Jul 112014

Image: Rotoprone

Acute respiratory distress syndrome (ARDS) injures the lungs in a heterogeneous pattern, and the damaged areas are particularly vulnerable to further ventilator-induced lung injury. This is why a lung-protective ventilator strategy using low tidal volumes reduces mortality from ARDS, experts believe. Tidal volumes of 6 mL/kg ideal body weight (calculated from height) using conventional ventilation are recommended for all patients with ARDS. (High-frequency oscillatory ventilation or HFOV was believed by some to be an even better lung protective ventilator strategy, until 2 large randomized trials showed HFOV does not help, and may be harmful, compared to conventional ventilation with low tidal volumes for first-line treatment of early ARDS).

Prone positioning (lying face-down) extends the lung-protective physiologic paradigm a bit further. Lying prone results in a greater proportion of alveoli aerated at equivalent delivered volumes or pressures (i.e., prone positioning improves lung compliance and ventilation-perfusion matching). During prone positioning, less of the lung is compressed or collapsed (atelectatic) due to anatomy and gravity, meaning more of the ventilator-delivered tidal volumes (and pressure) will aerate uninjured lung, with less volume (pressure) "left over" to distend and further damage the injured lung.

That's the theory, anyway.

Prone positioning has been a mostly boutique therapy since its first suggestion in 1974. Initial large randomized trials (published 2001-2004 in NEJM and JAMA) did not show benefit, and prone positioning never took hold as standard therapy for ARDS. Leaders at several medical centers around the world nevertheless committed their institutions to prone positioning for ARDS, putting in place the training and culture over decades to make this "experimental" therapy their own local standard of care for ARDS. Along the way, many of these centers continued to perform large randomized trials enrolling patients with more-severe ARDS.

PulmCCM reported on the most recent and remarkable of these trials, published by Claude Guérin et al in NEJM in June 2013, which showed a dramatic >50% reduction in 28-day and 90-day mortality among 466 patients treated with prone positioning for severe ARDS at 26 centers in France. While unblinded, the trial's results demanded attention.

Sachin Sud et al provide some in the July 8 2014 CMAJ, with a meta-analysis that combines Guérin et al's data with 5 other trials that used lung-protective ventilation in both prone positioning and control groups (6 trials, n=1,016 total), finding significant benefits from prone positioning:

  • Reduced mortality (risk ratio 0.74)
  • Number needed to treat with prone positioning to save one life: 11
  • These benefits are over and above those of standard low tidal volume ventilation, which all patients received.

A dose-response relationship existed for prone positioning in ARDS:

  • Mortality was lower with long durations of prone positioning (>16 hours/day), but not with durations <16 hours/day.
  • Mortality was reduced among patients with severe hypoxemia, but not those with mild or moderate hypoxemia.

Authors report a consistent effect across the randomized trials analyzed, a high quality of evidence overall, and persistence of their findings through numerous sensitivity analyses.

Notably, prone positioning did not reduce mortality in the authors' pooled analysis of 5 other trials that did not require low-tidal volume ventilation. This, along with the enrollment of patients with less-severe ARDS, may explain the negative results in early randomized trials testing prone positioning for ARDS, authors suggest.

Prone positioning is not easy, requires significant effort by staff, and carries its own risks. Frequent turning (often requiring multiple staff members) and special positioning is required to prevent pressure ulcers, which occur in unfamiliar locations (most notably the face). Enteral feeding is possible during prone positioning, but promotility drugs or post-pyloric feeding tubes have been recommended to prevent aspiration. Pressure ulcers and unplanned extubations were both more common in the prone positioning arms of the analyzed trials, although these events were unusual. Most trials at experienced centers used manual turning; specialized (and expensive) rotating prone beds are used by many U.S. hospitals in the hope of reducing the risks and staff burden of prone positioning.

Surveys of ICU nurses have found reluctance to initiate prone positioning for ARDS, an effect I experienced when I was informed firmly by 2 respiratory therapists and a nurse that rather than prone positioning, "this patient needs to be on the oscillator!" (He received prone positioning for his severe ARDS, and fortunately survived.)

Sachin Sud et al. Effect of prone positioning during mechanical ventilation on mortality among patients with acute respiratory distress syndrome: a systematic review and meta-analysis. CMAJ July 8, 2014 vol. 186 no. 10.

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Prone positioning reduces ARDS mortality by 26%: meta-analysis