October 10, 2017
Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome
What was the research question?
Does lung recruitment using PEEP titration according to the best respiratory-system compliance decreases 28-day mortality in patients with moderate to severe ARDS compared with a conventional low-PEEP strategy?
How did they do it?
A multicenter randomized clinical trial in 120 intensive care units (ICUs) from 9 countries (Brazil, Argentina, Colombia, Italy, Poland, Portugal, Malaysia, Spain, and Uruguay).
Patients were randomized to lung recruitment associated with PEEP titration according to the best respiratory-system compliance (501 patients) compared with a conventional low-PEEP strategy as per ARDSnet study(509 patients). All patients received volume-assist control mode until weaning.
The patient was given neuromuscular bolus before increasing the PEEP to 25 for 1 minute, then 35 for 1 minute, then 45 cmH2O for 2 minutes. Then the PEEP was reduced to 23 cmH2O and down titrated by 3 cmH2O at a time to a minimum of 11, each step lasting for 4 minutes, after which respiratory-system static compliance was measured. The optimal PEEP was then determined at a value of the highest compliance, + 2 cmH2O.
Primary outcome was 28-day mortality. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality.
What did they find?
28-day mortality was significantly higher in the experimental group compared to the control group (55.3% vs. 49.3%, [HR], 1.20; 95% CI, 1.01 to 1.42; P = .041).
6-month mortality was significantly higher in the experimental group strategy compared to the control group (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; P = .04).
Other secondary outcomes included a decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, −1.1; 95% CI, −2.1 to −0.1; P = .03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; P = .03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; P = .001).
There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality.
Are there any limitations?
No blinding due to the nature of the intervention.
Probably lack of external validity (most centers were in south America).
What is the best titration method (compliance or oxygenation as in the PHARLAP study).
Is there subgroup that may benefit?
Proning was used only in about 10% of patients.
What does it mean?
Lung recruitment and titrated PEEP increased 28-day all-cause mortality in patients with moderate to severe ARDS compared to low-PEEP strategy.
This study does not support the routine use of recruitment maneuvers in moderate to severe ARDS patients. However the study has fragile outcome results and lack external validity. Specific subgroup of patients (especially PEEP-responders) may need to be investigated.