scholarly journals Mathematical modelling of post-filter ionized calcium during citrate anticoagulated continuous renal replacement therapy

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247477
Author(s):  
Innas Forsal ◽  
Anders Nilsson ◽  
Mikael Bodelsson ◽  
Anders Wieslander ◽  
Marcus Broman
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
University Hospital ◽  
Ionized Calcium ◽  
Blood Gas ◽  
Total Calcium ◽  
Blood Gas Analyses ◽  
Initial Blood ◽  
Post Filter

Background/Aims Post-filter ionized calcium (iCa) measured on a blood gas analyzer (BGA) during regional citrate anticoagulated continuous renal replacement therapy (CRRT) are needed to control the regime. This increases the workload and requires attention including interpretation of blood analyses. Two algorithms were developed to calculate the post-filter iCa instead. The first algorithm used measured systemic total calcium and the second used a selected set of values from an initial blood gas sample as input. Methods Calculated post-filter iCa values were compared to real blood gas analyses. 57 patients treated at the intensive care unit at Skåne University Hospital in Lund during 2010–2017 were included after applying inclusion and exclusion criteria. Clinical and machine parameters were collected from the electronic medical records. Non-quality checked data contained 1240 measurements and quality checked data contained 1034 measurements. Results The first algorithm using measured systemic total calcium resulted in slightly better precision and trueness with an average difference between the predicted and measured post-filter iCa concentration of 0.0185±0.0453 mmol/L for quality checked data, p<0.001. Neither algorithm could detect all instances requiring intervention. Conclusion The algorithms were able to estimate in range postfilter iCa values with great trueness and precision. However, they had some difficulties to estimate out-of-range postfilter iCa values. More work is needed to improve the algorithms especially in their citrate-modelling.

The possibility of using effluent ionized calcium to assess regional citrate anticoagulation in continuous renal replacement therapy

2019 ◽  
Vol 43 (6) ◽  
pp. 379-384
Author(s):  
Qi Zhang ◽  
Feng Zhuang ◽  
Qichen Fan ◽  
Wenyan Yu ◽  
Feng Ding
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Ionized Calcium ◽  
Regional Citrate Anticoagulation ◽  
Altman Analysis ◽  
Bland Altman Analysis ◽  
Citrate Anticoagulation ◽  
The Mean ◽  
Post Filter

Aim: This study aimed to investigate whether effluent ionized calcium was an appropriate indicator to assess anticoagulant effect in continuous renal replacement therapy with regional citrate anticoagulation instead of post-filter ionized calcium. Methods: In total, 48 paired samples of effluent fluid and post-filter blood were obtained from critically ill patients who required continuous renal replacement therapy. All samples were taken for ionized calcium measurements and were assessed by point-of-care analyzer. Correlations and agreements between two methods were performed by Pearson linear analysis and Bland–Altman analysis accordingly. Results: The mean post-filter ionized calcium was 0.42 ± 0.12 mmol/L, and mean ionized calcium level of effluent fluid was 0.39 ± 0.11 mmol/L. The ionized calcium level of effluent fluid was significantly correlated with post-filter ionized calcium in all continuous renal replacement therapy patients. Bland–Altman analysis showed that the mean difference of ionized calcium between two sampling sites in all continuous renal replacement therapy patients was −0.02 mmol/L with 95% confidence interval ranging from −0.09 to 0.04 mmol/L. The significant correlations and agreements were also demonstrated in continuous veno-venous hemofiltration, continuous veno-venous hemodialysis, and continuous veno-venous hemodiafiltration modalities separately. Conclusion: The effluent ionized calcium could be a considerable substitute for post-filter ionized calcium to monitor the validity of regional citrate anticoagulation in continuous renal replacement therapy with less blood loss.

Differences of Ionized Calcium Concentrations in Continuous Renal Replacement Therapy Among Three Analyzers

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S7-S8
Author(s):  
Maryam Salehi ◽  
Janetta Bryksin ◽  
Lisa Cole ◽  
Michael J Connor ◽  
Tammy Posey ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Reference Method ◽  
Standard Of Care ◽  
Ionized Calcium ◽  
Hospital System ◽  
Blood Samples ◽  
Low Levels ◽  
Automated Line

Abstract Continuous renal replacement therapy (CRRT) is a standard of care for critically ill patients according to the guidelines for Kidney Disease Improving Global Outcomes Clinical Practice. Within the CRRT dialysis instrument, blood requires anticoagulation with citrate with a goal to have ionized calcium (iCa) <0.4 mmol/L. In our hospital system, nephrologists who manage the therapy rotate through these hospitals, although in each of the hospitals, instruments that measure iCa are different. The objective of this study was to demonstrate the differences in measurement by these instruments. Method Twelve patient samples were drawn in triplicate and compared in the three different analyzers: RAPIDPoint, Nova Biomedical, and GEM4000 analyzers. One of the analyzers uses whole blood while the other two measure iCa in plasma. In one of the facilities, samples were spun, decapped, sent to the automated line outlet, and tested after having been exposed to air, and thus an experiment in another facility decapped the specimens for an hour and retested. Results Postfilter iCa measurements ranged from 0.18 to 0.64 mmol/L; however, range was different for each of the instruments: The Nova measurements averaged 0.55 mmol/L (range 0.42-0.64), the Rapid Point 0.36 (0.28-0.45), and the GEM 0.30 (0.18-0.39). The average difference between results of the Nova and GEM was 0.25 mmol/L, between Nova and RAPIDPoint 0.19 mmol/L, and GEM and RAPIDPoint 0.06 mmol/L. The differences between the values measured 1 hour after the sample had been decapped were negligible. Conclusion This study demonstrates inconsistency among instruments when measuring iCa in CRRT blood samples. The Nova analyzer tends to give higher results while the Rapid Point and GEM are lower and with values closer together. Currently, there is no reference material or reference method established for low iCa in CRRT samples. This study helped our clinicians understand the differences that occur between the different analyzers for low levels of iCa in CRRT blood samples.

scholarly journals Efficacy and Complications of Regional Citrate Anticoagulation During Continuous Renal Replacement Therapy in Critically Ill Patients with COVID-19

2021 ◽  
Author(s):  
Dmytro Khadzhynov ◽  
Uwe von dem Berge ◽  
Frédéric Muench ◽  
Stoyan Karaivanov ◽  
Roland Koerner ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
University Hospital ◽  
Regional Citrate Anticoagulation ◽  
Close Monitoring ◽  
Acid Base Balance ◽  
Metabolic Disturbances ◽  
Citrate Anticoagulation ◽  
Significant Difference

Abstract Background: Enhanced coagulation in coronavirus disease 2019 (COVID-19) patients is considered a major obstacle for continuous renal replacement therapy (CRRT), but systematic analyses are sparse. We compared filter survival and citrate-induced complications during CRRT with regional citrate anticoagulation (RCA) in COVID-19 and Non-COVID-19 patients.Methods: In this retrospective study we included all consecutive adult patients (n=97) with acute kidney injury (AKI) treated with RCA-CRRT at seven ICUs of a tertiary university hospital over the tree month period. Medical data were collected to compare the efficacy and complications of RCA-CRRT between COVID-19 (n=44) and Non-COVID-19 patients (n=53).Results: There was no significant difference in the number of CRRT filters used per patient in COVID-19 vs. Non-COVID-19 patients (median 5 vs 3 filters, p=0.103). Mean filter run-time was significantly higher in COVID-19 patients compared to Non-COVID-19 patients (68.4 (95%CI 67.0-69.9) vs. 65.2 (95%CI 63.2-67.2) hours, respectively; log-rank 0.014). COVID-19 patients showed significantly higher activated partial thromboplastin time (aPTT) throughout the CRRT due to systemic anticoagulation compared to Non-COVID-19 patients (54 (IQR 45 – 61) vs. 47 (IQR 41 - 58) seconds, respectively; p<0.001). A significantly higher incidence of combined metabolic disturbances (metabolic alkalosis, hypercalcemia and hypernatremia), consistent with reduced filter patency and citrate overload during RCA, was observed in COVID-19 patients compared to Non-COVID-19 patients (19.1% vs. 12.7%, respectively; p=0.04). These metabolic disarrangements were resistant to per-protocol adjustments and disappeared after replacement of the CRRT-filter. Conclusions: In contrast to initial concerns, adequate filter life-span can be achieved with RCA during CRRT in COVID-19 patients. However, close monitoring of the acid-base balance appears warranted, as these patients tend to develop reduced filter patency leading to a higher incidence of citrate overload and metabolic disturbances. Trial Registration (local authority): EA1/285/20 (Ethikkommission der Charité - Universitätsmedizin Berlin); date of registration 08.10.2020.

Elimination Rates of Electrolytes, Vitamins, and Trace Elements during Continuous Renal Replacement Therapy with Citrate Continuous Veno-Venous Hemodialysis: Influence of Filter Lifetime

2017 ◽  
Vol 44 (3) ◽  
pp. 210-216 ◽  
Author(s):  
Thomas Datzmann ◽  
Karl Träger ◽  
Helmut Reinelt ◽  
Philipp von Freyberg
Keyword(s):  
Trace Elements ◽  
Folic Acid ◽  
Renal Replacement Therapy ◽  
Prospective Study ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Inorganic Phosphate ◽  
Significant Loss ◽  
Ionized Calcium ◽  
Clinically Significant

Background/Aims: During continuous renal replacement therapy, relevant losses of nutritional substrates, vitamins, and trace elements via the filter may occur. We investigated filter lifetime efficiency during a 72-h treatment period. Methods: This prospective study included 40 patients undergoing citrate continuous veno-venous hemodialysis (CVVHD). The elimination rates were measured at 24, 48, and 72 h. To assess the influence of filter lifetime, we determined substrate loss every 24 h over a 72-h interval. Results: Filter lifetime did not affect the loss of ionized calcium, inorganic phosphate, magnesium, zinc, folic acid, and vitamin B12. Nevertheless, we did observe clinically significant loss of ionized calcium and inorganic phosphate during CVVHD that required supplementation. Conclusions: CVVHD leads to significant loss of ionized calcium and inorganic phosphate that is independent of the filter lifetime.

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.

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