Study Design Summary: Multicenter, randomized, open label, noninferiority trial of 980 patients without ARDS comparing low vs high PEEP with a primary outcome being number of ventilator free days at day 28.
Notes: Patients included were those who did not have ARDS, were intubated less than 12 hours prior to randomization and not expected to be extubated within 24 hours of randomization. Morbidly obese patients and those with COPD or restrictive lung disease were also excluded from the study. Patients were randomized to a low PEEP group (0-5 cm H2O) and high PEEP group (8 cm H2O). Both groups had similar FiO2 ranges, the low PEEP group had the PEEP titrated down every 15 minutes to a minimum of 0 cm H2O. This was a non blinded study. There was standardized protocol for both groups to respond to hypoxemia and hemodynamic instability, both of which were predefined. In both groups the oxygenation targets were 92% to 96% for SpO2 and 60 to 85mmHg for PaO2.
The primary outcome was number of ventilator free days, however it was designed as as non-inferiority trial. There were a total of 980 patients included in the final study. The high and low PEEP groups were fairly well balanced, however, the high peep group had slightly higher APACHE IV scores (83.5 [IQR 60-103] vs 90 [IQR 67-111]). SOFA scores were similar between the two groups. Time from intubation to randomization was the same for both groups and roughly just under one hour. Only about 30% of patients were intubated because of respiratory failure, others were intubated for surgery or cardiac arrest. More patients in the low PEEP group were intubated for planned post operative ventilation where as the high PEEP group had more intubations for cardiac arrested and depressed mental status.
The low PEEP group had an average PEEP of 4 where as the high PEEP group had an average PEEP of 8. The lower PEEP group had roughly 1 more day of intubation compared to the high PEEP group 17.7 (0-26.6) vs 16.7 (0-26.5), however this did not fall outside of their predefined non-inferiority margin of 10%. More patients in the low PEEP group had atelectasis, hypoxemia, need for recruitment maneuvers and interestingly more pneumothoracies as well. While it wasn’t the primary outcome, the lower PEEP group also had a longer duration of ICU stay with mean days of 8.1 vs 7.2.
Overall, the high PEEP group was sicker and experienced less adverse events such as hypoxemia. This study doesn’t change my practice but does point to the need for a designated RCT looking at whether non-ARDS patients could benefit from higher PEEP.
Some good comments from PulmCrit: “The primary endpoint is the number of ventilator-free days. This doesn’t really make sense. Most patients were not intubated due to respiratory failure. Do we truly expect that a PEEP of 4 cm vs. 8 cm will affect timing of extubation in a postoperative patient, or a patient intubated for airway protection? Most patients in the study weren’t intubated for respiratory failure – so their timing of extubation is likely to be determined by non-pulmonary considerations. In terms of this study, the low-PEEP arm seems bizarre and unrealistic. Using zero PEEP (“ZEEP”) is likely to promote atelectotrauma, so ZEEP is generally avoided in critical care practice. Likewise, 8 cm of PEEP is occasionally used, but this doesn’t seem like usual care either (at least at units that I’ve worked in). As such, neither arm of this trial resembles standard practice. A more realistic and clinically useful comparison would be between 5 cm PEEP vs. 8 cm of PEEP. However, there is less separation between these two groups, so performing a study would be challenging.”
Study Conclusion: In patients without ARDS, lower PEEP is noninferior to higher PEEP with regard to number of ventilator free days at day 28.
Fusion Beat Bottom Line Impression: My current practice of PEEP of 5 cm H2O on most patients increasing as each case demands is unchanged by this study. I do endorse a PEEP of 0 and thus this study does not provide comment on whether PEEP of 5 or 8 is better for clinical outcomes.
A Fusion Beat 