A study investigating the use of lorazepam for analgosedation during mechanical ventilation in children in the pediatric intensive care unit as an off-label alternative to midazolam. Lorazepam has an intermediate duration of action suitable for continuous sedation, but dosing in children has limited evidence. Using pharmacokinetic modeling and clinical trial simulations on a virtual cohort of 100 children aged 1–12 years, optimized dosing regimens with a target concentration of 500 ng/ml were identified. The model described concentration profiles with population estimates of clearance of 0.23 L/h/kg and volume of distribution of 2.3 L/kg. The recommended regimen includes an initial bolus dose of 0.2 mg/kg every 4 hours for the first 24 hours, then 0.1 mg/kg every 4 hours for the next 24 hours, and a continuous infusion of 0.03 mg/kg/h. This regimen maintains concentrations around the target value and balances efficacy with safety. It is proposed to be evaluated in a prospective clinical trial. Data are from a pilot study in 6 children aged 0.8–4 years using the COMFORT-B score.