What are the differences between early and late prone responders in Acute Respiratory Distress Syndrome (ARDS) patients?

Differences Between Early and Late Prone Responders in ARDS Patients

Early responders to prone positioning in ARDS show improved 28-day mortality outcomes compared to non-responders, making early oxygenation improvement a critical indicator for continuing prolonged prone positioning in severe ARDS. 1

Definition of Responders

• Early prone responders are defined as patients who show significant improvement in oxygenation (increase in PaO₂/FiO₂ ratio ≥20 mmHg) within the first 8-12 hours after initial prone positioning 1
• Late responders may show delayed improvement in oxygenation, sometimes requiring a second attempt at prone positioning to achieve benefits 2
• Some patients initially classified as non-responders may become "secondary responders" when turned prone a second time 2

Clinical Significance of Early Response

• Early oxygenation improvement after prone positioning is associated with improved 28-day outcomes compared to non-responders 1
• Early response to prone positioning serves as an indicator to maintain prolonged prone positioning (≥12 hours per day) in patients with severe ARDS 1, 3
• The physiological benefits of prone positioning include improved ventilation-perfusion matching, increased end-expiratory lung volume, and decreased ventilator-induced lung injury through more uniform distribution of tidal volume 3

Timing of Prone Positioning

• Current guidelines recommend early application of prone positioning in severe ARDS patients (PaO₂/FiO₂ <150 mmHg) 3
• Subgroup analyses reveal a positive effect on mortality when patients are placed in prone position within 48 hours of starting mechanical ventilation 3
• The PROSEVA trial demonstrated significant mortality benefits with early application of prone positioning in severe ARDS 4

Duration of Prone Positioning

• Guidelines strongly recommend that adult patients with severe ARDS receive prone positioning for more than 12 hours per day 3
• Meta-analyses show prone positioning reduced mortality in trials with prone duration greater than 12 hours per day (RR, 0.74; 95% CI, 0.56–0.99) 3
• The mean duration of prone positioning in clinical studies ranges from 12-78 hours, with some patients requiring multiple prone sessions 1, 5

Physiological Mechanisms Behind Response Differences

• Early responders likely have more recruitable lung tissue that responds rapidly to changes in ventilation-perfusion matching 3
• Non-responders or late responders may have more severe or heterogeneous lung injury patterns requiring longer time for recruitment 2
• Prone positioning improves oxygenation by:
  • Redistributing lung densities with recruitment of well-perfused dorsal regions 3
  • Increasing end-expiratory lung volume 3
  • Creating a more homogeneous distribution of ventilation 3

Ventilator Management for Prone Responders

• Both early and late responders benefit from lung-protective ventilation strategies with limited tidal volumes (4-8 ml/kg PBW) 3
• Evidence suggests that the limitation of tidal volume is necessary for mortality benefit from prone positioning 3
• Prone positioning and PEEP have an additive effect on improving oxygenation 3

Monitoring and Assessment

• PaO₂ response (increase in PaO₂/FiO₂ ratio ≥20 mmHg) after 8-12 hours is a better predictor of improved outcomes than PaCO₂ response 1
• Based on the PROSEVA trial results, prone positioning should continue until there is improvement in oxygenation (PaO₂/FiO₂ ≥150) under de-escalated ventilation (PEEP ≤10 cmH₂O and FiO₂ ≤0.6) 4 hours after returning to supine position 3
• For non-responders, experts recommend terminating prone positioning therapy after two unsuccessful attempts (lack of improvement in oxygenation) 3

Complications and Considerations

• Both early and late responders face similar risks with prone positioning, including:
  • Endotracheal tube obstruction (RR, 1.76; 95% CI, 1.24–2.50) 3
  • Pressure sores (RR, 1.22; 95% CI, 1.06–1.41) 3
  • Potential increases in intra-abdominal pressure from 12±4 mmHg to 14±5 mmHg 3
• Special considerations are needed for patients with:
  • Increased intracranial pressure, as prone positioning may increase ICP from 11 to 24 mmHg 3
  • Obesity or recent abdominal surgery 3
  • Concurrent ECMO therapy, which requires experienced centers 3, 5

Clinical Implications

• Early identification of prone responders allows for more targeted and effective use of prone positioning 1
• For patients who don't respond initially, a second attempt at prone positioning may be beneficial before abandoning the strategy 2
• The mortality benefit of prone positioning is most pronounced in patients with severe ARDS (PaO₂/FiO₂ <150 mmHg) 3, 4