The objective of the present prospective pharmacokinetic study was to describe the variability of plasma gentamicin concentrations in critically ill patients with acute kidney injury (AKI) necessitating extended daily diafiltration (EDD-f) using a population pharmacokinetic model and to subsequently perform Monte Carlo dosing simulations to determine which dose regimen achieves the pharmacodynamic targets the most consistently. We collected data from 28 gentamicin doses in 14 critically ill adult patients with AKI requiring EDD-f and therapeutic gentamicin. Serial plasma samples were collected. A population pharmacokinetic model was used to describe the pharmacokinetics of gentamicin and perform Monte Carlo simulations with doses of between 3 mg/kg of body weight and 7 mg/kg and at various time points before commencement of EDD-f to evaluate the optimal dosing regimen for achieving pharmacodynamic targets. A two-compartment pharmacokinetic model adequately described the gentamicin clearance while patients were on and off EDD-f. The plasma half-life of gentamicin during EDD-f was 13.8 h, whereas it was 153.4 h without EDD-f. Monte Carlo simulations suggest that dosing with 6 mg/kg every 48 h either 30 min or 1 h before the commencement of EDD-f results in 100% attainment of the target maximum concentration drug in plasma (<10 mg/liter) and sufficient attainment of the target area under the concentration-time curve from 0 to 24 h (AUC0-24; 70 to 120 mg·h/liter). None of the simulated dosing regimens satisfactorily achieved the targets of the minimum concentrations of drug in plasma (<1.0 mg/liter) at 24 h. In conclusion, dosing of gentamicin 30 min to 1 h before the commencement of an EDD-f treatment enables attainment of target peak concentrations for maximal therapeutic effect while enhancing drug clearance to minimize toxicity. Redosing in many patients should occur after 48 h, and we recommend the use of therapeutic drug monitoring to guide dosing to optimize achievement of the AUC0-24 targets.

This is the first population pharmacokinetic study of vancomycin in patients receiving PIRRT and we observed large pharmacokinetic variability. Empirically, weight-based doses that are appropriate for the duration of PIRRT, should be selected and supplemented with therapeutic drug monitoring.

Background: Early warning tools have been widely implemented without evidence to guide (a) recognition and (b) response team expertise optimisation. With growing databases from MET-calls and digital hospitals, we now have access to guiding information. The Queensland Adult-Deterioration-Detection-System (Q-ADDS) is widely used and requires validation.Aim: Compare the accuracy of Q-ADDS to National Early Warning Score (NEWS), Between-the-Flags (BTF) and the electronic Cardiac Arrest Risk Triage Score (eCART)).Methods: Data from the Chicago University hospital database were used. Clinical deterioration was defined as unplanned admission to ICU or death.Currently used NEWS, BTF and eCART trigger thresholds were compared with a clinically endorsed Q-ADDS variant.Results: Of 224,912 admissions, 11,706 (5%) experienced clinical deterioration. Q-ADDS (AUC 0.71) and NEWS (AUC 0.72) had similar predictive accuracy, BTF (AUC 0.64) had the lowest, and eCART (AUC 0.76) the highest. Early warning alert (advising ward MO review) had similar NPV (99.2À99.3%), for all the four tools however sensitivity varied (%: Q-ADDS = 47/NEWS = 49/BTF = 66/eCART = 40), as did alerting rate (% vitals sets: Q-ADDS = 1.4/NEWS = 3.5/ BTF = 4.1/eCART = 3.4). MET alert (advising MET/critical-care review) had similar NPV for all the four tools (99.1À99.2%), however sensitivity varied

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