic cholestasis leading to accumulation of cytotoxic bile acids. Extracorporeal liver support systems efficiently remove bile acids, but their effect on bile acid composition in ACLF is unknown. The aim of the present study was to compare elimination of individual plasma bile acids by albumin dialysis (Molecular Adsorbents Recirculating System, MARS) and fractionated plasma separation (Prometheus). Eight consecutive patients with ACLF underwent alternating 6-hour sessions with MARS or Prometheus in a randomized, cross-over design. Serum samples were obtained before, during, and after each treatment, and individual bile acids including cholic acid and chenodeoxycholic acid (CDCA) were measured by gas chromatography. MARS and Prometheus removed total bile acids to a similar extent (reduction ratio, 45% and 46%, respectively). Both devices cleared cholic acid more efficiently than did CDCA. The molar fraction of CDCA (fCDCA) was elevated at baseline and correlated with the degree of liver dysfunction. Prometheus but not MARS treatments further increased fCDCA. Although both devices eliminate total bile acids to a similar extent, clearance of individual bile acids is different, leading to a slight change of the bile acid profile toward hydrophobic bile acids during Prometheus treatments.

Validity of self-reported weight and height in Austrian adults: sociodemographic determinants and consequences for the classification of BMI categories

OBJECTIVE Epidemiological studies have shown that adults tend to underestimate their weight and overestimate their height. This may lead to a misclassification of their BMI in studies based on self-reported data. The aim of the present study was to assess the validity of self-reported weight and height in Austrian adults. DESIGN Data on weight, height, health behaviour and sociodemographic characteristics of adults were collected in a standardized procedure via a self-filling questionnaire and a medical examination including measurements of weight and height. SETTING A publicly accessible out-patient clinic in southern Austria. SUBJECTS Austrian residents (n 473) aged 18 years and older who attended a health check participated in the study. RESULTS The mean difference between reported and measured BMI was not significant in younger adults (<35 years: mean difference -0·21 kg/m2; P < 0·08) but increased significantly with age (≥55 years: mean difference -0·68 kg/m2; P < 0·001). The prevalence of normal weight (BMI = 18·5-24·9 kg/m2) and overweight (BMI = 25·0-29·9 kg/m2) was overestimated based on the self-reported data on BMI, while that for underweight (BMI < 18·5 kg/m2) and obesity (BMI ≥ 30·0 kg/m2) was underestimated (P < 0·001). The self-reported data showed an obesity prevalence of 12·5 %, while measurement showed a prevalence of 15·4 % (P < 0·001). CONCLUSIONS Our results indicate that prevalence rates of obesity are probably underestimated for Austrian adults when using self-reported weight and height information. The deviations from the measured data clearly increased with age. Analyses based on self-reported data should therefore be adjusted for the age dependency of the validity.

Orthostatic Stimuli Rapidly Change Plasma Adrenomedullin in Humans

The aim of this study was to evaluate the effect of orthostasis on the time course of plasma adrenomedullin concentration. On 5 different days, normotensive subjects were randomized to undergo for 30 minutes either 12 degrees, 30 degrees, 53 degrees, or 70 degrees passive head-up tilt or to remain supine. Venous blood was collected from each subject in the supine position before tilting, at 3 and 27 minutes during tilting, and at 2 and 50 minutes after orthostasis. Plasma adrenomedullin increased significantly with tilt of >/=30 degrees in a stimulus-dependent manner. Approximately half of the increase seen at 27 minutes occurred during the first 2 minutes of upright positioning; the maximum effect with 70 degrees tilt was +70%. Elevations in norepinephrine, epinephrine, aldosterone, plasma renin activity, vasopressin, heart rate, and mean arterial pressure were also significant. Hematocrit, blood density, plasma density, and plasma volume loss rose (P<0.05) at 53 degrees and 70 degrees tilt. Our results indicate that adrenomedullin may play an important role in stabilization of hemodynamics during passive orthostasis. In conclusion, plasma adrenomedullin rapidly increases with orthostatic challenge in a stimulus-dependent manner and also swiftly returns to baseline levels after the subject resumes the supine position.

Brain natriuretic peptide at altitude: relationship to diuresis, natriuresis, and mountain sickness.

BACKGROUND Acute mountain sickness (AMS) affects some new arrivals above an altitude of 2500 m. Hypobaric hypoxia is known to produce diuresis and has natriuretic effects due to the release of natriuretic peptides. We tested the hypothesis that increases in brain natriuretic peptide (BNP) at altitude correlates with increased urination and natriuresis as well as symptomatic AMS. METHODS Subjects were 14 mountaineers who undertook a Himalayan expedition that began at 100 m and passed through 3440 m en route to a final altitude of 5050 m. We measured the severity of AMS (Lake Louise Score), BNP values, nocturnal urine volume, and urine sodium concentration. RESULTS Nocturnal urine volume increased from 490 +/- 90 mi at 3440 m to 1100 +/- 104 ml at 5050 m. BNP levels at the higher altitude were 10.6 +/- 4.7 pg x ml(-1) and were correlated with the severity of AMS in all mountaineers (Lake Louise Score 4 +/- 0.5 for AMS subjects). However, AMS severity did not correlate with urine volume or urine sodium concentration. CONCLUSIONS Our results suggest that BNP secretion is not the cause of high-altitude diuresis. Further studies are needed to evaluate the possible role of BNP in individual responses to high altitude.

EFFECTS OF A PRE-DIALYSIS PATIENT EDUCATION PROGRAM ON THE RELATIVE FREQUENCIES OF DIALYSIS MODALITIES

♦ Background: Pre-dialysis education can guide the choice of the dialysis modality best tailored to meet the needs and preferences of individual patients with chronic kidney disease. ♦ Methods: In a retrospective single-center cohort study, we evaluated the impact of a pre-dialysis education program on the incidence rates of patients using hemodialysis (HD) and peritoneal dialysis (PD) in our unit. The frequency distribution of dialysis modalities between people attending our education program and people not attending the program (control group) was analyzed for the 4-year period 2004 - 2008. ♦ Results: From among all the incident chronic kidney disease 5D patients presenting during the 4-year period, we analyzed 227 who started dialysis either with an arteriovenous fistula or a PD catheter. In that cohort, 70 patients (30.8%) took part in the education program, and 157 (69.2%) did not receive structured pre-dialysis counseling. In the group receiving education, 38 patients (54.3%) started with PD, and 32 (45.7%), with HD. In the standard-care group not receiving education, 44 patients (28%) started with PD, and 113 (72%), with HD (p < 0.001). ♦ Conclusions: Our multidisciplinary pre-dialysis program had a significant impact on the frequency distribution of dialysis modalities, increasing the proportion of patients initiating dialysis with PD.

How Are Physical Activity Behaviors and Cardiovascular Risk Factors Associated with Characteristics of the Built and Social Residential Environment

Background The aim of our study was to identify perceptions of built and social residential characteristics and their association with behaviors such as physical activity (PA), nutrition and smoking and with cardiovascular risk factors (elevated BMI and fasting blood glucose). Methods Among participants of a preventive medical checkup at an Austrian District Health Insurance Fund (n=904, response rate = 82.2%, 42% women, 18-91 years) self-reported and measured data were collected. Results Total PA was positively associated with the presence of trees along the streets and high levels of pro-physical activity social modeling (SM) and it was negatively related to perceived safety from crime. More leisure-time PA was associated with higher levels of cycling/walking infrastructure and high levels of SM. PA for transportation was positively related to high levels of connectivity and high levels of SM. Better behavioral cardiovascular risk factor profiles (smoking and nutrition) were associated with high levels of SM and high levels of total PA. Lower BMI values were associated with high levels of infrastructure and high levels of SM. Conclusions Both built and social residential characteristics are important correlates of PA as well as of major cardiovascular risk factors besides PA.

Volume regulating hormone responses to repeated head-up tilt and lower body negative pressure

Eur J Clin Invest 2011; 41 (8): 863–869

Efficacy and Safety of Anticoagulation With Heparin Versus Heparin Plus Epoprostenol in Patients Undergoing Extracorporeal Liver Support With Prometheus

Anticoagulation for extracorporeal liver support is delicate due to underlying coagulation disorders in patients with liver failure and to the associated elevated bleeding risk. To date, there has been no detailed report on anticoagulation issues in patients treated with Prometheus, a device based on the principle of fractionated plasma separation and adsorption. We studied 17 patients from two centers treated with Prometheus, comparing standard anticoagulation with heparin (15 treatments) and a combination of heparin and the synthetic prostacyclin epoprostenol (22 treatments). Standard coagulation tests, proteins C and S, and thrombin-antithrombin (TAT) complex were determined, and adverse events were recorded. All but two treatments could be completed as scheduled, although filter exchange due to filter clotting was required in 24% of the treatments. Three out of 17 patients developed severe bleeding complications within 24 h of treatment. There were no overt thrombotic events. Addition of epoprostenol neither reduced coagulation-related adverse events nor improved standard coagulation parameters. Protein C, but not protein S, showed a significant reduction (23 +/- 18%) after Prometheus treatments, but levels rebounded to baseline within 18 h. TAT levels--a measure for activation of coagulation--were only altered by Prometheus in patients where TAT was already elevated before treatment. In conclusion, anticoagulation of Prometheus with heparin is feasible but still associated with a relatively high frequency of filter clotting and a considerable risk of severe bleeding in this high-risk patient population. As addition of epoprostenol did not prove beneficial, other strategies, such as regional anticoagulation with citrate, should be further evaluated.

Bilirubin Kinetic Modeling for Quantification of Extracorporeal Liver Support

Background/Aim: To provide a measure of treatment dose for extracorporeal liver support (ELS). Methods: The kinetics of conjugated bilirubin were described by a two-compartment model (Vc, Vp) with central elimination (K) and constant generation rate (G). The transfer of solute between compartments was modeled by intercompartmental clearance (Kpc). The central compartment (Vc) was assumed as a constant fraction of total volume (Vc = 0.3*Vt). Results: Eight patients were studied during 35 treatments lasting 6 h each. The average K, Vt, Kpc, G, and mass of conjugated bilirubin removed were 18.6 ± 3.9 ml/min, 9.1 ± 3.8 liters, 103 ± 108 ml/min, 0.33 ± 0.15 mg/min, and 641 ± 275 mg, respectively. The reduction ratio (48 ± 10%) measured as the change in post- to pre-treatment concentrations underestimated the modeled fraction of bilirubin mass removed (54 ± 13%) essentially because of significant conjugated bilirubin appearance during treatments. Conclusions: Kinetic analysis provides an improved measure of treatment dose as generation, distribution, and elimination of conjugated bilirubin are jointly considered.