2. ARDS (Acute Respiratory Distress Syndrome)

Quick Recap

Nests under Acute Respiratory Failure once bilateral infiltrates + hypoxemia + non-cardiogenic origin are confirmed.

1. Definition — Berlin Criteria

All four required:

• Timing: new/worsening respiratory symptoms within 1 week of a known clinical insult
• Imaging: bilateral opacities on CXR/CT not fully explained by effusion, collapse, or nodules
• Origin of edema: not fully explained by cardiac failure or fluid overload (objective assessment - echo - if no ARDS risk factor present)
• Oxygenation (PEEP/CPAP >=5 cmH2O):
• Mild: 200 < P/F <= 300
• Moderate: 100 < P/F <= 200
• Severe: P/F <= 100

2. Pathophysiology

Insult (direct or indirect) triggers alveolar-capillary barrier breakdown -> protein-rich, non-cardiogenic pulmonary edema. Three overlapping phases:

• Exudative (0-7 days): neutrophilic infiltration, hyaline membranes, type 1 pneumocyte necrosis, intra-alveolar hemorrhage -> reduced compliance, shunt, increased work of breathing
• Proliferative (days-3 weeks): type 2 pneumocyte proliferation, early fibrosis
• Fibrotic (weeks+): in a subset, progressive fibrosis

Direct causes: pneumonia, aspiration, inhalation injury, blunt chest trauma, near drowning, drug toxicity.

Indirect causes: sepsis (most common overall), severe trauma/shock, massive transfusion (TRALI, >15 units), pancreatitis, ischemia-reperfusion post-bypass/transplant.

Recognized phenotypes (hyper- vs hypo-inflammatory) respond differently to PEEP strategy — hyperinflammatory phenotype benefits from higher PEEP, hypoinflammatory may be harmed by it.

3. Immediate Stabilization (ABCDE)

Airway: Secure early if work of breathing escalating; do not delay intubation for a trial of NIV/HFNC in moderate-severe hypoxemia with hemodynamic compromise.

Breathing — default lung-protective ventilation:

• Vt 6 mL/kg predicted body weight (PBW), can start at 8 and titrate down
• Plateau pressure <30 cmH2O; driving pressure (Pplat − PEEP) <15 cm H2O — strongest mortality correlate (Amato 2015)
• Permissive hypercapnia acceptable to pH ~7.20
• FiO2/PEEP per ARDSnet low or high table (e.g., FiO2 0.5 -> PEEP 8-10; FiO2 1.0 -> PEEP 18-23)
• SpO2 target >=92%, FiO2 weaned to <=60% as tolerated

Circulation: conservative fluid strategy once shock resolved (see Section 11); avoid volume overload which worsens edema.

Disability: sedation to allow synchrony; consider early NMB if severe ARDS with dyssynchrony/refractory hypoxemia.

Exposure: monitor for barotrauma, pressure injury from prone positioning if used.

Checklist:

4. Focused History

Identify the inciting insult specifically — pneumonia symptoms, aspiration event, transfusion history, pancreatitis, trauma, sepsis source, drug/toxin exposure, recent surgery/bypass. Timing of symptom onset relative to insult (must be <1 week). Comorbid cardiac disease (to help exclude cardiogenic edema). Baseline lung function/frailty for prognostication.

5. Examination + POCUS

Diffuse bilateral crackles, tachypnea, accessory muscle use. POCUS: diffuse bilateral B-lines (interstitial syndrome); focused echo to assess LV function/exclude cardiogenic cause and screen for cor pulmonale/RV strain from high intrathoracic pressures.

6. Syndrome Identification

Confirm this is the alveolar-filling/interstitial syndrome, non-cardiogenic in origin, meeting full Berlin criteria — distinguish from cardiogenic pulmonary edema, multifocal pneumonia alone, or diffuse alveolar hemorrhage (which can mimic ARDS radiographically).

7. Differential Diagnosis

8. Severity Assessment

Berlin categories (mild/moderate/severe) drive both prognosis and rescue-therapy thresholds. Also apply SOFA/APACHE II for overall ICU severity, and driving pressure as an ongoing bedside risk marker.

9. Investigations

• Bedside: ABG (P/F ratio), plateau/driving pressure calculation, POCUS lung + cardiac
• Labs: CBC, renal, LFTs, coagulation, lactate, BNP (helps exclude cardiogenic cause), inflammatory markers/cultures per suspected trigger
• Imaging: CXR (bilateral opacities); CT chest if diagnosis unclear or to assess pattern/extent
• Echo: formal TTE to exclude cardiogenic edema if no clear ARDS risk factor present (Berlin requirement)
• Repeat: ABG after every major vent change; daily driving pressure trend

10. POCUS

Diffuse, bilateral, multi-zone B-lines with spared/irregular areas support ARDS over cardiogenic edema (which tends toward more homogeneous, gravity-dependent B-lines with a plethoric IVC and reduced EF). RV strain from elevated airway pressures should be actively screened for and may modify PEEP strategy.

11. Evidence-Based Management

First hour: Confirm Berlin criteria; set lung-protective ventilation; treat underlying trigger (e.g., antibiotics for pneumonia/sepsis source control).

First 6 hours: Titrate FiO2/PEEP table; assess driving pressure; initiate conservative fluid strategy (once shock resolved) targeting even-to-negative fluid balance following a FACTT-like protocol (CVP/PAOP, presence of shock, oliguria, cardiac output-guided).

First 24 hours: Reassess P/F ratio; if moderate-severe (P/F <150) despite optimized ventilation for ~12-24h, initiate prone positioning (16-20 h/24h cycles) — PROSEVA showed 28-day mortality 16% vs 32.8% supine. Consider NMB (cisatracurium 48h) if severe ARDS with dyssynchrony — evidence mixed (ACURASYS positive, ROSE neutral); reasonable in a targeted, not routine, fashion.

Ongoing: Daily reassessment of P/F, driving pressure, fluid balance; wean FiO2/PEEP as tolerated; consider steroids (methylprednisolone 1 mg/kg bolus then 1 mg/kg/day, or dexamethasone 20 mg then 10 mg daily x5+5 days) within 72h-14 days of onset if no contraindication — evidence conflicting, reassess for benefit at 3-5 days and stop if none; avoid after day 14 (possible harm).

Rescue therapies (P/F <150 refractory despite above, or FiO2 >0.7 with plateau >30):

• Prone positioning (first-line rescue, mortality benefit)
• Neuromuscular blockade
• Inhaled pulmonary vasodilators (epoprostenol/nitric oxide) — improves oxygenation, no mortality benefit, bridge measure only
• VV-ECMO (EOLIA criteria): P/F <50 for >3h, or P/F <80 for >6h despite optimization, or pH <7.25 with PCO2 >60 despite Pplat <32 and RR <=35
• Avoid HFOV (OSCILLATE trial showed harm)

12. Organ Support

Lung-protective ventilation is the core organ support intervention. Add: conservative fluid management, vasopressors only as needed for perfusion (avoid liberal fluids to support pressors), nutrition (early enteral), glucose control, VV-ECMO for refractory cases (Section 11).

13. Disease-Specific Therapy

Treat the underlying trigger aggressively (source control for sepsis, antibiotics for pneumonia, cessation of causative transfusion/drug). No proven ARDS-specific pharmacotherapy beyond supportive/ventilatory strategies above; steroids remain adjunctive and controversial.

14. Consultation Matrix

15. Monitoring Framework

Continuous SpO2/ventilator waveforms; ABG per protocol; daily driving pressure and P/F trend; fluid balance every shift; watch for barotrauma (sudden desaturation, asymmetric chest, high peak pressure -> pneumothorax). Escalate for rising FiO2/PEEP requirement or falling P/F despite optimization; de-escalate as P/F and compliance improve.

16. ICU Bundle Checklist (Daily)

17. Complications

Early: barotrauma/pneumothorax, hemodynamic compromise from high PEEP, proning-related pressure injury/ETT dislodgement.

Late: ICU-acquired weakness (esp. with prolonged NMB/steroids), ventilator-associated pneumonia, pulmonary fibrosis, critical illness myopathy/neuropathy.

Prevention: lung-protective ventilation, judicious steroid/NMB use, proning protocol adherence, VAP bundle.

Rescue: chest tube for pneumothorax, ECMO for refractory hypoxemia.

18. Escalation & De-escalation

Escalate: P/F falling despite optimized vent -> add proning -> consider NMB -> refer for ECMO evaluation early (before FiO2 >90% for >7 days, a relative ECMO contraindication).

Wean: improving P/F, driving pressure trending down, FiO2 <=50%, PEEP <=10 -> begin SBTs.

Step-down: extubated or stable on minimal support, hemodynamically stable, underlying trigger controlled.

19. ICU Discharge Criteria

P/F >300 or back to baseline, extubated or stable on low-level support, hemodynamically stable, underlying cause controlled, no ongoing organ failure requiring ICU-level monitoring.

20. Documentation & Medicolegal Checklist

21. Key Guidelines

ATS/ERS/ESICM/SCCM ARDS clinical practice guideline; Berlin Definition (ARDS Definition Task Force, JAMA 2012); Surviving Sepsis Campaign (if sepsis-triggered).

22. Landmark Trials

• ARMA (ARDSNet, 2000): Vt 6 vs 12 mL/kg PBW — 22% relative mortality reduction with low Vt. Foundational trial for lung-protective ventilation.
• ALVEOLI (2004): high vs low PEEP — no overall mortality difference.
• Amato et al. 2015: driving pressure best predicts survival among ventilator variables.
• FACTT (2006): conservative vs liberal fluid strategy — no mortality difference, but conservative arm had shorter ventilation/ICU duration.
• PROSEVA (2013): prone positioning in P/F <150 — 28-day mortality 16% vs 32.8% supine.
• ACURASYS (2010): 48h cisatracurium in P/F <150 — mortality benefit.
• ROSE (2019): larger NMB trial — no significant mortality benefit (excluded patients with a clear clinical NMB indication, limiting comparability).
• EOLIA / CESAR: VV-ECMO trials informing current referral criteria.
• OSCILLATE: HFOV associated with harm — avoid.

23. Controversies

Routine vs targeted NMB use (ACURASYS vs ROSE discordance); optimal PEEP titration strategy (protocol table vs individualized via esophageal pressure/EIT/stress index); steroid use — timing, dose, and patient selection remain unresolved; ECMO referral timing (early proactive vs reserved for strict EOLIA failure) varies by center capability.

24. References

1. Grotberg JC, Kraft BD. The Acute Respiratory Distress Syndrome. Washington Manual of Critical Care, 4th ed, 2025.
2. ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, et al. Acute respiratory distress syndrome: the Berlin definition. JAMA. 2012;307(23):2526-2533.
3. 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.
4. Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372(8):747-755.
5. Guerin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome (PROSEVA). N Engl J Med. 2013;368(23):2159-2168.
6. Papazian L, Forel JM, Gacouin A, et al. Neuromuscular blockers in early acute respiratory distress syndrome (ACURASYS). N Engl J Med. 2010;363(12):1107-1116.
7. National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Comparison of two fluid-management strategies in acute lung injury (FACTT). N Engl J Med. 2006;354(24):2564-2575.
8. Chawla R, Todi S, eds. ICU Protocols: A Step-wise Approach. 2nd ed. Springer; 2020.