Key PointsQuestion
In patients with an acute exacerbation of chronic obstructive pulmonary disease and hypercapnia who first received 6 hours of low-intensity noninvasive positive pressure ventilation (NPPV), does high-intensity NPPV decrease the likelihood of meeting prespecified criteria for the need for endotracheal intubation compared with continuing low-intensity NPPV?
Findings
In this randomized clinical trial involving 300 patients, 4.8% of patients randomized to high-intensity NPPV met prespecified criteria for the need for endotracheal intubation vs 13.7% randomized to low-intensity NPPV, which is a significant difference. However, the rates of endotracheal intubation did not differ significantly between the high-intensity NPPV group (3.4%) and the low-intensity NPPV group (3.9%).
Meaning
Patients with an acute exacerbation of chronic obstructive pulmonary disease and persistent hypercapnia were significantly less likely to meet criteria for the need for endotracheal intubation when randomized to high-intensity vs low-intensity NPPV, although patients in the low-intensity NPPV group were allowed to crossover to high-intensity NPPV and the endotracheal intubation rate did not significantly differ between groups.
Importance
The effect of high-intensity noninvasive positive pressure ventilation (NPPV) on the need for endotracheal intubation in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) is unknown.
Objective
To determine whether the use of high-intensity NPPV vs low-intensity NPPV reduces the need for endotracheal intubation in patients with an acute exacerbation of COPD and hypercapnia.
Design, Setting, and Participants
Randomized clinical trial conducted at 30 general respiratory non–intensive care unit wards of Chinese hospitals from January 3, 2019, to January 31, 2022; the last 90-day follow-up was on April 22, 2022. The included patients had an acute exacerbation of COPD and a Paco2 level greater than 45 mm Hg after receiving 6 hours of low-intensity NPPV.
Interventions
Patients were randomized 1:1 to receive high-intensity NPPV with inspiratory positive airway pressure that was adjusted to obtain a tidal volume 10 mL/kg to 15 mL/kg of predicted body weight (n = 147) or to continue receiving low-intensity NPPV with inspiratory positive airway pressure that was adjusted to obtain a tidal volume of 6 mL/kg to 10 mL/kg of predicted body weight (n = 153). Patients in the low-intensity NPPV group who met the prespecified criteria for the need for endotracheal intubation were allowed to crossover to high-intensity NPPV.
Main Outcomes and Measures
The primary outcome was the need for endotracheal intubation during hospitalization, which was defined by prespecified criteria. There were 15 prespecified secondary outcomes, including endotracheal intubation.
Results
The trial was terminated by the data and safety monitoring board and the trial steering committee after an interim analysis of the first 300 patients. Among the 300 patients who completed the trial (mean age, 73 years [SD, 10 years]; 68% were men), all were included in the analysis. The primary outcome of meeting prespecified criteria for the need for endotracheal intubation occurred in 7 of 147 patients (4.8%) in the high-intensity NPPV group vs 21 of 153 (13.7%) in the low-intensity NPPV group (absolute difference, −9.0% [95% CI, −15.4% to −2.5%], 1-sided P = .004). However, rates of endotracheal intubation did not significantly differ between groups (3.4% [5/147] in the high-intensity NPPV group vs 3.9% [6/153] in the low-intensity NPPV group; absolute difference, −0.5% [95% CI, −4.8% to 3.7%], P = .81). Abdominal distension occurred more frequently in the high-intensity NPPV group (37.4% [55/147]) compared with the low-intensity NPPV group (25.5% [39/153]).
Conclusions and Relevance
Patients with COPD and persistent hypercapnia in the high-intensity NPPV group (vs patients in the low-intensity NPPV group) were significantly less likely to meet criteria for the need for endotracheal intubation; however, patients in the low-intensity NPPV group were allowed to crossover to high-intensity NPPV, and the between-group rate of endotracheal intubation was not significantly different.
Trial Registration
ClinicalTrials.gov Identifier: NCT02985918