Solutes removal characteristics at various effluent rates during different continuous renal replacement therapy modalities

Background:Some studies suggest the effluent as a surrogate solute removal indicator in continuous hemodialysis or hemofiltration, but the delivered clearance is frequently smaller than prescribed. This study aims at testing whether the effluent, represented by mL/kg/h, could measure solute clearance and whether increasing effluent increases clearance proportionately in continuous hemodialysis or hemofiltration.Methods:Patients treated with continuous renal replacement therapy for various diagnoses were included. The range of dialysate flow rate or substitution fluid flow rate was 1–5 L/h; solutes in the effluent and in the plasma entering the filter were measured, and the ratio of solutes in the effluent and in the plasma entering the filter and the clearance of blood urea nitrogen, creatinine, phosphate, and β2-microglobulin were calculated.Results:The ratio of solutes in the effluent and in the plasma entering the filter showed a decreasing trend with increased dialysate flow rate or substitution fluid flow rate ( p < 0.05), but solute clearance showed an increasing trend. The increase in solute clearance was less than expected from the increased effluent ( p < 0.01), and actual delivered clearance was always below the corresponding prescribed clearance ( p < 0.001).Conclusion:With increasing prescribed clearance of continuous renal replacement therapy, effluent rate overestimated the delivered clearance.

Download Full-text

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

BMC Nephrology ◽

10.1186/s12882-021-02248-7 ◽

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.

Download Full-text

Blood flow rate and circuit life in continuous renal replacement therapy (CRRT): A pilot randomised controlled trial

Australian Critical Care ◽

10.1016/j.aucc.2015.12.011 ◽

2016 ◽

Vol 29 (2) ◽

pp. 114

Author(s):

Nigel Fealy ◽

Leanne Aitken ◽

Eugene du Toit ◽

Ian Baldwin

Keyword(s):

Blood Flow ◽

Renal Replacement Therapy ◽

Randomised Controlled Trial ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Flow Rate ◽

Controlled Trial ◽

Blood Flow Rate ◽

Pilot Randomised Controlled Trial ◽

Randomised Controlled

Download Full-text

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

Frontiers in Pharmacology ◽

10.3389/fphar.2021.702455 ◽

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.

Download Full-text

A comparison of solute clearance and ultrafiltration volume in peritoneal dialysis with total or fractional (50%) intraperitoneal volume exchange with the same dialysate flow rate.

Nephrology Dialysis Transplantation ◽

10.1093/ndt/12.10.2128 ◽

1997 ◽

Keyword(s):

Peritoneal Dialysis ◽

Flow Rate ◽

Dialysate Flow ◽

Dialysate Flow Rate ◽

Solute Clearance

Download Full-text

Faster Blood Flow Rate Does Not Improve Circuit Life in Continuous Renal Replacement Therapy

Critical Care Medicine ◽

10.1097/ccm.0000000000002568 ◽

2017 ◽

Vol 45 (10) ◽

pp. e1018-e1025 ◽

Cited By ~ 8

Author(s):

Nigel Fealy ◽

Leanne Aitken ◽

Eugene du Toit ◽

Serigne Lo ◽

Ian Baldwin

Keyword(s):

Blood Flow ◽

Renal Replacement Therapy ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Flow Rate ◽

Blood Flow Rate

Download Full-text

Imipenem/Relebactam Ex Vivo Clearance during Continuous Renal Replacement Therapy

Antibiotics ◽

10.3390/antibiotics10101184 ◽

2021 ◽

Vol 10 (10) ◽

pp. 1184

Author(s):

Soo Min Jang ◽

Lenar Yessayan ◽

Michael Dean ◽

Gabrielle Costello ◽

Ravi Katwaru ◽

...

Keyword(s):

Renal Replacement Therapy ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Critically Ill ◽

Critically Ill Patients ◽

Ex Vivo ◽

Continuous Hemofiltration ◽

Flow Rates ◽

Drug Dosing ◽

Dialysate Flow

(1) Purpose of this study: determination of adsorption and transmembrane clearances (CLTM) of imipenem and relebactam in ex vivo continuous hemofiltration (CH) and continuous hemodialysis (CHD) models. These clearances were incorporated into a Monte Carlo Simulation (MCS), to develop drug dosing recommendations for critically ill patients requiring continuous renal replacement therapy (CRRT); (2) Methods: A validated ex vivo bovine blood CH and CHD model using two hemodiafilters. Imipenem/relebactam and urea CLTM at different ultrafiltrate/dialysate flow rates were evaluated in both CH and CHD. MCS was performed to determine dose recommendations for patients receiving CRRT; (3) Results: Neither imipenem nor relebactam adsorbed to the CRRT apparatus. The CLTM of imipenem, relebactam, and urea approximated the effluent rates (ultrafiltrate/dialysate flow rates). The types of hemodiafilter and effluent rates did not influence CLTM except in a dialysis flow rate of 1 L/h and 6 L/h in the CHD with relebactam (p < 0.05). Imipenem and relebactam 200 mg/100 mg every 6 h were sufficient to meet the standard time above the MIC pharmacodynamic targets in the modeled CRRT regimen of 25 kg/mL/h. (4) Conclusions: Imipenem and relebactam are not removed by adsorption to the CRRT apparatus, but readily cross the hemodiafilter membrane in CH and CHD. Dosage adjustment of imipenem/relebactam is likely required for critically ill patients receiving CRRT.

Download Full-text

Novel use of premixed dialysate bags during water supply interruption in acute hospital setting

Kidney360 ◽

10.34067/kid.0004762020 ◽

2020 ◽

pp. 10.34067/KID.0004762020

Author(s):

Orly F. Kohn ◽

Miguel Plascencia ◽

Yolanda Taylor ◽

Jay L. Koyner

Keyword(s):

Renal Replacement Therapy ◽

Replacement Therapy ◽

Hospital Setting ◽

Water System ◽

Low Flow ◽

Intermittent Hemodialysis ◽

Dialysis Patients ◽

Dialysate Flow ◽

Dialysate Flow Rate ◽

The Impact

Dialysis patients are exposed to large amounts of water during conventional intermittent hemodialysis (IHD) hence strict regulations exist for the quality of water used to prepare dialysate. Occasionally water systems fail due to natural disasters or structural supply issues such as water main breaks or unplanned changes in municipal or facility water quality. It is critical to regularly monitor and immediately recognize such a failure and take steps to avoid exposing the patients to contaminants. In addition to the recognition of the problem, the ability to pivot and continue to provide safe treatment to dialysis dependent inpatients is essential both from ultrafiltration and clearance standpoint. At our hospital, an unforeseen water disruption occurred and we were able to continue to provide renal replacement therapy with pre-made bagged dialysate to mitigate the impact on our dialysis patients. This is a novel method in utilizing available machines and dialysate, which we normally stock for continuous renal replacement therapy, for short dialysis sessions. The methodology is similar to that which has been widely used for short daily home hemodialysis with low dialysate flow rate. As this situation occurred in the midst of the Sars CoV2 pandemic we had to be mindful of dialysate volumes as well as staffing time. Here we present our investigation into the cause of water system failure and how we quickly implemented the alternative dialysis method. Short dialysis with low flow dialysate will not deliver the same Kt/V per session as standard dialysis, however it was successful as implemented and tailored with adjustments for patients requiring higher clearance for specific indication such as severe hyperkalemia.

Download Full-text