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Mechanistic Deep Dive
VILI (Ventilator-Induced Lung Injury)
- Volutrauma (large Vt â stretch injury)
- Barotrauma (high pressure)
- Atelectotrauma (cyclic opening/closing â stress)
- Biotrauma (mechanical â biological inflammation cascade)
Lung Mechanics in ARDS
- Reduced compliance
- Heterogeneous disease (baby lung concept)
- Driving pressure reflects lung mechanics
- Stress-strain relationship
ARDS Pathobiology
- Type I + II pneumocyte injury
- Endothelial dysfunction
- Inflammation cascade (TNF, IL-6, IL-8)
- Coagulation activation (PAI-1, microthrombi)
- Surfactant dysfunction
- Fibrosis in proliferative phase
Recent Trials & Updates
EOLIA (2018) â VV-ECMO
- Severe ARDS
- ECMO referral early
- Borderline mortality benefit (high crossover)
- Bayesian analysis suggests probable benefit
- Practice: refer early to ECMO center
COVID-19 ARDS Trials (2020-2024)
- RECOVERY: dexamethasone
- REMAP-CAP: tocilizumab, baricitinib
- COV-BARRIER: baricitinib
- Awake proning: PROPI, COVID-PRONE â mixed
- Steroids + anti-IL-6 + JAK inhibitor backbone
ARDSnet Trials Series
- ARMA: lung-protective ventilation
- ALVEOLI: PEEP titration
- LOVS: high PEEP strategy
- ExPress: 6 cohort
- FACTT: fluid management
MENDS-2 (2024) â Dexmedetomidine vs Propofol
- ARDS sedation
- Equivalent outcomes
- Less delirium with dex
- Useful for sedation strategy
TLR-4 Pathway (Future Therapy)
- Investigational antagonists
- Inflammation modulation
Specific Biomarkers
- IL-6, IL-8, sTNFR1, RAGE
- Stratify subphenotypes
- Predict response to therapies
High-Yield Specialist Points
Recruitment Maneuver
- Brief high PEEP (30-40) to open collapsed alveoli
- ART trial (2017): NO improvement, may harm
- Reserved for selected severe with hypoxia
High Flow Nasal Cannula (HFNC)
- Heated humidified high-flow O2
- For hypoxemic respiratory failure
- FLORALI (2015): comparable to mask O2 + NIV
- Awake proning + HFNC for COVID
- Comfortable, well-tolerated
Awake Proning
- For non-intubated patients with hypoxemic respiratory failure
- COVID-19 era widespread use
- COVID-PRONE, others mixed evidence
- Practical, low-cost intervention
Cytokine Storm + ARDS
- COVID-19 highlighted role
- Anti-IL-6 (tocilizumab, sarilumab) effective
- Baricitinib (JAK inhibitor) effective
- IL-1β blockade (anakinra) less effective in trials
Driving Pressure-Based Ventilation
- â Vt + â PEEP to optimize driving pressure
- Personalized titration
- Future direction
Esophageal Pressure Monitoring
- Estimates transpulmonary pressure
- For obesity, abdominal compartment syndrome
- EPVent trial: 2023 results modest
Prone Positioning Logistics
- Multidisciplinary team
- ICU resources
- Complications: pressure injuries, line displacement, eye injury
- 12-16 hours/day in severe ARDS
Lung Transplant Post-ARDS
- For severe ongoing respiratory failure + irreversible lung injury
- Rare; selected
- Complex post-ICU rehabilitation
Long-Term Outcomes ARDS
- Survivors have:
- Reduced exercise capacity
- Pulmonary function abnormalities (DLCO â most consistent)
- Cognitive impairment
- Mood disorders
- Functional decline
- Multidisciplinary rehabilitation
Pearls
- ARDS Berlin Criteria 2012: timing + bilateral + not cardiac + PaO2/FiO2 < 300 PEEP ⥠5
- Severity: mild 200-300, moderate 100-200, severe †100
- ARMA (lung-protective): Vt 6 mL/kg PBW, plateau < 30
- Driving pressure < 15 cm H2O (Amato): best survival predictor
- PROSEVA: prone for severe ARDS â mortality 16%
- NMB: ACURASYS positive; ROSE neutral; use for refractory dyssynchrony
- FACTT: conservative fluid â ventilator-free days
- ECMO: refractory (PaO2/FiO2 < 80, pH < 7.20); CESAR + EOLIA
- RECOVERY: dexamethasone for COVID-ARDS
- REMAP-CAP: tocilizumab + baricitinib