Seam – ARDS phenotypes 6-29-17

Summary by Dr. Basel

Acute Respiratory Distress Syndrome

• Histopathology Definition: Diffuse alveolar damage (DAD)
  • In reality, it likely more heterogeneous than that.

• The First ARDS Consensus Definitions
  • 1994 American-European Consensus conference: “syndrome of inflammation and increased permeability”
    • Acute onset
    • Bilateral Infiltrates on CXR
    • PaO1/FIO2 <300
    • No evidence of cardiogenic edema

2012 Berlin Definition

2017 Clinical Practice Guidelines for Mechanical Ventilation in adult patients with ARDS

• Asked 6 questions

• Should patients with ARDS receive mechanical ventilation using low tidal volume ventilation and inspiratory pressures?
  • Recommendation: Patients with ARDS should receive MV with strategies that limit tidal volumes to 4-8ml/kg ideal body weight and plateau pressures <30cm H20 (strong recommendation, moderate confidence in effect estimates)

• Should Patients with ARDS receive prone positioning?
  • Recommendation: Patients with severe ARDS receive prone positioning for >12hrs/day (strong recommendation, moderate-high confidence in effect estimates)

• Should patients with ARDS receive High-Frequency Oscillatory Ventilation?
  • Recommendation: HFOV not be used rountinely in patients with modeate or severe ARDS (strong recommendation, moderate-high confidence in effect estimates).

• Should patients with ARDS receive higher, as compared with lower PEEP?
  • Recommendation: Patients with moderate or severe ARDS receive higher rather than lower levels of PEEP (conditional recommendation, moderate confidence in effect estimates).

• Should patients with ARDS receive Recruitment Maneuvers?
  • Recommendation: Patients with ARDS receive Recruitment Maneuvers (conditional recommendation, low-moderate confidence in effect estimates).

• Should patients with ARDS receive ECMO?
  • Recommendation: Additional evidence is necessary to make a definitive recommendation for or against the use of ECMO in patients with severe ARDS. In the Interim, we recommend ongoing research measuring clinical outcomes among patients with severe ARDS who undergo ECMO

A mechanistic approach for low tidal volume and optimal PEEP:  the inflection points

• Attempting to minimize
  • Volutrauma
  • High shear forces occurring at normal/abnormal lung junctions
  • RACE (repeated alveolar collapse and expansion)

Personalizing Low Tidal Volume?  (ARMA, ALVEOLI, FACTT, SAILS)

• After the ARMA trial showed a significant mortality benefit with LTV strategies
  • Further ARDSnet studies (ALVEOLI, FACTT, SAILS) failed to show a similar reduction in mortality
    • Maybe, after ARMA we became very meticulous in our vent management which explains why these trials failed to reproduce the same mortality reducitons…
    • But can we do better?
• There is No Safe Plateau pressure

• “Baby Lung” concept: the significantly reduced portion of “normal” lung not affected by lung injury. 
  • Problem: the “baby lung” is different in every patient
  • Current Question: Is 6-8cc/kg of Vt going to that “baby lung” injurious?
    • Not clear: ongoing studies on how to measure the baby lung and if there is increased lung injury.  See EpiVENT 1
    • Clinical Point: If you do a recruitment maneauver and see little effect, this may indicate you may be maximally inflating the “baby lung” and so.
      • This patient is likely higher risk and would probably benefit from lower Vt 4-5cc/kg
      • Minimize ventilator/patient interaction: lower threshold for paralytics

Personalizing PEEP? (ALVEOLI, LOV, EXPRESS)

• ALVEOLI: went by a PEEP table
  • No mortality benefit
  • Lower P/F ratios on Day 7
  • No difference in Ventilator free days or organ failure
• LOV: went by a PEEP table
  • No mortality benefit
  • Less rescue therapies
• EXPRESS: PEEP titrated to a Plateau pressure of 30cm H20
  • No mortality benefit
  • Lower P/F ratios on Day 7
  • More ventilator free days
  • Less organ failure
  • Less rescue therapies

A table-based approach, although easier to do at the bedside, may not be the best thing to do. Too much PEEP may lead to overexpansion in some patients

Current ongoing literature is focused on trans pulmonary pressures as a way to guide PEEP dosing (EPIVENT 1, EPIVENT 2)

Systemic Therapies?  The New Frontier

• Surfactant Protein D: marker of epithelial injury; higher in patients with direct lung injury
• Ang-2: marker of endothelial injury; higher in indirect lung injury
• Protein C levels: normalized after steroid treatment in patients with an infectious etiology
• Gene phenotyping and latent class anaylsis: ongoing literature, hypothesis generating