Drug Dosing in Critically Ill Adult Patients with Augmented Renal Clearance.

Augmented renal clearance (ARC) is a phenomenon of enhanced renal function seen in critically ill patients. ARC alters the disposition of renally eliminated medications currently used in the intensive care unit, resulting in underdosing and potential therapy failure. Our review addresses the rising concern of inadequate dosing in patients with ARC by summarizing the currently available evidence. To our knowledge, this guide is the first to provide clinicians with dose recommendation insights for renally eliminated agents in adult critically ill patients with ARC. A comprehensive literature search using MEDLINE, Embase, Cochrane Library, CINAHL, Scopus, and ProQuest Dissertations and Theses Global was conducted until 3 November 2021. Screening and data extraction were conducted in two steps: title and abstract screening followed by full-text review. Full text review resulted in a total of 51 studies included in this review. The results demonstrated the need for higher-than-standard doses for meropenem, imipenem, and vancomycin and reduced dosing intervals for ceftriaxone in patients with ARC. The potential need for increased dosing frequency in patients with ARC was also found for both enoxaparin and levetiracetam. In conclusion, ARC has been shown to influence the probability of target attainment in several medications requiring dosing changes to mitigate the risk of therapeutic failure.

Prevalence and Risk Factors of Augmented Renal Clearance: A Systematic Review and Meta-Analysis.

Kidney function assessment in the critically ill overlooks the possibility for hyperfunctioning kidneys, known as augmented renal clearance (ARC), which could contribute to therapeutic failures in the intensive care unit (ICU). The aim of this research is to conduct a systematic review and meta-analysis of prevalence and risk factors of ARC in the critically ill. MEDLINE, Embase, Cochrane Library, CINAHL, Scopus, ProQuest Dissertations and Theses Global databases were searched on 27 October 2020. We included studies conducted in critically ill adults who reported the prevalence and/or risk factors of ARC. We evaluated study quality using the Joanna Briggs Institute appraisal tool. Case reports, reviews, editorials and commentaries were excluded. We generated a random-effects meta-analytic model using the inverse variance method and visualized the pooled estimates using forest plots. Seventy studies were included. The pooled prevalence (95% CI) was 39% (34.9-43.3). Prevalence for neuro, trauma, mixed and sepsis ICUs were 74 (55-87), 58 (48-67), 36 (31-41) and 33 (21-48), respectively. Age, male sex and trauma were associated with ARC with pooled OR (95% CI) of 0.95 (0.93-0.96), 2.36 (1.28-4.36), 2.60 (1.21-5.58), respectively. Limitations included variations in ARC definition, inclusion and exclusion criteria and studies design. In conclusion, ARC is prevalent in critically ill patients, especially those in the neurocritical care and trauma ICU population. Young age, male sex and trauma are risk factors for ARC in those with apparently normal renal function. Further research on optimal dosing of drugs in the setting of ARC is warranted. (Prospero registration: CRD42021246417).