Iohexol Transmembrane Clearance during Modeled Continuous Renal Replacement Therapy

2015 ◽  
Vol 39 (1-3) ◽  
pp. 188-192
Author(s):  
J. Michael Yardman-Frank ◽  
Renee-Claude Mercier ◽  
Craig S. Wong ◽  
A. Mary Vilay
Keyword(s):  
Molecular Weight ◽  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
In Vitro Model ◽  
Ultrafiltration Rate ◽  
Continuous Hemofiltration ◽  
The Mean ◽  
Vitro Model

Background/Aims: Urea clearance during continuous renal replacement therapy (CRRT) is not representative of middle molecular weight solute clearances. We aimed to characterize iohexol, molecular weight 821 Da, clearance during continuous hemofiltration (CH) and continuous hemodialysis (CHD). Methods: Using an in vitro model, iohexol sieving coefficients (SC) and saturation coefficients (SA) were determined with the M100 membrane at ultrafiltration/dialysate rates of 1, 2, 3, 4, and 6 l/h. Iohexol transmembrane clearance was calculated using the measured SC and SA. Results: During CH, the value of iohexol SC remained approximately 1 at all ultrafiltration rates studied. In contrast, during CHD iohexol the mean SA was 1.02 ± 0.05 at a dialysate rate 1 l/h and decreased significantly with higher dialysate rates to a mean SA of 0.57 ± 0.12 at a dialysate rate of 6 l/h. Conclusions: At higher effluent flow rates, CH was more effective in removing iohexol than CHD. CH transmembrane clearance of iohexol appears to approximate the ultrafiltration rate.

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.

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

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.

scholarly journals 1340. The Effect of Continuous Renal Replacement Therapy on Body Temperature in Patients with and without Infection

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S485-S485
Author(s):  
Douglas W Challener ◽  
Kianoush Kashani ◽  
John C O’Horo
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Kidney Injury ◽  
Generation Cephalosporin ◽  
Temperature Data ◽  
Fourth Generation ◽  
Antibiotic Administration ◽  
Mean Temperature ◽  
The Mean

Abstract Background Sepsis frequently leads to acute kidney injury. In severe cases, patients may require continuous renal replacement therapy (CRRT) which involves placement of a dialysis catheter and an extracorporeal blood filtration circuit. CRRT is commonly considered to “mask” fever, though this phenomenon has not been investigated. Methods We queried an institutional database of all patients on CRRT from 2007 to 2015 for inpatient temperature data and antibiotic administration records. Receipts of piperacillin–tazobactam, a carbapenem, or a third or fourth-generation cephalosporin, indicating a serious infection, were considered intervention arm. We analyzed temperatures recorded in the intensive care unit before, during, and after CRRT. Patients were divided into groups that did not receive antibiotics as well as those who did. Temperature data were Winsorized to correct for outliers. We also performed descriptive statistics for each group. Results There were 237,988 temperature readings for 1,568 ICU patients on CRRT. 1,153 patients received broad-spectrum antibiotics in ICU. In patients who received antibiotics in ICU and were presumed to have an infection, the mean temperature was 37.2°C prior to initiation of CRRT, 36.8°C while on CRRT, and 37.2°C following discontinuation of CRRT. In the 415 patients who did not receive IV antibiotics, the mean temperature was 36.9°C prior to initiation of CRRT, 36.6°C while on CRRT, and 37.0°C following discontinuation of CRRT. During each of the periods before, during, and after CRRT, patients who received antibiotics had significantly higher temperatures than those who did not (P < 0.001). Patients receiving antibiotics were generally younger (mean 60 years vs. 64 years, P < 0.001), had longer ICU stays (mean 29 days vs. 12 days, P < 0.001) and spent more time being ventilated (mean 23 days vs. 7 days, P < 0.001). The mean SOFA score on day one was similar (mean 11.1 in the antibiotic group and 10.5 in the other group). Conclusion This investigation suggests that patients have slightly lower temperatures while on CRRT, by on average less than half a degree. A similar effect is seen in both patients with infections as well as those without. Further work will be needed to determine what constitutes a true febrile response in this population. Disclosures All authors: No reported disclosures.

scholarly journals Net ultrafiltration rate and its impact on mortality in patients with acute kidney injury receiving continuous renal replacement therapy

2019 ◽  
Author(s):  
Shahrzad Tehranian ◽  
Khaled Shawwa ◽  
Kianoush B Kashani
Keyword(s):  
Acute Kidney Injury ◽  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
High Intensity ◽  
Kidney Injury ◽  
Ultrafiltration Rate ◽  
Baseline Serum ◽  
Fluid Removal ◽  
The Impact

Abstract Background Fluid overload, a critical consequence of acute kidney injury (AKI), is associated with worse outcomes. The optimal fluid removal rate per day during continuous renal replacement therapy (CRRT) is unknown. The purpose of this study is to evaluate the impact of the ultrafiltration rate on mortality in critically ill patients with AKI receiving CRRT. Methods This was a retrospective cohort study where we reviewed 1398 patients with AKI who received CRRT between December 2006 and November 2015 at the Mayo Clinic, Rochester, MN, USA. The net ultrafiltration rate (UFNET) was categorized into low- and high-intensity groups (&lt;35 and ≥35 mL/kg/day, respectively). The impact of different UFNET intensities on 30-day mortality was assessed using logistic regression after adjusting for age, sex, body mass index, fluid balance from intensive care unit (ICU) admission to CRRT initiation, Acute Physiologic Assessment and Chronic Health Evaluation III and sequential organ failure assessment scores, baseline serum creatinine, ICU day at CRRT initiation, Charlson comorbidity index, CRRT duration and need of mechanical ventilation. Results The mean ± SD age was 62 ± 15 years, and 827 (59%) were male. There were 696 patients (49.7%) in the low- and 702 (50.2%) in the high-intensity group. Thirty-day mortality was 755 (54%). There were 420 (60%) deaths in the low-, and 335 (48%) in the high-intensity group (P &lt; 0.001). UFNET ≥35 mL/kg/day remained independently associated with lower 30-day mortality (adjusted odds ratio = 0.47, 95% confidence interval 0.37–0.59; P &lt; 0.001) compared with &lt;35 mL/kg/day. Conclusions More intensive fluid removal, UFNET ≥35 mL/kg/day, among AKI patients receiving CRRT is associated with lower mortality. Future prospective studies are required to confirm this finding.

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