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Biomedical subjects

Heidrun Zuckermann-Becker

Publications and source records attributed to Heidrun Zuckermann-Becker.

7 recordsLinked to original sources

Reduced monocyte CD86 expression in postinflammatory immunodeficiency.

OBJECTIVE: Major surgery, polytrauma, stroke, and pancreatitis frequently lead to a compensatory anti-inflammatory response syndrome that often predisposes patients to lethal infections. This temporary postinflammatory immunodeficiency is characterized by altered function of blood monocytes. These cells show strongly reduced inflammatory and antigen-presentation capacity. Diminished monocyte expression of the major histocompatibility complex class II molecule human leukocyte antigen (HLA)-DR is a well-established diagnostic marker of this immunodeficiency. To further characterize the monocytic cells in this clinical state, we analyzed their expression of CD86, the most important co-stimulatory molecule. DESIGN: Analysis of blood samples that entered the clinical immunologic diagnostics and of cells from an in vitro model of postinflammatory immunodeficiency. SETTING: University laboratory. SUBJECTS: Healthy donors and intensive care unit (ICU) patients at the university hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The expression of HLA-DR on monocytes and of CD86 and CD80 on monocytes and B cells was analyzed by flow cytometry. Messenger RNA expression of CD86 was analyzed in isolated monocytes by real-time polymerase chain reaction on reverse transcribed. The normal range of monocyte CD86 expression in healthy subjects was established to be from 2128 to 5102 surface molecules per cell and was independent of age, gender, and leukocyte and monocyte count. The CD86 expression on monocytes in ICU patients correlated with HLA-DR expression. Approximately 40% of the ICU patients with long-term reduced monocyte HLA-DR expression had a long-term reduction of CD86 expression. Patients in whom the expression of both molecules was diminished had an unfavorable prognosis. The diminished number of CD86 surface molecules on monocytes was associated with reduced CD86 messenger RNA levels in these cells. The expression of CD86 in B cells was not diminished in immunodeficient patients. The expression of CD80 in both monocytes and B-cells was minimal in healthy donors and not clearly changed in patients. CONCLUSIONS: The monocyte CD86 expression may be a helpful diagnostic variable in ICU patients.

Adolescent↗

Pilot study on the effects of high cutoff hemofiltration on the need for norepinephrine in septic patients with acute renal failure.

OBJECTIVE: High cutoff hemofilters are characterized by an increased effective pore size designed to facilitate the elimination of inflammatory mediators in sepsis. Clinical data on this new renal replacement modality are lacking. DESIGN: Prospective, randomized clinical trial. SETTING: University hospital, intensive care units. PATIENTS: : Thirty patients with sepsis-induced acute renal failure. INTERVENTION: Patients were allocated to high cutoff (n = 20) or conventional (n = 10) hemofiltration in a 2:1 ratio. Median renal replacement dose was 31 mL/kg/hr. For high cutoff hemofiltration, a high-flux hemofilter with an in vivo cutoff point of approximately 60 kilodaltons was used. Conventional hemofiltration was performed with a standard high-flux hemofilter (PF11S). The impacts of high cutoff hemofiltration on the need for norepinephrine and on plasma levels and clearance rates for interleukin (IL)-6 and IL-1 receptor antagonist (IL-1ra) were analyzed. Absolute values, but also adjusted values (expressed as proportion of baseline), were analyzed. The observation period was restricted to 48 hrs. MAIN RESULTS: Apart from higher antithrombin III levels at entry into the study, main clinical and laboratory parameters were comparable between both groups. The median norepinephrine dose at entry into the study was 0.30 microg/kg/min in the high cutoff group and 0.21 microg/kg/min in the conventional hemofiltration group (p = .448). Only the high cutoff group showed a significant decline (p = .0002) in "adjusted" norepinephrine dose over time. Clearance rates for IL-6 and IL-1ra were significantly higher in the high cutoff hemofiltration group (p < .0001), which translated into a significant decline of the corresponding plasma levels (p = .0465 for IL-6; p = .0293 for IL-1ra). CONCLUSION: In this pilot study, high cutoff hemofiltration has been shown to exert a beneficial effect on the need for norepinephrine in septic patients with acute renal failure. In addition, we demonstrate that high cutoff hemofiltration is superior to conventional hemofiltration in the elimination of IL-6 and IL-1ra from the circulating blood of septic patients.

Acute Kidney Injury↗

Regional citrate anticoagulation in continuous hemodialysis--acid-base and electrolyte balance at an increased dose of dialysis.

BACKGROUND: Citrate anticoagulation is an excellent alternative to heparin anticoagulation for patients at high risk of bleeding requiring continuous renal replacement therapy. However, citrate anticoagulation has some potential adverse effects such as metabolic alkalosis and acidosis, hypernatremia, hypo- and hypercalcemia. Thus, most citrate anticoagulation protocols use specially designed dialysis fluids to compensate for most of these disarrangements. This study aimed at establishing a citrate anticoagulation protocol designed for a dialysate flow rate of about 2 l/h. METHODS: Based on theoretical considerations we composed a dialysis fluid suitable for a 2 l/h dialysis flow rate. The dialysate contained 133 mmol/l sodium, 2 mmol/l potassium, 1.1 mmol/l magnesium, 25 mmol/l lactate, and 112.2 mmol/l chloride. RESULTS: Twenty-three patients were included in the study. During the treatments minor flow rate adaptations were needed and the treatments were well tolerated. Filter life was appropriate (51.3 +/- 24.6 h). Thirteen patients developed a mild metabolic alkalosis (pH > 7.45 plus BE > +3) which was easily counteracted by increasing the dialysis fluid flow (by increments of 500 ml). Acid-base values returned to normal within 24 h after increasing the dialysate flow. The maximum dialysate flow was 3,000 ml/h. Hypernatremia and hypocalcemia were not observed. The systemic ionized calcium concentration was successfully controlled by adjustments of a continuous calcium infusion made with respect to the results of 6-hourly measurements. CONCLUSION: The analyzed citrate anticoagulation protocol was well tolerated and filter lifetime was appropriate. Regional anticoagulation with trisodium citrate in combination with a customized calcium-free dialysate is a safe and effective alternative to a heparin-based anticoagulation regimen.

Acute Kidney Injury↗

Renal replacement therapy with high-cutoff hemofilters: Impact of convection and diffusion on cytokine clearances and protein status.

BACKGROUND: High-cutoff hemofilters are characterized by an increased effective pore size designed to facilitate the elimination of inflammatory mediators in sepsis. This study compares diffusive versus convective high-cutoff renal replacement therapy (RRT) in terms of cytokine clearance rates and effects on plasma protein levels. METHODS: Twenty-four patients with sepsis-induced acute renal failure were studied. A polyflux hemofilter with a cutoff point of approximately 60 kd was used for RRT. Patients were randomly allocated to either continuous venovenous hemofiltration (CVVH) with an ultrafiltration rate of 1 L/h (group 1) or 2.5 L/h (group 2) or continuous venovenous hemodialysis (CVVHD) with a dialysate flow rate of 1 L/h (group 3) or 2.5 L/h (group 4). Interleukin-1 (IL-1) receptor antagonist (IL-1ra), IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), and plasma proteins were measured daily. RESULTS: CVVH achieved significantly greater IL-1ra clearance compared with CVVHD (P = 0.0003). No difference was found for IL-6 (P = 0.935). Increasing ultrafiltration volume or dialysate flow led to a highly significant increase in IL-1ra and IL-6 clearance rates (P < 0.00001). Peak clearances were 46 mL/min for IL-1ra and 51 mL/min for IL-6. TNF-alpha clearance was poor for both RRT modalities. A significant decline in plasma IL-1ra and IL-6 clearance was observed in patients with high baseline levels. Protein and albumin losses were greatest during the 2.5-L/h hemofiltration mode. CONCLUSION: High-cutoff RRT is a novel strategy to clear cytokines more effectively. Convection has an advantage over diffusion in the clearance capacity of IL-1ra, but is associated with greater plasma protein losses.

Adult↗

Metabolic complications during regional citrate anticoagulation in continuous venovenous hemodialysis: single-center experience.

BACKGROUND: Regional anticoagulation with trisodium citrate is an effective form of anticoagulation for continuous renal replacement therapy (CRRT) in patients at a high risk of bleeding. In a prospective, observational study we compared an established regional citrate anticoagulation protocol [Mehta R et al: Kidney Int 1990;38:976-981] versus a standard heparin anticoagulation protocol focusing on acid-base and electrolyte derangements as well as on cost effectiveness. METHODS AND RESULTS: 209 patients were included in the study. In 37 patients, citrate was used as the sole anticoagulant, 87 patients received low-dose heparin plus citrate, and 85 patients received only heparin as anticoagulant. A customized dialysate solution was used for citrate-anticoagulated CRRT (no buffer, no calcium, reduced sodium concentration). Filter life was significantly higher during citrate anticoagulation compared to heparin anticoagulation (80.2 +/- 60 vs. 30.2 +/- 32 h; p < 0.001). No difference was found between citrate and citrate-heparin anticoagulation (p = 0.310). Metabolic alkalosis was observed in more than 50% of patients on citrate anticoagulation. Alkalosis developed within the first 72 h after initiating treatment and could be reversed in almost all cases by increasing the dialysate flow rate. Hypercalcemia was observed in 13 patients on citrate anticoagulation. Patients with impaired liver function were particularly at risk. Systemic hypocalcemia, hypernatremia, and anion gap acidosis were not observed. Citrate anticoagulation was well tolerated hemodynamically. A longer filter life during citrate anticoagulation translated into a significant cost reduction compared to standard heparin anticoagulation (p < 0.01). CONCLUSION: Regional anticoagulation with trisodium citrate in combination with a customized calcium-free dialysate is a safe and effective alternative to a heparin-based anticoagulation regimen.

Acid-Base Imbalance↗

High permeability haemofiltration improves peripheral blood mononuclear cell proliferation in septic patients with acute renal failure.

BACKGROUND: Continuous veno-venous haemofiltration (HF) with high permeability (HP) haemofilters is a novel approach in the adjuvant therapy of septic patients. HP haemofilters are characterized by an increased pore size which facilitates the filtration of inflammatory mediators. The present study examines whether HP-HF has an impact on peripheral blood mononuclear cell (PBMC) proliferation and whether ultrafiltrate can alter PBMC function in isolates from healthy volunteers. METHODS: Twenty-eight septic patients with acute renal failure were randomly allocated to either HP-HF or conventional HF (C-HF). HP-HF was performed with a newly developed high-flux polyamide membrane (P2SH) with a nominal cut-off point of 60 kDa. For C-HF, a high-flux polyamide haemofilter (Polyflux 11S; cut-off, 30 kDa) was used. RESULTS: Septic patients demonstrated a significantly reduced proliferation of anti-CD3-stimulated PBMCs compared to healthy controls (P = 0.016). Initiating HF led to a restoration of the PBMC proliferation in HP-HF but not in C-HF. Exposing PBMCs isolated from healthy donors to ultrafiltrates from patients with sepsis demonstrated a significant suppressive effect of HP ultrafiltrates on the anti-CD3-stimulated PBMC proliferation (P = 0.011). Ultrafiltrate from patients with sepsis who received C-HF had no impact on PBMC proliferation. CONCLUSION: HP-HF restores PBMC proliferation in septic patients probably by eliminating immunomodulatory mediators. HP-HF may represent a new renal replacement therapy able to modulate PBMC function in sepsis.

Acute Kidney Injury↗

Conventional monitoring and intravascular volume measurement can lead to different therapy after upper gastrointestinal tract surgery.

OBJECTIVE: The purpose of this study was to compare the judgment of intravascular volume based either on conventional monitoring or on the data of COLD measurement. DESIGN: Single-blinded, observational study. SETTING: Intensive care unit (ICU). PATIENTS: Ten consecutive patients after upper gastrointestinal tract surgery for carcinoma. MEASUREMENTS AND RESULTS: Judgments ( n=59) about intravascular volume (hypo-, iso- or hypervolemic) were given twice a day until the 2nd postoperative day by two physicians. Physician A's judgment was based on conventional monitoring and physician B's judgment on COLD monitoring. Both were blinded for each other's judgment. The inter-rater agreement between A and B was analyzed using the weighted kappa statistic. Both physicians gave a recommendation about the volume therapy during the following 12 h. The therapeutic regimen, including volume therapy, was defined by physician A. The inter-rater-agreement regarding intravascular volume was poor (overall weighted kappa =0.095). The sum of absolute differences between A and B in their recommendation about infusion administration reached a median of 4,875 ml per patient. CONCLUSIONS: The poor inter-rater agreement between the two physicians and the consecutive difference in the infusion therapy may have clinical consequences and should be evaluated in further studies. These data cannot confirm which decision strategy should be preferred.

Aged↗