Effect of a driving pressure-limiting strategy for patients with acute respiratory distress syndrome secondary to community-acquired pneumonia: the STAMINA randomised clinical trial

Abstract

Background: This study aimed to assess whether a driving pressure-limiting strategy based on positive end-expiratory pressure (PEEP) titration according to best respiratory system compliance and tidal volume adjustment increases the number of ventilator-free days within 28 days in patients with moderate to severe acute respiratory distress syndrome (ARDS).

Methods: This is a multi-centre, randomised trial, enrolling adults with moderate to severe ARDS secondary to community-acquired pneumonia. Patients were randomised to a driving pressure-limiting strategy or low PEEP strategy based on a PEEP:FiO₂ table. All patients received volume assist-control mode until day 3 or when considered ready for spontaneous modes of ventilation. The primary outcome was ventilator-free days within 28 days. Secondary outcomes were in-hospital and intensive care unit mortality at 90 days.

Results: The trial was stopped because of recruitment fatigue after 214 patients were randomised. In total, 198 patients (n=96 intervention group, n=102 control group) were available for analysis (median age 63 yr, [interquartile range 47-73 yr]; 36% were women). The mean difference in driving pressure up to day 3 between the intervention and control groups was -0.7 cm H₂O (95% confidence interval -1.4 to -0.1 cm H₂O). Mean ventilator-free days were 6 (sd 9) in the driving pressure-limiting strategy group and 7 (9) in the control group (proportional odds ratio 0.72, 95% confidence interval 0.39-1.32; P=0.28). There were no significant differences regarding secondary outcomes.

Conclusions: In patients with moderate to severe ARDS secondary to community-acquired pneumonia, a driving pressure-limiting strategy did not increase the number of ventilator-free days compared with a standard low PEEP strategy within 28 days.

Clinical trial registration: NCT04972318.

Keywords: acute respiratory distress syndrome; driving pressure; positive end-expiratory pressure; tidal volume; ventilator-induced lung injury.

Fig 1

Enrolment, randomisation, and follow-up of the study participants. The screening process, selection, and flow of patients through the trial are presented. Patients or next of kin were asked to provide consent after randomisation. The reason for the post-randomisation exclusions was the death of the participants before their next of kin could provide consent, combined with the lack of authorisation from the ethics committee to include data from these patients. Patients can have more than one reason for exclusion from the trial.

Fig 2

Primary outcome distribution. Data derived from the intention-to-treat population, consisting of all randomised patients with informed consent, are presented. A primary outcome is defined as ventilator-free days in 28 days. The figure illustrates a line graph mapping the cumulative frequency of ventilator-free days on the y-axis against the number of ventilator-free days on the x-axis, for two distinct groups. The intervention group is represented by a blue line, whereas the control group is depicted with an orange line. Each point along the lines corresponds to the cumulative frequency of patients achieving up to that number of ventilator-free days. Despite the visual trends suggested by the lines, statistical analysis indicates no significant differences between the two groups across the range of categories represented. The graph thus conveys the comparative outcomes of the intervention and control groups with respect to the duration of ventilator-free periods.

Fig 3

Ordinal primary outcome divided into 28 categories. The figure presents a categorical distribution of mechanical ventilation-free days among patients, depicted across 28 categories. The category representing zero ventilator-free days is highlighted in dark green, signifying the highest frequency within the dataset. Progressively, categories indicating a greater number of ventilator-free days are denoted with progressively more intense shades of orange.