JAMA SEPTEMBER 27, 2017

Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome

Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators

Bottom Line

In patients with moderate-to-severe ARDS, an aggressive 'open lung' strategy involving lung recruitment maneuvers and PEEP titration resulted in higher 28-day all-cause mortality compared to a conventional low-PEEP strategy.

Key Findings

1. The 28-day all-cause mortality was significantly higher in the recruitment and titrated PEEP group (55.3%) compared to the low-PEEP control group (49.3%), with an adjusted hazard ratio of 1.20 (95% CI, 1.01 to 1.42; P = 0.04).
2. The intervention arm experienced higher rates of barotrauma, with 3.2% of patients requiring pneumothorax drainage compared to 1.2% in the control group.
3. Patients in the recruitment group had an increased incidence of cardiovascular instability, necessitating more frequent use of neuromuscular blocking agents and higher volumes of intravenous fluids or vasopressors during the procedures.

Study Design

Design
RCT
Open-Label
Sample
1,010
Patients
Duration
28 days
Median
Setting
Multicenter, 9 countries
Population Patients with moderate-to-severe ARDS (PaO2/FiO2 ≤ 200 mmHg) receiving mechanical ventilation for less than 72 hours.
Intervention Lung recruitment maneuvers using stepwise increases in PEEP, followed by decremental PEEP titration based on best respiratory-system compliance.
Comparator Conventional protective mechanical ventilation using a low-PEEP strategy based on the ARDSNet protocol.
Outcome 28-day all-cause mortality.

Study Limitations

The recruitment maneuver protocol was highly aggressive, and the study was modified mid-trial due to safety concerns, including reports of cardiac arrest potentially associated with the intervention.
The findings may not be generalizable to less aggressive or intermittent recruitment techniques that utilize different pressure parameters.
The study did not account for individual heterogeneity in lung recruitability, potentially exposing non-responders to harmful overdistension.

Clinical Significance

This trial fundamentally shifted clinical practice away from the routine, aggressive application of recruitment maneuvers and titrated high-PEEP strategies in ARDS, emphasizing that such interventions may do more harm than good in a general moderate-to-severe ARDS population.

Historical Context

The 'open lung approach' was historically theorized to improve oxygenation and prevent atelectrauma in ARDS by opening collapsed alveoli and maintaining them with higher PEEP. While smaller studies and systematic reviews previously suggested potential benefits, the ART trial was the definitive, large-scale investigation designed to test this hypothesis in clinical practice, ultimately contradicting the prevailing enthusiasm for routine recruitment maneuvers.

Guided Discussion

High-yield insights from every perspective

Med Student
Medical Student

Physiologically, why might a 'recruitment maneuver' using high airway pressures (up to 60 cm H2O) lead to hemodynamic instability in an ARDS patient?

Key Response

High intrathoracic pressures generated during recruitment maneuvers increase pleural pressure, which decreases the pressure gradient for venous return (reducing preload) and increases right ventricular afterload. This can lead to a sudden drop in cardiac output and potentially cardiac arrest, especially in patients who are not fluid-responsive.

Resident
Resident

The ART trial showed higher mortality in the recruitment group. How should this finding influence your bedside decision to use recruitment maneuvers for a patient with refractory hypoxemia in the ICU?

Key Response

Recruitment maneuvers should not be used routinely in moderate-to-severe ARDS. While they may transiently improve oxygenation, the ART trial demonstrated a significant increase in 28-day mortality and pneumothorax. Clinicians should reserve recruitment only for salvage therapy in life-threatening hypoxemia, recognizing it as a high-risk intervention rather than standard care.

Fellow
Fellow

Considering the 'decremental PEEP' titration protocol used in the ART trial, how might the concept of lung stress and strain explain the increased mortality compared to the low-PEEP strategy?

Key Response

The ART protocol often resulted in very high PEEP levels based on static compliance. In many patients, this likely caused alveolar overdistension (increased strain) in the non-recruitable portions of the lung. This 'volutrauma' and 'barotrauma' from excessive PEEP potentially outweighed the benefits of preventing 'atelectrauma' in recruitable segments, shifting the balance toward iatrogenic injury.

Attending
Attending

The ART trial is often cited as a turning point in ARDS management. What does this study teach us about the reliability of physiological surrogates, such as the PaO2/FiO2 ratio, as markers for long-term clinical outcomes?

Key Response

The study is a classic example of a 'dissociation' between physiological improvement and survival. The experimental group showed improved oxygenation and compliance initially, yet had higher mortality. It serves as a teaching point that interventions improving gas exchange can still be lethal if the mechanical cost of that improvement (lung injury/hemodynamic stress) is too high.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD
PhD

The ART trial utilized a highly standardized, multi-step intervention (maneuver + titration). From a trial design perspective, how does the complexity of the 'experimental bundle' limit our ability to identify whether the harm was caused by the recruitment maneuver itself or the subsequent high PEEP levels?

Key Response

Because the intervention was a composite of a high-pressure maneuver (up to 60 cm H2O) and a titration strategy, the study cannot isolate the specific driver of mortality. This 'black box' effect of bundled interventions means we cannot definitively say if a gentler recruitment maneuver or a different titration target (e.g., driving pressure-based) would have yielded the same results.

Journal Editor
Journal Editor

A critical reviewer might argue that the ART trial was stopped early for harm, but the control group's PEEP levels were lower than those used in many previous 'high-PEEP' trials. Does this 'low-PEEP' control group represent a fair contemporary standard of care, or does it bias the results toward the intervention group's harm?

Key Response

If the control group received 'sub-optimal' low PEEP, the mortality gap might actually be underestimated. However, a reviewer would focus on the safety signal: the fact that three patients had cardiac arrest during maneuvers. This objective safety signal often outweighs concerns about the control group's specific PEEP settings when determining editorial significance and clinical safety.

Guideline Committee
Guideline Committee

How do the results of the ART trial reconcile with the 2017 ATS/ESICM/SCCM clinical practice guidelines, which initially gave a conditional recommendation for recruitment maneuvers?

Key Response

The 2017 guidelines were written as ART was being finalized. Post-ART, the consensus shifted significantly. While older meta-analyses suggested benefit, ART (as the largest trial) provides high-level evidence against routine recruitment maneuvers. Current guidelines (like the ESICM 2023 update) now recommend against the routine use of high-pressure recruitment maneuvers in patients with ARDS, effectively downgrading the previous conditional recommendation.

Clinical Landscape

Noteworthy Related Trials

2004

ARDSNet ALVEOLI Trial

n = 767 · NEJM

Tested

Higher PEEP strategy

Population

Patients with acute lung injury and ARDS

Comparator

Lower PEEP strategy

Endpoint

Hospital mortality

Key result: There was no statistically significant difference in hospital mortality between the higher PEEP and lower PEEP groups.
2008

EXPRESS Trial

n = 767 · JAMA

Tested

Mechanical ventilation with high PEEP set to achieve plateau pressure 28-30 cm H2O

Population

Patients with moderate to severe ARDS

Comparator

Minimal PEEP to keep FiO2 low

Endpoint

Day-28 mortality

Key result: The use of high PEEP did not result in a statistically significant reduction in 28-day mortality compared to low PEEP.
2008

LOVS Trial

n = 983 · NEJM

Tested

High PEEP and recruitment maneuver strategy

Population

Patients with acute lung injury or ARDS

Comparator

Conventional low PEEP strategy

Endpoint

Death at 28 days

Key result: The high PEEP/recruitment strategy did not reduce mortality and was associated with a higher risk of barotrauma compared to the low PEEP strategy.

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