Effect of a Lower vs Higher Positive End-Expiratory Pressure Strategy on Ventilator-Free Days in ICU Patients Without ARDS: A Randomized Clinical Trial.

Abstract

Importance:

It is uncertain whether invasive ventilation can use lower positive end-expiratory pressure (PEEP) in critically ill patients without acute respiratory distress syndrome (ARDS).

Objective:

To determine whether a lower PEEP strategy is noninferior to a higher PEEP strategy regarding duration of mechanical ventilation at 28 days.

Design, Setting, and Participants:

Noninferiority randomized clinical trial conducted from October 26, 2017, through December 17, 2019, in 8 intensive care units (ICUs) in the Netherlands among 980 patients without ARDS expected not to be extubated within 24 hours after start of ventilation. Final follow-up was conducted in March 2020.

Interventions:

Participants were randomized to receive invasive ventilation using either lower PEEP, consisting of the lowest PEEP level between 0 and 5 cm H2O (n = 476), or higher PEEP, consisting of a PEEP level of 8 cm H2O (n = 493).

Main Outcomes and Measures:

The primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for the difference in ventilator-free days at day 28 of -10%. Secondary outcomes included ICU and hospital lengths of stay; ICU, hospital, and 28- and 90-day mortality; development of ARDS, pneumonia, pneumothorax, severe atelectasis, severe hypoxemia, or need for rescue therapies for hypoxemia; and days with use of vasopressors or sedation.

Results:

Among 980 patients who were randomized, 969 (99%) completed the trial (median age, 66 [interquartile range {IQR}, 56-74] years; 246 [36%] women). At day 28, 476 patients in the lower PEEP group had a median of 18 ventilator-free days (IQR, 0-27 days) and 493 patients in the higher PEEP group had a median of 17 ventilator-free days (IQR, 0-27 days) (mean ratio, 1.04; 95% CI, 0.95-∞; P = .007 for noninferiority), and the lower boundary of the 95% CI was within the noninferiority margin. Occurrence of severe hypoxemia was 20.6% vs 17.6% (risk ratio, 1.17; 95% CI, 0.90-1.51; P = .99) and need for rescue strategy was 19.7% vs 14.6% (risk ratio, 1.35; 95% CI, 1.02-1.79; adjusted P = .54) in patients in the lower and higher PEEP groups, respectively. Mortality at 28 days was 38.4% vs 42.0% (hazard ratio, 0.89; 95% CI, 0.73-1.09; P = .99) in patients in the lower and higher PEEP groups, respectively. There were no statistically significant differences in other secondary outcomes.

Conclusions and Relevance:

Among patients in the ICU without ARDS who were expected not to be extubated within 24 hours, a lower PEEP strategy was noninferior to a higher PEEP strategy with regard to the number of ventilator-free days at day 28. These findings support the use of lower PEEP in patients without ARDS.

Trial Registration:

ClinicalTrials.gov Identifier: NCT03167580.

• Authors: Writing Committee and Steering Committee for the RELAx Collaborative Group, Anna Geke Algera, Luigi Pisani, Ary Serpa Neto, Sylvia S den Boer, Frank F H Bosch, Karina Bruin, Pauline M Klooster, Nardo J M Van der Meer, Ralph O Nowitzky, Ilse M Purmer, Mathilde Slabbekoorn, Peter E Spronk, Jan van Vliet, Jan J Weenink, Marcelo Gama de Abreu, Paolo Pelosi, Marcus J Schultz, Frederique Paulus
• Journal: JAMA (JAMA) Vol. 324 Issue 24 Pg. 2509-2520 (12 22 2020) ISSN: 1538-3598 [Electronic] United States
• PMID: 33295981 (Publication Type: Comparative Study, Equivalence Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Oxygen

Topics

• APACHE
• Aged
• Critical Illness
• Female
• Humans
• Intensive Care Units
• Kaplan-Meier Estimate
• Length of Stay
• Male
• Middle Aged
• Oxygen (blood)
• Pneumonia, Ventilator-Associated
• Pneumothorax (etiology)
• Positive-Pressure Respiration (adverse effects, methods)
• Respiratory Insufficiency (therapy)
• Ventilator Weaning