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Introduction: Vancomycin is used in intensive care unit (ICU) patients for the treatment of infections caused by gram-positive bacteria. The vancomycin pharmacokinetic/pharmacodynamic index is a ratio of the area under the concentration to the minimum inhibitory concentration ≥400-600 h∗mg/L. This target can generally be achieved by a plasma concentration of 20-25 mg/L. Together with the pathophysiological alterations and pharmacokinetic variability associated with critical illness, the use of continuous renal replacement therapy (CRRT) may complicate the attainment of adequate vancomycin concentrations. The primary objective was the prevalence of attainment of vancomycin concentrations 20-25 mg/L after 24 h in adult ICU patients receiving CRRT. Secondary outcomes were to evaluate target attainment at days 2 and 3 and to calculate vancomycin clearance (CL) by CRRT and residual diuresis. Methods: We performed a prospective observational study in adult ICU patients on CRRT, which received at least 24 h continuous infusion of vancomycin. Between May 2020 and February 2021, daily vancomycin residual blood gas and dialysate samples were collected from 20 patients, every 6 h and if possible vancomycin urine samples. Vancomycin was analysed with an immunoassay method. The CL by CRRT was calculated by a different approach correcting for the downtime and providing insight into the degree of filter patency. Results: The proportion of patients with vancomycin concentrations <20 mg/L was 50% 24 h after starting vancomycin (n = 10). No differences were observed in patient characteristics. The target vancomycin concentration 20-25 mg/L was only achieved in 30% of the patients. On days 2 and 3, despite the use of TDM and albeit in lower percentages, sub- and supratherapeutic levels were still observed. Taking downtime and filter patency into account resulted in lower vancomycin CL. Conclusions: 50% of the studied ICU patients on CRRT showed subtherapeutic vancomycin concentr

Background and Objective: Many patients treated for COVID-19 related acute respiratory distress syndrome in the intensive care unit are sedated with the benzodiazepine midazolam. Midazolam undergoes extensive metabolism by CYP3A enzymes, which may be inhibited by hyperinflammation. Therefore, an exaggerated proinflammatory response, as often observed in COVID-19, may decrease midazolam clearance. To develop a population pharmacokinetic model for midazolam in adult intensive care unit patients infected with COVID-19 and to assess the effect of inflammation, reflected by IL-6, on the pharmacokinetics of midazolam. Methods: Midazolam blood samples were collected once a week between March 31 and April 30 2020. Patients were excluded if they concomitantly received CYP3A4 inhibitors, CYP3A4 inducers and/or continuous renal replacement therapy. Midazolam and metabolites were analyzed with an ultra-performance liquid chromatography–tandem mass spectrometry method. A population pharmacokinetic model was developed, using nonlinear mixed effects modelling. IL-6 and CRP, markers of inflammation, were analyzed as covariates. Results: The data were described by a one-compartment model for midazolam and the metabolites 1-OH-midazolam and 1-OH-midazolam-glucuronide. The population mean estimate for midazolam clearance was 6.7 L/h (4.8–8.5 L/h). Midazolam clearance was reduced by increased IL-6 and IL-6 explained more of the variability within our patients than CRP. The midazolam clearance was reduced by 24% (6.7–5.1 L/h) when IL-6 increases from population median 116 to 300 pg/mL. Conclusions: Inflammation, reflected by high IL-6, reduces midazolam clearance in critically ill patients with COVID-19. This knowledge may help avoid oversedation, but further research is warranted.

PURPOSE: Innovative and sustainable sampling strategies for bioanalytical quantification of drugs and metabolites have gained considerable interest. Scavenging can be stratified as a sustainable sampling strategy using residual material because it aligns with the green principles of waste reduction and sampling optimization. Scavenged sampling includes all biological fluids' (eg, blood, liquor, and urine) leftover from standard clinical care. This review elaborates on the past and current landscape of sustainable sampling within therapeutic drug monitoring, with a focus on scavenged sampling. METHODS: In February 2021, 4 databases were searched to assess the literature on the clinical use of innovative and sustainable sampling techniques without applying publication date restrictions. Studies reporting the clinical use of scavenged blood sampling and bridging studies of scavenged sampling and normal blood sampling were eligible for inclusion. RESULTS: Overall, 19 eligible studies concerning scavenged sampling were identified from 1441 records. Scavenged sampling is mainly applied in the pediatric population, although other patient groups may benefit from this strategy. The infrastructure required for scavenged sampling encounters several challenges, including logistic hurdles, storage and handling conditions, and documentation errors. A workflow is proposed with identified opportunities that guide the implementation of scavenged sampling. CONCLUSIONS: This review presents current evidence on the clinical use of scavenged sampling strategies. Scavenged sampling can be a suitable approach for drug quantification to improve dosage regimens, perform pharmacokinetic studies, and explore the value of therapeutic drug monitoring without additional sample collection.