The efficacy of P0.1-guided sedation protocol in critically ill patients receiving invasive mechanical ventilation: A randomized controlled trial

Background: Mechanical ventilation is a lifesaving treatment in patients with acute respiratory failure. Despite optimal support, some patients still exhibit excessive respiratory drive, leading to patient self-inflicted lung injury (P-SILI) and diaphragmatic dysfunction. Sedation and muscle relaxants are commonly used to reduce respiratory efforts and manage patient-ventilator asynchrony (PVA). Conventionally, sedative drugs are adjusted based on the sedation level assessed by the Richmond Agitation-Sedation Scale (RASS), which may not correlate with the patient’s respiratory drive. Drop in airway pressure at the first 100 milliseconds of the beginning of the inspiration after the end-expiratory occlusion (P0.1) is a simple and reliable method of respiratory drive monitoring by mechanical ventilation at the bedside and may be the more suitable sedation target. Objectives: To assess the efficacy of a sedation protocol targeting optimal P0.1 and RASS score compared to conventional sedation strategy in patients requiring invasive mechanical ventilation in the medical intensive care units in terms of successful extubation. Methods: This is an open-labeled, single-center, randomized controlled trial conducted in medical intensive care units at a tertiary care hospital in Bangkok, Thailand. We randomly allocated mechanically ventilated patients in a 1:1 ratio to receive a sedation protocol targeting both optimal respiratory drive measured by P0.1 (intervention group) and light sedation (RASS 0 to -2) or standard of care (control group targeting RASS alone). The primary outcome is the rate of successful extubation within 14 days after randomization. Hypothesis: We hypothesize that sedation protocol targeting optimal P0.1 and light sedation will increase the rate of successful extubation at 14 days in mechanically ventilated patients compared to conventional sedation strategy. Conclusions: This study aims to evaluate the efficacy of a sedation protocol using P0.1 measurement to monitor and target optimal respiratory drive, in conjunction with sedation scores, in critically ill patients receiving invasive mechanical ventilation. Ethics and dissemination: This study protocol was approved by the Human Research Protection Unit of the Faculty of Medicine, Siriraj Hospital, Mahidol University (Certificate of Approval no. Si 915/2023). Trial registration: NCT06203405