We hypothesized that placing the arm in 90° abduction, through 90° flexion and 90° external rotation, could improve ultrasound visualization of the subclavian vein. In 49 healthy volunteers, a single operator performed a view of the subclavian vein in neutral position and abduction position. A second blinded operator measured the cross-sectional area of the subclavian vein. Abduction position increased the cross-sectional area of the subclavian vein from 124 ± 46 (mean ± SD) to 162 ± 58 mm (P = 0.001). An increase of the cross-sectional area of ≥50% was observed in 41% volunteers (95% confidence interval, 27%-56%, n = 20); this technique offers an alternative approach (maybe safer) for ultrasound-guided catheterization of the subclavian vein.
Isavuconazole is a triazole antifungal agent recently recommended as first-line therapy for invasive pulmonary aspergillosis. With the COVID-19 pandemic, cases of COVID-19-associated pulmonary aspergillosis (CAPA) have been described with a prevalence ranging from 5 to 30%. We developed and validated a population pharmacokinetic (PKpop) model of isavuconazole plasma concentrations in intensive care unit patients with CAPA. Nonlinear mixed-effect modeling Monolix software were used for PK analysis of 65 plasma trough concentrations from 18 patients. PK parameters were best estimated with a one-compartment model. The mean of ISA plasma concentrations was 1.87 [1.29–2.25] mg/L despite prolonged loading dose (72 h for one-third) and a mean maintenance dose of 300 mg per day. Pharmacokinetics (PK) modeling showed that renal replacement therapy (RRT) was significantly associated with under exposure, explaining a part of clearance variability. The Monte Carlo simulations suggested that the recommended dosing regimen did not achieve the trough target of 2 mg/L in a timely manner (72 h). This is the first isavuconazole PKpop model developed for CAPA critical care patients underlying the need of therapeutic drug monitoring, especially for patients under RRT.
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