A safe citrate anticoagulation protocol with variable treatment efficacy and excellent control of the acid-base status.

OBJECTIVE: Citrate anticoagulation is an excellent alternative to heparin anticoagulation for critically ill patients requiring continuous renal replacement therapy. In this article, we provide a safe and an easy-to-handle citrate anticoagulation protocol with variable treatment doses and excellent control of the acid-base status. DESIGN: Prospective observational study. SETTING: University hospital. PATIENTS: One hundred sixty-two patients with acute renal failure requiring renal replacement therapy were enrolled in the study. INTERVENTION: A continuous venovenous hemodialysis-based citrate anticoagulation protocol using a 4% trisodium solution, a specially designed dialysate fluid, and a continuous calcium infusion were used. The study period was 6 days. Hemofilters were changed routinely after 72 hours of treatment. The patients were grouped according to body weight, with patients below 60 kg body weight in group 1, patients with at least 60 kg and up to 90 kg body weight in group 2, and patients with a body weight of above 90 kg in group 3. Dialysate flow was adapted according to body size and matched approximately 2 L/hr for a patient with average body size. Blood flow, citrate flow, and calcium flow were adjusted according to the dialysate flow used. MEASUREMENTS AND MAIN RESULTS: Median filter run time was 61.5 hours (interquartile range: 34.5-81.1 hours). Only 5% of all hemofilters had to be changed because of clotting. The prescribed treatment dose was achieved in all patients. Acid-base and electrolyte control were excellent in all groups. In the rare cases of metabolic disarrangement during citrate anticoagulation, acid-base values were rapidly corrected by modifying either the dialysate flow or alternatively the blood flow rate. Eight patients (5%) developed signs of citrate accumulation indicated by an increase of the total calcium >3 mmol/L or a need for high calcium substitution. CONCLUSIONS: We provide a safe and an easy-to-handle citrate anticoagulation protocol that allows an excellent acid-base and electrolyte control in critically ill patients with acute renal failure. The protocol can be adapted to patients' need, allowing a wide spectrum of treatment doses.

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.

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.

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.

Intermittent high-permeability hemofiltration modulates inflammatory response in septic patients with multiorgan failure.

BACKGROUND/AIM: Continuous venovenous hemofiltration with high-permeability hemofilters is a novel approach in the adjuvant therapy of septic patients. High-permeability hemofilters are characterized by an increased pore size which facilitates the filtration of inflammatory mediators. The present study examines whether intermittent high-permeability hemofiltration has an immunomodulatory effect on polymorphonuclear leukocytes and mononuclear cells. METHODS: Twenty-eight septic patients with acute renal failure were randomly allocated to either receive intermittent high-permeability or conventional hemofiltration. Intermittent high-permeability hemofiltration consisted of a daily 12-hour course of high-permeability hemofiltration alternated by conventional hemofiltration. For high-permeability hemofiltration, a newly developed high-flux polyamide membrane (P2SH) with a nominal cutoff point of 60 kD was used. For conventional hemofiltration a high-flux polyamide hemofilter (Polyflux 11S, cutoff point 30 kD) was used. RESULTS: The polymorphonuclear leukocyte phagocytosis activity before starting hemofiltration was almost double the rate of healthy controls in both groups (p < 0.001). The phagocytosis rate decreased significantly during the course of intermittent high-permeability hemofiltration (p < 0.05), whereas the values remained unchanged in the conventional hemofiltration group. Incubation of high-permeability filtrates with blood from healthy donors resulted in a significant induction of phagocytosis (p < 0.001), whereas conventional filtrates had no phagocytosis-stimulating effects. In addition, incubation of healthy-donor mononuclear cells with high-permeability but not conventional filtrates resulted in a significant tumor necrosis factor alpha release (p < 0.001). CONCLUSIONS: Intermittent high-permeability hemofiltration is a novel extracorporeal elimination modality which exhibits immunomodulatory effects on leukocytes, attenuating polymorphonuclear neutrophil phagocytosis. Further studies are necessary to elucidate whether these effects translate in a clinical improvement in patients suffering from sepsis.

Impact of kidney function on plasma troponin concentrations after coronary artery bypass grafting.

BACKGROUND: To date, there have been no studies reliably showing an influence of the kidney on the concentration of troponins. We therefore analysed the concentration curves in patients after coronary artery bypass grafting (CABG) according to their dependence on renal function. METHODS: We determined cardiac troponin I (cTnI), cardiac troponin T (cTnT) and creatinine in plasma in 28 patients after CABG. Discrimination into patients with normal (n=13) and impaired (n=15) renal function was based on creatinine clearance (Crea-Clear). The curves for cTnI and cTnT, as recorded by post-operative measurements, were approximated using mathematical functions. The curve parameters peak maximum (P(max)), peak position (P(pos)), half-height breadth (HHB) and area under the curve (AUC) were established after this. Assuming an exponential function, the half-life (t(1/2)) of cTnI was determined from the declining part of the curve. RESULTS: For both, cTnI and cTnT, significant differences in P(max), P(pos), HHB and AUC were detected after curve approximation. The t(1/2) values of cTnI were 25.1 h (22.0-35.3) for the group with normal renal function and 38.4 h (35.9-51.9) for patients with impaired renal function (P=0.001). An influence of diabetes mellitus (Dm), renal replacement therapy or the age of the patients could not be verified. CONCLUSION: The results of this study clearly demonstrate that kidney function has an impact on plasma troponin concentrations. In everyday clinical practice this has to be considered when interpreting elevated plasma troponin concentration in patients with impaired renal function.

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.

Torsemide versus furosemide after continuous renal replacement therapy due to acute renal failure in cardiac surgery patients.

Diuretic therapy in ARF (acute renal failure) is mainly done with loop diuretics, first of all furosemide. Torsemide has a longer duration of action and does not accumulate in renal failure. In chronic and acute renal failure, both diuretics have been effectively applied, with a more pronounced diuretic effect for torsemide. In this study, the effects of torsemide versus furosemide on renal function in cardiac surgery patients recovering from ARF after continuous renal replacement therapy (CRRT) were studied. Twenty-nine critically ill patients admitted to an intensive care unit at a university teaching hospital after cardiac surgery recovering from ARF after CRRT were included in this prospective, controlled, single-center, open-labeled, randomized clinical trial. Inclusion criteria were urine output >0.5 mL/kg/h over 6 h under CRRT. Torsemide and furosemide dosages were adjusted with the target urine output being 0.8-1.5 mL/kg/h. Hemodynamic data, urine output, volume balance, serum creatinine clearance, electrolytes, blood urea nitrogen, serum creatinine, renin, and aldosterone concentrations were measured. Fourteen patients were included in the furosemide group and 15 patients in the torsemide group. Dosages of 29 (0-160) mg torsemide and a dosage of 60 (0-240) mg furosemide were given every 6 h in each group, respectively. The dosage given at the end of the study decreased significantly in furosemide and torsemide treated patients. Urine output, 24 h balance, and serum creatinine clearance did not differ significantly between groups. Urine output decreased in both groups, mostly dose-dependent in the torsemide group. The intragroup comparison of the first time-interval after inclusion with the last time-interval showed a significant increase in serum creatinine and blood urea nitrogen in the furosemide group. Renin and aldosterone concentrations did not show significant differences. In conclusion, torsemide and furosemide were effective in increasing urine output. Torsemide might show a better dose-dependent diuretic effect in ARF patients after CRRT treatment. Serum creatinine and blood urea nitrogen elimination were less pronounced in the furosemide group.

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.