Augmented renal clearance: a common condition in critically ill children

Heggen, Tatjana Van Der; Dhont, Evelyn; Peperstraete, Harlinde; Delanghe, Joris; Walle, Johan Vande; Paepe, Peter De; Cock, Pieter De

doi:10.1007/s00467-019-04205-x

Cited by 60 publications

(66 citation statements)

References 46 publications

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“…This counter-intuitive finding of reduced exposure in critically ill children, may be explained by a high incidence of ARC. Contrary to AKI, ARC has been identified in up to 67% of both critically ill adults [8] and children [10]. This is in line with several studies in this review showing extremely high drug Cl and/or eGFR in this patient population [21,26,50,52].…”

Section: Discussionsupporting

confidence: 87%

“…This non-target attainment in critically ill patients is caused by pathophysiological changes in volume of distribution (Vd), protein binding and/ or drug clearance (Cl) [4][5][6]. Contrary to renal dysfunction, an increased renal clearance caused by hemodynamic alterations during critical illness, described as augmented renal clearance (ARC), is reported in up to 65% of critically ill adults [7,8] and children [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics and Target Attainment of Antibiotics in Critically Ill Children: A Systematic Review of Current Literature

et al. 2019

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Background Pharmacokinetics (PK) are severely altered in critically ill patients due to changes in volume of distribution (Vd) and/or drug clearance (Cl). This affects the target attainment of antibiotics in critically ill children. We aimed to identify gaps in current knowledge and to compare published PK parameters and target attainment of antibiotics in critically ill children to healthy children and critically ill adults. Methods Systematic literature search in PubMed, EMBASE and Web of Science. Articles were labelled as relevant when they included information on PK of antibiotics in critically ill, non-neonatal, pediatric patients. Extracted PK-parameters included Vd, Cl, (trough) concentrations, AUC, probability of target attainment, and elimination half-life. Results 50 relevant articles were identified. Studies focusing on vancomycin were most prevalent (17/50). Other studies included data on penicillins, cephalosporins, carbapenems and aminoglycosides, but data on ceftriaxone, ceftazidime, penicillin and metronidazole could not be found. Critically ill children generally show a higher Cl and larger Vd than healthy children and critically ill adults. Reduced target-attainment was described in critically ill children for multiple antibiotics, including amoxicillin, piperacillin, cefotaxime, vancomycin, gentamicin, teicoplanin, amikacin and daptomycin. 38/50 articles included information on both Vd and Cl, but a dosing advice was given in only 22 articles. Conclusion The majority of studies focus on agents where TDM is applied, while other antibiotics lack data altogether. The larger Vd and higher Cl in critically ill children might warrant a higher dose or extended infusions of antibiotics in this patient population to increase target-attainment. Studies frequently fail to provide a dosing advice for this patient population, even if the necessary information is available. Our study shows gaps in current knowledge and encourages future researchers to provide dosing advice for special populations whenever possible.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and Target Attainment of Antibiotics in Critically Ill Children: A Systematic Review of Current Literature

et al. 2019

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“…The main classes of time-dependent antibiotics include beta-lactams (penicillins, cephalosporins, carbapenems, monobactams) and lincosamides (clindamycin and lincomycin). For amoxicillin-clavulanic acid, current published dosing regimens in critically ill children can result in sub-therapeutic concentrations in the early period of sepsis due to augmented renal clearance [119,120]. In sepsis, the use of continuous or extended infusions with loading doses, as opposed to intermittent dosing, may lead to improved outcomes in patients treated with beta-lactam antibiotics [121].…”

mentioning

confidence: 99%

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

et al. 2020

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Objectives: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction.Design: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those The Society of Critical Care Medicine guidelines are intended for general information only, are not medical advice, and do not replace professional advice, which should be sought for any medical condition. The full disclaimer for guidelines can be accessed at https ://www.sccm.org/Resea rch/Guide lines /Guide lines . panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. Methods:The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. Results:The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 52 research priorities were identified. Conclusions:A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research. S14 the group heads, panel members, and methodologists. Searches utilized ...

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“…Van Der Heggen and colleagues observed that approximately two-thirds of the 105 critically ill pediatric study patients had ARC [ 21 ]. Similar to in the adult population, calculated estimates of renal function pale in comparison to direct measurement [ 21 , 22 ] and subtherapeutic concentrations are a natural consequence [ 22 ]. As will be discussed, the same strategies used to address ARC in adults can theoretically be used for pediatric patients.…”

Section: Identifying Augmented Renal Clearancementioning

confidence: 99%

Augmented Renal Clearance and How to Augment Antibiotic Dosing

Chen

Nicolau

2020

Antibiotics

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Augmented renal clearance (ARC) refers to the state of heightened renal filtration commonly observed in the critically ill. Its prevalence in this patient population is a consequence of the body’s natural response to serious disease, as well as the administration of fluids and pharmacologic therapies necessary to maintain sufficient blood pressure. ARC is objectively defined as a creatinine clearance of more than 130 mL/min/1.73 m2 and is thus a crucial condition to consider when administering antibiotics, many of which are cleared renally. Using conventional dosing regimens risks the possibility of subtherapeutic concentrations or clinical failure. Over the past decade, research has been conducted in patients with ARC who received a number of antibacterials frequently used in the critically ill, such as piperacillin-tazobactam or vancomycin. Strategies to contend with this condition have also been explored, though further investigations remain necessary.

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Augmented renal clearance: a common condition in critically ill children

Cited by 60 publications

References 46 publications

Pharmacokinetics and Target Attainment of Antibiotics in Critically Ill Children: A Systematic Review of Current Literature

Pharmacokinetics and Target Attainment of Antibiotics in Critically Ill Children: A Systematic Review of Current Literature

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

Augmented Renal Clearance and How to Augment Antibiotic Dosing

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