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Abstract Altered physiology caused by critical illness may change midazolam pharmacokinetics and thereby result in adverse reactions and outcomes in this vulnerable patient population. This study set out to determine which critical illness‐related factors impact midazolam pharmacokinetics in children using population modeling. This was an observational, prospective, controlled study of children receiving IV midazolam as part of routine care. Children recruited into the study were either critically‐ill receiving continuous infusions of midazolam or otherwise well, admitted for elective day‐case surgery (control) who received a single IV bolus dose of midazolam. The primary outcome was to determine the population pharmacokinetics and identify covariates that influence midazolam disposition during critical illness. Thirty‐five patients were recruited into the critically ill arm of the study, and 54 children into the control arm. Blood samples for assessing midazolam and 1‐OH‐midazolam concentrations were collected opportunistically (critically ill arm) and in pre‐set time windows (control arm). Pharmacokinetic modeling demonstrated a significant change in midazolam clearance with acute inflammation (measured using C‐Reactive Protein), cardio‐vascular status, and weight. Simulations predict that elevated C‐Reactive Protein and compromised cardiovascular function in critically ill children result in midazolam concentrations up to 10‐fold higher than in healthy children. The extremely high concentrations of midazolam observed in some critically‐ill children indicate that the current therapeutic dosing regimen for midazolam can lead to over‐dosing. Clinicians should be aware of this risk and intensify monitoring for oversedation in such patients.

The CYGNO project aims at developing a high resolution Time Projection Chamber with optical readout for directional dark matter searches and solar neutrino spectroscopy. Peculiar CYGNO’s features are the 3D tracking capability provided by the combination of photomultipliers and scientific CMOS camera signals, combined with a helium-fluorine-based gas mixture at atmospheric pressure amplified by gas electron multipliers structures. In this paper, the performances achieved with CYGNO prototypes and the prospects for the upcoming underground installation at Laboratori Nazionali del Gran Sasso of a 50-L detector in fall 2021 will be discussed, together with the plans for a 1-m3 experiment. The synergy with the ERC consolidator, grant project INITIUM, aimed at realising negative ion drift operation within the CYGNO 3D optical approach, will be further illustrated.