Removal of branched-chain amino acids by peritoneal dialysis, continuous arteriovenous hemofiltration, and continuous arteriovenous hemodialysis in rabbits: implications for maple syrup urine disease treatment

Renal elimination of branched-chain amino acids (BCAA) is low in maple syrup urine disease, and peritoneal dialysis may be required in an emergency situation for removal of the three BCAA (leucine, isoleucine, and valine). However, failures of BCAA removal by peritoneal dialysis have been reported, especially in neonates. Therefore, we tested the ability of continuous hemofiltration and continuous hemodialysis to remove BCAA as compared with peritoneal dialysis. Experiments were conducted in 15 anesthetized adult rabbits infused with leucine, isoleucine, and valine. In group 1 (n = 7), peritoneal dialysis (dialysate = 75 mL/kg) and continuous arteriovenous hemofiltration with a polysulfone 800-cm2 hemofilter were simultaneously performed during 40 min. In group 2 (n = 8), continuous arteriovenous hemofiltration and continuous arteriovenous hemodialysis were successively performed during 30 min in a randomly settled order. Animals had high and stable BCAA plasma levels during the experimental procedure. As compared with peritoneal dialysis, continuous arteriovenous hemofiltration constantly showed a significant increase in clearances of leucine (+159 +/- 99%), isoleucine (+176 +/- 107%), and valine (+125 +/- 76%). In comparison with continuous arteriovenous hemofiltration, continuous arteriovenous hemodialysis constantly showed significant increased values in clearances of leucine (+90 +/- 43%), isoleucine (+95 +/- 45%), and valine (+99 +/- 52%). During continuous arteriovenous hemofiltration and continuous arteriovenous hemodialysis, a significant positive correlation was established between urea clearance and clearances of leucine (r2 = 0.953 and 0.927, respectively), isoleucine (r2 = 0.948 and 0.910, respectively), and valine (r2 = 0.953 and 0.864, respectively).     

Pharmacokinetics of imipenem-cilastatin in critically ill patients undergoing continuous venovenous hemofiltration

The pharmacokinetics of imipenem-cilastatin were investigated in 12 critically ill patients with acute renal failure (ARF) managed by continuous veno-venous hemofiltration (CVVH) while receiving a fixed combination of 500 mg of imipenem-cilastatin intravenously three or four times daily. No adverse drug reactions were observed. Plasma and hemofiltrate samples were taken at specified times during one dosing interval, and the concentrations of imipenem and cilastatin were determined by high-performance liquid chromatography. Pharmacokinetic variables were calculated by a first-order, two-compartment pharmacokinetic model for both substances. Total clearances of imipenem and cilastatin (mean +/- standard deviations) were 122.2 +/- 28.6 and 29.2 +/- 13.7 ml/min, respectively, with hemofiltration clearances of 22.9 +/- 2.5 and 16.1 +/- 3.1 ml/min, respectively, and nonrenal, nonhemofiltration clearances of 90.8 +/- 26.3 and 13.2 +/- 13.9 ml/min, respectively. Mean imipenem dosage requirements were approximately 2,000 mg/24 h (2,111.8 +/- 493.4 mg/24 h). They were calculated in order to achieve an average steady-state concentration of 12 mg/liter to ensure that concentrations in plasma exceeded the MICs at which 90% of intermediately resistent bacteria are inhibited (8 mg/liter) during the majority of the dosing interval. By contrast, the recommended dosage for patients with end-stage renal failure (ESRF) and infections caused by intermediately resistant bacteria is 1,000 mg/24 h. This remarkable difference may be due (i) to differences in the nonrenal clearance of imipenem between patients with ARF and ESRF and (ii) to the additional clearance by the hemofilter. Since the total clearance of cilastatin was low, marked accumulation occurred, and this was particularly pronounced in patients with additional liver dysfunction. Thus, in patients with ARF managed by CVVH, rather high imipenem doses are required, and these inevitably result in a marked accumulation of cilastatin. The doses of imipenem recommended for patients with ESRF, however, will lead to underdosing and inadequate antibiotic therapy.     

Evaluation of myoglobin clearance during continuous hemofiltration in a swine model of acute renal failure

Rhabdomyolysis is characterized by extensive damage of striated muscle, while the major complication of this disease is the development of acute myoglobinuric renal failure. Although first described more than five decades ago very little has changed with regard to the management of this entity as conventional hemodialysis has not been shown to effect myoglobin elimination. However, continuous arteriovenous hemofiltration (CAVH) offers an alternative to conventional hemodialysis as this procedure is more effective particularly for removing larger molecular weight substances such as myoglobin. We studied the effect of CAVH on myoglobin clearance in an animal model of acute myoglobinuric renal failure. Swine (n = 6) were given 4 grams of equine myoglobin intravenously and underwent the CAVH procedure for six hours each. Once the filtering process was initiated there was a rapid and sustained production of ultrafiltrate. The clearance of myoglobin via the hemofilter was 2.05 +/- 1.48 L/day. The amount of myoglobin excreted in the ultrafiltrate over the six hour filtering period was 410 +/- 234 mg which accounts for 10.27 +/- 5.85 percent of the administered dose. Based on these findings, it appears that the hemofiltration system is a viable option for the removal of myoglobin from the systemic circulation.     

A comparison of molecular clearance rates during continuous hemofiltration and hemodialysis with a novel volumetric continuous renal replacement system

We developed a continuous, volumetrically controlled veno-venous renal replacement system that can be operated in filtration or dialysis modes. We compared the clearances of substances with a range of molecular weights (MW) in each mode. Ten patients with acute renal failure underwent serial postdilutional hemofiltration and hemodialysis, for 30 min each, in sequence and in randomized order. All were receiving vancomycin for concurrent sepsis. The system incorporated a Filtral 10 AN69 artificial kidney; blood flow rate was 200 ml/min, and dialysate/filtrate flow rate was 25 ml/min. Sieving (SC) and diffusion (DC) co-efficients, for hemofiltration and hemodialysis, respectively, were identical for urea (MW 60; 1.01 +/- 0.05 vs 1.01 +/- 0.07) and creatinine (MW 113; 1.00 +/- 0.09 vs 1.01 +/- 0.06), and clearance equated with dialysate/filtrate flow. There was a modest difference in uric acid clearance (MW 168; SC 1.01 +/- 0.04 vs DC 0.97 +/- 0.04; p < 0.05). Vancomycin (MW 1,800) removal was 19% greater during filtration compared with dialysis (SC 0.87 +/- 0.10 vs DC 0.74 +/- 0.06; p < 0.01). For small solutes, the two modalities were equivalent. Vancomycin clearance was appreciably greater with hemofiltration, which is consistent with a greater potential for convection-based therapy in the removal of uremic and other middle molecules.     

Achievements and new directions in continuous renal replacement therapies

The evolution of renal replacement therapy has permitted the treatment of critically ill patients with acute renal failure. In intensive care settings, continuous renal replacement therapies have been shown to be better tolerated and clinically useful. Continuous hemofiltration is now performed with blood pumps and double-lumen venous catheters, thus avoiding the complications found in previous arteriovenous treatments. The use of countercurrent dialysate flow has overcome problems related to low treatment efficiency. High clearances can now be obtained during continuous hemodialysis or hemodiafiltration, and adequate blood purification can be achieved even in severely catabolic patients. New replacement solutions allow for a more effective correction of acidosis and electrolyte imbalances. Finally, newly designed machines permit continuous therapies while minimizing staff workload. Continuous therapies are today moving toward newer indications and applications. The ability to remove proinflammatory substances by filtration and/or adsorption has opened a series of potential indications. The concept that renal support and protection take place during hemofiltration suggests that very early use of this technique is desirable, even before the onset of oliguria or azotemia.     

Effects of ultrafiltration on solute clearances in hollow fiber artificial kidneys

Although solute clearances in artificial kidney coils increase with ultrafiltration (UF), we have previously shown that increases are usually less than UF rate (most likely because of decreases in diffusive transport with UF coils and, for larger solutes, molecular sieving). The present studies demonstrate the effects of UF on clearances of Na and bromsulphalein (BSP) (mol. wt. 838) in hollow fiber dialyzers. Clearances were measured at increasing transmembrane hydrostatic pressures at perfusion rates of 200 and 500 ml. per minute. Fractions of total clearance attributable to diffusion as compared to solvent drag forces were calculated. Sieving coefficients were determined in studies where diffusion was minimized and clearance was primarily by solvent drag. Clearance increases were less than UF rate only for BSP; molecular sieving most likely accounts for the difference at high perfusion rates. Only at 200 ml. per minute was slight decrease of diffusion with UF suggested. Thus, in contrast to coils, there is minimal or no decrease in diffusion with UF in hollow fiber dialyzers.     

Low-flow membrane oxygenation of blood in patients with diffuse purulent peritonitis

Small-flow membranous oxygenation of the blood was used in 45 patients with peritonitis in the multiple organ failure phase. In ten cases blood oxygenation was combined with hemofiltration. MOCT 19-03 (Kvant Research and Production Unit) and Gambro FH hemofilters (Sweden) were employed. Combination of small-flow membranous oxygenation of the blood combined with hemofiltration appreciably improved the oxygen-transporting function of the blood in adult patients with the respiratory distress syndrome, which was due to mutual potentiation of the two methods' effects. Small-flow membraneous oxygenation alone improved cellular immunity and decreased the laboratory manifestations of endogenous intoxication due to biotransformation of toxic products.     

A recurrent glycine substitution mutation, G2043R, in the type VII collagen gene (COL7A1) in dominant dystrophic epidermolysis bullosa

OBJECTIVE: To evaluate the effect of hemofilter pore size on the efficacy of continuous arteriovenous hemofiltration (CAVH) in improving morbidity and mortality in an immature swine model of Staphylococcus aureus-induced septicemia. DESIGN: Prospective, randomized study with age-matched controls. SETTING: Biomedical research facility. SUBJECTS: Fourteen 4 to 8-wk-old, weaned Poland-China swine, weighing 5 to 10 kg. INTERVENTIONS: Spontaneously breathing, ketamine-sedated swine (4 to 8 wks of age) were given an intravenous lethal dose of live S. aureus. Animals were then filtered with either a 50-kilodalton (kD) pore size filter (control) or a 100-kD pore size filter (experimental). No animals received antibiotics. MEASUREMENTS AND MAIN RESULTS: Physiologic, biochemical, and hematologic parameters were measured in all animals every 1 to 3 hrs. Animals were monitored continuously and survival time (hr) was recorded (permanent survival = 168 hrs/7 days). Animals filtered with the 100-kD filter survived significantly longer than control animals (103 +/- 18 [SEM] vs. 56 +/- 9 hrs). The 100-kD-filtered group had one permanent survivor (168 hrs). Protein concentration of the ultrafiltrate obtained from the 100-kD-filtered animals was eight-fold higher than control ultrafiltrate. The protein removed did not contain a high percentage of albumin (as determined by autoanalyzer methods). No significant differences were seen in any of the other measured parameters. CONCLUSIONS: CAVH significantly improved survival in swine with S. aureus-induced sepsis. The superior performance of the 100-kD filter vs. the 50-kD filter suggests that higher molecular weight mediators that are not removed efficiently by the 50-kD filter may be responsible for the morbidity and mortality seen in this model of sepsis. These mediators may be removed in greater proportion by our customized (100-kD pore size) filter.     

The benefits of daily hemofiltration in the management of anuria in patients with severe heart failure (NYHA IV)

The aim of the study was to evaluate the daily use of hemofiltration in patients with anuria and heart failure IV NYHA, and not reacting to pharmacological therapy. Patients were submitted to daily hemofiltration therapy considering: the dry weight, BP, pO2, creatininemia, natriemia, kaliemia, and magnesiemia. Every month an echocardiogram and an ECG were done. Two patients passed from IV to III class NYHA, with a reduction in the telediastolic diameter and improvement in the ejection fraction and in the cardiothoracic index. In NYHA IV patients, it was possible to obtain a very good improvement in the clinical situation, echocardiographic parameters and survival with daily hemofiltration.     

The role of extraneuronal amine transport systems for the removal of extracellular catecholamines in the rabbit

As selective inhibitors of the extraneuronal monoamine uptake system (uptake2) suitable for in-vivo studies were not available, the question of whether uptake2 plays a definite role in vivo is largely unresolved. We attempted to resolve the question by using 1,1'-diisopropyl-2,4'-cyanine iodide (disprocynium24), a novel agent that blocks uptake2 in vitro with high potency. Anaesthetized rabbits were infused with 3H-labelled noradrenaline, adrenaline and dopamine, and catecholamine plasma clearances as well as rates of spillover of endogenous catecholamines into plasma were measured before and during treatment with either disprocynium24 or vehicle. Four groups of animals were studied: group I, no further treatment: group II, monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) inhibited; group III, neuronal uptake (uptake1) inhibited; group IV, uptake1 as well as MAO and COMT inhibited. Disprocynium24 (270 nmol kg-1 i.v. followed by an i.v. infusion of 80 nmol kg-1 min-1) did not alter heart rate and mean arterial blood pressure, but increased cardiac output by 22% and decreased the total peripheral vascular resistance by 16% with no difference between groups. When compared with vehicle controls, catecholamine clearances (normalized for the cardiac output of plasma) were decreased and spillover rates increased in response to disprocynium24. Although there were statistically significant between-group differences in baseline clearances (which decreased in the order: group I > group II > group III > group IV), the drug-induced clearance reductions relative to vehicle controls were similar in groups I to IV and amounted to 29-38% for noradrenaline, 22-31% for adrenaline and 16-22% for dopamine. Hence, there was still a significant % reduction in catecholamine clearances even after the combined inhibition of MAO and COMT, and there was no increase in the % reduction of clearances after inhibition of uptake1. Noradrenaline spillover increased in response to disprocynium24 in all four groups by 1.6- to 1.9-fold, whereas a 1.5- to 2.0-fold increase in adrenaline and dopamine spillover was observed in groups II and IV only. The results indicate that disprocynium24 interferes with the removal of circulating catecholamines not only by inhibiting uptake2, but also by inhibiting related organic cation transporters. As disprocynium24 increased the spillover of endogenous catecholamines into plasma even after inhibition of MAO and COMT, organic cation transporters may also be involved in the removal of endogenous catecholamines before they enter the circulation.     

Decision analysis of prophylactic mastectomy and oophorectomy in BRCA1-positive or BRCA2-positive patients

BACKGROUND: Hemodialysis using high flux membranes today is a commonly used therapy. The primary advantage is the larger spectrum of molecules removed with these membranes, and the mechanism of removal is in part due to a phenomenon of filtration and backfiltration along the length of the hollow fibers. We hypothesized that increasing the filtration and backfiltration fluxes by modifying the structure of the dialyzer could enhance the convective transport of various solutes. METHODS: A modified high flux dialyzer was compared to the standard model in terms of pressure profiles, filtration-backfiltration rates and solute clearances. The modification consisted on the placement of a O-ring around the fiber bundle to create a resistance for the flow of the dialysis solution external to the fibers. The study on filtration fluxes was carried out using a scintigraphic method previously described, and solute clearances were studied during ultrafiltration-controlled hemodialysis sessions. RESULTS: Utilizing a net filtration condition proximal to zero, the rates of proximal filtration and distal backfiltration in the experimental dialyzer were significantly enhanced in comparison with the standard dialyzer. The pressure drop in the dialysate compartment could be increased significantly, thus permitting an increase in the positive transmembrane pressure in the first half of the dialyzer and a parallel increase in the negative transmembrane pressure in the second half of the dialyzer. This resulted in a significant enhancement of the convective transport of middle-large solutes as demonstrated by the increase in vitamin B12 and inulin clearances. CONCLUSIONS: This approach suggests that changes in design of the dialyzer may affect its performance. The use of internal filtration is suggested to improve convection and dialyzer efficiency for larger solutes without the requirement for high volumes of replacement fluid, as is the case for current hemodiafiltration techniques.     

Pharmacokinetics of anti-infective agents in continuous hemofiltration

NEW ASSIST TECHNIQUES: Continuous hemofiltration and hemodiafiltration are two new renal replacement techniques offering continuous electrolyte regulation and hemodynamic stability in patients with multiple organ failure. These continuous techniques are being used more and more in intensive care, especially as renal replacement in case of septic shock, and probably have the additional benefit of removing toxins. EFFECT ON ANTIMICROBIALS: Little is known about the removal of drugs and in particular antimicrobials during continuous hemofiltration although both the specific pharmacokinetics of each drug and the patient's particular clinical situation plays an important role. DRUG DOSING: In the intensive care unit, knowledge of the effect of continuous hemofiltration on drug removal and pharmacokinetic profile is crucial for practical management due to the importance of avoiding infratherapeutic serum levels, or inversely toxic levels, in these seriously ill patients. Titration equations provided in most of the recent articles are helpful but usually based on a large number of parameters not always easily available in clinical practice. An approximation of the dose can be estimated from dosing guides for continuous dialysis which can be useful in avoiding poorly adapted dosage.     

Regional chemotherapy with hemofiltration: a rationale for a different treatment approach to advanced pancreatic cancer

BACKGROUND/AIMS: Since 1989, thirty-two patients with advanced, intra-abdominal pancreatic cancer were treated with regional chemotherapy in combination with extracorporeal hemofiltration. PATIENTS and METHODS: Eleven patients had locally advanced, unresectable cancer, and ten had advanced disease with liver metastases. Three patients had developed liver metastases following a radical resection. One patient had an incomplete resection with local residual disease, and a second had developed a local recurrence after a radical resection. One patient had an unresectable cystadenocarcinoma. Five patients had failed prior systemic therapies for unresectable pancreatic cancer. The patients underwent 85 treatments with regional chemotherapy plus hemofiltration, an average of 2.7 treatments per patient. RESULTS: Of 21 patients treated primarily with regional chemotherapy plus hemofiltration, there were two complete responses (9%) and eight partial responses (38%), an overall total response rate of 47%. The average survival for patients with Stage II/III localized, unresectable disease is 13 months and that for Stage IV unresectable disease with liver metastases is 9 months. CONCLUSIONS: Patients with recurrent disease following a radical resection or having failed prior systemic therapies generally had no benefit from regional chemotherapy plus hemofiltration.     

Estimation of peritoneal mass transport by three-pore model in children

BACKGROUND: Computerized modeling is increasingly used to optimize the efficacy of peritoneal dialysis (PD). The Personal Dialysis Capacity (PDC) test is a new tool to model PD efficacy based on the three-pore model of peritoneal mass transport. We sought to evaluate (i) whether the PDC test is applicable to children on chronic PD, and (ii) whether the physiological mass transport coefficients defined in the three pore model are dependent on age or body size in childhood. METHODS: A validation study was performed in 32 pediatric chronic PD patients. Twenty tests were performed using a standard CAPD regimen, and 22 tests using a simplified automated PD (APD) protocol. Test accuracy and precision were evaluated by comparison of predicted with measured 24-hour dialysate clearances of urea, creatinine, beta2-microglobulin and albumin and ultrafiltration rates. Long-term reproducibility was assessed in 16 patients by repeated clearance studies after a median time interval of 10 weeks. RESULTS: While daily clearances of urea and creatinine were predicted with good precision and accuracy with both test protocols (concordance correlation coefficients 0.90 to 0.98, mean difference predicted-calculated -0.6 to +0.6 ml/min/1.73 m2), ultrafiltration rates were predicted more closely by the APD (r = 0.97) than by the CAPD test (0.80). Middle and large molecule clearances were predicted less precisely in both test settings (r = 0.48 to 0.83). Re-test reproducibility was slightly lower than the predictive precision observed in the original test (r = 0.80 to 0.91). The calculated total peritoneal pore area increased in absolute terms, decreased with body size when standardized to weight, and was independent of body size when normalized to body surface area. The body size-normalized fluid reabsorption rate was slightly increased in young infants compared to older children or adults. CONCLUSIONS: The PDC test permits to model peritoneal solute and water transport with remarkable precision in children of all age groups. While the peritoneal pore area is a linear function of body surface area, fluid reabsorption appears to be slightly increased in young infants.     

The effects of large doses of fentanyl and fentanyl with nitrous oxide on renal function in the dog

Renal effects of large doses of fentanyl (1 mg/kg) were determined in 14 mongrel dogs before and after addition of 50 per cent nitrous oxide. Fentanyl significantly increased urine osmolarity and decreased urine output and free water clearance but did not change inulin or PAH clearances. The arterial blood pressure and cardiac output were significantly decreased after 0.1 mg/kg fentanyl and these changes were then maintained during the remainder of the study period. Addition of nitrous oxide produced no further changes in cardiac output and arterial blood pressure but did increase urine output, PAH, inulin and free water clearances and decreased urine osmolarity. These data demonstrate that high doses of fentanyl have significant antidiuretic properties in the dog and these probably are related to the release of antidiuretic hormone. Our results also indicate that addition of nitrous oxide reverses fentanyl induced antidiuresis.     

Lactogenic hormone signal transduction

Dialyzers are reused in approximately three quarters of the dialysis units in the United States, but the effect of reprocessing on dialyzer performance has not been extensively evaluated. In a crossover study of six chronic hemodialysis patients, we determined urea, creatinine, phosphate, and beta2-microglobulin clearances and dialysate protein loss for two types of low-flux and two types of high-flux dialyzers during use numbers 1, 2, 5, and 15. Dialyzers were reprocessed by an automated machine using Renalin (Renal Systems, Plymouth, MN) as the germicide. Dialyzer arterial and venous blood and dialysate outflow samples were obtained at 5 and 180 minutes of each dialysis session to evaluate solute clearances. Urea, creatinine, and phosphate clearances were calculated using dialysate concentrations, whereas beta2-microglobulin clearance was calculated using plasma concentrations to include its removal by adsorption to the dialysis membrane. There was a trend for urea, creatinine, and phosphate clearances to decrease with reuse for both low-flux and high-flux dialyzers, but these differences were not statistically significant. The clearance of beta2-microglobulin and dialysate total protein concentration was small for low-flux dialyzers; these values were not dependent on reuse. There was a trend for beta2-microglobulin clearance and dialysate total protein concentration to decrease during a dialysis treatment using high-flux dialyzers. More significantly, beta2-microglobulin clearance and dialysate total protein concentration decreased substantially with the reuse of high-flux dialyzers. These observations show that the maintenance of small solute clearances during reuse of high-flux dialyzers does not ensure the maintenance of large solute clearances.     

Determination of zinc in serum, blood, and ultrafiltrate fluid from patients on hemofiltration by graphite furnace/atomic absorption spectroscopy or flow injection analysis/atomic absorption spectroscopy

Two methods were optimized for the determination of zinc in samples of blood, serum, and ultrafiltrate fluid from patients with chronic renal impairment undergoing hemofiltration. In the first procedure, after acid digestion of the samples, Zn in blood and serum is determined by a system coupled to flow injection analysis and atomic absorption spectroscopy. The method is rapid, automated, simple, needs small amounts of sample, and has acceptable analytical characteristics. The analytical characteristics obtained were as follows: determination range of method, 0.05-2.0 ppm of Zn; precision as coefficient of variation (CV), 5.3%; recovery, 95-105%; and detection limit (DL), 0.02 ppm. The second method is optimized for ultrafiltrate fluid because the sensitivity of the first procedure is not suitable for the levels of Zn (ppb or ng/mL) in these samples. The technique chosen was atomic absorption spectroscopy with electrothermal atomization in a graphite furnace. The analytical characteristics obtained were as follows: determination range of method, 0.3-2.0 ppb Zn; CV, 5.7%; recovery, 93-107%; and DL, 0.12 ppb. The methods were used to determine zinc in samples of blood, serum, and ultrafiltrate fluid from 5 patients with chronic renal impairment undergoing hemofiltration to discover whether there were significant differences in the zinc contents of blood, serum, and ultrafiltrate fluid after the hemofiltration process. An analysis of variance of the experimental data obtained from a randomly selected group of 5 patients showed that zinc concentrations in the ultrafiltrate fluid, venous blood, and venous serum do not vary during hemofiltration (p < 0.05), whereas in arterial blood and serum, the time factor has a significant effect.     

The optimization of instrumental hemofiltration

47 hemofiltration procedures were performed in 10 patients. A self-made balancer based on the volumic hydrodynamics dependent on substitute from filtrate was used. An APD-02 peritoneal dialysis machine served the source of the substitute. It provided change of the concentration and was used for prophylaxis of osmodisturbances, massive dehydration and for obtaining bicarbonate substitute. The technology for F-60 cartridges reuse has been elaborated and tested. One of the patients received the isolated hemofiltration programme for more than 2 months. Antiuremic efficacy of hemofiltration was studied.     

PET and CBF studies of chronic hydrocephalus: a contribution to surgical indication and prognosis

The management of acute myoglobinuric renal failure, the major complication of rhabdomyolysis, continues to be a treatment dilemma for the clinician as limited therapeutic options are available. Previously, we have demonstrated that continuous arteriovenous hemofiltration (CAVH) is an effective technique for removing myoglobin in an animal model. In the present study, swine were administered four grams of equine myoglobin intravenously and underwent the continuous veno-venous hemofiltration (CVVH) procedure for six hours each. Animals were studied in each of the following groups: CVVH at a pump rate 100 ml/minute, CVVH at a pump rate 200 ml/minute and CVVH at a pump rate 100 ml/minute plus dialysis at a dialysate flow rate of one Liter/h. Once the filtering process was initiated there was a rapid and sustained production of ultrafiltrate in all groups. The amount of myoglobin excreted in the ultrafiltrate over the six-hour filtering period was 688, 948 and 570 mg which corresponded to 17, 24 and 14 percent of the administered dose, respectively, for the three treatments. In comparison to previous CAVH experiments, CVVH removed more circulating myoglobin and the addition of the dialysis component did not appear to improve removal. Based on these findings, it appears that the CVVH hemofiltration system is a viable option for the removal of systemic myoglobin.     

Ogilvie''s syndrome: a new approach to an old problem

The effect of glucose infusion on renal handling of purine bases and oxypurinol was examined in 6 normal subjects. Five hundred milliliters of 1.1 M glucose solution were administered intravenously in 1 h. Fractional clearances of uric acid, xanthine and oxypurinol were significantly increased during glucose infusion, but that of hypoxanthine was not changed, while a 1-hour infusion of 500 ml of 1.1 M mannitol had no effect on the fractional clearances of purine bases and oxypurinol. These data indicate that the effect of glucose infusion on the renal clearances of uric acid, xanthine and oxypurinol was not related to osmotic diuresis but induced by glycosuria and/or hyperglycemia. Accordingly, the glycosuria- and/or hyperglycemia-induced decrease in the biological half-life of oxypurinol must be considered in the administration of allopurinol to gouty patients with uncontrolled diabetes mellitus.