Prone Positioning and the Emerging Paradigm for Managing Severe ARDS

Prone Positioning and the Emerging Paradigm for Managing Severe ARDS

Abstract & Commentary

By Richard H. Kallet, MS, RRT, FAARC, FCCM

Director of Quality Assurance, Respiratory Care Services, San Francisco General Hospital

Mr. Kallet reports no financial relationships relevant to this field of study.

SYNOPSIS: In this prospective, multicenter, randomized, controlled trial, 466 patients with severe acute respiratory distress syndrome were managed with protocolized lung-protective ventilation, with either supine positioning or prone positioning for at least 16 hours/day. Both 28-day and 90-day mortality were significantly reduced in those managed with prone positioning.

SOURCE: Guérin C, et al for the PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013; 368:2159-2168.

The study was conducted in 26 ICUs that had at least 5 years’ experience with prone positioning (PP). Only patients with acute respiratory distress syndrome (ARDS) and a sustained (12-24 hours) arterial oxygen tension-to-inspired oxygen fraction (PaO2/FiO2) ratio < 150 mmHg after enrollment were eligible for randomization. Ventilator management similar to the original ARDS Net protocol was applied in both treatment arms. Also, protocols for paralytics, sedation, inhaled nitric oxide, and other measures were used. At study entry, there were no differences in ventilator settings or arterial blood gas values. Likewise, baseline demographic and physiologic profiles of the patients were similar. However, there were statistically significant increases in Sepsis-related Organ Failure Assessment (SOFA) scores and vasopressor use in the supine group, and more use of paralytics in the PP group.

Both 28- and 90-day mortality were reduced in the PP vs supine positioning groups (16.0 vs 32.8%, and 23.6 vs 41%, respectively; P < 0.001), differences that remained significant even after adjustment for both SOFA score and paralytics. There also was a trend toward higher use of rescue therapies in the supine group. Patients in the PP arm had a greater number of ventilator-free days at 28 and 90 days compared to the supine arm (14 ± 9 vs 10 ± 10 and 57 ± 34 vs 43 ± 38; P < 0.001, respectively). Likewise, the proportion of patients successfully extubated by day 90 was higher in the PP group (80.5%) vs the supine group (65%; P < 0.001).

COMMENTARY

The PROSEVA study confirms a recent meta-analysis of seven randomized, controlled trials (RCTs) that found a survival benefit with the use of PP only in ARDS patients whose PaO2/FiO2 ratio was < 100 mmHg (relative risk, 0.84; 95% confidence interval, 0.74-0.96; P = 0.01, n = 555).1 Previous RCTs enrolled patients with varying severity of ARDS, sometimes limited the exposure to PP to 7-9 hours per day, and did not always include lung-protective ventilation in all patients. In contrast, the PROSEVA study design was admirable both in its attempt to exclude patients who recovered rapidly and in its incorporation of protocols to control for other potential confounders.

PP favorably alters the pulmonary hydrostatic pressure gradient, thus increasing trans-pulmonary pressure within dorsal lung regions. This accentuates the relative effect of applied airway pressure (both driving pressure and PEEP), so that relatively higher proportions of both tidal ventilation and end-expiratory volume are preferentially redistributed to these areas. Alterations in gravitational forces also reduce the compressive effects of the mediastinum on lung tissue. In effect, PP in ARDS functions as a recruitment maneuver. Moreover, as less pulmonary vasculature is oriented toward the ventral lungs, blood flow resistance remains lower in the dorsal regions so that pulmonary perfusion remains relatively intact. Therefore, overall ventilation-perfusion matching, and thus oxygenation, typically improve.

That PP promotes lung-protective ventilation likely explains the improved survival in severe ARDS. Functional residual capacity (FRC) is a key determinant of oxygenation. It also affects pulmonary elastic recoil properties, and therefore determines the strain-stress relationships believed responsible for ventilator-induced lung injury. By returning FRC toward normal (through recruitment of collapsed alveoli), both shear injury and excessive regional strains and stresses are reduced. In addition, improvements in oxygenation may reduce exposure to potentially toxic oxygen levels (e.g., FiO2 ≥ 0.80). Therefore, a mortality benefit associated with PP would more likely be manifested in severe ARDS, in which FRC and lung compliance are highly abnormal and patients must endure prolonged exposure to high strains-stresses and high FiO2 that exacerbate lung inflammation.

The current study is consistent with a recent meta-analysis suggesting a survival benefit from high-PEEP only in those with more severe ARDS.2 An emerging picture is that early intervention with low tidal volume ventilation, restoring FRC, and a period of complete control over the ventilatory pattern with paralytics3 reduces mortality in ARDS. With severe infection or trauma, the body’s inflammatory response is hyperstimulated. In these situations, therapies that exacerbate inflammation further may be overwhelming. Nonetheless, accumulating evidence from well-executed RCTs may now provide us with a more complete, evidence-based model to effectively treat severe ARDS.

REFERENCES

1. Sud S, et al. Prone ventilation reduces mortality in patients with acute respiratory failure and severe hypoxemia: Systematic review and meta-analysis. Intensive Care Med 2010;36:585-599.
2. Briel M, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome. JAMA 2010;303:865-873.
3. Alhazzani W, et al. Neuromuscular blocking agents in acute respiratory distress syndrome: A systematic review and meta-analysis of randomized controlled trials. Crit Care 2013;17R43.