scholarly journals Pressure-related flow rates for continuous renal replacement therapy in very small children: an in vitro study

2017 ◽  
Vol 1 (1) ◽  
pp. e000013 ◽  
Author(s):  
Isabella Stevens-Harris ◽  
Dusan Raffaj ◽  
Patrick Davies
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
In Vitro Study ◽  
Vitro Study ◽  
Flow Rates ◽  
Small Children

Use of Fluoride as a Marker Solute to Quantify the Current Effective Delivered Dose in Continuous Renal Replacement Therapy: An “in vitro” Study

2020 ◽  
Vol 49 (6) ◽  
pp. 685-691
Author(s):  
Gianluca Villa ◽  
Vittorio Bocciero ◽  
Mauro Neri ◽  
Diego Pomarè Montin ◽  
Elena Angeli ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
In Vitro Study ◽  
Experimental Models ◽  
Vitro Study ◽  
Fluoride Removal ◽  
Routine Practice ◽  
Delivered Dose

<b><i>Background:</i></b> The <i>current effective delivered dose</i> is a quality indicator for continuous renal replacement therapy. Its periodic assessment might enable physicians to deliver personalised treatments. Yet, its quantification as by extracorporeal urea clearance (Cl) is cumbersome and thus often neglected in routine practice. The aim of this in vitro study is to demonstrate the non-inferior effectiveness of assessing the <i>current effective delivered dose</i> using a simpler, cheaper and faster approach based on measurement of fluoride rather than urea extracorporeal Cl. <b><i>Methods:</i></b> We compared urea and fluoride removal in 3 post-dilution continuous veno-venous haemofiltration (CVVH) and 3 continuous veno-venous haemodialysis (CVVHD) in vitro experimental models. Experiments ran for 180 min, using 3 L of human blood, heparin anticoagulation and a machine dose of 30 mL/kg/h. Urea and fluoride were measured in the inflow, outflow and effluent lines to compare sieving coefficients (SC), saturation coefficients (SA) and transmembrane Cls. <b><i>Results:</i></b> In CVVH, the median SC values were 1.06 (1.02–1.07) and 1.02 (1.01–1.04) for fluoride and urea, respectively (discrepancy of 4.3%), while transmembrane convective Cls were 31.28 (30.01–31.31) mL/kg/h and 30.30 (29–31.85) mL/kg/h (discrepancy of 3.13%), respectively. In CVVHD, the median SA values were 1.01 (0.96–1.02) and 1 (0.95–1.01) for fluoride and urea, respectively (discrepancy of 1.6%), while transmembrane dialytic Cls were 30.26 (29.52–31.32) mL/kg/h and 31.16 (30–31.75) mL/kg/h (discrepancy of –2.97%), respectively. <b><i>Conclusion:</i></b> Fluoride transmembrane removal was close to that observed with urea, in terms of SC, SA and transmembrane Cl. Fluoride seems as much accurate as urea in assessing the <i>current effective delivered dose</i> during both CVVH and CVVHD and might therefore be adopted for dose measurement. Besides accuracy, fluoride bedside assessment could present many advantages over urea, particularly in terms of availability, costs, time requirement and rapidity of assessment.

scholarly journals Pharmacokinetics and dialytic clearance of apixaban during in vitro continuous renal replacement therapy

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lauren Andrews ◽  
Scott Benken ◽  
Xing Tan ◽  
Eric Wenzler
Keyword(s):  
Renal Replacement Therapy ◽  
Linear Regression ◽  
Protein Binding ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Flow Rate ◽  
Systemic Exposure ◽  
Flow Rates ◽  
Filter Type

Abstract Background To evaluate the transmembrane clearance (CLTM) of apixaban during modeled in vitro continuous renal replacement therapy (CRRT), assess protein binding and circuit adsorption, and provide initial dosing recommendations. Methods Apixaban was added to the CRRT circuit and serial pre-filter bovine blood samples were collected along with post-filter blood and effluent samples. All experiments were performed in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes, with varying filter types, flow rates, and point of CVVH replacement fluid dilution. Concentrations of apixaban and urea were quantified via liquid chromatography-tandem mass spectrometry. Plasma pharmacokinetic parameters for apixaban were estimated via noncompartmental analysis. CLTM was calculated via the estimated area under the curve (AUC) and by the product of the sieving/saturation coefficient (SC/SA) and flow rate. Two and three-way analysis of variance (ANOVA) models were built to assess the effects of mode, filter type, flow rate, and point of dilution on CLTM by each method. Optimal doses were suggested by matching the AUC observed in vitro to the systemic exposure demonstrated in Phase 2/3 studies of apixaban. Linear regression was utilized to provide dosing estimations for flow rates from 0.5–5 L/h. Results Mean adsorption to the HF1400 and M150 filters differed significantly at 38 and 13%, respectively, while mean (± standard deviation, SD) percent protein binding was 70.81 ± 0.01%. Effect of CVVH point of dilution did not differ across filter types, although CLTM was consistently significantly higher during CRRT with the HF1400 filter compared to the M150. The three-way ANOVA demonstrated improved fit when CLTM values calculated by AUC were used (adjusted R2 0.87 vs. 0.52), and therefore, these values were used to generate optimal dosing recommendations. Linear regression revealed significant effects of filter type and flow rate on CLTM by AUC, suggesting doses of 2.5–7.5 mg twice daily (BID) may be needed for flow rates ranging from 0.5–5 L/h, respectively. Conclusion For CRRT flow rates most commonly employed in clinical practice, the standard labeled 5 mg BID dose of apixaban is predicted to achieve target systemic exposure thresholds. The safety and efficacy of these proposed dosing regimens warrants further investigation in clinical studies.

Diafiltration flowrate is a determinant of the extent of adsorption of amikacin in renal replacement therapy using the ST150®-AN69 filter: An in vitro study

2020 ◽  
Vol 43 (12) ◽  
pp. 758-766 ◽  
Author(s):  
Frédéric Joseph Baud ◽  
Pascal Houzé ◽  
Jean-Herlé Raphalen ◽  
Anaïs Winchenne ◽  
Pascal Philippe ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Drug Disposition ◽  
Inverse Correlation ◽  
In Vitro Study ◽  
Central Compartment ◽  
Continuous Filtration ◽  
Vitro Model

Introduction: In continuous renal replacement therapy, conduction and convection are controlled allowing prescribing dosage regimen improving survival. In contrast, adsorption is an uncontrolled property altering drug disposition. Whether adsorption depends on flowrates is unknown. We hypothesized an in vitro model may provide information in conditions mimicking continuous renal replacement therapy in humans. Methods: ST150®-AN69 filter and Prismaflex dialyzer, Baxter-Gambro were used. Simulated blood flowrate was set at 200 mL/min. The flowrates in the filtration (continuous filtration), dialysis (continuous dialysis), and diafiltration (continuous diafiltration) were 1500, 2500, and 4000 mL/h, respectively. Routes of elimination were assessed using NeckEpur® analysis. Results: The percentages of the total amount eliminated by continuous filtration, continuous dialysis, and continuous diafiltration were 82%, 86%, and 94%, respectively. Elimination by effluents and adsorption accounted for 42% ± 7% and 58% ± 5%, 57% ± 7% and 43% ± 6%, and 84% ± 6% and 16% ± 6% of amikacin elimination, respectively. There was a linear regression between flowrates and amikacin clearance: Y = 0.6 X ± 1.7 (R2 = 0.9782). Conversely, there was a linear inverse correlation between the magnitude of amikacin adsorption and flowrate: Y = –16.9 X ± 84.1 (R2 = 0.9976). Conclusion: Low flowrates resulted in predominant elimination by adsorption, accounting for 58% of the elimination of amikacin from the central compartment in the continuous filtration mode at 1500 mL/h of flowrate. Thereafter, the greater the flowrate, the lower the adsorption of amikacin in a linear manner. Flowrate is a major determinant of adsorption of amikacin. There was an about 17% decrease in the rate of adsorption per increase in the flowrate of 1 L/min.

Continuous renal replacement therapy in the treatment of severe hyperkalemia: An in vitro study

2019 ◽  
Vol 43 (2) ◽  
pp. 87-93 ◽  
Author(s):  
Pascal Houzé ◽  
Frédéric Joseph Baud ◽  
Jean-Herlé Raphalen ◽  
Anaïs Winchenne ◽  
Sonia Moreira ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
In Vitro Study ◽  
Central Compartment ◽  
Life Threatening ◽  
Severe Hyperkalemia ◽  
Continuous Filtration ◽  
Vitro Model

Introduction: Continuous renal replacement therapy is not presently recommended in the treatment of life-threatening hyperkalemia. There are no specific recommendations in hemodialysis to treat hyperkalemia. We hypothesized an in vitro model may provide valuable information on the usefulness of continuous renal replacement therapy to treat severe hyperkalemia. Methods: A potassium-free solute was used instead of diluted blood for continuous renal replacement therapy with a simulated blood flowrate set at 200 mL/min. The mode of elimination included continuous filtration, continuous dialysis, and continuous diafiltration using a flowrate of 4000 mL/min for continuous filtration and continuous dialysis modes, and a ratio of 2500/1500 in the continuous diafiltration mode. Results: The mean initial potassium in the central compartment was 10.1 ± 0.4 mmol/L. The clearances in the continuous diafiltration, continuous filtration, and continuous dialysis were 3.4 ± 0.5, 3.6 ± 0.1, and 3.7 ± 0.1 L/h, respectively, not significantly different. Continuous dialysis resulted in the lowest workload for staff. Increasing the continuous dialysis flowrates from 2000 to 8000 mL/h increased clearance from 2.3 ± 0.3 to 6.2 ± 0.8 L/h. The delays in decreasing the potassium concentration to 5.5 mmol/L dropped from 120 to 45 min, respectively. Potassium eliminated in the first hour increased from 18 to 38 mmol that compared favorably with hemodialysis. Decrease in simulated blood flowrate from 200 to 50 mL/min moderately but significantly decreased the clearance from 3.7 to 3.0 L/h. Conclusion: Hyperkalemia is efficiently treated by continuous renal replacement therapy using the dialysis mode. Caution is needed to prevent the onset of severe hypokalemia within 40 min after initiation of the session.

scholarly journals Pharmacokinetics and Dialytic Clearance of Apixaban During In Vitro Continuous Renal Replacement Therapy

2020 ◽  
Author(s):  
Lauren Andrews ◽  
Scott Benken ◽  
Xing Tan ◽  
Eric Wenzler
Keyword(s):  
Renal Replacement Therapy ◽  
Linear Regression ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Flow Rate ◽  
Systemic Exposure ◽  
Flow Rates ◽  
Filter Type ◽  
Post Filter

Abstract Objective: To evaluate the transmembrane clearance (CLTM) of apixaban during modeled in vitro continuous renal replacement therapy (CRRT), assess protein binding and circuit adsorption, and provide initial dosing recommendations. Design: In vitro pharmacokinetic (PK) study.Setting: University research laboratory.Subjects: Not applicable. Interventions: Apixaban was added to the CRRT circuit and serial, undiluted pre-filter bovine blood samples were collected along with analogous post-filter blood and effluent samples. All experiments were performed in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes, with varying filter types (M150 and HF1400), flow rates (2 and 4 L/h), and point of CVVH replacement fluid dilution (pre, post, and pre/post filter). Concentrations of apixaban and urea were quantified via liquid chromatography-tandem mass spectrometry. Plasma PK parameters for apixaban were estimated via noncompartmental analysis in WinNonlin. CLTM was calculated via the estimated area under the curve (AUC) and by the product of the sieving/saturation coefficient (SC/SA) and flow rate. Two and three-way ANOVA models were built to assess the effects of mode, filter type, flow rate, and point of dilution on CLTM by each method. Optimal doses were suggested by matching the AUC observed in vitro to the systemic exposure demonstrated in Phase 2/3 studies of apixaban. Linear regression was then utilized to provide dosing estimations for flow rates from 0.5-5 L/h. Measurements and Main Results: Mean adsorption to the HF1400 and M150 filters differed significantly at 38% and 13%, respectively, while mean (±SD) percent protein binding was 70.81±0.01%. Effect of CVVH point of replacement fluid dilution did not differ across filter types, although CLTM was consistently significantly higher during CRRT with the HF1400 filter compared to the M150. The three-way ANOVA demonstrated improved fit when CLTM values calculated by AUC were used (adjusted R2 0.87 vs. 0.52), and therefore, these values were used to generate optimal dosing recommendations. Linear regression revealed significant effects of filter type and flow rate on CLTM by AUC, suggesting doses of 5-10 mg BID may be needed for flow rates ranging from 0.5-5 L/h respectively. Conclusion: CLTM of apixaban during CRRT resulted in estimated dosing recommendations ranging from 5 mg BID for flow rates ≤3 L/h up to 7.5-10 mg BID for rates >3 L/h, depending on filter type, in order to match target systemic exposure thresholds. The safety and efficacy of these proposed dosing regimens warrants further investigation in clinical studies.

scholarly journals Pharmacokinetics and Dialytic Clearance of Apixaban During In Vitro Continuous Renal Replacement Therapy

2020 ◽  
Author(s):  
Lauren Andrews ◽  
Scott Benken ◽  
Xing Tan ◽  
Eric Wenzler
Keyword(s):  
Renal Replacement Therapy ◽  
Linear Regression ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Flow Rate ◽  
Systemic Exposure ◽  
Flow Rates ◽  
Filter Type ◽  
Post Filter

Abstract Objective: To evaluate the transmembrane clearance (CLTM) of apixaban during modeled in vitro continuous renal replacement therapy (CRRT), assess protein binding and circuit adsorption, and provide initial dosing recommendations. Design: In vitro pharmacokinetic (PK) study.Setting: University research laboratory.Subjects: Not applicable. Interventions: Apixaban was added to the CRRT circuit and serial pre-filter bovine blood samples were collected along with analogous post-filter blood and effluent samples. All experiments were performed in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes, with varying filter types (M150 and HF1400), flow rates (2 and 4 L/h), and point of CVVH replacement fluid dilution (pre, post, and pre/post filter). Concentrations of apixaban and urea were quantified via liquid chromatography-tandem mass spectrometry. Plasma PK parameters for apixaban were estimated via noncompartmental analysis in WinNonlin. CLTM was calculated via the estimated area under the curve (AUC) and by the product of the sieving/saturation coefficient (SC/SA) and flow rate. Two and three-way ANOVA models were built to assess the effects of mode, filter type, flow rate, and point of dilution on CLTM by each method. Optimal doses were suggested by matching the AUC observed in vitro to the systemic exposure demonstrated in Phase 2/3 studies of apixaban. Linear regression was then utilized to provide dosing estimations for flow rates from 0.5-5 L/h. Measurements and Main Results: Mean adsorption to the HF1400 and M150 filters differed significantly at 38% and 13%, respectively, while mean (±SD) percent protein binding was 70.81±0.01%. Effect of CVVH point of replacement fluid dilution did not differ across filter types, although CLTM was consistently significantly higher during CRRT with the HF1400 filter compared to the M150. The three-way ANOVA demonstrated improved fit when CLTM values calculated by AUC were used (adjusted R2 0.87 vs. 0.52), and therefore, these values were used to generate optimal dosing recommendations. Linear regression revealed significant effects of filter type and flow rate on CLTM by AUC, suggesting doses of 2.5-7.5 mg BID may be needed for flow rates ranging from 0.5-5 L/h, respectively. Conclusion: For CRRT flow rates most commonly employed in clinical practice, the standard labeled 5 mg BID dose of apixaban is predicted to achieve target systemic exposure thresholds. The safety and efficacy of these proposed dosing regimens warrants further investigation in clinical studies.

scholarly journals In vivo / in vitro Correlation of Pharmacokinetics of Gentamicin, Vancomycin, Teicoplanin and Doripenem in a Bovine Blood Hemodialysis Model

2021 ◽  
Vol 12 ◽  
Author(s):  
M G Vossen ◽  
S Pferschy ◽  
C Milacek ◽  
M Haidinger ◽  
Mario Karolyi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Replacement Therapy ◽  
Protein Binding ◽  
Replacement Therapy ◽  
Flow Rate ◽  
Blood Flow Rate ◽  
Bovine Blood ◽  
Flow Rates ◽  
Dialysate Flow Rate

Background: Elimination of a drug during renal replacement therapy is not only dependent on flow rates, molecular size and protein binding, but is often influenced by difficult to predict drug membrane interactions. In vitro models allow for extensive profiling of drug clearance using a wide array of hemofilters and flow rates. We present a bovine blood based in vitro pharmacokinetic model for intermittent renal replacement therapy.Methods: Four different drugs were analyzed: gentamicin, doripenem, vancomicin and teicoplanin. The investigated drug was added to a bovine blood reservoir connected to a hemodialysis circuit. In total seven hemofilter models were analyzed using commonly employed flow rates. Pre-filter, post-filter and dialysate samples were drawn, plasmaseparated and analyzed using turbidimetric assays or HPLC. Protein binding of doripenem and vancomycin was measured in bovine plasma and compared to previously published values for human plasma.Results: Clearance values were heavily impacted by choice of membrane material and surface as well as by dialysis parameters such as blood flow rate. Gentamicin clearance ranged from a minimum of 90.12 ml/min in a Baxter CAHP-170 diacetate hemofilter up to a maximum of 187.90 ml/min in a Fresenius medical company Fx80 polysulfone model (blood flow rate 400 ml/min, dialysate flow rate 800 ml/min). Clearance of Gentamicin vs Vancomicin over the F80s hemofilter model using the same flow rates was 137.62 mL vs 103.25 ml/min. Doripenem clearance with the Fx80 was 141.25 ml/min.Conclusion: Clearance values corresponded very well to previously published data from clinical pharmacokinetic trials. In conjunction with in silico pharmacometric models. This model will allow precise dosing recommendations without the need of large scale clinical trials.

Ex vivo Ceftolozane/Tazobactam Clearance during Continuous Renal Replacement Therapy

2017 ◽  
Vol 44 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Weerachai Chaijamorn ◽  
Alexander R. Shaw ◽  
Susan J. Lewis ◽  
Bruce A. Mueller
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Important Determinant ◽  
Ex Vivo ◽  
Pharmacokinetic Parameters ◽  
No Adsorption ◽  
Continuous Hemofiltration ◽  
Flow Rates ◽  
Dosing Regimens

Background/Aims: To determine ceftolozane/tazobactam transmembrane clearances (CLTM) in continuous hemofiltration (CHF) and continuous hemodialysis (CHD) and to determine optimal ceftolozane/tazobactam dosing regimens for patients receiving continuous renal replacement therapy (CRRT). Method: Validated, ex vivo CHF and CHD bovine blood models using polysulfone (HF1400) and AN69 (Multiflow 150-M) hemofilters were used to evaluate adsorption and CLTM at different effluent flow rates. Monte Carlo simulations (MCS) using pharmacokinetic parameters from published studies and CLTM from this study were used to generate ceftolozane/tazobactam dosing for patients receiving CRRT. Results: CHF and CHD CLTM did not differ at equivalent effluent rates. CLTM approximated effluent flow rates. No adsorption of ceftolozane/tazobactam occurred for either hemofilter. Effluent flow was the most important determinant of MCS-derived doses. Conclusion: CRRT clearances of ceftolozane/tazobactam depended on effluent flow rates but not hemofilter types. MCS-derived ceftolozane/tazobactam doses of 750 (500/250)-1,500 (1,000/500) mg every 8 h met pharmacodynamic targets for virtual patients receiving CRRT at contemporary effluent rates.

Elimination of fluconazole during continuous renal replacement therapy. An in vitro assessment

2020 ◽  
pp. 039139882097614
Author(s):  
Frédéric J Baud ◽  
Vincent Jullien ◽  
Tarik Abarou ◽  
Benoît Pilmis ◽  
Jean-Herlé Raphalen ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Central Compartment ◽  
Sieving Coefficient ◽  
Continuous Filtration ◽  
In Vitro Assessment ◽  
The Mean ◽  
Made In

Introduction: Continuous renal replacement therapy (CRRT) efficiently eliminates fluconazole. However, the routes of elimination were not clarified. Adsorption of fluconazole by filters is a pending question. We studied the elimination of fluconazole in a model mimicking a session of CRRT in humans using the NeckEpur® model. Two filters were studied. Methods: The AV1000®-polysulfone filter with the Multifiltrate Pro. Fresenius and the ST150®-polyacrylonitrile filter with the Prismaflex. Baxter-Gambro were studied. Continuous filtration used a flowrate of 2.5 L/h in post-dilution only. Session were made in duplicate. Routes of elimination were assessed using the NeckEpur® model. Results: The mean measured initial fluconazole concentration (mean ± SD) for the four sessions in the central compartment (CC) was 14.9 ± 0.2 mg/L. The amount eliminated from the CC at the end of 6 h-session at a 2.5 L/h filtration flowrate for the AV1000®-polysulfone and the ST150®-polyacrylonitrile filters were 90%–93% and 96%–94%, respectively; the clearances from the central compartment (CC) were 2.5–2.6 and 2.4–2.3 L/h, respectively. The means of the instantaneous sieving coefficient were 0.94%–0.91% and 0.99%–0.91%, respectively. The percentages of the amount eliminated from the CC by filtration/adsorption were 100/0%–95/5% and 100/0%–100/0%, respectively. Conclusion: Neither the ST150®-polyacrylonitrile nor the AV1000®-polysulfone filters result in any significant adsorption of fluconazole.

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