What are the recommended ventilation strategies for patients with acute respiratory distress syndrome (ARDS)?

Critical Appraisal of the ACURASYS Trial for DrNB Practical Exam

What Was ACURASYS?

ACURASYS (2010) was a landmark French multicenter RCT that demonstrated early neuromuscular blockade with cisatracurium for 48 hours improved 90-day mortality in patients with severe early ARDS (PaO₂/FiO₂ <150 mmHg). The trial randomized 340 patients to receive either continuous cisatracurium infusion or placebo for 48 hours within 48 hours of ARDS onset, while maintaining deep sedation in both groups 1.

Key Findings & Clinical Impact

Primary Outcome: Mortality Benefit

• 90-day mortality was significantly reduced: 31.6% in the cisatracurium group versus 40.7% in placebo (adjusted HR 0.68,95% CI 0.48-0.98, P=0.04) 1
• The absolute risk reduction of approximately 9% translates to a number needed to treat of roughly 11 patients 1
• This mortality benefit occurred without increased ICU-acquired weakness, which was a major safety concern 1

Secondary Outcomes: Ventilator Mechanics

• Patients receiving cisatracurium had more ventilator-free days and organ failure-free days 1
• The intervention group showed improved oxygenation (higher PaO₂/FiO₂ ratios) and lower plateau pressures during the first 48-120 hours 1
• Barotrauma rates were not significantly different between groups 1

Mechanism of Benefit

The proposed mechanisms for improved outcomes include:

• Prevention of ventilator dyssynchrony, which can cause self-inflicted lung injury and ventilator-induced lung injury 1
• Facilitation of lung-protective ventilation by eliminating spontaneous breathing efforts that can generate high transpulmonary pressures 1
• Reduction in oxygen consumption and metabolic demand during the acute inflammatory phase 1
• Improved patient-ventilator synchrony allowing better delivery of low tidal volume ventilation and higher PEEP 1

Current Guideline Recommendations

The 2017 American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine guidelines do NOT make a strong recommendation for routine neuromuscular blockade in ARDS 2. However:

• For early severe ARDS with PaO₂/FiO₂ <150 mmHg, neuromuscular blocking agents may be used for up to 48 hours 1
• Administer as intermittent boluses rather than continuous infusion when possible 1
• Use continuous infusion only for persistent ventilator dyssynchrony, need for deep sedation, prone positioning, or persistently high plateau pressures 1

The conditional nature of this recommendation reflects subsequent evidence that has tempered enthusiasm for routine use.

Critical Limitations & Subsequent Evidence

Study Design Issues

• Both groups received deep sedation (Ramsay 6), making it impossible to determine whether the benefit came from neuromuscular blockade itself or simply from preventing patient-ventilator dyssynchrony 1
• Modern practice favors lighter sedation strategies, which may reduce the need for paralysis 1
• The trial was conducted before prone positioning became standard of care for severe ARDS 2

The ROSE Trial (2019) - Game Changer

The subsequent ROSE trial (1006 patients with moderate-to-severe ARDS) found no mortality benefit from early neuromuscular blockade with cisatracurium when compared to lighter sedation without routine paralysis. This larger, more recent trial used contemporary sedation practices (lighter sedation in control group) and found:

• No difference in 90-day mortality
• No difference in ventilator-free days
• Similar rates of ICU-acquired weakness

This suggests the ACURASYS benefit may have been due to deep sedation preventing dyssynchrony rather than paralysis per se 1.

Integration with Other ARDS Therapies

Lung-Protective Ventilation (Foundation)

• Tidal volume 4-8 mL/kg predicted body weight (target 6 mL/kg) 2, 1
• Plateau pressure <30 cmH₂O 2, 1
• Accept permissive hypercapnia (pH >7.20) 1

Prone Positioning (Takes Priority)

• For severe ARDS (PaO₂/FiO₂ <150 mmHg), prone positioning for >12 hours daily is STRONGLY recommended and should be implemented before considering neuromuscular blockade 2, 1
• Prone positioning has stronger evidence (RR 0.74 for mortality) and is a strong recommendation, whereas neuromuscular blockade is conditional 2

PEEP Strategy

• For moderate-to-severe ARDS (PaO₂/FiO₂ <200 mmHg), use higher PEEP (typically >10 cmH₂O) 1, 3
• Monitor for barotrauma when using PEEP >10 cmH₂O 1

Practical Application for DrNB Exam

When to Consider Neuromuscular Blockade

1. Severe ARDS with PaO₂/FiO₂ <150 mmHg within 48 hours of onset 1
2. Persistent ventilator dyssynchrony despite optimized sedation 1
3. Inability to maintain plateau pressure <30 cmH₂O due to patient effort 1
4. During prone positioning to facilitate safe turning and positioning 1
5. Refractory hypoxemia despite lung-protective ventilation and prone positioning 1

When NOT to Use Routine Paralysis

• Mild-to-moderate ARDS (PaO₂/FiO₂ >150 mmHg) - no evidence of benefit 1
• After the first 48 hours - prolonged paralysis increases risk of ICU-acquired weakness 1
• When adequate patient-ventilator synchrony can be achieved with sedation alone 1
• Before implementing prone positioning - prone positioning should be tried first as it has stronger evidence 2

Common Exam Pitfalls to Avoid

• Do NOT state that neuromuscular blockade is standard of care for all severe ARDS - it is a conditional recommendation, not strong 1
• Do NOT forget that prone positioning has stronger evidence and should be prioritized 2
• Do NOT recommend continuous infusion as first-line - intermittent boluses are preferred when paralysis is needed 1
• Do NOT extend paralysis beyond 48 hours routinely - this increases complications without proven benefit 1
• Do NOT use paralysis as a substitute for optimizing ventilator settings and sedation 1

Bottom Line for Exam Answers

ACURASYS showed mortality benefit from early cisatracurium in severe ARDS, but subsequent evidence (ROSE trial) suggests this benefit may not persist with modern lighter sedation strategies. Current guidelines give a conditional recommendation for neuromuscular blockade in severe ARDS (PaO₂/FiO₂ <150 mmHg) for up to 48 hours, but only after implementing lung-protective ventilation and prone positioning, and only when ventilator dyssynchrony persists despite optimized sedation 2, 1.