BACKGROUND: Considerable variability exists regarding CO2 management in early 
ARDS, with the impact of arterial CO2 tension on management and outcomes poorly 
understood.
RESEARCH QUESTION: To determine the prevalence and impact of hypocapnia and 
hypercapnia on the management and outcomes of patients with early ARDS enrolled 
in the Large Observational Study to Understand the Global Impact of Severe Acute 
Respiratory Failure (LUNG SAFE) study, an international multicenter 
observational study.
STUDY DESIGN AND METHODS: Our primary objective was to examine the prevalence of 
day 1 and sustained (day 1 and 2) hypocapnia (Paco2 < 35 mm Hg), normocapnia 
(Paco2 35-45 mm Hg), and hypercapnia (Paco2 > 45 mm Hg) in patients with ARDS. 
Secondary objectives included elucidating the effect of CO2 tension on 
ventilatory management and examining the relationship with ARDS outcome.
RESULTS: Of 2,813 patients analyzed, 551 (19.6%; 95%CI, 18.1-21.1) were 
hypocapnic, 1,018 (36.2%; 95% CI, 34.4-38.0) were normocapnic, and 1,214 (43.2%; 
95% CI, 41.3-45.0) were hypercapnic, on day 1. Sustained hypocapnia was seen in 
252 (9.3%; 95% CI, 8.2-10.4), sustained normocapnia in 544 (19.3%; 95% CI, 
17.9-20.8), and sustained hypercapnia in 654 (24.1%; 95% CI, 22.5-25.7) 
patients. Hypocapnia was more frequent and severe in patients receiving 
noninvasive ventilation but also was observed in patients on controlled 
mechanical ventilation. Sustained hypocapnia was more frequent in middle-income 
countries, whereas sustained hypercapnia was more frequent in Europe. ARDS 
severity profile was highest in sustained hypercapnia, and these patients 
received more protective ventilation. No independent association was seen 
between arterial CO2 and outcome. In propensity-matched analyses, the hospital 
mortality rate was 36% in both sustained normocapnic and hypercapnic patients 
(P = 1.0). ICU mortality was higher in patients with mild to moderate ARDS 
receiving sustained hypocapnia (38.1%) compared with normocapnia (27.1%).
INTERPRETATION: No evidence was found for benefit or harm with hypercapnia. Of 
concern, ICU mortality was higher with sustained hypocapnia in mild to moderate 
ARDS.