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A computerized model to analyze transcellular fluid shift during hemofiltration.

Using urea and inulin as markers, we have developed a simple method to calculate intracellular and extracellular fluid volume in patients before and after hemofiltration therapy. During conventional hemofiltration using substitution fluid with a Na+ concentration of 140 mEq/L, a decrease in extracellular fluid volume was noted whereas the intracellular fluid volume was unaltered. Furthermore, we have developed a computerized mathematical model to analyze transcellular fluid shifts during hemofiltration. This model also indicates a decrease in extracellular fluid volume only, the intracellular fluid volume remaining unchanged. High-Na+ hemofiltration using substitution fluid with an Na+ concentration of 160 mEq/L has enabled us to remove fluid from both intracellular and extracellular compartments. Thus, high-Na+ hemofiltration is expected to normalize the intracellular hydration in uremic patients, and to reduce the decrease in extracellular fluid volume during hemofiltration therapy. Our data therefore suggest that high-Na+ hemofiltration could prevent hypotension due to large decreases in extracellular fluid volume by inducing a transcellular fluid shift out of body cells. Our computerized model can be a useful tool in the prescription of the optimal Na+ concentration in substitution fluid for individualized hemofiltration therapy.

Adult↗

Removal of sulfonamides by hemofiltration.

Hemofiltration is a relatively new technique for removing toxic substances from the body. Unlike hemodialysis or hemoperfusion, the driving force behind hemofiltration is ultrafiltration. There have been several studies examining the clearance of drugs by hemofiltration but to date no study has investigated in a systematic way the effects of protein binding, perfusate flow, transmembrane pressure, and the duration of treatment on drug clearance by hemofiltration. The influence of these factors on the hemofiltration clearance of three sulfonamides with differing degrees of protein binding was investigated. It was found that hemofiltration drug clearance decreased with the duration of hemofiltration and protein binding but increased with perfusate flow and transmembrane pressure.

Animals↗

Removal of mediators by continuous hemofiltration in septic patients.

Continuous hemofiltration currently represents standard renal replacement therapy in critically ill patients. Because higher ultrafiltration rates are related to better survival rates in experimental and clinical studies and hemofiltration results in fewer cardiovascular side effects than does conventional hemodialysis, the use of inflammatory mediator removal by this extracorporeal procedure has emerged. This article reviews clinically relevant principles of compound transport and the experimental and clinical effects of hemofiltration during sepsis. Hemofiltration did not have a major impact on plasma concentrations of prominent inflammatory cytokines (tumor necrosis factor-a and interleukins 1b, 6, and 8) and seems therefore not to be able to counterbalance endogenous cytokine production despite considerable cytokine removal in the filtrate. Contradictory results in the literature are discussed under the viewpoint of membrane-related sieving coefficients and plasma cytokine measurement. A significant reduction in plasma anaphylatoxin concentrations by hemofiltration is associated with impressive immunomodulatory and cardiodepressive ultrafiltrate effects. Thus far, however, the use of hemofiltration for nonrenal indications remains experimental and is not supported by controlled clinical trials. Modern strategies of blood purification that may be associated with a high degree of effectiveness for mediator removal (high-volume hemofiltration and heparin-induced extracorporeal lipoprotein-fibrinogen precipitation) are discussed.

Anaphylatoxins↗

Pharmacokinetics of meropenem in critically ill patients with acute renal failure undergoing continuous venovenous hemofiltration.

OBJECTIVE: Meropenem is a broad-spectrum antibiotic used for severe infections. In patients with chronic end-stage renal failure, meropenem clearance is reduced and doses must be adjusted according to the creatinine clearance. The aim of this study was to assess pharmacokinetic data of meropenem in patients with acute renal failure and to determine the amount of drug removed by continuous venovenous hemofiltration, an often-used renal replacement therapy in patients with acute renal failure. METHODS: Nine critically ill anuric patients with acute renal failure undergoing continuous venovenous hemofiltration received 500 mg meropenem 2 or 3 times daily. Plasma and hemofiltrate concentrations were determined during 1 dosing interval at steady state. Pharmacokinetic parameters were calculated for a 2-compartment open model and dose requirements were calculated. RESULTS: The total meropenem clearance was 52.0 +/- 8.4 mL/min, with a hemofiltration clearance of 22.0 +/- 4.7 mL/min and a nonrenal-nonhemofiltration clearance of 29.9 +/- 5.4 mL/min; 235.9 +/- 88.6 mg, or 47.2% +/- 17.7%, of the dose were removed through continuous venovenous hemofiltration. The terminal elimination half-life was 8.7 +/- 3.5 hours and the volume of distribution at steady state was 12.4 +/- 1.8 L. Peak and trough concentrations for a dosing interval of 12 hours were 38.9 +/- 9.7 mg/L and 7.3 +/- 1.3 mg/L, respectively. The corresponding concentrations for a dosing interval of 8 hours were 44.7 +/- 10.4 mg/L and 11.9 +/- 0.7 mg/L, respectively. CONCLUSION: Pharmacokinetic data of anuric patients with acute renal failure were similar to those of patients with end-stage renal failure. Because hemofiltration contributes significantly to meropenem elimination, the recommended dose for critically ill anuric patients receiving continuous venovenous hemofiltration should be increased by 100% to avoid potential underdosing.

Acute Kidney Injury↗

Continuous veno-venous hemofiltration with dialysis removes cytokines from the circulation of septic patients.

OBJECTIVE: To determine whether continuous veno-venous hemofiltration with dialysis leads to extraction of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) from the circulation of critically ill patients with sepsis and acute renal failure and to quantitate the clearance and removal rates of these cytokines and their effect on serum cytokine concentrations. DESIGN: Prospective, controlled study of TNF-alpha IL-1 beta extraction by continuous veno-venous hemofiltration with dialysis in patients with septic acute renal failure. SETTING: Intensive care unit of a tertiary institution. PATIENTS: Eighteen critically ill patients with sepsis and acute renal failure. Control group of six patients experiencing an acute illness while undergoing chronic hemodialysis. INTERVENTIONS: Collection of blood samples before continuous veno-venous hemofiltration with hemodialysis. Simultaneous collection of prefilter blood and ultradiafiltrate after 4 and 24 hrs of treatment. MEASUREMENTS AND MAIN RESULTS: TNF-alpha and IL-1 beta concentrations were measured in blood and ultradiafiltrate. Their clearances and daily extraction were calculated and compared with a control group. TNF-alpha was detected in 66.6% of serum samples of patients with septic acute renal failure; IL-1 beta was detected in 55% of patients' sera samples. Both TNF-alpha and IL-1 beta were cleared by the hemofilter during continuous veno-venous hemofiltration with dialysis. The mean clearance for TNF-alpha was 30.7 L/day (95% confidence interval 22.4 to 39) with a daily mean excretion of 14.1 micrograms (95% confidence interval 1.7 to 26.5). Mean IL-1 beta clearance was 36.1 L/day (95% confidence interval 25.4 to 46.8) equivalent to a mean daily IL-1 beta excretion of 1 microgram (95% confidence interval 0.9 to 1.1). No measurable concentrations of TNF-alpha or IL-1 beta were found in the serum or ultrafiltrate specimens of control patients. CONCLUSIONS: These findings demonstrate that continuous veno-venous hemofiltration with dialysis can remove both TNF-alpha and IL-1 beta from the circulation of septic, critically ill patients. This cytokine extraction may prove to be of benefit in attenuating the progression of multiple organ dysfunction in patients with sepsis-associated renal failure, who are receiving continuous veno-venous hemofiltration with dialysis. This potential benefit of existing hemofiltration therapies supports their preferential implementation in patients with renal failure associated with severe sepsis. These observations may stimulate the modification of filtration membrane design seeking to specifically augment the clearance from the circulation of a variety of such cytokines.

Acute Kidney Injury↗

Continuous arteriovenous hemofiltration therapy for Staphylococcus aureus-induced septicemia in immature swine.

OBJECTIVES: The goals of this study were: a) to evaluate the efficacy of controlled, continuous arteriovenous hemofiltration in improving morbidity and mortality rates in an immature swine model of Staphylococcus aureus-induced septicemia; b) to determine if ultrafiltrate from septic animals contained mediators that produce pathophysiologic changes observed in untreated S. aureus septic pigs. DESIGN: Prospective, randomized, controlled study with age-matched controls. SETTING: U.S. Department of Agriculture-licensed biomedical research facility. SUBJECTS: Sixty-five weaned Poland-China swine (4 to 6 wks of age; 5 to 10 kg). INTERVENTIONS: Part 1: Animals received a lethal dose of live S. aureus (8 x 10(9) colony-forming units/kg) over 1 hr. The three treatment groups included: hemofiltration group 1 (eight filtered, eight nonfiltered animals), plasma filtration fraction = 5.5%; hemofiltration group 2 (six filtered, six nonfiltered animals), filtration fraction = 16.6%; and hemofiltration group 3 (six filtered, six nonfiltered animals), filtration fraction = 33.4%. A control, nonseptic group of animals (n = 4) was filtered to obtain "clean" ultrafiltrate (hemofiltration group 4). Part 2: Sterile ultrafiltrate concentrate batches obtained from each group of filtered, septic animals were concentrated and infused into healthy, nonseptic pigs (reinfusion groups 1 through 3). MEASUREMENTS AND MAIN RESULTS: Physiologic, biochemical, and hematologic variables were measured in all animals every 1 to 3 hrs. Overall length of survival was also recorded. In hemofiltration groups 1 through 3, filtered animals survived significantly longer than matched, nonfiltered (sham-filtered) animals. Increments in survival time increased directly with filtration fraction. Ultrafiltrate concentrate from septic pigs produced death (LD41) and disease similar to those rates observed in untreated S. aureus-septic pigs. Infusion of clean ultrafiltrate concentrate produced no response. CONCLUSIONS: Continuous arteriovenous hemofiltration significantly improved survival rates in swine with S. aureus-induced sepsis. Resultant ultrafiltrate concentrate contained mediators responsible for some pathophysiologic responses observed in this animal model.

Age Factors↗

Continuous hemofiltration and platelet function in critically ill patients.

OBJECTIVE: To evaluate platelet function in patients undergoing continuous pump-driven veno-venous hemofiltration. DESIGN: Prospective study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Twenty consecutive, critically ill patients with acute renal failure (serum creatinine concentration > 3.0 mg/dL (> 265 mumol/L), serum urea > 200 mg/dL (> 33 mmol/L), urine output < 20 mL/hr) secondary to sepsis or trauma. A comparable group (n = 20) without renal failure and not undergoing hemofiltration served as a control group. INTERVENTIONS: Continuous pump-driven veno-venous hemofiltration was used in patients with renal insufficiency. Pump flow ranged from 60 to 100 mL/hr. MEASUREMENTS AND MAIN RESULTS: Platelet function was assessed by a turbidimetric technique using a double-channel aggregometer. Aggregation was induced by adenosine diphosphate (ADP) (2.0 mumol/L), collagen (4 micrograms/mL), epinephrine (25 mumol/L), and saline solution (control). Maximum aggregation was considered to be the maximum increase in light transmission after the addition of the aggregating agents. The maximum gradient of aggregation was considered to be the maximum increase per minute. Measurements were carried out before hemofiltration (baseline values) and during the following 5 days. In the control group, blood samples were taken at corresponding data points. Eight patients undergoing continuous hemofiltration survived during the investigation period; 16 patients in the control group survived. There were no significant differences among the two groups with respect to standard coagulation variables. Maximum platelet aggregation was lower than in normal patients after the addition of all three inductors (ADP, collagen, and epinephrine). In control patients, all aggregation variables remained almost stable during the entire investigation period. In the hemofiltered patients, maximum platelet aggregation was significantly reduced (ADP, decrease of 62 relative % from baseline values; collagen, decrease of 86 relative % from baseline values; epinephrine, decrease of 77 relative % from baseline values). Maximum platelet aggregation was also depressed in these patients (ADP, decrease of 40 relative % from baseline values; collagen, decrease of 88 relative % from baseline values; epinephrine, decrease of 85 relative % from baseline values). When platelet aggregation variables were reduced greater than a decrease of 60 relative % from baseline values (in all induction groups), the mortality rate was 100%. CONCLUSIONS: Continuous pump-driven veno-venous hemofiltration significantly changed platelet aggregability, which became obvious 2 to 3 days after the start of hemofiltration.

Acute Kidney Injury↗

Nadroparin versus dalteparin anticoagulation in high-volume, continuous venovenous hemofiltration: a double-blind, randomized, crossover study.

OBJECTIVES: To compare filter survival times during high-volume, continuous venovenous hemofiltration in patients with normal coagulation variables, using anti-factor Xa bioequivalent doses of nadroparin and dalteparin. To evaluate which other factors influence filter survival time. DESIGN: Randomized, prospective, double-blind, crossover study. SETTING: An 18-bed intensive care unit in a 530-bed teaching hospital. PATIENTS: Thirty-two critically ill patients with renal failure, treated with high-volume, continuous venovenous hemofiltration. INTERVENTIONS: High-volume, postdilutional continuous venovenous hemofiltration, with a standard blood flow rate of 200 mL/min and an ultrafiltrate volume of 100 L in 24 hrs, was performed with a highly permeable, large-surface cellulose triacetate membrane. Anticoagulation with anti-Xa bioequivalent doses of nadroparin and dalteparin was administered in the extracorporeal line before the filter. Blood was sampled for determination of coagulation variables before hemofiltration, 0.5, 2, 4, 6, and 12 hrs after starting the treatment, and at the end of the hemofiltration run. MEASUREMENTS AND MAIN RESULTS: Anti-Xa peak activity, time of anti-Xa peak activity, area under the curve for 0-3 hrs and filter survival time were not significantly different using nadroparin or dalteparin. When analyzing the patients according to the length of filter survival time, no relationship among anti-Xa peak activity, area under the curve for 0-3 hrs, and filter survival time was found. However, there was a strong trend toward a negative correlation between baseline platelet count and filter survival time (r2 = .11; p = .07). Mean blood urea nitrogen decreased from 81.0+/-31.9 to 41.1+/-21.2 mg/dL (p<.01) and mean creatinine decreased from 3.4+/-1.8 to 1.9+/-1.2 mg/dL (p<.01). There were no clinically important bleeding complications. CONCLUSIONS: Nadroparin and dalteparin are bioequivalent with respect to their anti-Xa activities. Using either drug, we did not find a difference in filter survival time during high-volume, continuous venovenous hemofiltration. No relationship between anti-Xa activity and filter survival time could be found. However, there is a strong trend toward a negative correlation between baseline platelet count and filter survival time. This suggests that during high-volume, continuous venovenous hemofiltration, patients with a higher baseline platelet count might need a different anticoagulation regimen to obtain longer filter survival times.

Aged↗

Comparison of a lactate-versus acetate-based hemofiltration replacement fluid in patients with acute renal failure.

The objective of the study was to determine the impact of a lactate- and an acetate-based hemofiltration replacement fluid (HF) on the acid-base status in patients with acute renal failure (ARF) and continuous venovenous hemofiltration (CVVH). The prospective, cohort study was carried out in the intensive care unit of the Heinrich-Heine University Hospital, Düsseldorf, FRG. Subjects were 84 critically ill patients with ARF and CVVH. Fifty-two patients were subjected to lactate-based (group 1) and 32 to acetate-based hemofiltration (group 2). Thirty-eight patients had a septic, 46 a cardiovascular origin of the ARF. Creatinine, BUN, serum bicarbonate, arterial pH, lactate and APACHE II score were noted daily. Mean CVVH duration was 9.8 +/- 8.1 days; mortality was 65%. The groups did not differ with regard to the main clinical parameters. Lacate-based hemofiltration led to significantly higher serum bicarbonate and arterial pH values as compared to the acetate-based hemofiltration. Baseline serum bicarbonate values were 23.3 +/- 8.3 mmol/L in group 1 and 21.6 +/- 4.3 mmol/L in group 2 (NS); values at 48 h after initiating CVVH treatment were 25.7 +/- 3.8 mmol/L and 20.6 +/- 3.1 mmol/L, respectively (p < 0.001). Arterial pH prior to CVVH treatment was 7.36 +/- 0.1 in group 1 and 7.34 +/- 0.1 in group 2 (NS), and 7.43 +/- 0.07 versus 7.37 +/- 0.06 (p < 0.001) on day 2. These findings were maintained throughout therapy. While a lack of increase in serum bicarbonate and arterial pH was correlated to a poor prognosis in lactate-based hemofiltration, no such observation could be made in acetate-based hemofiltration. Septic patients did not differ in their acid-base status from nonseptic patients. Lactic acidosis occurred in 8 septic patients irrespective of the substitution fluid. All 8 patients died. There was a significant increase in HCO3 and arterial pH values in lactate-based as compared to acetate-based HF.

APACHE↗

Which organic acids does hemofiltrate contain in the presence of acute renal failure?

It is not generally possible to measure most organic acids in the serum of critically ill patients, due to rapid metabolism and methodological problems. Only the regular measurement of lactic acid and the arterial ketone body ratio (acetoacetate/beta-hydroxybutyrate, AKBR) have been introduced in clinical practice, but these parameters can represent only a part of the disturbed metabolism. In pediatric patients, a chromatographical urine analysis has been established for detection of inborn errors of metabolism, which allows the determination of more than 50 organic acids simultaneously (gas chromatographic (GC) analysis in combination with mass spectrometry (MS)]. In continuous treatment of acute renal failure, hemofiltrate is always available, but it contains only low protein concentrations and after the filtration process, metabolism is rapidly stopped. The sieving coefficient of lactic acid is nearly one in hemofiltration. The aim of our study was to compare results of the regular and CG/MS methods in blood and hemofiltrate for lactic acid, and to find other organic acids of possible clinical importance. We investigated serum (lactic acid) and hemofiltrate of 40 critically ill patitens, similar to the urine analysis method for infants. All patients suffered from acute renal failure and were treated by continuous veno-venous hemofiltration (CVVH). The conditions of treatment were standardized (spontaneous ultrafiltration in the first hour), and the material (blood/hemofiltrate) was taken one hour after the beginning of extracorporeal circulation. Statistical methods included correlation analysis, nonparametric ANOVA with Wilcoxon scores (ranks of data), and stepwise discriminant analysis. Regular and GC/MS methods in hemofiltrate showed a good correlation for lactic acid. The best correlation with lactic acid was found for 4-hydroxy-phenyllactic acid (n=20, r=0.866), 2-hydroxy-valeric acid (n=22, r=0.7491) and 2-hydroxybutyric acid (n=32, r=0.5148). Age, sex, diagnosis, and APACHE II score play a subordinate role, but the presence of glyceric and citric acid possibly have prognostic importance [nonparimetric ANOVA with Wilcoxon scores (ranks of data)], as does the combination of 3-hydroxypropionic acid, glyceric acid, and threonic-acid-4-lacton (stepwise discriminant analysis). It can be concluded that in acute renal failure, the measurement of lactic acid and AKBR can reflect only a small part of disturbed metabolism. Hemofiltrate can be a useful medium in describing metabolic processes in critically ill patients with acute renal failure. Some inherited metabolic diseases in infants (phenylketonuria, maple syrup disease) and ketoacidosis show similar metabolic modifications.

APACHE↗

Continuous arteriovenous hemofiltration after cardiac operations in infants and children.

Acute renal insufficiency after cardiopulmonary bypass can lead to a significant morbidity from fluid overload and electrolyte disturbance, impede pulmonary gas exchange, and postpone weaning from mechanical ventilation. The limitations placed on free water intake result in severe restriction of nutrition while diuretic therapy causes electrolyte imbalance. Artificial renal support either in the form of peritoneal dialysis or hemodialysis may be complicated by sepsis and hemodynamic instability. We reviewed our experience with the use of continuous arteriovenous hemofiltration, an extracorporeal technique for removal of solutes, toxins, and water in critically ill patients with cardiac failure complicated by acute renal insufficiency and hemodynamic instability after cardiopulmonary bypass. Ten infants and children with renal insufficiency caused by low cardiac output had continuous arteriovenous hemofiltration instituted for indications including sepsis, volume overload, oliguria for more than 24 hours nonresponsive to diuretic therapy, and the need for hyperalimentation. All were supported by mechanical ventilation and receiving high-dose inotropic support. Arterial and venous vascular access was successfully obtained by cannulation of the femoral artery and vein in nine patients. Anticoagulation of the circuit was achieved with heparin infusion (6 to 20 micrograms/kg/hr) and monitored by measurement of activated clotting time. The continuous arteriovenous hemofiltration circuit was replaced if there was clot formation, or at 3 days after placement. Dialysis solution (Dianeal) 1.5% or 0.5% was infused as prefilter dilution. With the use of continuous arteriovenous hemofiltration, 20 to 100 m/hr of ultrafiltrate was removed, which allowed correction of hypervolemia, and caloric intake increased from 13.5 kcal/kg/day to 79.5 kcal/kg/day. Continuous arteriovenous hemofiltration was maintained between 5 hours and 8 days and was well tolerated in all patients. Serum urea and creatinine levels declined during continuous arteriovenous hemofiltration. We conclude that continuous arteriovenous hemofiltration is a safe and effective method for fluid and electrolyte homeostasis and that it thus allows hyperalimentation in infants and children after cardiac operations.

Acute Kidney Injury↗

Acute continuous hemofiltration with dialysis: effect on insulin concentrations and glycemic control in critically ill patients.

OBJECTIVES: To quantitate insulin losses and glucose absorption during acute continuous hemofiltration with dialysis and to assess the clinical importance of these changes. DESIGN: Prospective collection of serum and ultradiafiltrate fluid in patients receiving acute continuous hemofiltration with dialysis. Measurements of serum and ultradiafiltrate insulin and glucose concentrations. Calculations of insulin excretion and glucose absorption. Correlation of findings with patient outcome. SETTING: University medical center. PATIENTS: Sixteen ICU patients with acute renal failure. MEASUREMENTS AND MAIN RESULTS: The mean serum glucose concentration before acute continuous hemofiltration with dialysis was 178 mg/dL (9.9 mmol/L) (95% confidence interval 112 to 244 mg/dL [6.2 to 13.6 mmol/L]), increasing to 257 mg/dL (14.3 mmol/L) (95% confidence interval 167 to 347 mg/dL [9.3 to 19.3 mmol/L]) after 4 hrs of acute continuous hemofiltration with dialysis, and stabilizing at 207 mg/dL (11.5 mmol/L) (95% confidence interval 160 to 254 mg/dL [8.9 to 14.1 mmol/L]) at 24 hrs. Mean plasma insulin concentration before acute continuous hemofiltration with dialysis was 34.4 mU/L (95% confidence interval 8.6 to 60.2 mU/L), increasing to 54.4 mU/L at 4 hrs (95% confidence interval 25 to 83.8 mU/L; NS). There was no significant decrease in mean insulin concentration across the filter (51.8 mU/L before filtration vs. 51.9 mU/L after filtration). Insulin was detected in the ultradiafiltrate but its overall mean clearance rate was only 6.2 mL/min, with mean daily losses of 689 mU/day (95% confidence interval 325 to 1053 mU/day). During acute continuous hemofiltration with dialysis, glucose absorption through the filter averaged 134 g/day (95% confidence interval 96.2 to 171.8 g/day). Plasma insulin concentrations were significantly (p < .05) lower in survivors than nonsurvivors (51.7 vs. 123.6 mU/L). CONCLUSIONS: Significant glucose absorption occurs during acute continuous hemofiltration with dialysis and is coupled with minor insulin losses (< 1 U/day) through the filter. These events do not appear to have major clinical impact. A low plasma insulin concentration is associated with diminished mortality rates in this group of patients.

Acute Kidney Injury↗

Blood conservation in cardiac operations. Cell separation versus hemofiltration.

The effects of hemoconcentration performed during and after extracorporeal circulation by either centrifugation (cell separation group, n = 20) or hemofiltration (n = 20) were investigated in 40 patients undergoing elective aorta-coronary bypass grafting. Interest was focused on the quality of the blood concentrated from the blood remaining in the extracorporeal circuit and on the reaction of the patients after retransfusion of the concentrated products. Hemofiltration was easy to perform and produced whole blood quicker than the cell separation technique. Coagulation studies revealed no significant differences in heparin concentration, levels of fibrinogen and antithrombin III, or platelet counts. Various coagulation parameters tended to normalize completely and more quickly after hemofiltration than after centrifugation. None of the patients had severe bleeding postoperatively. Free hemoglobin levels were not affected by hemofiltration; elastase concentration was higher only immediately after retransfusion of the concentrated blood, with no effect on organ function. We conclude that both methods were effective means of hemoconcentration during extracorporeal circulation and in salvaging the diluted pump blood after extracorporeal circulation. Loss of plasma fraction is an important disadvantage in the centrifugation technique, which can be avoided by hemofiltration; derangement in colloid osmotic pressure and coagulation parameters was less pronounced after hemofiltration. Costs were lower, as well. Therefore, when a high volume of cardioplegic solution and two-stage cannulation are used, hemofiltration seems to be the method of choice for blood conservation during cardiac operations.

Aged↗

A comparison of solute clearance during continuous hemofiltration, hemodiafiltration, and hemodialysis using a polysulfone hemofilter.

The clearance of urea, creatinine, amino acids, vancomycin, and phenytoin was measured in vivo in a small animal model during continuous venovenous (CVV) hemofiltration, CVV hemodiafiltration, and CVV hemodialysis using a 0.25 m2 polysulfone hemofilter. Six domestic piglets (weighing 6-11.8 kg) each received 1 hr of all three techniques in random order. Blood flow was 50 ml/min. During CVV hemofiltration, filtrate production was 500 ml/hr and dialysate flow was zero. During CVV hemodiafiltration, filtrate production was 250 ml/hr and dialysate flow was 250 ml/hr. During CVV hemodialysis, net filtrate production was zero and dialysate flow was 500 ml/hr. The ratio of concentration of solute in filter effluent to concentration in whole plasma was derived for each solute during each of the three techniques. Mean (SD) effluent:plasma ratio for urea during CVV hemofiltration was 0.957 (0.038), CVV hemodiafiltration 0.876 (0.109), and CVV hemodialysis 0.754 (0.123); creatinine 0.942 (0.05), 0.934 (0.056), and 0.814 (0.057); amino acids 0.996 (0.344), 0.904 (0.196), and 0.778 (0.18). For small unbound solutes, there is a decrease in clearance of 6% from CVV hemofiltration to CVV hemodiafiltration and a further decrease of 14% from hemodiafiltration to hemodialysis. The effluent:plasma ratio for vancomycin during CVV hemofiltration was 0.739 (0.082), CVV hemodiafiltration 0.643(0.063), and CVV hemodialysis 0.509 (0.081), corresponding to a decrease of 30% from CVV hemofiltration to CVV hemodialysis. The effluent:plasma ratio for phenytoin was 0.302 (0.028) during CVV hemofiltration and was not significantly different during CVV hemodiafiltration or CVV hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Which bicarbonate concentration is adequate to lactate-buffered substitution fluids in maintenance hemofiltration?

We investigated the metabolic and hemodynamic effects of a lactate- and a bicarbonate-buffered (bicarbonate concentration 31.4 mmol/l, type I) hemofiltration substitution fluid in a prospective crossover study of 3 weeks each in 11 patients on maintenance hemofiltration. The lactate-buffered hemofiltration (lactate concentration 34-44.5 mmol/l) lead to hyperlactatemia in all patients without signs of overt lactic acidosis but showed a better control of acid-base balance (pH, base excess, standard bicarbonate) than the type I bicarbonate-buffered fluid (p < 0.01). In 6 patients a higher concentration of bicarbonate- (39.7 mmol/l, type II) buffered fluid was tested. The parameters of acid-base balance showed a better control during type II than during type I bicarbonate hemofiltration and were similar to the lactate-buffered phase. Plasma lactate levels between type I and type II bicarbonate hemofiltration were not different. Also in the steady state phase of the treatment (days 7-9 [week 3]) parameters of acid-base balance rose more to normal values during type II than during lactate-buffered hemofiltration. Hemodynamic parameters showed no differences between the three types of buffers used. Furthermore, also the type II bicarbonate fluid was well tolerated. Bicarbonate in a higher concentration (39.7 mmol/l) proved to be a safe and practical alternative to lactate-buffered hemofiltration.

Acid-Base Equilibrium↗

High resolution gas chromatography mass spectrometry of the methyl esters of organic acids from uremic hemofiltrates.

The organic acid fraction of hemofiltrates was investigated in the form of methylates by glass capillary gas chromatography-mass spectrometry. The pattern obtained is similar to that of urinary organic acid methylates from healthy individuals. A marked difference was noted for N-phenylacetyl-alpha-aminoglutarimide, present in hemofiltrate at levels 50-100 times higher than those in urine. Analysis of hemofiltrate samples taken at different times during a hemofiltration with post-dilution technique revealed that the hemofiltrate concentration of most compounds was drastically reduced the course of the hemofiltration treatment. Compared to the other compounds, the reduction in hemofiltrate concentration of N-phenylacetyl-alpha-aminoglutarimide was extremely rapid.

Adult↗

Disposition of vancomycin during hemofiltration.

The disposition of vancomycin was assessed in five patients receiving hemofiltration after intravenous dosing with an 18 mg/kg dose after a hemofiltration procedure. The serum concentration-time profile was characterized before, during, and after the next hemofiltration procedure. The t 1/2 of vancomycin was 136.0 +/- 27.2 hours (mean +/- SD) before hemofiltration and 4.1 +/- 1.2 during hemofiltration. Approximately 400 mg of vancomycin was recovered in the filtrate and the hemofiltration clearance was 152.6 +/- 21.5 ml/min. A significant relationship was observed between vancomycin clearance and ultrafiltration flow rate (r = 0.9914). A marked rebound in vancomycin serum concentration (52.4% +/- 15.6%) was observed in all patients. Hemofiltration has a significant effect on the disposition of vancomycin. Because of the marked interpatient variability in elimination t 1/2 and the degree and time course of the rebound, an individualized approach to vancomycin therapy in this patient population is recommended.

Aged↗

Hemofiltration as treatment for patients with refractory heart failure.

Hemofiltration was performed in 15 patients with refractory congestive heart failure. All of these patients had oliguria, although intensive treatment with diuretics, digitalis, vasodilators, and catecholamines was prescribed. Hemofiltration was performed under hemodynamic monitoring in 14 patients. The water removal by hemofiltration decreased pulmonary arterial pressure, pulmonary capillary wedge pressure and right atrial pressure. Despite these hemodynamic improvements, nine patients (60%) died within one month after the start of hemofiltration; the causes were fatal arrhythmia in three, renal failure in two, sepsis in one and irreversible cardiogenic shock in three. Oliguria for over 15 h or a serum creatinine concentration of more than 4.0 mg/dl at the start of hemofiltration related to poor prognosis. In view of these results, hemofiltration for refractory heart failure should be started earlier and performed carefully in order to avoid arrhythmia, cardiogenic shock, and other complications.

Adult↗