ARMA: Low Tidal Volumes for ARDS (2000)

“In patients with acute lung injury and the acute respiratory distress syndrome, a ventilation strategy that used lower tidal volumes than were traditionally used resulted in lower mortality and an increase in the number of days without ventilator use.”

  • The ARDS Network

1. Publication Details

  • Trial Title: Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome
  • Citation: The Acute Respiratory Distress Syndrome Network. Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome. N Engl J Med. 2000;342(18):1301-1308. DOI: 10.1056/NEJM200005043421801
  • Published: May 4, 2000, in The New England Journal of Medicine
  • Author: The Acute Respiratory Distress Syndrome (ARDS) Network
  • Funding: The National Heart, Lung, and Blood Institute (NHLBI).

2. Keywords

  • ARDS, Acute Lung Injury, Mechanical Ventilation, Low Tidal Volume, Lung Protective Ventilation, Randomized Controlled Trial

3. The Clinical Question

  • In patients with acute lung injury (ALI) and ARDS (Population), does a lung-protective ventilation strategy using lower tidal volumes (Intervention) compared to a traditional strategy with higher tidal volumes (Comparison) reduce mortality and increase ventilator-free days (Outcome)?

4. Background and Rationale

  • Existing Knowledge: By the late 1990s, there was growing experimental evidence that mechanical ventilation, while life-saving, could also cause or worsen lung injury through a process called ventilator-induced lung injury (VILI). It was believed that the high volumes and pressures used in traditional ventilation strategies were contributing to this damage by over-stretching and injuring fragile alveoli.
  • Knowledge Gap: While the concept of VILI was established, there was no definitive, large-scale clinical trial to prove that a strategy aimed at limiting this over-distention by using lower tidal volumes would improve patient survival.
  • Proposed Hypothesis: The authors hypothesized that a ventilation strategy using a lower tidal volume (6 ml/kg of predicted body weight) would be superior to a traditional strategy (12 ml/kg) in reducing mortality and increasing the number of days breathing without assistance.

5. Study Design and Methods

  • Design: A multicenter, prospective, randomized, controlled trial (used to test the effectiveness of interventions).
  • Setting: 10 university-based medical centers in the United States.
  • Trial Period: Enrollment ran from March 1996 to March 1999.
  • Population:
    • Inclusion Criteria: Adult patients intubated and receiving mechanical ventilation who met criteria for ALI or ARDS, including a PaO2:FiO2 ratio of ≤300.
    • Exclusion Criteria: Included pregnancy, increased intracranial pressure, severe chronic respiratory disease, and morbid obesity.
  • Intervention: A lung-protective strategy with an initial tidal volume of 6 ml/kg of predicted body weight, with a goal to maintain an end-inspiratory plateau pressure of ≤30 cm H2O.
  • Control: A traditional ventilation strategy with an initial tidal volume of 12 ml/kg of predicted body weight, with a goal plateau pressure of ≤50 cm H2O.
  • Management Common to Both Groups: All patients were managed according to protocols for PEEP, FiO2, weaning, and sedation.
  • Power and Sample Size: The trial was designed to have at least 85% power to detect a 25% relative reduction in mortality, with a planned enrollment of 1000 patients. (Power is a study’s ability to find a real difference between treatments if one truly exists; 80-90% is considered standard).
  • Outcomes:
    • Primary Outcome: All-cause mortality before discharge home to unassisted breathing.
    • Secondary Outcomes: Included the number of ventilator-free days during the first 28 days and the incidence of non-pulmonary organ failure.

6. Key Results

  • Enrollment and Baseline: 861 patients were randomized (432 to the lower-volume group and 429 to the traditional-volume group). The baseline characteristics were well-matched.
  • Trial Status: The trial was stopped early after enrolling 861 patients because the mortality rate was significantly lower in the lower tidal volume group at a pre-planned interim analysis.
  • Primary Outcome: In-hospital mortality was significantly lower in the lower-volume group: 133 of 432 patients (31.0%) died, compared with 171 of 429 patients (39.8%) in the traditional-volume group (p=0.007).
  • Secondary Outcomes: The number of days without mechanical ventilation was significantly higher in the lower-volume group (mean, 12 vs. 10 days; p=0.007).
  • Adverse Events: There were no significant differences in the rates of major complications like barotrauma between the two groups.

7. Medical Statistics

  • Analysis Principle: The trial was analyzed using an intention-to-treat principle.
  • Statistical Tests Used: The primary outcome was analyzed by comparing the proportions of death between the two groups using a chi-square test.
  • Primary Outcome Analysis: The primary outcome was a comparison of 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 0.007 is well below the 0.05 threshold, indicating that the observed difference in mortality is highly statistically significant and very unlikely to be a result of random chance (a result is conventionally considered statistically significant if the p-value is less than 0.05).
  • Clinical Impact Measures:
    • Absolute Risk Reduction (ARR):
      • Formula: ARR = (Risk in Control Group) – (Risk in Intervention Group)
      • Calculation: ARR = 39.8% – 31.0% = 8.8%.
      • Clinical Meaning: For every 100 patients with ARDS treated with a low-volume strategy, about 9 additional deaths were prevented.
    • Number Needed to Treat (NNT):
      • Formula: NNT = 1 / ARR
      • Calculation: NNT = 1 / 0.088 = 11.4, which is rounded down to 11.
      • Clinical Meaning: You would need to treat 11 patients with a low-volume ventilation strategy to prevent one additional death.
  • Subgroup Analyses: The benefit of the low-volume strategy was consistent across all predefined subgroups.

8. Strengths of the Study

  • Study Design and Conduct: The large, multicenter, randomized controlled trial design is the gold standard for minimizing selection bias and producing high-quality evidence.
  • Generalizability: The multicenter design and broad inclusion criteria make the findings widely applicable to the general population of patients with ARDS.
  • Statistical Power: The study was adequately powered and found a significant difference, increasing confidence in the results.
  • Patient-Centered Outcomes: The study focused on mortality and ventilator-free days, which are robust, objective, and highly relevant outcomes for patients.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was unblinded, as it was impossible to blind clinicians to the ventilator settings. This introduces a potential for performance bias, where knowledge of the intervention could influence other aspects of care.
  • External Validity (Generalizability): The study was conducted in academic centers, and the results might be different in community settings with different resources, though the intervention itself is not resource-intensive.
  • Other: The trial was stopped early for benefit. While ethically necessary, this statistical approach can sometimes lead to an overestimation of the true treatment effect.

10. Conclusion of the Authors

  • In patients with ALI and ARDS, mechanical ventilation with a lower tidal volume (6 ml/kg PBW) and limited plateau pressures resulted in significantly lower mortality and more ventilator-free days than a traditional strategy with higher tidal volumes.

11. To Summarize

  • Impact on Current Practice: This trial was practice-changing, providing the foundational evidence for the lung protective ventilation strategy that is now the undisputed standard of care for ARDS worldwide.
  • Specific Recommendations:
    • Patient Selection: These results apply to all adult patients with ARDS or ALI requiring mechanical ventilation.
    • Actionable Intervention: Ventilate patients with a tidal volume of 6 ml/kg of predicted body weight and maintain an end-inspiratory plateau pressure of ≤30 cm H2O.
    • Expected Benefit: This intervention can be expected to prevent approximately one death for every 11 patients treated.
  • What This Trial Does NOT Mean: This trial does NOT mean that 6 ml/kg is the perfect tidal volume for every patient, nor does it define the optimal PEEP strategy. It established the principle of limiting volume and pressure.
  • Implementation Caveats: Adherence to the low tidal volume strategy is crucial, and clinicians must be comfortable with the potential for “permissive hypercapnia” (allowing a higher CO2 level) that may result.

12. Context and Related Studies

  • Building on Previous Evidence: The ARMA trial (2000) was the first large, multicenter RCT to provide definitive evidence for a concept that had been developing for years based on smaller studies and animal models of VILI.
  • Influence on Subsequent Research: This trial’s success established the ARDSNet as a major research consortium and set the stage for their subsequent landmark trials, which investigated other aspects of ventilation in ARDS, such as the ALVEOLI trial (2004) on PEEP levels.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: This trial did not determine the optimal PEEP strategy, the best approach to sedation, or how to best ventilate patients with non-ARDS respiratory failure.
  • Future Directions: The results of this trial spurred a new era of research into lung protection, focusing on refining PEEP titration, understanding the role of driving pressure, and exploring adjunctive therapies like prone positioning and neuromuscular blockade.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, addressing a fundamental aspect of life support in the ICU with the potential to reduce iatrogenic harm.
  • Methods: The multicenter RCT design was appropriate and robust. The intervention was a clear and protocolized change in ventilator strategy, and the control group represented the standard of care at the time, making the comparison fair. The primary outcome of mortality was objective and patient-centered.
  • Results: The study reported a large and clinically meaningful effect size (NNT of 11). The result was statistically significant and precise, and the findings were consistent across multiple important outcomes (mortality and ventilator-free days).
  • Conclusions and Applicability: The authors’ conclusion is strongly supported by the data and has stood the test of time. The high external validity, due to the multicenter design and the non-resource-intensive nature of the intervention, has allowed for its successful adoption as the standard of care in ICUs worldwide.

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.
Scroll to Top