EBQ:ARDSnet Trial

Complete Journal Club Article

Brower RG, et al. "Ventilation With Lower Tidal Volumes As Compared With Traditional Tidal Volumes For Acute Lung Injury And The Acute Respiratory Distress Syndrome". The New England Journal of Medicine. 2000. 342(18):1301-1308.
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Clinical Question

Does a lung protective strategy of low tidal volumes in patients with Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) decrease mortality and ventilator-free days when compared to traditional ventilation strategies.

Conclusion

In patients with ALI/ARDS, lower tidal volumes of 6mL/kg predicted body weight reduces mortality and decreases length of time on mechanical ventilation.

Major Points

• Acute Respiratory Distress Syndrome results from alveolar damage and barotrauma are associated with elevated plateau pressures and higher tidal volume ventilations
• The trial was stopped early when patients in the low tidal volumes arm showed a significant decrease in mortality and more ventilator-free days compared to the traditional tidal volumes arm.

Guidelines

See Sepsis for guideline recommendations

Design

• Multicenter, randomized trial of 861 patients in parallel-group in 10 university-affiliated ARDSNet centers
  • Low tidal volumes: Starting at 6ml/kg PBW and plateau pressure ≤30cmH2O (n=432)
  • Traditional tidal volumes: starting at 12ml/kg PBW and plateau pressure of ≤50cmH2O (n=429)
• Enrollment: March 1996 to March 1999 (terminated early after the fourth interim analysis)
• Follow-up: 180 days or until home breathing independently

Population

Inclusion Criteria

• Age ≥18 years
• Receiving mechanical ventilation
• Diagnosis of ALI/ARDS ≤36h prior to enrollment; defined as:
  • Acute decrease in PaO2/FiO2ratio to ≤300
  • CXR: Bilateral pulmonary infiltrates
  • PCWP of ≤18mmHg without evidence of left atrial hypertension

Exclusion Criteria

• Pregnancy
• Increased ICP, neuromuscular disease imparing spontaneous breathing, sickle cell disease, or severe chronic respiratory disease
• Weight more than 1kg/cm of height
• Burns >30% of BSA
• Estimated 6-month mortality rate >50%
• History of bone marrow or lung transplantation
• Child-Pugh class C liver disease
• Participation in other trials w/in 30 days

Baseline Characteristics

• Mean age: 51.5 years
• Sex: Female (40.5%)
• Ethnicity:
  • White: 73%
  • Black: 17.5%
  • Hispanic: 6%
• APACHE III score: 82.5
• Mean PaO2:FiO2: 136
• Mean tidal volume: 670 mL
• Mean minute ventilation: 13.4 vs. 12.7 L/min (P=0.01)

Interventions

Patients randomly assigned to receive mechanical ventilation (volume-assist-control mode) with following strategies for tidal volume:

• Low tidal volumes (lung protective strategy): Starting at 6ml/kg PBW to maintain plateau pressure ≤30cm H₂O (n=432)
• Traditional tidal volumes: Starting at 12ml/kg to maintain plateau pressure of ≤50cm H₂O (n=429)

Patients monitored until day 28 or death for signs of system failure:

• Circulatory failure: SBP ≤90mmHg or need for vasopressor
• Coagulation failure: Platelets ≤80,000 mm3
• Hepatic failure: Bilirubin ≥2mg/dL
• Renal failure: Creatinine ≥2mg/dL

Outcomes

Primary Outcomes

• 180-day mortality
  • 31.0% vs. 39.8% (RR 0.78; P=0.007)
• Ventilator-free days (Days 1-28)
  • 12 vs. 10 (P=0.007)
• Breathing without assistance by day 28
  • 65.7% vs. 55.0% (P<0.001; NNT 9)

Secondary Outcomes

• Days w/o non-pulmonary organ or system failure (Days 1 to 28)
  • 15 vs. 12 (P=0.006)
• Days w/o circulatory failure
  • 19 vs. 17 (P=0.004)
• Days w/o coagulation failure
  • 21 vs. 19 (P=0.004)
• Days w/o renal failure
  • 20 vs. 18 (P=0.005)
• Barotrauma (New PTX, pneumomediastinum, subcutaneous emphysema, pneumatocele)
  • 10% vs. 11% (P=0.43)
• Mean tidal volumes (ml/kg PBW)
  • 6.2 vs. 11.8 (P<0.001)
• Mean plateau pressures (cm H2O)
  • 25 vs. 33 (P<0.001)
• Peak inspiratory pressures (cm H2O)
  • 32 vs. 39 (P<0.05)

Funding

The National Heart, Lung, and Blood Institute.