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).

Background: Nimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH) and current guidelines suggest that patients with aSAH receive nimodipine for 21 days. Patients with no difficulty swallowing will swallow the whole capsules or tablets; otherwise, nimodipine liquid must be drawn from capsules, tablets need to be crushed, or the commercially available liquid product be used to facilitate administration through an enteral feeding tube (FT). It is not clear whether these techniques are equivalent. The goal of the study was to determine if different nimodipine formulations and administration techniques were associated with the safety and effectiveness of nimodipine in aSAH.Methods: This was a retrospective multicenter observational cohort study conducted in 21 hospitals across North America. Patients admitted with aSAH and received nimodipine by FT for ≥3 days were included. Patient demographics, disease severity, nimodipine administration, and study outcomes were collected. Safety end points included the prevalence of diarrhea and nimodipine dose reduction or discontinuation secondary to blood pressure reduction. Predictors of the study outcomes were analyzed using regression modeling.Results: A total of 727 patients were included. Administration of nimodipine liquid product was independently associated with higher prevalence of diarrhea compared to other administration techniques/formulations (Odds ratio [OR] 2.28, 95% confidence interval [CI] 1.41–3.67, p‐value = 0.001, OR 2.76, 95% CI 1.37–5.55, p‐value = 0.005, for old and new commercially available formulations, respectively). Bedside withdrawal of liquid from nimodipine capsules prior to administration was significantly associated with higher prevalence of nimodipine dose reduction or discontinuation secondary to hypotension (OR 2.82, 95% CI 1.57–5.06, p‐value = 0.001). Tablet crushing and bedside withdrawal of liquid from capsules prior to administration were associated with increased odds of delayed cerebral ischemia (OR 6.66, 95% CI 3.48–12.74, p‐value <0.0001 and OR 3.92, 95% CI 2.05–7.52, p‐value <0.0001, respectively).Conclusions: Our findings suggest that enteral nimodipine formulations and administration techniques might not be equivalent. This could be attributed to excipient differences, inconsistency and inaccuracy in medication administration, and altered nimodipine bioavailability. Further studies are needed.