OK to RELAx PEEP levels for ventilation of ICU patients without ARDS: latest study

Invasive ventilation using a lower positive end-expiratory pressure (PEEP) strategy was noninferior to higher PEEP in ICU* patients without acute respiratory distress syndrome (ARDS), according to the RELAx** study presented at eCCR 2021.

“Higher levels of PEEP have been increasingly used in ICUs in recent years, despite lack of evidence for benefit or harm,” experts have noted.

The quandary

While PEEP is beneficial by keeping lung units open and improve oxygen delivery in patients with ARDS, higher PEEP levels may lead to overdistension of the lung and more ventilator-induced lung injury.

“The net benefit or harm from PEEP therefore depends on this balance of alveolar recruitment [vs] overdistension and should be particularly beneficial in disease states with substantial alveolar collapse, such as ARDS,” said invited discussant Dr Ewan Goligher from University of Toronto, in Toronto, Canada.

A meta-analysis of three RCTs*** suggests that ventilation using high PEEP was protective in moderate-to-severe ARDS but detrimental in mild ARDS, pointed out principal investigator Professor Marcus Schultz from Amsterdam University Medical Centers, Location AMC in Amsterdam, the Netherlands, who presented the study during eCCR 2021.

Use of PEEP is even less clear in ICU patients without ARDS. 

“The optimum PEEP level in patients without ARDS would be expected to be lower and the risk-benefit ratio higher because they have relatively less lung collapse than patients with ARDS and require less pressure to open the collapsed lung,” explained Goligher.

Optimal PEEP: High vs low?

In the noninferiority RELAx trial, 980 patients (median age 66 years, 36 percent women) in ICU without ARDS who were expected to be intubated for >24 hours were randomized 1:1 to receive invasive ventilation using lower PEEP (between 0–5 cm H₂O) or higher PEEP (of 8 cm H₂O). Patients were randomized within 1 hour of starting ventilation in the ICU. [JAMA 2020;324:2509-2520]

The primary outcome of ventilator-free days and alive at day 28 was similar between the low and the high PEEP arms (median, 18 vs 17 days), which met the noninferiority criteria (mean ratio, 1.04; p=0.007 for noninferiority).  

Although the incidence of severe hypoxaemia (20.6 percent vs 17.6 percent; risk ratio [RR], 1.17; p=0.99) and need for rescue^# strategy (19.7 percent vs 14.6 percent; RR, 1.35; adjusted p=0.54) was numerically higher with lower PEEP, the difference was not statistically significant between the two arms.

“These findings support the use of lower PEEP in patients without ARDS,” Schultz stated. “It may not be better to use a lower PEEP strategy, but it could be as good as higher PEEP.”

Or in between?

However, the association with numerically higher rates of hypoxaemia and need for rescue therapy suggests “the possibility that lower PEEP may have been inferior for some patients,” according to Goligher. [JAMA 2020;324:2590-2592]

In addition, Schultz was also careful to point out that the comparator of a higher PEEP of 8 cm H₂O, rather than 5 cm H₂O, may not represent the standard care. 

“Ultimately, clinicians will need to decide what the results of this study mean for the care of patients receiving mechanical ventilation,” said Goligher.

“Given the concern about possible increased rates of hypoxemia and need for rescue strategies in the lower PEEP group, an intermediate option of 5 to 8 cm H₂O that is consistent with the current PEEP management for many non-ARDS patients is likely reasonable and may be safer than a very low PEEP strategy,” he added.

*ICU: Intensive care unit
**RELAx: The REstricted vs LiberAl positive end-expiratory pressure in patients without ARDS
***RCTs: Randomized controlled trials
^#short-lasting increases in PEEP or other rescue recruitment manoeuvres, prone positioning, or bronchoscopy