ART: Alveolar Recruitment for ARDS (2017)

“Among patients with moderate to severe ARDS, a strategy of lung recruitment and titrated PEEP, compared with a conventional low-PEEP strategy, was associated with increased 28-day all-cause mortality.”

  • The ART Investigators

1. Publication Details

  • Trial Title: Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: The ART Randomized Clinical Trial
  • Citation: Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators. Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: The ART Randomized Clinical Trial. JAMA. 2017;318(14):1335-1345. DOI: 10.1001/jama.2017.14171
  • Published: October 10, 2017, in The Journal of the American Medical Association (JAMA)
  • Author: The ART Investigators
  • Funding: Brazilian Ministry of Health

2. Keywords

  • ARDS, Mechanical Ventilation, Lung Recruitment Maneuver, PEEP, Patient-Centered Outcomes, Randomized Controlled Trial

3. The Clinical Question

  • In adult patients with moderate to severe ARDS (Population), does a strategy involving a lung recruitment maneuver and PEEP titrated according to best respiratory system compliance (Intervention) compared to a conventional low-PEEP strategy (Comparison) reduce 28-day all-cause mortality (Outcome)?

4. Background and Rationale

  • Existing Knowledge: The “open lung” hypothesis suggested that actively recruiting (opening) collapsed lung units and then using higher levels of PEEP to keep them open could reduce ventilator-induced lung injury and improve survival in ARDS. Previous trials on PEEP (like ALVEOLI) had been inconclusive, and the true benefit or harm of aggressive recruitment maneuvers was unknown.
  • Knowledge Gap: There was a need for a large, multicenter trial to determine if a strategy of maximal alveolar recruitment followed by a physiologically titrated PEEP was superior to a standard, low-PEEP approach.
  • Proposed Hypothesis: The authors hypothesized that a strategy of lung recruitment and titrated PEEP would reduce 28-day mortality compared to a conventional low-PEEP strategy.

5. Study Design and Methods

  • Design: A multicenter, prospective, randomized, controlled trial (used to test the effectiveness of interventions).
  • Setting: 120 intensive care units (ICUs) in 9 countries (primarily Brazil).
  • Trial Period: Enrollment ran from November 2011 to April 2017.
  • Population:
    • Inclusion Criteria: Adult patients intubated for less than 72 hours with moderate to severe ARDS (PaO2:FiO2 ratio ≤ 200).
    • Exclusion Criteria: Included contraindications to high airway pressures (e.g., pneumothorax, high intracranial pressure) and patients for whom death was deemed imminent.
  • Intervention: Patients underwent a maximal lung recruitment maneuver (stepwise increases in PEEP up to 45 cm H2O and driving pressure up to 15 cm H2O), followed by a decremental PEEP trial to set the PEEP level that resulted in the best respiratory system compliance.
  • Control: Patients were managed with a conventional low-PEEP strategy according to the ARDSNet PEEP/FiO2 table used in the original ARMA trial.
  • Management Common to Both Groups: All patients were managed with a low tidal volume ventilation strategy (6 ml/kg PBW).
  • Power and Sample Size: The authors calculated that a sample size of 1010 patients would provide 90% power to detect an 8.5% absolute risk reduction in 28-day mortality. (Power is a study’s ability to find a real difference between treatments if one truly exists; 90% power means the study had a 90% chance of detecting the specified effect, which is considered very high).
  • Outcomes:
    • Primary Outcome: All-cause mortality at 28 days.
    • Secondary Outcomes: Included 6-month mortality, ventilator-free days, and incidence of complications like barotrauma and hypotension.

6. Key Results

  • Enrollment and Baseline: 1010 patients were randomized (501 to the recruitment group and 509 to the control group). The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: 28-day mortality was significantly higher in the lung recruitment group: 277 of 501 patients (55.3%) died, compared with 241 of 509 patients (47.4%) in the control group (p=0.041).
  • Secondary Outcomes: 6-month mortality was also significantly higher in the recruitment group (65.3% vs. 59.9%). Patients in the recruitment group had fewer ventilator-free days.
  • Adverse Events: The incidence of barotrauma and hypotension requiring vasopressors was significantly higher in the lung recruitment group.

7. Medical Statistics

  • Analysis Principle: The trial was analyzed using an intention-to-treat principle.
  • Statistical Tests Used: The primary outcome was analyzed using a chi-square test.
  • Primary Outcome Analysis: The primary outcome was a comparison of the proportions of death between the two groups.
  • Key Statistic(s) Reported: The key statistics were the absolute mortality rates and the associated P-value.
  • Interpretation of Key Statistic(s):
    • P-value: The p-value of 0.041 is below the 0.05 threshold, indicating that the observed increase in mortality in the recruitment group was statistically significant and unlikely to be due to chance (a result is conventionally considered statistically significant if the p-value is less than 0.05).
  • Clinical Impact Measures:
    • Absolute Risk Increase (ARI):
      • Formula: ARI = (Risk in Intervention Group) – (Risk in Control Group)
      • Calculation: ARI = 55.3% – 47.4% = 7.9%.
      • Clinical Meaning: For every 100 patients treated with this recruitment strategy, about 8 additional deaths occurred.
    • Number Needed to Harm (NNH):
      • Formula: NNH = 1 / ARI
      • Calculation: NNH = 1 / 0.079 = 12.7, which is rounded up to 13.
      • Clinical Meaning: You would only need to treat 13 patients with this recruitment strategy to cause one additional death.
  • Subgroup Analyses: The finding of increased mortality was consistent across all pre-specified subgroups.

8. Strengths of the Study

  • Study Design and Conduct: The large, multicenter, randomized controlled design provided high-quality evidence.
  • Generalizability: The inclusion of 120 diverse ICUs increases the applicability of the findings.
  • Statistical Power: The study was adequately powered for its primary outcome.
  • Patient-Centered Outcomes: The primary outcome of 28-day mortality is a robust and patient-centered endpoint.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was unblinded, which introduces a risk of performance bias.
  • External Validity (Generalizability): The specific, aggressive recruitment maneuver used in this trial may not be representative of all recruitment strategies.
  • Other: The control group received a very conservative, low-PEEP strategy, which may not represent the “optimal” PEEP setting for all patients.

10. Conclusion of the Authors

  • In patients with moderate to severe ARDS, a strategy of lung recruitment and titrated PEEP was associated with increased 28-day all-cause mortality compared with a conventional low-PEEP strategy.

11. To Summarize

  • Impact on Current Practice: This was a major practice-changing trial. It provided strong evidence that a routine, aggressive lung recruitment maneuver as performed in this study is not only ineffective but harmful.
  • Specific Recommendations:
    • Patient Selection: For adult patients with moderate to severe ARDS.
    • Actionable Intervention: The specific maximal recruitment maneuver followed by a decremental PEEP trial used in this study should be avoided.
    • Expected Benefit: Avoiding this strategy prevents one additional death for every 13 patients treated.
  • What This Trial Does NOT Mean: This trial does NOT mean that all recruitment maneuvers or all attempts to optimize PEEP are harmful. Its findings are specific to the aggressive, high-pressure protocol that was used.
  • Implementation Caveats: The findings highlight the potential dangers of very high airway pressures and suggest that the physiological goal of “opening the lung” at all costs can be detrimental.

12. Context and Related Studies

  • Building on Previous Evidence: The ART trial (2017) was designed to definitively test the “open lung” hypothesis that had been debated since the neutral results of earlier PEEP trials like ALVEOLI (2004) and ExPress (2008).
  • Influence on Subsequent Research: The definitive finding of harm in this trial has led to a significant de-escalation in the routine use of aggressive recruitment maneuvers and has shifted the focus of research towards less aggressive recruitment strategies and other methods of optimizing PEEP, such as driving pressure.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: The key unresolved question is whether less aggressive, more individualized recruitment maneuvers might be beneficial in specific patients.
  • Future Directions: Future research is focused on identifying which patients are most likely to be “recruiters” and on using more advanced physiological monitoring to guide PEEP and recruitment in a safer, more personalized way.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, addressing a common and physiologically appealing but unproven strategy in ARDS management.
  • Methods: The multicenter RCT design was appropriate and robust. The main methodological weakness is the lack of blinding. The specific, aggressive nature of the intervention is a key factor in interpreting the results.
  • Results: The study reported a statistically significant and clinically important increase in harm (NNH of 13) for its primary outcome. The findings were consistent across multiple important outcomes, including 6-month mortality and the incidence of barotrauma.
  • Conclusions and Applicability: The authors’ conclusion is a direct and fair reflection of the data. The high external validity of this pragmatic trial means its findings are broadly applicable. This trial is a classic example of how a high-quality trial can be profoundly practice-changing by providing strong evidence to stop a common but harmful practice.

16. Disclaimer and Contact

  • This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.
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