Pharmacology of Respiratory Failure and Mechanical Ventilation
ARDS management, ICU sedation, neuromuscular blockade, and inhaled vasodilators
ARDS: Severity and Pharmacology
Berlin Severity
PaO2/FiO2 Thresholds
- Mild: 201–300 mmHg
- Moderate: 101–200 mmHg
- Severe: ≤100 mmHg
- All measured with PEEP ≥5 cmH2O
Lung Protection
ARDSNet Ventilation
- Tidal volume: 6 mL/kg predicted body weight
- Plateau pressure: <30 cmH2O
- ARDSNet trial: 22% mortality reduction
- Prevents volutrauma and atelectrauma
Corticosteroid
Dexamethasone
- 20 mg IV daily ×5 days, then 10 mg ×5 days
- DEXA-ARDS: reduced mortality + vent days
- Moderate-to-severe ARDS only
- Early use (<14 days) — not late fibroproliferative phase
ICU Sedation and Analgesia
|
Drug |
Mechanism |
Key Point |
| Sedative | Propofol | GABA-A potentiator | Rapid offset; propofol infusion syndrome at high dose >48h |
| Sedative | Dexmedetomidine | Alpha-2 agonist | Cooperative sedation; no respiratory depression; bradycardia |
| Sedative | Midazolam | Benzodiazepine / GABA-A | Accumulates with infusion → prolonged sedation, delirium |
| Analgesic | Fentanyl | Opioid receptor agonist | No histamine release; continuous infusion in ICU |
Neuromuscular Blockade and Inhaled Vasodilators
NMB in ARDS
Cisatracurium
- Hofmann elimination → organ-independent clearance
- Used for severe ventilator dyssynchrony
- Risk: ICU-acquired weakness
- Monitor with train-of-four (target 1–2/4)
- Rocuronium + sugammadex for rapid reversal
Rescue Oxygenation
Inhaled Vasodilators
- Inhaled nitric oxide: activates sGC → cGMP in ventilated units
- Inhaled epoprostenol: IP receptor → cAMP in ventilated units
- Both: selective V/Q improvement; no systemic hypotension
- Neither improves mortality in ARDS (rescue only)
- iNO: rebound hypertension if abruptly stopped; methemoglobinemia
Propofol Infusion Syndrome
High dose (>5 mg/kg/h) + prolonged (>48h): metabolic acidosis, rhabdomyolysis, cardiac arrhythmias, acute kidney injury. Mechanism: mitochondrial dysfunction. Monitor: lactate, triglycerides, creatine kinase.