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Hemofilter clotting is a major challenge in continuous venovenous hemofiltration (CVVH). Experts recommend keeping filtration fraction, the fraction of plasma water that is removed by ultrafiltration, below 20% or 30% to avoid clotting ([1][1]). Clotting risk is believed to markedly increase when

The optimal dosing regimen of vancomycin for critically ill patients receiving continuous venovenous hemofiltration (CVVH) remains controversial, not to mention those with concurrent use of extracorporeal membrane oxygenation (ECMO). We aimed to determine if a new dosing regimen can achieve the target vancomycin trough concentration (Ctrough) of 10-20 mcg/mL in patients receiving CVVH with or without ECMO.We conducted a retrospective study by enrolling patients who received vancomycin while undergoing CVVH. The vancomycin dosing regimen was 15-20 mg/kg as the loading dose and 7.5 mg/kg every 12 hours as the maintenance doses. Serum concentration was determined after at least 4 doses of vancomycin were given.A total of 38 patients were enrolled, of which 21 were also on ECMO. The ultrafiltration rate of CVVH was 30.6 ± 5.5 mL·kg·h with the Ctrough of 14.7 ± 3.5 mcg/mL. Ctrough was within the target range in 82% of patients. All CVVH-only patients achieved the target concentration, whereas only 76.2% of those with concurrent ECMO did (P = 0.031).All patients receiving CVVH achieved the target Ctrough with this new dosing regimen, but those with concurrent ECMO did not. Ctrough must be more closely monitored in patients using ECMO simultaneously.

Voriconazole represents an essential part of antimicrobial therapy in critically ill patients. The aim of this study was to exclude a significant alteration in voriconazole pharmacokinetics in critically ill patients undergoing continuous venovenous hemofiltration (CVVH).Six patients dependent on CVVH with evidence of an invasive mycotic infection treated with intravenous voriconazole at the standard dosing regimen were investigated. The total serum concentration of voriconazole in arterial blood and the concentration in ultrafiltrate were measured by reverse-phase high-performance liquid chromatography with ultraviolet detection. The authors profiled a 5-point pharmacokinetic concentration-time curve during the 12-hour standard maintenance dosing interval and derived the basic pharmacokinetic parameters.The serum voriconazole concentration did not decrease1.0 mg/L at any time point, and the mean was 4.3 ± 2.6 mg/L and the median (range) 3.6 (9.0) mg/L. The sieving coefficient of the drug did not exceed 0.30 in any patient (0.22 ± 0.08). The mean serum AUC0-12, the mean total clearance, and the mean clearance via CVVH were 53.52 ± 29.97 mg·h/L [the median (range) of 57.74 (62.34) mg·h/L], 0.11 ± 0.07 L·h-1·kg-1, and 0.007 ± 0.003 L·h-1·kg-1, respectively. The clearance by the CVVH method ranged from 4% to 20% of the total drug clearance. The disposition of voriconazole was not compromised. The mean elimination half-life was 27.58 ± 35.82 hours [the median of 13.10 (92.21) hours], and the mean distribution volume value was 3.28 ± 3.10 L/kg [the median of 2.01 (8.10) L/kg]. Marked variability in serum concentrations, elimination half-life, distribution volume, and total clearance was seen. Half of the patients showed some drug accumulation.The clearance of voriconazole by CVVH is not clinically significant. In view of this finding, voriconazole dose adjustment in patients undergoing the standard method of CVVH is not required. However, the observed potential for an unpredictable voriconazole accumulation suggests the usefulness for monitoring its levels in critically ill patients.

We conducted a prospective observational study to assess the efficacy of continuous venovenous hemofiltration (CVVH) with no anticoagulation. A standard anticoagulation protocol for CVVH, which prescribed no anticoagulation for patients at risk of bleeding, was applied to 48 critically ill patients treated with CVVH. Circuit life was prospectively observed, and the following data were obtained for each circuit: heparin use and dose, protamine use, daily prothrombin time-international normalized ratio, activated partial thromboplastin time, and platelet count. Out of 300 consecutive circuits, 143 (47.6%) received no anticoagulation, 31 (10.3%) received regional anticoagulation, and 126 received low dose heparin. No patients experienced bleeding complications secondary to CVVH. Platelet count was significantly lower in the no anticoagulation group (73 x 10(3)/microl) compared with the low dose heparin group (119 x 10(3)/microl) and the protamine group (104 x 10(3)/microl) (p < 0.01 for both comparisons). There was no significant difference in mean circuit life among the three groups (heparin, 20.9 hours; no anticoagulation, 19.3 hours; protamine, 21.2 hours; not significant). In conclusion, for a group of patients deemed to be at risk of bleeding, CVVH without anticoagulation achieved an acceptable circuit life, which was similar to that obtained in other patients with low dose heparin anticoagulation or regional anticoagulation with heparin/protamine.

Continuous renal replacement therapy (CRRT), such as continuous venovenous hemofiltration, has theoretical advantages over intermittent hemodialysis (IHD) that are related to cardiorespiratory stability, metabolic control, and fluid balance allowing nutritional supplementation. However, retrospective and controlled studies fail to show these advantages because of comorbidity associated with triage to CRRT. To compare outcomes using IHD versus CRRT, we applied published risk stratification models (Cleveland Clinic Foundation, Lohr index, and APACHE II) to the 349 patients with acute renal failure requiring renal replacement therapy at University of Michigan over the 2 year period including 1995 and 1996. The Cleveland Clinic Foundation model best predicted overall mortality, but our CRRT patients had excess, unpredicted mortality that was particularly prominent in the lower risk categories. The Lohr clinical score predicted mortality less accurately but also was associated with higher, unpredicted mortality at lower risk scores among the CRRT patients. APACHE II scores did not predict mortality very well among IHD, CRRT, or the combined group of patients. We conclude that the need for CRRT itself predicts mortality over and above that included in published risk models. Either CRRT is associated with some unidentified morbidity (e.g., treatment associated infection) or, more likely, triage to CRRT is associated with as yet unspecified comorbidity not detected in existing risk stratification schemes. It will be important to address these issues in any future studies evaluating outcome or comparing renal replacement therapy modalities among patients with severe acute renal failure.

To evaluate continuous venovenous hemofiltration and hemodiafiltration with a conventional infusion pump in a pediatric sized animal model. Fourteen Maryland pigs weighing 8 to 13 kg were used. A conventional infusion pump (IVAC 571), with a flow of 900 ml/h and a pediatric hemofilter of 0.22 m2 were used. Ringer's solution was used for both the dialysate and the replacement fluid. Each experiment included 1 hour of hemofiltration and 1 hour of hemodiafiltration. Heart rate, arterial blood pressure, pH, Na, K, Cl, and hematocrit were measured every 30 minutes. Mean ultrafiltrate flow was 249.7 +/- 100.3 ml/hr, 240.5 +/- 109.5 ml/hr with hemofiltration and 271 +/- 101.1 ml/hr with hemodiafiltration, the differences not being significant. No significant changes were seen in heart rate, blood pressure, hematocrit, electrolytes, or pH. Pressure in the circuit rose from 107.7 +/- 70.3 mm Hg at the beginning of the experiment to 234.2 +/- 118.1 mm Hg after 2 hours (p < 0.05). The technique was well tolerated by all the pigs. Continuous venovenous hemofiltration and hemodiafiltration with a conventional infusion pump is a possible alternative to conventional methods of extrarenal replacement therapy in neonates and infants.

The study assessed the removal of mycophenolic acid (MPA) and its major glucuronide metabolite (MPAG) during continuous venovenous hemofiltration (CVVHF) and continuous venovenous hemodiafiltration (CVVHDF) in 4 heart transplant recipients treated for at least 6 days with mycophenolate mofetil (MMF) in addition to cyclosporine and corticosteroids. The sieving coefficient ranged from 0.02 to 0.04 for MPA and from 0.15 to 0.33 for MPAG. The clearance of MPAG by CVVHDF or CVVHF ranged from 7.52 mL/min to 19.45 mL/min, and that of MPA was lower than 2.28 mL/min, with no significant difference between the two continuous replacement therapies. Whereas MPA percentage recovered by hour following CVVHDF or CVVHF was negligible, the percentage of MPAG represents up to 12.9% of the administered dose. A relevant decrease in the free fraction of MPA and MPAG was observed after continuous renal replacement therapy (CRRT). These preliminary results demonstrate that MPAG is able to permeate the filter. In light of the alteration in protein binding following CRRT and the competition between MPA and MPAG to albumin site, drug monitoring of MPA and MPAG in patients undergoing CVVHDF or CVVHF may be suggested. Moreover, monitoring of free MPA may be of interest for these patients.

OBJECTIVE To compare a standard and an experimental method of rewarming in 5-wk-old goats with induced moderate hypothermia. DESIGN Hypothermia was induced in ten juvenile Nubian goats. Five goats were randomly assigned to be rewarmed using standard techniques, and five were assigned to the experimental rewarming technique of a modified continuous venovenous hemofiltration circuit. SETTING Animal research facility, Greenville Hospital System/Clemson University Biomedical Cooperative, Clemson, S.C. SUBJECTS Ten 5-wk-old goats. INTERVENTIONS Hypothermia to a body temperature of 29.4 degrees C was induced in the goats. Each of the control group of five goats was rewarmed using standard methods. Each of the experimental group of five goats was rewarmed using a modified continuous venovenous hemofiltration circuit. MEASUREMENTS AND MAIN RESULTS At 2 hrs, the median temperature increase in the experimental group was 6.5 degrees C, compared with an increase of only 1.5 degrees C in the control group (p=.02). The mean increase in core body temperature over time (from baseline to 150 mins) was also significantly greater in the experimental group (p=.006). CONCLUSIONS The use of a modified continuous venovenous hemofiltration circuit for rewarming in a juvenile goat model after induction of moderate hypothermia is more effective than are standard methods.

To evaluate the effect of continuous venovenous hemofiltration with dialysis on lactate elimination by critically ill patients.Prospective, clinical study.Surgical intensive care unit of a university hospital.Ten critically ill patients with acute renal failure and stable blood lactate concentrations.Two-stage investigation: a) measurement of lactate concentrations in samples of serum and ultradiafiltrate from patients receiving continuous venovenous hemofiltration with dialysis to calculate lactate clearance by the hemofilter; b) evaluation of total plasma lactate clearance by infusing sodium L-lactate (1 mmol/kg of body weight) over 15 mins.Arterial lactate concentration was determined before, during, and after the infusion. Lactate elimination variables were calculated from the plasma curve using model-independent and model-dependent estimates (by software). At the end of the infusion, median blood lactate concentration increased from 1.4 mmol/L (range 0.8 to 2.6) to 4.8 mmol/L (range 2.4 to 5.7) and returned to 1.6 mmol/L (range 0.9 to 3.4) 60 mins later. The median total plasma lactate clearance was 1379 mL/min (range 753.7 to 1880.7) and the median filter lactate clearance was 24.2 mL/min (range 7.1 to 35.6). Thus, filter lactate clearance accounted for3% of total lactate clearance.Continuous venovenous hemofiltration with dialysis cannot mask lactate overproduction, and its blood concentration remains a reliable marker of tissue oxygenation in patients receiving this renal replacement technique.

We report a 48-year-old man presenting with refractory hyperammonemia after orthotopic liver transplantation. On investigation he was found to have acquired hepatic glutamine synthetase deficiency, a rare condition that occurs after organ transplantations. The patient was started on continuous venovenous hemofiltration treatment, but the hyperammonemia did not respond. The patient was then subjected to molecular adsorption recirculation system (MARS) therapy and the ammonia level gradually improved with successive treatments. In conclusion, the response was unlikely due to the hemofiltration component of MARS alone but more probably due to the removal of putative albumin-bound toxin by the adsorption circuit that had ameliorated the internal milieu of the graft and reversed the enzyme deficiency.

Continuous renal replacement therapy (CRRT) has become a popular treatment modality but may have the disadvantage of producing substantial protein losses. With use of the Biuret method, a relatively insensitive assay, dialysate/ultrafiltrate protein losses have been reported to be as high as 1.3 g/L. With CRRT outputs of up to 50 L/day, these values would amount to protein losses of up to 65 g/day. In this study, dialysate/ultrafiltrate protein losses were reanalyzed by using a highly sensitive microprotein reagent (pyrogallol red) considered to be more accurate than previously available methods. Twenty-two dialysate/ultrafiltrate samples were obtained from Amicon-20 Diafilters or Fresenius F-80 dialyzers during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodialysis/hemodiafiltration (CVVHD/F). Mean hourly output for all treatments was 1637 +/- 694 mL/h. Mean protein concentration for all 22 dialysate/ultrafiltrate samples was 4.2 +/- 4.0 mg/dL. Mean dialysate/ultrafiltrate protein concentrations were similar for the Amicon 20 (3.4 +/- 4.4 mg/dL, N = 9) and the Fresenius F-80 (4.7 +/- 3.9 mg/dL, N = 13) (P = not significant). Protein losses were higher during convection-based CVVH (6.0 +/- 5.1 mg/dL, N = 10; range, 1 to 15 mg/dL) than during the mixed convection and diffusion-based CVVHD/F (2.7 +/- 1.9 mg/dL, N = 12; range, 0 to 6 mg/dL) (P = 0.049). Mean serum protein concentration at the time of dialysate/ultrafiltrate sampling was 4.7 +/- 1.8 g/dL. There was a weak, but statistically significant correlation between the dialysate/ultrafiltrate samples and the corresponding value for serum protein (r = 0.468, P < 0.03). It was concluded that protein losses during CRRT treatments are substantially lower than previously reported, are dependent on the serum protein concentration and the predominant nature of solute removal (convection versus diffusion), and can vary between 1.2 and 7.5 g/day.

In this issue of JASN , Tumlin et al. [1][1] report results of a revolutionary phase 2 multicenter, randomized clinical trial comparing 72 h of continuous venovenous hemofiltration (CVVH) with and without a bioartificial kidney (referred to as a renal tubule assist device [RAD]) in the management of