Pharmacokinetics of Commonly Used Medications in Children Receiving Continuous Renal Replacement Therapy: A Systematic Review of Current Literature

Dubinsky, Samuel; Watt, Kevin M.; Saleeb, Steven; Ahmed, Bilal; Carter, Caitlin; Yeung, Cindy H. T.; Edginton, Andrea N.

doi:10.1007/s40262-021-01085-z

Cited by 10 publications

(4 citation statements)

References 143 publications

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“…The impact of CRRT on altering the drug disposition of small molecular weight drugs has been studied extensively (3,4,8,(34)(35)(36)(37)(38); however, the effects on large molecular compounds, such as anakinra remain mostly unknown. We studied the pharmacokinetics of anakinra in a closed-loop CRRT circuit.…”

Section: Discussionmentioning

confidence: 99%

Anakinra Removal by Continuous Renal Replacement Therapy: An Ex Vivo Analysis

Dubinsky,

Watt,

Imburgia

et al. 2023

Critical Care Explorations

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OBJECTIVES: Patients with sepsis are at significant risk for multiple organ dysfunction, including the lungs and kidneys. To manage the morbidity associated with kidney impairment, continuous renal replacement therapy (CRRT) may be required. The extent of anakinra pharmacokinetics in CRRT remains unknown. The objectives of this study were to investigate the anakinra–circuit interaction and quantify the rate of removal from plasma. DESIGN: The anakinra–circuit interaction was evaluated using a closed-loop ex vivo CRRT circuit. CRRT was performed in three phases based on the method of solute removal: 1) hemofiltration, 2) hemodialysis, and 3) hemodiafiltration. Standard control samples of anakinra were included to assess drug degradation. SETTING: University research laboratory. PATIENTS: None. INTERVENTIONS: Anakinra was administered to the CRRT circuit and serial prefilter blood samples were collected along with time-matched control and hemofiltrate samples. Each circuit was run in triplicate to assess inter-run variability. Concentrations of anakinra in each reference fluid were measured by enzyme-linked immunosorbent assay. Transmembrane filter clearance was estimated by the product of the sieving coefficient/dialysate saturation constant and circuit flow rates. MEASUREMENTS AND MAIN RESULTS: Removal of anakinra from plasma occurred within minutes for each CRRT modality. Average drug remaining (%) in plasma following anakinra administration was lowest with hemodiafiltration (34.9%). The average sieving coefficient was 0.34, 0.37, and 0.41 for hemodiafiltration, hemofiltration, and hemodialysis, respectively. Transmembrane clearance was fairly consistent across each modality with the highest during hemodialysis (5.53 mL/min), followed by hemodiafiltration (4.99 mL/min), and hemofiltration (3.94 mL/min). Percent drug remaining within the control samples (93.1%) remained consistent across each experiment, indicating negligible degradation within the blood. CONCLUSIONS: The results of this analysis are the first to demonstrate that large molecule therapeutic proteins such as anakinra, are removed from plasma with modern CRRT technology. Current dosing recommendations for patients with severe renal impairment may result in subtherapeutic anakinra concentrations in those receiving CRRT.

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Section: Discussionmentioning

confidence: 99%

Anakinra Removal by Continuous Renal Replacement Therapy: An Ex Vivo Analysis

Dubinsky,

Watt,

Imburgia

et al. 2023

Critical Care Explorations

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“…Honoré et al summarized that the daily doses of methylprednisolone and prednisone need to be higher by 70-100% during continuous RRT, but they do not explain in detail the doses depending on the RRT method used [16]. Dubinsky et al in their manuscript point out the pharmacokinetics of frequently used drugs in children treated with RRT and provide wide evidence on how to adjust the doses [17].…”

Section: Discussionmentioning

confidence: 99%

Treatment of extreme overhydration in an adolescent boy with idiopathic nephrotic syndrome

Szydłowski¹,

Szydłowska²,

Masłocha³

et al. 2022

polp

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The key factors in the diagnosis of nephrotic syndrome (NS) in children are as follows: proteinuria > 50 mg/kg/day and serum albumin level ≤ 30 g/l (prevalence: 16/100,000; incidence: 2-7/100,000 cases per year). Glucocorticoids are preferred to obtain remission. Diuretics and albumin infusions are used in oedema reduction. In cases of extreme overhydration, renal replacement therapy (RRT) is advised. A 16-year-old boy with no past medical history was admitted in critical condition due to massive oedema and anuria. Standard NS treatment was introduced on admission. The patient underwent continuous RRT combined with loop diuretics and albumin administration. Thirty-six litres of ultrafiltrate was achieved. No relapse was observed within 6 months of discharge. The presented case is unusual due to the enormous oedema, reaching approximately 30% of the initial body weight, which led to a vital clinical problem. The use of continuous RRT combined with steroid therapy allowed for a safe evacuation of the oedema and remission.

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“…From July 2018 through June 2021, the authors identified 77 unique antimicrobial agents administered during 812 admissions requiring CRRT [19]. In a recent systematic review of published studies from 1990 to 2021 focusing on drugs administered during pediatric CRRT, Dubinsky et al [20] identified 45 relevant studies containing data on 33 unique medications, with 29 (64%) studies providing dosing recommendations. Antibiotics represented the most frequently studied drug class (42%), followed by antivirals (12%), antifungals (12%), vasoactives (12%), and anticonvulsants (6%).…”

Section: Current State Of Pk Knowledge In Pediatric Ecmo and Crrtmentioning

confidence: 99%

Pharmacokinetic Research in Pediatric Extracorporeal Therapies: Current State and Future Directions

Stitt,

Thibault,

Mueller

et al. 2024

Blood Purif

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Extracorporeal life support (ECLS), including extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT), are life-saving therapies for critically ill children. Despite this, these modalities carry frustratingly high mortality rates. One driver of mortality may be altered drug disposition due to a combination of underlying illness, patient-circuit interactions, and drug-circuit interactions. Children receiving ECMO and/or CRRT routinely receive 20 or more drugs, and data supporting optimal dosing is lacking for most of these medications. The Pediatric Paracorporeal and Extracorporeal Therapies Summit (PPETS) gathered an international group of experts in the fields of ECMO, CRRT, and other ECLS modalities to discuss the current state of these therapies, disseminate innovative support strategies, share clinical experiences, and foster future collaborations. Here, we summarize the conclusions of PPETS and put forward a pathway to optimize pharmacokinetic (PK) research in this population. We must prioritize specific medications for in-depth study to improve drug use in ECLS and patient outcomes. Based on frequency of use, potential for adverse outcomes if dosed inappropriately, and lack of existing PK data, a list of high priority drugs was compiled for future research. Researchers must additionally reconsider study designs, emphasizing pooling of resources through multi-center studies and the use of innovative PK modeling techniques. Finally, the integration of validated PK models into clinical practice must be streamlined to deliver optimal medication use at the bedside. Focusing on the proposed list of highlighted medications and key methodological considerations will maximize the impact of future research.

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Pharmacokinetics of Commonly Used Medications in Children Receiving Continuous Renal Replacement Therapy: A Systematic Review of Current Literature

Cited by 10 publications

References 143 publications

Anakinra Removal by Continuous Renal Replacement Therapy: An Ex Vivo Analysis

Anakinra Removal by Continuous Renal Replacement Therapy: An Ex Vivo Analysis

Treatment of extreme overhydration in an adolescent boy with idiopathic nephrotic syndrome

Pharmacokinetic Research in Pediatric Extracorporeal Therapies: Current State and Future Directions

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