Ceftolozane/tazobactam exposure in critically ill patients undergoing continuous renal replacement therapy: a PK/PD approach to tailor dosing

2020 ◽  
Vol 76 (1) ◽  
pp. 199-205 ◽  
Author(s):  
Milo Gatti ◽  
Maddalena Giannella ◽  
Emanuel Raschi ◽  
Pierluigi Viale ◽  
Fabrizio De Ponti
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Flow Rate ◽  
Case Reports ◽  
Blood Flow Rate ◽  
Pubmed Database ◽  
Effluent Flow Rate ◽  
Dosing Regimens ◽  
Trough Concentrations

Abstract Objectives To investigate the influence of continuous renal replacement therapy (CRRT) intensity on the clearance of ceftolozane/tazobactam in critical care patients, and to evaluate if the reported doses would achieve an optimal pharmacokinetic/pharmacodynamic (PK/PD) target against Pseudomonas aeruginosa exhibiting different MICs. Methods The MEDLINE–PubMed database was searched from inception to January 2020 to retrieve observational studies or case reports investigating the PK behaviour of ceftolozane/tazobactam during CRRT. Relevant CRRT settings and PK variables were extracted, and the influence of CRRT intensity on ceftolozane/tazobactam total clearance (CLtot) was determined by simple linear regression. The optimal PK/PD target for the reported doses was deemed to be achieved when ceftolozane trough concentrations (Cmin) were above the MIC (less intensive target) or four times the MIC (intensive target) for P. aeruginosa. Results Data from six studies including 11 patients (mean age 56.6 years) were analysed. Mean blood flow rate and effluent flow rate were 161.8 mL/min and 2383.4 mL/h, respectively. Ceftolozane Cmin ranged from 25.8 to 79.4 mg/L. A significant correlation was found for ceftolozane CLtot and effluent flow rate (P = 0.027). The intensive PK/PD target was achieved by 100% and 50% of the reported doses for MIC, respectively, up to 4 and 8 mg/L. Conclusions A significant correlation between effluent flow rate and ceftolozane clearance during CRRT could be identified. Higher dosing regimens coupled with continuous/extended infusion may be required in the case of higher CRRT intensity, deep-seated infections or poorly susceptible isolates. Larger studies assessing ceftolozane PK in different CRRT settings are warranted.

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

2017 ◽  
Vol 45 (10) ◽  
pp. e1018-e1025 ◽  
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

scholarly journals The Effect of Continuous Renal Replacement Therapy with the AN69ST Membrane on Inflammatory Markers and the Level of Consciousness of Hemodialysis Patients with Stroke: Comparison with Hemodialysis with Low Blood Flow Rate

PRILOZI ◽  
2018 ◽  
Vol 39 (2-3) ◽  
pp. 29-35
Author(s):  
Tomohiro Matsui ◽  
Takafumi Nakagawa ◽  
Hitomi Kikuchi ◽  
Hiroyuki Horio ◽  
Kazuhiko Hashimura
Keyword(s):  
Blood Flow ◽  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Flow Rate ◽  
Blood Flow Rate ◽  
Current Standard ◽  
Reactive Protein ◽  
Inflammatory Parameters ◽  
Gcs Score

Abstract Introduction: Hemodialysis (HD) with low blood flow rate, continuous renal replacement therapy (CRRT), and peritoneal dialysis are recommended for patients with stroke complications to prevent intracranial hypertension because of the low diffusion capacity of the brain barrier. However, detailed guidelines are not currently available; thus, there is an urgent need to establish such guidelines. Material and Methods: We developed a novel protocol for performing CRRT with the AN69ST membrane, which has excellent adsorption capacity for various cytokines. The objective of this study was to compare the effect of the novel protocol with that of the current standard protocol, i.e. hemodialysis with low blood flow rate. To compare the effect of hemodialysis with low blood flow (HD group, n=27) and CRRT with AN69ST membrane (CRRT group, n=8), we measured the following consciousness and blood inflammatory parameters in patients with stroke complications at baseline and after 1 week of treatment: Glasgow Coma Scale (GCS) score, C-reactive protein (CRP) levels, and white blood cell (WBC) and platelet count. Results: After 1 week, the total GCS score did not improve in the HD group, but improved significantly in the CRRT group (HD group: 13.1±3.0 to 13.3±3.1, p=0.5508, CRRT group: 8.9±3.9 to 11.5±3.9, p=0.0313). Improvement in the CRRT group was significantly higher than in the HD group (p=0.0039). CRP levels did not change significantly in either the HD (3.8±5.5 to 5.3±4.3 n.s.) or CRRT groups (7.7±10.0 to 3.7±3.2 n.s.); however, they tended to increase in the HD group and decrease in the CRRT group. No significant changes were observed in WBC and platelet counts after 1 week of treatment in either group. Conclusion: CRRT with the AN69ST membrane might have a beneficial effect on the consciousness level and inflammation of patients with stroke.

Effect of Blood Flow Rate on the Accuracy of Central Venous Pressure Measurement during Continuous Renal Replacement Therapy

2021 ◽  
pp. 1-8
Author(s):  
Aijie Yu ◽  
Yanxia Li ◽  
Xiuqin Hong ◽  
Kai Gao ◽  
Dongdong Guo ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Central Venous Pressure ◽  
Replacement Therapy ◽  
Flow Rate ◽  
Negative Correlation ◽  
Venous Pressure ◽  
Blood Flow Rate ◽  
Central Venous

<b><i>Background:</i></b> The objective of this study was to study the influence of extracorporeal blood flow rate (BFR) on the accuracy of central venous pressure (CVP) measurement during continuous renal replacement therapy (CRRT). <b><i>Methods:</i></b> Eligible patients were randomly divided into 3 groups based on the location of catheters used for their CRRT and CVP measurement. CVP levels measured at increased extracorporeal BFR (from 0 to 300 mL/min) in the normal and reverse positions of inlet and outlet lines connected to the CV catheter (CVC) in the course of the CRRT session were collected. <b><i>Results:</i></b> CVP levels measured at different extracorporeal BFRs did not significantly differ between and among the 3 groups. Inversion of inlet and outlet lines connected to the catheters did not affect the accuracy of CVP measurement. BFR had a negative correlation with inflow/access pressure but a positive correlation with outflow/return pressure. Neither inflow pressure nor outflow pressure was correlated with CVP. <b><i>Conclusions:</i></b> Extracorporeal BFR has no influence on the accuracy of CVP measurement during CRRT with the net machine balance adjusted to zero regardless of the location of the catheter and the connection method between catheters and CRRT lines. Thus, CRRT does not need to be discontinued to obtain an accurate CVP measurement.

scholarly journals Blood flow rate and circuit life in continuous renal replacement therapy (CRRT): a randomised controlled trial (RCT)

2017 ◽  
Vol 30 (2) ◽  
pp. 109
Author(s):  
Nigel Fealy ◽  
Leanne Aitken ◽  
Eugene du Toit ◽  
Ian Baldwin ◽  
Serigne Lo
Keyword(s):  
Blood Flow ◽  
Renal Replacement Therapy ◽  
Randomised Controlled Trial ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Flow Rate ◽  
Controlled Trial ◽  
Blood Flow Rate ◽  
Randomised Controlled

scholarly journals Clinical Survey of Decreased Blood Flow Rate in Continuous Renal Replacement Therapy: A Retrospective Observational Study

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Makoto Harada ◽  
Masafumi Ooki ◽  
Kaede Kohashi ◽  
Tohru Ichikawa ◽  
Mamoru Kobayashi
Keyword(s):  
Blood Flow ◽  
Intensive Care ◽  
Renal Replacement Therapy ◽  
Observational Study ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Flow Rate ◽  
Blood Flow Rate ◽  
Retrospective Observational Study ◽  
Clinical Factors

Background. Continuous renal replacement therapy (CRRT) is an essential procedure for patients with acute kidney injury in intensive care. It is important to maintain an adequate blood flow rate during CRRT. Several previous studies have reported the relationships between blood flow rate and filter lifespan, or circuit life, in CRRT. Here, we aim at elucidating the incidence and factors associated with a decreased blood flow rate in CRRT. Methods. This is a retrospective observational study. From January 2014 to June 2017, 119 patients who underwent CRRT in the intensive care unit were enrolled. The definition of a decreased blood flow rate included situations in which the medical staff needed to decrease the blood flow volume. We statistically analyzed the association of the decreased blood flow rate with patients’ clinical characteristics. Results. Of 119 patients, 52 required a decreased blood flow rate during CRRT. Almost half of the cases occurred within one day of starting CRRT. None of the clinical factors (age, sex, height, sequential organ failure assessment (SOFA) score, catheter position, systemic infection, albumin, hemoglobin, and activating coagulation time) were significantly associated with decreased blood flow rate. Conclusions. A decreased blood flow rate often occurs during CRRT. Clinical factors significantly associated with the occurrence of the decreased blood flow rate were not detected in the current study. Further investigation regarding the occurrence of a decreased blood flow is warranted.

scholarly journals Continuous Renal Replacement Therapy (CRRT) in Children and the Specialized CRRT Team: A 14-Year Single-Center Study

2019 ◽  
Vol 9 (1) ◽  
pp. 110 ◽  
Author(s):  
Keum Hwa Lee ◽  
In Suk Sol ◽  
Jung Tak Park ◽  
Ji Hong Kim ◽  
Jae Won Shin ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Flow Rate ◽  
Blood Flow Rate ◽  
Critically Ill Children ◽  
Single Center ◽  
Group A ◽  
Group B

Continuous renal replacement therapy (CRRT) has been used as an important intervention in critically ill children. Our center has the only specialized CRRT team (SCT) for children in Korea, which consists of pediatric intensivists, a pediatric nephrologist and CRRT-specialized-nurses. This study was a retrospective single-center analysis, including all pediatric patients admitted to the intensive care unit (ICU) of Severance hospital in Korea and received CRRT between 2003 and 2016, grouped as before SCT (group A, n = 51) and after SCT (group B, n = 212). We obtained the data for sex, age, weight, diagnosis, blood flow rate or type of CRRT machine used, administration of inotropic agents or anticoagulants, and ICU duration before CRRT (hours). A total of 263 patients were included. The age was significantly younger (p < 0.001) and blood flow rate was lower (p = 0.001) in group B than group A. Vasopressors (p < 0.001), continuous veno-venous hemodiafiltration (CVVHDF) (p < 0.001), nafamostat mesilate (p < 0.001), and extracorporeal membrane oxygenation (ECMO)-CRRT (p = 0.004) were more frequently used in group B. Based on our 14-year experience, we conclude that SCT operation could have played an important role in increasing the amount of CRRT utilization.

scholarly journals Blood flow rate and solute maintenance in continuous renal replacement therapy (CRRT): a randomised controlled trial (RCT)

2017 ◽  
Vol 30 (2) ◽  
pp. 126-127
Author(s):  
Nigel Fealy ◽  
Leanne Aitken ◽  
Eugene du Toit ◽  
Ian Baldwin ◽  
Michael Bailey
Keyword(s):  
Blood Flow ◽  
Renal Replacement Therapy ◽  
Randomised Controlled Trial ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Flow Rate ◽  
Controlled Trial ◽  
Blood Flow Rate ◽  
Randomised Controlled

scholarly journals Continuous Renal Replacement Therapy with High Flow Rate Can Effectively, Safely, and Quickly Reduce Plasma Ammonia and Leucine Levels in Children

Children ◽  
2019 ◽  
Vol 6 (4) ◽  
pp. 53
Author(s):  
Fatih Aygun ◽  
Fatih Varol ◽  
Cigdem Aktuglu-Zeybek ◽  
Ertugrul Kiykim ◽  
Halit Cam
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Flow Rate ◽  
Metabolic Diseases ◽  
Age Distribution ◽  
Reduction Rate ◽  
Blood Flow Rate ◽  
Treatment Modalities ◽  
Plasma Ammonia

Introduction: Peritoneal dialysis and continuous renal replacement therapy (CRRT) are the most frequently used treatment modalities for acute kidney injury. CRRT is currently being used for the treatment of several non-renal indications, such as congenital metabolic diseases. CRRT can efficiently remove toxic metabolites and reverse the neurological symptoms quickly. However, there is not enough data for CRRT in children with metabolic diseases. Therefore, we aimed a retrospective study to describe the use of CRRT in metabolic diseases and its associated efficacy, complications, and outcomes. Materials and Methods: We performed a retrospective analysis of the records of all patients admitted in the pediatric intensive care unit (PICU) for CRRT treatment. Results: Between December 2014 and November 2018, 97 patients were eligible for the present study. The age distribution was between 2 days and 17 years, with a mean of 3.77 ± 4.71 years. There were 13 (36.1%) newborn with metabolic diseases. The patients were divided into two groups: CRRT for metabolic diseases and others. There was a significant relationship between the groups, including age (p ≤ 0.001), weight (p = 0.028), blood flow rate (p ≤ 0.001); dialysate rate (p ≤ 0.001), and replacement rate (p ≤ 0.001). The leucine reduction rate was 3.88 ± 3.65 (% per hour). The ammonia reduction rate was 4.94 ± 5.05 in the urea cycle disorder group and 5.02 ± 4.54 in the organic acidemia group. The overall survival rate was 88.9% in metabolic diseases with CRRT. Conclusion: In particularly hemodynamically unstable patients, CRRT can effectively and quickly reduce plasma ammonia and leucine.

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.

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