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Presence of factor-VII and -XIII activity in ultrafiltrate during hemofiltration.

UNLABELLED: Bleeding complications during renal replacement therapies can be attributed to coagulation system and platelet function alterations in uremia, and the application of heparin in extracorporeal circulation. Small protein losses during hemofiltration are always described, however the high molecular weight of coagulation factors should significantly prevent their removal during hemofiltration. To exclude degradation of coagulation factors under conditions of spontaneous ultrafiltration, the hemofiltrate of 40 patients with acute renal failure (treated with continuous veno-venous hemofiltration, CVVH) was sampled from the filtrate line after 1 h from the beginning of treatment and in 5 patients also after 12 and 24 h. Samples were investigated with human factor deficient plasma (VII, X, XI, XII) from donors with a congenital deficiency and with human plasma depleted of factor V, VIII, IX, and protein S and C. Factor XIII was detected photometrically. Subsequently the presence of factor- XIII and -VII activity was investigated in plasma and hemofiltrate from 16 patients treated with intermittent hemofiltration before (plasma) and after (plasma, hemofiltrate) therapy. These patients also suffered from acute renal failure and needed renal replacement therapies. Quality control was carried out with a buffer solution (<1% activity in the assays according to recommended protocols). RESULTS: Factor-V, -VIII, -IX, -X, -XI, and -XII activity, and protein C and S could not be detected in the hemofiltrate from continuous hemofiltration. Factor-VII and -XIII activity was present in the hemofiltrate (mean activity in CVVH: 1.93% for factor VII and 6.9% for factor XIII, mean activity in intermittent hemofiltration: <1% for factor-VII and 7.3% for factor-XIII). Three were no significant differences (Student's t-test) in plasma activity before and after intermittent hemofiltration of factor VII (44 vs. 47%, p = 0.39) and factor XIII (44 vs. 52%, p = 0.24). The presence of factor-VII and -XIII activity in the hemofiltrate cannot influence plasma activities in intermittent hemofiltration. Rapid new synthesis and short half-life should neutralize these effects. Elimination of coagulation factor-XIII activity should be excluded by the next generation of highly permeable membranes and on-line hemodiafiltration.

Acute Kidney Injury↗

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.

Acute Kidney Injury↗

Renal replacement therapy after repair of congenital heart disease in children. A comparison of hemofiltration and peritoneal dialysis.

The development of renal failure necessitating peritoneal dialysis after cardiac operations is associated with a reported mortality greater than 50%. Improved fluid removal and nutritional support have been reported with the use of continuous arteriovenous hemofiltration and continuous venovenous hemofiltration techniques. We have compared our experience with all three techniques in managing children who required renal replacement therapy after cardiac operations in terms of efficacy (fluid removal, calorie intake, and clearance of urea and creatinine), complications, and outcome. Over a 5-year period renal replacement therapy was initiated in 42 children, and in 34 of them it was successfully established for more than a 24-hour period: 17 were managed with peritoneal dialysis, 8 with continuous arteriovenous hemofiltration, and 9 with continuous venovenous hemofiltration. A net negative fluid balance was achieved in only 6 (35%) patients treated with peritoneal dialysis compared with 50% of those treated with continuous venovenous hemofiltration and 89% of those treated with continuous venovenous hemofiltration. In terms of nutritional support, calorie intake increased by 43% after peritoneal dialysis was started compared with 515% and 409% in the arteriovenous and venovenous hemofiltration groups, respectively, (p < 0.005). The serum urea levels fell by 36% (p = 0.02) and 39% (p = 0.005) compared with pre-therapy levels with arteriovenous and venovenous hemofiltration, respectively, and the creatinine content was reduced by 19% and 33% (p = 0.003). Neither parameter was reduced in the peritoneal dialysis group. We conclude that the use of hemofiltration as a renal replacement therapy after surgical correction of congenital heart disease offers significant advantages over the more traditional approach of peritoneal dialysis. In addition, we suggest that a more aggressive approach to the management of fluid overload and nutritional depletion with hemofiltration may result in a decrease in the very high mortality seen in renal failure after cardiac operations.

Acute Kidney Injury↗

Hemofiltration during cardiopulmonary bypass: the effect on anti-Xa and anti-IIa heparin activity.

Previous studies have demonstrated that heparin concentrations during cardiopulmonary bypass (CPB) may vary considerably, which may be related to variability in redistribution, cellular and plasma protein binding, and clearance of heparin. The purpose of this study was to determine whether hemofiltration removes lower molecular weight fractions of heparin from plasma and thus contributes to variability of blood levels of heparin. Twenty patients undergoing cardiac surgery with CPB were enrolled in this study after informed consent was obtained. The study was subdivided into two phases. The first 10 patients were enrolled in Phase I, which was designed to determine whether hemofiltration removes lower molecular weight fractions of heparin from blood. Blood specimens obtained from the inflow line and outflow lines of the hemofiltration unit were used to measure complete blood counts (CBC) and plasma heparin activity by anti-Xa and anti-IIa assays. Phase II was designed to evaluate the effect of hemofiltration on circulating plasma heparin activity. In Phase II, blood specimens were obtained from 10 patients via the arterial cannula of the extracorporeal circuit prior to and after hemofiltration for measurements of CBCs, anti-Xa plasma heparin, as well as whole blood heparin concentration using an automated protamine titration assay (Hepcon instrument, Medtronic Inc., Parker, CO). Ultrafiltrate and reservoir volumes were measured in both phases of the study. Hemofiltration did not remove lower (anti-Xa measurable) molecular weight heparin, but it resulted in a considerable increase in heparin activity in the outflow line, as measured by both anti-Xa and anti-IIa assays. The plasma anti-Xa heparin activity obtained after hemofiltration (5 +/- 1.8 U/mL) was substantially (P = 0.003) greater than heparin activity obtained prior to hemofiltration (3.9 +/- 1.7 U/mL). The increase in heparin activity with hemofiltration was directly related to ultrafiltrate volume (r = 0.63, P < 0.0001) and hematocrit (r = 0.73, P < 0.0001). Hemofiltration increases heparin concentration and may contribute to variability in heparin activity during CPB. Point-of-care heparin concentration methods would allow identification of the anticipated rise in heparin concentration, with the apparent clinical implication of a reduced need for supplemental heparin to maintain a target whole blood heparin concentration.

Cardiopulmonary Bypass↗

Hemofiltration increases IL-6 clearance in early systemic inflammatory response syndrome but does not alter IL-6 and TNF alpha plasma concentrations.

OBJECTIVE: To test the hypothesis that continuous hemofiltration increases interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) clearances and results in decreased cytokine plasma concentrations independent of renal function in patients with early SIRS. DESIGN: Prospective, controlled, randomized study. SETTING: Intensive care units at a university hospital. PATIENTS: 28 consecutive patients who fulfilled the criteria of the systemic inflammatory response syndrome (SIRS). INTERVENTIONS: Patients with SIRS were randomly assigned to either a hemofiltration or a control group irrespective of renal function. In patients of the hemofiltration group an isovolemic hemofiltration was initiated directly after the diagnosis of SIRS and maintained for at least 48 h. MEASUREMENTS AND RESULTS: A significant (p < 0.001) increase in total IL-6 clearance (hemofiltrate + urine), but not in TNF alpha clearance, was observed with hemofiltration. However, the plasma concentrations of both cytokines remained unchanged. Hemodynamic variables did not change significantly. CONCLUSIONS: Continuous hemofiltration increases IL-6 plasma clearance but not TNF alpha clearance. However, hemofiltration failed to decrease plasma concentrations of TNF alpha and IL-6 and, therefore, cannot be used effectively for cytokine elimination in SIRS. Accordingly, beneficial effects occasionally reported with hemofiltration are unlikely to be expected due to elimination of IL-6 or TNF alpha.

Adult↗

The use of different buffers during continuous hemofiltration in critically ill patients with acute renal failure.

OBJECTIVE: To determine the impact of different hemofiltration (HF) replacement fluids on the acid-base status and cardiovascular hemodynamics in patients with acute renal failure (ARF) and continuous veno-venous hemofiltration (CVVH). DESIGN: Prospective, cohort study. SETTING: Intensive Care Unit of the Heinrich Heine University Hospital, Düsseldorf, Germany. SUBJECT AND METHODS: One hundred and thirty-two critically ill patients with acute renal failure and continuous veno-venous HF were studied. Fifty-two patients were subjected to lactate-based (group 1), and 32 to acetate-based hemofiltration (group 2) while 48 (group 3) were treated with bicarbonate-based buffer hemofiltration fluid. Fifty-seven had a septic, and 75 a cardiovascular, origin of the ARF. Creatinine, blood urea nitrogen (BUN), serum bicarbonate, arterial pH, lactate and Apache II scores were noted daily. MAIN RESULTS: The mean CVVH duration was 9.8 +/- 8.1 days, mortality was 65%. No difference was present between the groups under investigation with regard to the main clinical parameters. Lactate- and bicarbonate-based hemofiltration led to significantly higher serum bicarbonate and arterial pH values as compared to the acetate-based hemofiltration. Serum bicarbonate values at 48 h after the initiation of CVVH treatment were 25.7 +/- 3.8 mmol/l (p < 0.001) in group 1, 20.6 +/- 3.1 mmol/l in group 2 and 23.3 +/- 3.9 mmol/l (p < 0.001) in group 3. While a lack of increase in serum bicarbonate and arterial pH was correlated to poor prognosis in lactate- and bicarbonate-based hemofiltration, no such observation was made in acetate-based hemofiltration. Cardiovascular hemodynamics were superior in patients treated with lactate- and bicarbonate-based buffer solution as compared to those treated with acetate-based buffer solution. CONCLUSIONS: The degree of correction of acidosis during hemofiltration was determined by patient outcome in patients treated with lactate- and bicarbonate-based buffer solutions, but not in patients receiving acetate-buffered solution. Bicarbonate and lactate-based buffer solutions were found to be superior to acetate-based replacement fluid.

APACHE↗

Comparison of two hemofiltration protocols for prevention of contrast-induced nephropathy in high-risk patients.

PURPOSE: Contrast-induced nephropathy is a complication of contrast medium administration during diagnostic and interventional procedures, with important prognostic relevance. Patients with chronic kidney disease have a higher risk for contrast-induced nephropathy and poorer outcome. In patients with chronic kidney disease, hemofiltration reduces contrast-induced nephropathy incidence and improves long-term survival. We assessed the mechanisms involved in the prophylactic effect of hemofiltration and of the most effective hemofiltration protocol to prevent contrast-induced nephropathy in patients with chronic kidney disease. SUBJECTS AND METHODS: We randomized 92 patients with chronic kidney disease (creatinine clearance < or =30 mL/min) to three different prophylactic treatments: intravenous hydration with isotonic saline (1 mL x kg x h for 12 hours before and after contrast exposure, control group; n = 30); intravenous hydration for 12 hours before contrast exposure, followed by hemofiltration for 18 to 24 hours after contrast exposure (post-hemofiltration group; n = 31), and hemofiltration performed for 6 hours before and for 18 to 24 hours after contrast exposure (pre/post-hemofiltration group; n = 31). The incidence of contrast-induced nephropathy (>25% increase in creatinine) and the in-hospital clinical course were compared in the three groups. RESULTS: Twelve patients (40%) in the control group, 8 patients (26%) in the post-hemofiltration group, and 1 patient (3%) in the pre/post-hemofiltration group experienced contrast-induced nephropathy (P = .0013); hemodialysis was required in 9 (30%), three (10%), and zero (0%) patients, respectively (P = .002). In-hospital mortality was 20%, 10%, and 0%, respectively (P = .03). CONCLUSIONS: Hemofiltration is an effective strategy for contrast-induced nephropathy prevention in patients with chronic kidney disease who are undergoing cardiovascular procedures. Pre-hemofiltration is required to obtain the full clinical benefit, suggesting that, among different mechanisms possibly involved, high-volume controlled hydration before contrast media exposure plays a major role.

Aged↗

The prevention of radiocontrast-agent-induced nephropathy by hemofiltration.

BACKGROUND: Nephropathy induced by exposure to radiocontrast agents, a possible complication of percutaneous coronary interventions, is associated with significant in-hospital and long-term morbidity and mortality. Patients with preexisting renal failure are at particularly high risk. We investigated the role of hemofiltration, as compared with isotonic-saline hydration, in preventing contrast-agent-induced nephropathy in patients with renal failure. METHODS: We studied 114 consecutive patients with chronic renal failure (serum creatinine concentration, >2 mg per deciliter [176.8 micromol per liter]) who were undergoing coronary interventions. We randomly assigned them to either hemofiltration in an intensive care unit (ICU) (58 patients, with a mean [+/-SD] serum creatinine concentration of 3.0+/-1.0 mg per deciliter [265.2+/-88.4 micromol per liter]) or isotonic-saline hydration at a rate of 1 ml per kilogram of body weight per hour given in a step-down unit (56 patients, with a mean serum creatinine concentration of 3.1+/-1.0 mg per deciliter [274.0+/-88.4 micromol per liter]). Hemofiltration (fluid replacement rate, 1000 ml per hour without weight loss) and saline hydration were initiated 4 to 8 hours before the coronary intervention and were continued for 18 to 24 hours after the procedure was completed. RESULTS: An increase in the serum creatinine concentration of more than 25 percent from the base-line value after the coronary intervention occurred less frequently among the patients in the hemofiltration group than among the control patients (5 percent vs. 50 percent, P<0.001). Temporary renal-replacement therapy (hemodialysis or hemofiltration) was required in 25 percent of the control patients and in 3 percent of the patients in the hemofiltration group. The rate of in-hospital events was 9 percent in the hemofiltration group and 52 percent in the control group (P<0.001). In-hospital mortality was 2 percent in the hemofiltration group and 14 percent in the control group (P=0.02), and the cumulative one-year mortality was 10 percent and 30 percent, respectively (P=0.01). CONCLUSIONS: In patients with chronic renal failure who are undergoing percutaneous coronary interventions, periprocedural hemofiltration given in an ICU setting appears to be effective in preventing the deterioration of renal function due to contrast-agent-induced nephropathy and is associated with improved in-hospital and long-term outcomes.

Aged↗

Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery. Effects on hemostasis, cytokines, and complement components.

BACKGROUND: This prospective study was intended to determine in a homogeneous population of children whether hemofiltration, performed during cardiopulmonary bypass rewarming, is able to improve hemodynamics and biologic hemostasis variables, to reduce postoperative blood loss, time to extubation, and plasma cytokines, and complement fragments. METHODS: Thirty-two children undergoing surgical correction of tetralogy of Fallot were randomly assigned to a hemofiltration or control group. Hemofiltration was performed with a polysulphone hemofilter during rewarming of cardiopulmonary bypass. Plasma clotting factors, D-dimers, antithrombin-III, complement fragments C3a and C5a, interleukin-1 beta, interleukin-6, interleukin-8, and tumor necrosis factor-alpha were measured before and after hemofiltration. Systemic mean arterial pressure, left atrial pressure, time to extubation, and postoperative blood loss were monitored. RESULTS: In the hemofiltration group, significant reductions in 24-h blood loss (250 (176-356) vs. 319 (182-500) ml/m2, median (minimum-maximum), time to extubation (15 (9-22) vs. 19 (11-24) h), plasma concentrations of C3a, C5a, interleukin-6, and tumor necrosis factor-alpha were observed compared to control. Arterial oxygen tension on admission to the intensive care unit was significantly greater in the hemofiltration group (136 +/- 20 vs. 103 +/- 25 mmHg, mean +/- SD). Significant increases in mean arterial pressure, clotting factors, and antithrombin-III were noted for the hemofiltration group. No intergroup difference was observed in left atrial pressure, platelets count, D-dimers, interleukin-8, and duration of stay in the intensive care unit. CONCLUSIONS: Hemofiltration during cardiopulmonary bypass in children improves hemodynamics and early postoperative oxygenation and reduces postoperative blood loss and duration of mechanical ventilation. Hemofiltration is able to remove some major mediators of the inflammatory response.

Cardiopulmonary Bypass↗

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↗

Hemofiltration in human sepsis: evidence for elimination of immunomodulatory substances.

Continuous hemofiltration is widely used for renal replacement therapy in patients with acute renal failure. It has been suggested that hemofiltration may also eliminate toxic mediators thought to be important in the pathophysiology of sepsis. The present study examined whether hemofiltration can activate or eliminate inflammatory mediators in patients with sepsis, and whether ultrafiltrate can alter specific functions of peripheral blood mononuclear leukocytes (PBMC) in vitro. Veno-venous hemofiltration was performed in 16 patients and in 5 healthy volunteers. Pre-filter (afferent), post-filter (efferent) and ultrafiltrate concentrations of cytokines (IL-1 beta, IL-6, IL-8, TNF alpha) and of complement components (C3, C3adesArg, C5adesArg, terminal complement complex) were measured after the beginning of hemofiltration (t0), and 60 minutes later (t60). PBMC, and monocyte and lymphocyte subfractions were incubated with ultrafiltrate, and cytokines were determined in the supernatants. Hemofiltration did not induce significant mediator activation. There was no evidence for significant cytokine elimination. However, pre-filter C3adesArg concentration showed a significant decline during hemofiltration (patients: t0 = 676.9 +/- 99.7 ng/ml, t60 = 545.4 +/- 83.2, P < 0.001; volunteers: t0 = 54.8 +/- 13.3 ng/ml, t60 = 33.9 +/- 10.7, P < 0.001). Ultrafiltrate from septic patients significantly stimulated PBMC and monocyte TNF alpha release, but suppressed lymphocyte IL-2 and IL-6 production. Ultrafiltrate from volunteers was without effect. Hemofiltration effectively eliminates certain mediators such as C3adesArg. Ultrafiltrate contains compounds with significant immunomodulatory qualities. Therefore, hemofiltration may represent a new modality for removal of immunomodulatory mediators.

Adjuvants, Immunologic↗

Effect of continuous venovenous hemofiltration with dialysis on hormone and catecholamine clearance in critically ill patients with acute renal failure.

OBJECTIVES: To measure the effect of continuous venovenous hemofiltration with dialysis on cardiovascular stability in the critically ill patients and to assess the extraction of a number of hormones and catecholamines by continuous venovenous hemofiltration with dialysis. DESIGN: Prospective, clinical study. SETTING: Intensive care unit of a tertiary medical center. PATIENTS: Twenty critically ill patients with acute renal failure. INTERVENTIONS: Timed collections of serum and ultradiafiltrate in patients receiving continuous venovenous hemofiltration with dialysis, with measurements of their catecholamine and hormonal content and calculation of continuous venovenous hemofiltration with dialysis clearances and daily extractions. Correlation of changes in catecholamines with prospectively collected hemodynamic data during the first 24 hrs of continuous venovenous hemofiltration with dialysis therapy. MEASUREMENTS AND MAIN RESULTS: No significant changes in dopamine, epinephrine, and norepinephrine requirements or plasma concentrations were seen during the first 24 hrs of continuous venovenous hemofiltration with dialysis. Overall daily losses of catecholamines in the ultradiafiltrate were small (dopamine 404 micrograms; epinephrine 32 micrograms; norepinephrine 29 micrograms). Hemodynamic variables remained stable during this period of continuous venovenous hemofiltration with dialysis therapy. All studied hormones were detected in the ultradiafiltrate, but their mean daily extractions were very small (aldosterone 0.37 micrograms; parathyroid hormone 53.4 pmol; cortisol 4.8 mg; T4 and T3 [trace amounts]; thyroid-stimulating hormone 2.6 mU; testosterone [trace amounts]). CONCLUSIONS: In critically ill patients with acute renal failure, continuous venovenous hemofiltration with dialysis results in minimal losses of catecholamines and is associated with cardiovascular stability. It causes only minor losses of several hormones. These losses are unlikely to be clinically important. Thus, blood purification achieved by continuous venovenous hemofiltration with dialysis does not produce significant catecholamine or hormonal losses and is associated with hemodynamic stability.

Acute Kidney Injury↗

Survival and renal function in pediatric patients following extracorporeal life support with hemofiltration.

OBJECTIVE: To determine variables associated with survival in pediatric patients treated with hemofiltration while receiving extracorporeal life support and to determine the probability for recovery of renal function among survivors. DESIGN: Retrospective database analysis. SETTING: University of Michigan pediatric nephrology database. PATIENTS: All pediatric patients treated with continuous hemofiltration while on extracorporeal life support at the University of Michigan between January 1990 and May 1999. A pediatric patient was defined as any child between birth and 18 yrs of age, including children treated in both the pediatric intensive care unit and neonatal intensive care unit. Indications for extracorporeal life support included both cardiac and pulmonary failure. INTERVENTIONS: Data analysis of patients who were treated with hemofiltration while on extracorporeal life support. Hemofiltration includes both ultrafiltration and hemofiltration with countercurrent dialysis. MEASUREMENTS AND MAIN RESULTS: Thirty-five patients with a mean age of 39 +/- 65 months (median, 3 months) underwent hemofiltration while on extracorporeal life support. Forty-three percent survived to hospital discharge (95% CI, 26%-60%). All deaths occurred in the intensive care unit. Recovery of renal function occurred in 93% of survivors (95% CI, 79%-108%). Mean duration of hemofiltration in survivors, including time during and after extracorporeal life support, was 9 +/- 6 days. All nonsurvivors were on renal replacement therapy at the time of death. In this analysis, decreased survival was significantly associated with the use of vasopressor infusions (p =.01) and the presence of complications (p =.006). Vasopressor infusions were required in 89% of patients, and 37% of patients experienced complications. CONCLUSIONS: In patients receiving hemofiltration while on extracorporeal life support, survival is comparable to that reported in other extracorporeal life support or hemofiltration populations. Decreased survival in these patients may be associated with the use of vasopressor infusions and the occurrence of complications. Recovery of renal function occurs in most survivors.

Journal Article↗

Hemofiltration and peritoneal dialysis in infection-associated acute renal failure in Vietnam.

BACKGROUND: In some parts of the world, peritoneal dialysis is widely used for renal replacement in acute renal failure. In resource-rich countries, it has been supplanted in recent years by hemodialysis and, most recently, by hemofiltration and associated techniques. The relative efficacy of peritoneal dialysis and hemofiltration is not known. METHODS: We conducted an open, randomized comparison of pumped venovenous hemofiltration and peritoneal dialysis in patients with infection-associated acute renal failure in an infectious-disease referral hospital in Vietnam. RESULTS: Seventy adult patients with severe falciparum malaria (48 patients) or sepsis (22 patients) were enrolled; 34 were assigned to hemofiltration and 36 to peritoneal dialysis. The mortality rate was 47 percent (17 patients) in the group assigned to peritoneal dialysis, as compared with 15 percent (5 patients) in the group assigned to hemofiltration (P=0.005). The rates of resolution of acidosis and of decline in the serum creatinine concentration in the group assigned to hemofiltration were more than twice those in the group assigned to peritoneal dialysis (P<0.005), and renal-replacement therapy was required for a significantly shorter period. In a multivariate analysis, the odds ratio for death was 5.1 (95 percent confidence interval, 1.6 to 16) and that for a need for future dialysis was 4.7 (95 percent confidence interval, 1.3 to 17) in the group assigned to peritoneal dialysis. The cost of hemofiltration per survivor was less than half that of peritoneal dialysis, and the cost per life saved was less than one third. CONCLUSIONS: Hemofiltration is superior to peritoneal dialysis in the treatment of infection-associated acute renal failure.

Acidosis↗

Cost-effectiveness of hemofiltration to prevent contrast nephropathy in patients with chronic kidney disease.

OBJECTIVE: Prophylactic hemofiltration has been reported, in one study, to reduce renal complications and death but necessitates additional up-front health care resource deployment in a critical care setting. We sought to explore the potential scope and cost-effectiveness of this strategy. DESIGN: Economic evaluation using decision analysis. SETTING: Tertiary or quaternary care hospital. PATIENTS: Subjects undergoing angiography at risk for developing contrast nephropathy. INTERVENTION: Prophylactic hemofiltration was compared with intravenous saline. Secondary models incorporated sodium bicarbonate and N-acetylcysteine as comparators. MEASUREMENT AND MAIN RESULTS: The cost per quality-adjusted life year (QALY) gained with hemofiltration compared with intravenous saline in high-risk subjects (mean serum creatinine, 265 micromol/L) was 3,900 US dollars. This finding was sensitive to variations in several important variables. For instance, the cost-effectiveness ratio became less attractive (i.e., >50,000 US dollars/QALY) when hemofiltration was used in lower-risk subjects (serum creatinine, <265 micromol/L). The cost-effectiveness remained <50,000 US dollars/QALY provided that the relative risk of hemofiltration compared with saline alone was below 0.65 (reported relative risk, 0.10). Although based on indirect comparison of clinical efficacy, when N-acetylcysteine or sodium bicarbonate was used as the comparator, the cost per QALY gained for hemofiltration became markedly less attractive (50,100 US dollars and >1,000,000 US dollars), although the relative effectiveness of these three strategies strongly influenced the results. CONCLUSIONS: Use of prophylactic hemofiltration in patients at high risk for contrast nephropathy may be potentially cost-effective only if certain conditions are satisfied, and its attractiveness is materially diminished when compared to other strategies. As this invasive therapy would entail certain immediate resource outlay, before considering its implementation it is crucial to confirm the clinical effectiveness and health care resource consequences of hemofiltration relative to current standards of care in future studies.

Aged↗

Multiple-dose pharmacokinetics of amikacin and ceftazidime in critically ill patients with septic multiple-organ failure during intermittent hemofiltration.

The pharmacokinetic parameters of amikacin and ceftazidime were assessed in four patients undergoing hemofiltration for septic shock. The parameters were assessed during hemofiltration and in the interim period. The concentration-time profiles of these two drugs in plasma, urine, and ultrafiltrate were investigated after intravenous perfusion (30 min). In all cases a 1-g dose of ceftazidime was administered; for amikacin, the dosage regimen was adjusted according to the patient's amikacin levels (250 to 750 mg). Concentrations of drug in all samples were assayed by high-performance liquid chromatography with UV detection for ceftazidime and by enzyme multiplied immunoassay for amikacin. The elimination half-life (t1/2) and the total clearance of amikacin ranged from 31.1 to 138.2 h and from 5.4 to 8.9 ml/min, respectively, during the interhemofiltration period in anuric patients. Hemofiltration substantially decreased the t1/2 (3.5 +/- 0.49 h) and increased the total clearance (89.5 +/- 11.8 ml/min). The hemofiltration clearance of amikacin represented 71% of the total clearance, and the hemofiltration process removed, on average, 60% of the dose. During hemofiltration, the elimination t1/2 of ceftazidime (2.8 +/- 0.69 h) was greatly reduced and the total clearance increased (74.2 +/- 11.2 ml/min) compared with those in the interhemofiltration period (9 to 43.7 h and 7.4 to 16.8 ml/min, respectively). About 55% of the administered dose was recovered in the filtrate, and the hemofiltration clearance of ceftazidime was 46 +/- 14.3 ml/min. A redistribution phenomenon (rebound) in the amikacin and ceftazidime concentrations in plasma (35 and 28%, respectively) was reported after hemofiltration in two patients. The MICs for 90% of the most important pathogens were exceeded by the concentrations of the two drugs in plasma during the whole treatment of these patients.

Adult↗

Effect of hemofiltration filter adsorption on circulating IL-6 levels in septic rats.

INTRODUCTION: Hemofiltration may modulate the inflammatory response in sepsis through a variety of mechanisms. We sought to distinguish clearance from adsorption as the principal mechanism responsible for reducing circulating IL-6 levels with hemofiltration. MATERIALS AND METHODS: Nine hours after cecal ligation and puncture in 18 adult male Sprague-Dawley rats, we divided the rats into three groups (6 animals each) and placed groups 2 and 3 on a hemofiltration circuit connected between the right carotid artery and femoral vein using an AN69 membrane. In the hemofiltration group (group 2), ultrafiltrate was replaced with lactated Ringer's solution; in the recirculation group (group 3), the ultrafiltrate was reinfused into the animal. A sham group (group 1) had an arteriovenous circuit inserted but no hemofiltration. Blood was obtained for measurement of IL-6 and tumor necrosis factor (TNF) at the start of hemofiltration and after 5 and 11 hours of treatment. RESULTS AND DISCUSSION: IL-6 levels increased only in the sham-treated animals (20.4 +/- 11.3 at baseline to 62.3 +/- 16.8 pg/ml at 11 hours, P = 0.03) (differences between groups 1 and 2, P = 0.015, and groups 1 and 3, P = 0.028). TNF levels were highly variable but not significantly different among the three groups. CONCLUSION: Hemofiltration-associated reductions in circulating IL-6 levels appear to be secondary to adsorption of mediators to the filter membrane. We do not know whether this is due to direct adsorption of IL-6 per se or to the absorption of other mediators with secondary downregulation of IL-6 production or release. In addition, we could not exclude an interaction between adsorption and hemofiltration.

Adsorption↗

Four years' experience of long-term hemofiltration in a Swedish center.

Thirty patients with end-stage renal disease were switched from maintenance hemodialysis to postdilution hemofiltration and observed for long-term effects. The study comprised totally 496 months of hemofiltration. Uremic and biochemical control was similar in the hemofiltration and in the hemodialysis period. Of the small molecules, only serum creatinine showed slight increase after 3 months. No other significant changes in creatinine, serum urea or potassium levels were associated with long-term hemofiltration. During each hemofiltration session there was significant decrease of serum parathyroid hormone (PTH) and serum beta 2-microglobulin, but over the first 8 months of hemofiltration the beta 2-microglobulin values did not fall, and significant PTH reduction was found only after 12 months. Although uremic control was similar with both methods, there were fewer complications of hemofiltration, which was preferred by the patients. Because it is currently more expensive, however, hemofiltration should be reserved for patients with dialysis related problems, that are not helped by other changes in the dialysis technique, such as sequential ultrafiltration changes in the dialysis membranes and in the dialysis buffer from acetate to bicarbonate.

Female↗