Continuous venovenous hemodiafiltration trace element clearance in pediatric patients: a case series.

Continuous renal replacement therapy (CRRT) is used to treat critically ill children with acute kidney injury. The effect of CRRT on trace element clearance is poorly characterized. The purpose of this study was to quantify the transmembrane clearance of chromium, copper, manganese, selenium and zinc during continuous venovenous hemodiafiltration (CVVHDF). The transmembrane clearance of trace elements was assessed prospectively in five critically ill children receiving CVVHDF at the pediatric intensive care unit of a tertiary care university hospital. Pre-filter blood and effluent samples were measured for trace element concentrations. Transmembrane clearance of trace elements was calculated, and daily loss of each trace element was determined. Daily trace element loss via CVVHDF was compared with daily standard supplementation of trace elements in pediatric parenteral nutrition. Five patients (age range 23 months to 15 years) with a body weight range of 10.5-53 kg completed the study. The median transmembrane clearance of chromium, copper, manganese, selenium and zinc during CVVHDF was calculated as 0 ml, 0.59 ml, 2.48 ml, 1.22 ml, and 1.90 ml, respectively, per 1.73 m(2) body surface area per minute. The calculated CVVHDF losses were substantially smaller than the daily parenteral supplementation for all trace elements.

Enhanced clearance of highly protein-bound drugs by albumin-supplemented dialysate during modeled continuous hemodialysis.

BACKGROUND: In 2006, there were 16 796 toxic exposures attributed to valproic acid (VPA), carbamazepine (CBZ) and phenytoin (PHT) reported to the US Toxic Exposure Surveillance System. Of these, 30% (5046) were treated in a health care facility with 12 cases resulting in death. These drugs are highly protein bound and poorly dialyzable; however, it has been suggested that albumin-supplemented dialysate may enhance dialytic clearance. We investigated whether the addition of albumin to dialysate affects dialytic clearance of VPA, CBZ and PHT. METHODS: VPA, CBZ and PHT were added to a bovine blood-based in vitro continuous hemodialysis circuit, which included a polysulfone or an AN69 hemodialyzer. VPA, CBZ and PHT clearances were calculated from spent dialysate and pre-dialyzer plasma concentrations. VPA, CBZ and PHT clearances with control (albumin-free) dialysate were compared to clearances achieved with 2.5% or 5% human albumin-containing dialysate. The influences of blood flow (180 and 270 mL/min) and dialysate flow (1, 2 and 4 L/h) on dialysis clearance were also assessed. RESULTS: The addition of 2.5% albumin to dialysate significantly enhanced dialytic clearance of VPA and CBZ, but not PHT. Use of 5% albumin dialysate further increased VPA and CBZ clearance. Overall, drug clearance was related directly to dialysate flow but independent of blood flow. CONCLUSION: Continuous hemodialysis with albumin-supplemented dialysate significantly enhanced VPA and CBZ, but not PHT, clearance compared to control dialysate. Continuous hemodialysis with albumin-supplemented dialysate may be a promising therapy to enhance dialytic clearance of selected highly protein-bound drugs.

Trace element removal during in vitro and in vivo continuous haemodialysis.

BACKGROUND: Continuous renal replacement therapy (CRRT) increasingly is being used to treat critically ill patients with renal disease. CRRT removes waste products but also nutrients. Our understanding of trace element CRRT clearance has been limited by poor assay sensitivity. The development of inductively coupled plasma mass spectrometry (ICP-MS) allows for the measurement of CRRT trace element removal. METHODS: Continuous venovenous haemodialysis (CVVHD) transmembrane clearances of trace elements and urea were assessed using a bovine blood-based in vitro model using two different haemodialyser types. These findings were validated in 10 critically ill adult patients receiving continuous venovenous haemodiafiltration (CVVHDF). Calculated daily trace element loss was compared with a typical dose of daily trace element supplementation. RESULTS: The mean +/- SD in vitro CVVHD transmembrane clearances (ml/min) for the polysulfone haemodialyser were chromium 0.97 +/- 0.23, copper 0.47 +/- 0.18, manganese 4.6 +/- 3.6, selenium 1.2 +/- 0.63 and zinc 2.3 +/- 0.32 and for the cellulose diacetate haemodialyser chromium 1.54 +/- 0.91, copper 0.21 +/- 0.07, manganese 7.8 +/- 4.1, selenium 0.76 +/- 0.39 and zinc 2.7 +/- 0.37. The in vivo CVVHDF transmembrane clearances (ml/min) were chromium 5.4 +/- 2.4, copper 0.45 +/- 0.33, manganese 1.9 +/- 4.6, selenium 1.6 +/- 1.2, and zinc 4.0 +/- 1.3. CONCLUSION: ICP-MS assays detected the five trace elements in the effluent of CVVHDF patients. Trace element CVVHD transmembrane clearance estimates for our in vitro model were supported by the in vivo CVVHDF findings. Calculated daily trace element loss attributed to CVVHD and CVVHDF with dialysate flow rates of 33.3 ml/min is less than what is provided in a daily dose of a trace element supplementation product.

In vitro clearance of trace elements via continuous renal replacement therapy.

OBJECTIVE: Trace element loss during continuous renal replacement therapy in patients with acute renal failure has not been quantified sufficiently. DESIGN: Trace element loss was quantified using an in vitro model of continuous venovenous hemofiltration. Bovine blood was used for the experiment, and the plasma was analyzed for its chromium, copper, selenium, manganese, and zinc content. Two different polysulfone hemodiafilters, a low-flux F8 and high-flux F70 were used, and tested at two different ultrafiltrate flow rates of 1 L/hr and 2 L/hr, respectively. Trace element concentrations in the plasma and ultrafiltrate were analyzed using inductively coupled plasma mass spectrometry. The sieving coefficient and clearance of each trace element were calculated and compared between the two hemodiafilters. SETTING: In vitro bovine model of continuous venovenous hemofiltration. PATIENTS OR OTHER PARTICIPANTS: Not applicable. RESULTS: Mean sieving coefficients of both F8 and F70 hemodiafilters were similar for each trace element. Copper, chromium, manganese, selenium, and zinc all were detected in the ultrafiltrate. Estimated trace element loss using typical trace element blood concentrations and study-derived sieving coefficients suggest that daily losses of selenium are greater than what is replenished with a standard daily trace element supplement in total parenteral nutrition. CONCLUSION: These data suggest that the degree of continuous venovenous hemofiltration clearance chromium, copper, selenium, manganese, and zinc differ between elements and that selenium and copper might need to be replaced with doses that exceed typical supplementation guidelines.