Effect of Automated Closed-Loop Ventilation vs Protocolized Conventional Ventilation on Ventilator-Free Days in Critically Ill Adults: A Randomized Clinical Trial

Abstract

Importance: Automated closed-loop ventilation systems continuously adjust ventilator settings based on real-time physiologic feedback and may optimize lung-protective ventilation. Their effect on patient-centered outcomes in critically ill patients receiving ventilation remains uncertain. Objective: To determine whether early initiation of automated closed-loop ventilation increases ventilator-free days at day 28 compared with protocolized conventional ventilation. Design, Setting, and Participants: International, multicenter, randomized clinical trial conducted at 7 intensive care units (ICUs) in the Netherlands and Switzerland. Adult patients with less than 1 hour elapsed after initiation of invasive ventilation and expected to require ventilation for 24 hours or longer were enrolled between October 2020 and June 2025, with final follow-up completed at 90 days. Interventions: Patients were randomly assigned (1:1) to receive automated closed-loop ventilation using INTELLiVENT adaptive support ventilation (n = 602) or protocolized conventional ventilation (n = 599). Both groups followed standardized ventilation management, sedation, and weaning protocols. Main Outcomes and Measures: The primary outcome was the number of ventilator-free days at day 28, defined as days alive and free from invasive ventilation. Secondary outcomes included mortality, duration of ventilation among survivors, ICU and hospital lengths of stay, and ventilation quality. Safety outcomes included severe hypoxemia, hypercapnia, and need for rescue therapies, including prone positioning, recruitment maneuvers, or bronchoscopy. Results: Among 1514 randomized patients, 1201 (79%) were included in the modified intention-to-treat analysis (36% women; median age, 63 years). The median of ventilator-free days at day 28 was 16.7 days (IQR, 0.0-26.1 days) in the closed-loop ventilation group and 16.3 days (IQR, 0.0-26.5 days) in the conventional ventilation group (odds ratio, 0.91; 95% CI, 0.77-1.06; P =.23). There were no differences between groups in components of the primary outcome, ie, duration of ventilation in survivors and 28-day mortality. There were no differences in secondary outcomes except for ventilation quality, which was higher with closed-loop ventilation. Severe hypercapnia and hypoxemia were less frequent in the closed-loop group, and fewer patients required rescue therapies, primarily prone positioning, compared with the conventional group (non-statistically significant after multiplicity adjustment). Conclusions and Relevance: Among critically ill adults receiving invasive mechanical ventilation, early use of an automated closed-loop ventilation system did not increase ventilator-free days at day 28 compared with protocolized conventional ventilation. Trial Registration: Clinicaltrials.gov Identifier: NCT04593810