AbstractIntroductionLow‐level pressure support ventilation (PSV) is most commonly adopted in spontaneous breathing trials (SBTs), and some have proposed setting the positive end‐expiratory pressure (PEEP) to 0 cmH2O in order to shorten the observation time of SBTs. This study aims to investigate the effects of two PSV protocols on the patients' respiratory mechanics.Material and methodA prospective randomized self‐controlled crossover design was adopted in this study, which involved enrolling 30 difficult‐to‐wean patients who were admitted to the intensive care unit of the First Affiliated Hospital of Guangzhou Medical University between July 2019 and September 2021. Patients were subjected to the S group (pressure support: 8 cmH2O, PEEP: 5 cmH2O) and S1 group (PS: 8 cmH2O, PEEP: 0 cmH2O) for 30 min in a random order, and respiratory mechanics indices were dynamically monitored via a four‐lumen multi‐functional catheter with an integrated gastric tube. Among the 30 enrolled patients, 27 were successfully weaned.ResultThe S group showed higher airway pressure (Paw), intragastric pressure (Pga) and airway pressure–time product (PTP) than the S1 group. The S group also showed a shorter inspiratory trigger delay, (93.80 ± 47.85) versus (137.33 ± 85.66) ms (P= 0.004); and fewer abnormal triggers, (0.97 ± 2.65) versus (2.67 ± 4.48) (P= 0.042) compared with the S1 group. Stratification based on the causes of mechanical ventilation revealed that under the S1 protocol, patients with chronic obstructive pulmonary disease (COPD) had a longer inspiratory trigger delay compared to both post‐thoracic surgery (PTS) patients and patients with acute respiratory distress syndrome. Despite providing greater respiratory support, S group led to significant reductions in inspiratory trigger delay and less abnormal triggers compared to S1 group, especially among patients with chronic obstructive pulmonary disease.ConclusionThese findings suggest that the zero PEEP group was more likely to induce a higher number of patient–ventilator asynchronies in difficult‐to‐wean patients.