In a patient with severe acute respiratory distress syndrome (PaO2/FiO2 ratio <80 mm Hg or SpO2 <88 % on FiO2 ≥0.9) despite low‑tidal‑volume ventilation (6 mL/kg predicted body weight) with optimal positive end‑expiratory pressure, what rescue strategies should be employed?

Rescue Strategies in Severe ARDS

Primary Rescue Strategy: Prone Positioning

For severe ARDS with PaO2/FiO2 <150 mm Hg (which includes your scenario of <80 mm Hg), prone positioning is the first-line rescue therapy and should be implemented immediately, as it is the only rescue intervention with proven mortality benefit. 1, 2, 3

• Prone positioning for at least 16 hours per day reduces mortality in severe ARDS (strong recommendation, moderate quality evidence) 1
• This intervention improves V/Q matching, recruits dorsal lung units, and redistributes ventilator-induced lung stress away from vulnerable regions 4
• Continue prone positioning sessions until PaO2/FiO2 improves to >150 mm Hg for >4 consecutive hours in supine position 4

Second-Line Rescue: Neuromuscular Blockade

If prone positioning alone is insufficient, add continuous neuromuscular blocking agents for up to 48 hours. 1, 5, 2, 3

• Use neuromuscular blockade when PaO2/FiO2 remains <150 mm Hg despite prone positioning (weak recommendation, moderate quality evidence) 1
• Limit duration to ≤48 hours to minimize ICU-acquired weakness 1, 5
• This reduces patient-ventilator dyssynchrony and prevents spontaneous breathing efforts that can worsen lung injury 5

Third-Line Rescue: Recruitment Maneuvers

Consider recruitment maneuvers as an adjunct, but recognize they provide only temporary improvement in oxygenation. 1, 5, 4

• Recruitment maneuvers are suggested for severe refractory hypoxemia (weak recommendation, moderate quality evidence) 1
• These can be combined with higher PEEP strategies (already optimized in your scenario) to maintain recruited alveoli 5
• Monitor hemodynamics closely during recruitment as transient hypotension may occur 4

Fourth-Line Rescue: Inhaled Pulmonary Vasodilators

Inhaled nitric oxide (iNO) can be used as a temporizing "bridge" measure but does not improve survival and should not delay definitive rescue therapies. 4, 6

• iNO improves oxygenation acutely but provides no mortality benefit in ARDS 7, 4
• The FDA label explicitly states iNO is "ineffective in adult respiratory distress syndrome" based on a 385-patient randomized trial showing no effect on ventilator-free days despite acute oxygenation improvements 7
• If used, start at 5-20 ppm and monitor methemoglobin levels (discontinue if >4%) 7
• Consider iNO only as a bridge while arranging ECMO or when other rescue therapies have failed 4, 6

Avoid These Interventions

Do not use high-frequency oscillatory ventilation (HFOV) as it increases mortality in ARDS. 1, 2

• HFOV is strongly recommended against (strong recommendation, moderate quality evidence) 1
• Despite theoretical benefits, randomized trials showed harm rather than benefit 1

Last Resort: Extracorporeal Membrane Oxygenation (ECMO)

When all the above rescue therapies fail to maintain adequate oxygenation (SpO2 ≥88% or PaO2 ≥55-60 mm Hg), transfer to an ECMO center for veno-venous ECMO. 4, 6

• ECMO should be reserved for patients unresponsive to the multimodal approach described above 4
• Early consultation with an ECMO center is appropriate when PaO2/FiO2 <80 mm Hg, even before exhausting all rescue options 4
• ECMO serves as the ultimate rescue when lung-protective ventilation combined with prone positioning, neuromuscular blockade, and recruitment maneuvers cannot maintain life-compatible gas exchange 4, 6

Concurrent Supportive Measures

Maintain conservative fluid management once tissue perfusion is adequate. 1, 5, 3

• Conservative fluid strategy reduces duration of mechanical ventilation in established ARDS (strong recommendation, moderate quality evidence) 1
• Avoid fluid overload which worsens pulmonary edema and impairs oxygenation 5

Ensure lung-protective ventilation parameters remain optimized throughout rescue therapy: 1, 2, 3

• Tidal volume 6 mL/kg predicted body weight (already achieved in your scenario) 1
• Plateau pressure ≤30 cm H2O 1, 2
• Driving pressure (plateau - PEEP) ideally ≤15 cm H2O 2

Critical Pitfalls to Avoid

• Do not delay prone positioning while trying other rescue therapies—it is the only intervention proven to reduce mortality and should be first-line 1, 4
• Do not continue neuromuscular blockade beyond 48 hours as prolonged paralysis increases ICU-acquired weakness without additional benefit 1, 5
• Do not rely on iNO as a primary rescue strategy given its lack of survival benefit and FDA designation as ineffective in ARDS 7, 4
• Do not use HFOV as it may increase mortality 1
• Do not hesitate to contact an ECMO center early when PaO2/FiO2 <80 mm Hg, as transport logistics may take time 4