Patient enrollment and clinical features
Of 1,778 patients with acute respiratory failure who needed invasive mechanical ventilation, 370 (20.8%) fulfilled the criteria of ARDS in the first 24 hours of ICU admission (Figure 1). The hospital mortality of patients with ARDS was 42.2%, while in those without ARDS it was just 21.0%. In this cohort of ARDS patients, the average age was 67.7 years old. There were more male (68.1%) than female (31.9%) patients. Most of these ARDS patients were admitted via the emergency room (81.9%) and there were more in the medical (79.7%) ICU compared with the surgical (20.3%) ICU. The overall disease severity in this cohort of ARDS patients was high in terms of APACHE II and SOFA scores at admission and on the following ICU days. Comorbidities were common among ARDS patients. Diabetes, renal disease and malignancy were the most common comorbidities in this cohort. The etiology of ARDS came primarily from pulmonary (80.5%) causes as opposed to extrapulmonary (19.5%) causes. The leading causes of ARDS were pneumonia and aspiration for pulmonary ARDS and sepsis for extrapulmonary ARDS. ADRS patients also consumed a substantial amount of medical resources, with long ICU stays (13, 8-22 days), hospital stays (29.5, 18-46 days) and ventilator days (13, 7-24 days) (Table 1).
ARDS severity
In this cohort of 370 patients, 103 (27.8%) had mild ARDS, 196 (53%) had moderate and 71 had severe (19.2%). The increasing severity of ARDS was paralleled by a worsening of the APCHE II and SOFA scores at admission and on the following ICU days. There was no significant difference in age, sex, admission source, ICU type, CCI and etiology among the three severity groups. Patients with higher severity ARDS had a higher body mass index (BMI). Among the co-morbidities, dementia was more common in milder ARDS patients. The clinical outcomes, including ICU stay, hospital stay, ventilator-days and hospital mortality, were not significantly different among the three groups (Table S1).
Mechanical ventilation and adjunctive treatments in ARDS
Mechanical ventilation management on the first day of ICU admission varies with ARDS severity. Volume-targeted ventilation (82.4%) was preferred in this cohort of patients. For the ventilator settings, FiO2, PEEP and respiratory rate increased with ARDS severity, whereas VT decreased. The measured pressures, including PIP, Pplat and driving pressure changed in parallel with ARDS severity. The average VT was 7.5 ± 1.6 mL/kg PBW and 65.5% of these patients had ≤8mL/kg PBW. Pplat was measured in 84.3% of patients and the average Pplat was 21.5 ± 5.2 cm H2O; 96.2% of these patients had ≤30 cm H2O. A total of 64.4% of these patients received protective mechanical ventilation as defined by a VT of ≤8 mL/kg PBW and a Pplat ≤30 cm H2O. The average driving pressure was 12.9 ± 4.1 cm H2O and 66.4% of these patients had ≤14 cm H2O. Positive end-expiratory pressure was relatively low with the average PEEP 8.8 ± 4.1 cm H2O in all patients and 10.2 ± 3.0 cm H2O in severe patients.
The use of adjunctive treatments in patients with ARDS was relatively low but increased with ARDS severity. In patients with severe ARDS, the percentages of patients using extracorporeal membrane oxygenation, prone position, and recruitment maneuver were 5.6% , 15.5%, and 26.8%, respectively. Neuromuscular blockade was used in 43.0% of all patients and in 64.8% of severe ARDS patients (Table S2).
Characteristics of ARDS patients according to driving pressure
We further analyzed the characteristics of patients by driving pressure. Driving pressure at admission was available in 318 (85.9%) of the patients. Those with a driving pressure >14 cmH2O had a significantly lower survival rate (33.6% vs 52.3%, p=0.001) (Table S3). There was no significant difference in age, gender, BMI, comorbidities, admission source, type of ICU, etiology, length of ICU stay, length of hospital stay or ventilator days between groups of driving pressure (DP) ≤14cmH2O and DP >14 cmH2O. In ARDS patients with different DPs, the ventilator parameters including PIP and Pplat, were significantly lower in the DP ≤14cmH2O group compared with the DP >14 cmH2O group (p<0.0001) (Table S4).
Mortality of ARDS
The hospital mortality in this ARDS cohort was 42.2% and the hospital mortality rate was paralleled by ARDS severity, which was 35.9% in mild, 43.9% in moderate and 46.5% in severe ARDS. There was no significant difference in age, sex, BMI, admission source, and type of ICU between the survivors and non-survivors. Non-survivors had higher APACHE II and SOFA scores on the days following ICU admission. Non-survivors also had higher CCI scores than survivors. Among the comorbidities, the incidence of rheumatic disease, hepatic disease and malignancy were higher in the non-survivors, but diabetes was more common in survivors (Table 1). Among mechanical ventilator parameters, VT and PEEP were not significantly different between the survivors and non-survivors. However, PIP, Pplat and driving pressure were higher in non-survivors compared with survivors (Table 2). A multivariate regression model was adopted by adjusting for possible confounders, including prone position ventilation, aspiration of gastric content, CCI, mean arterial pressure, BMI, APACHE II score and driving pressure, to evaluate independent risk factors for hospital mortality. Three independent factors were identified, including APACHE II score (adjusted odds ratio (OR) 1.094, 95% confidence interval (CI) 1.045-1.145; p<0.0001), CCI (OR 1.12, 95% CI 1.012-1.222, p=0.27), and driving pressure (OR 1.100, 95% CI 1.027-1.179, p=0.007) (Table 3).
As oxygenation (P/F ratio) and respiratory mechanics (driving pressure) were both associated with mortality in ARDS, we constructed an analysis which combined these two factors. Patients with a driving pressure >14 cm H2O (Fig. 2A, p=0.025) and a P/F ratio ≤150 (Fig.2B, p=0.002) had a higher hospital mortality rate. By combining these factors, patients with worse oxygenation and higher driving pressure had the highest hospital mortality rate (Fig. 2C, p<0.0001).