MILAN, ITALY—Although prone positioning is known to improve oxygenation in many patients with acute respiratory failure, its effect on mortality has been unclear. Italian and Swiss investigators led by Luciano Gattinoni, MD, recently undertook a multicenter trial in hopes of finding an answer.[1]

As Dr. Gattinoni and his colleagues expected, oxygenation was markedly greater when patients were prone rather than supine. Prone positioning was also associated with slightly lower mortality rate—but the difference was not statistically significant. This finding has raised a new question: Were too few patients studied to detect a difference in outcome, or is prone positioning simply ineffective in improving survival?

“We had to stop the trial after enrolling only 304 patients because most of the centers were reluctant to forego the prone position when they saw its effect on oxygenation,” explained Dr. Gattinoni, Director of the Institute of Anesthesia and Intensive Care at the University of Milan. “If we had [enrolled] 700 patients as we planned, the mortality decrease may have been significant.” This trial is merely a starting point in addressing the effect of pronation on survival, he told PULMONARY REVIEWS.

ELIGIBILITY CRITERIA

Mechanically ventilated patients were eligible for the trial if they met the modified criteria of Bernard et al[2] for acute lung injury or acute respiratory distress syndrome (ARDS). Patients had to have:
• A PaO2:FIO2 ratio of 300 or less in association with a PEEP level of at least 10 cm H2O (findings consistent with acute lung injury) or a PaO2:FIO2 ratio of 200 or less with a PEEP level of at least 5 cm H2O (characteristic evidence of ARDS).
• Bilateral pulmonary infiltrates.
• A pulmonary capillary wedge pressure (if measured) of 18 mm Hg or less in the absence of clinical evidence of left atrial hypertension.

Patients were excluded if they were younger than 16 years or had clinical evidence of cardiogenic pulmonary edema, cerebral edema, or intracranial hypertension. Having a clinical condition that would contraindicate prone positioning (eg, spine fractures or severe hemodynamic instability) was also reason for exclusion.

The 304 participants were recruited from 28 Italian and two Swiss intensive care units (ICUs) and randomly assigned to the prone or supine group. All participants were assessed each morning while supine. Those in the prone group were kept face down at least six hours a day for 10 days.

All participants’ physicians were asked to comply with the American-European Consensus Conference mechanical ventilation guidelines for routine ventilation.[3] They were also asked not to change the ventilator settings when participants were prone to help standardize assessment of the changes in gas exchange produced by that position.

RELATIVE RISK OF DEATH UNCHANGED

After 10 days, mortality was 21.1% in the prone group and 25.0% in the supine group; thus, the relative risk of death at 10 days was 0.84 in the prone group. Furthermore, the relative risks of death by ICU discharge and at six months in the prone group were 1.05 and 1.06, respectively. These differences were nonsignificant.

Results were similar when patients with protocol violations were excluded from the analysis. The prone group did, however, have a significantly greater mean rise in the PaO2:FIO2 ratio during the study (63.0 vs 44.6 in the supine group).

The two groups had comparable rates of accidental tracheal or thoracotomy tube displacement, unintentional loss of venous access, and new or worsening pressure sores. They also had a similar mean number of days with pressure sores per patient. The mean number of new or worsening pressure sores per patient was greater in the prone group, however.

BENEFIT FOR MOST SEVERELY ILL?

A post hoc analysis suggested that prone positioning markedly lowered 10-day mortality in patients with one or more of the following: a PaO2:FIO2 ratio in the bottom quartile, a severity-of-illness score in the top quartile, and a tidal volume in the top quartile. However, these differences did not persist beyond ICU discharge. The authors said this may indicate that the duration of prone positioning was insufficient or that pronation simply delayed an inevitable outcome. Thus, another trial is needed to clarify the role of prone positioning in patients with severe ARDS. However, its routine use in acute respiratory failure is not justified, the investigators concluded.

—Timothy Begany

References
1. Gattinoni L, Tognoni G, Pesenti A, et al. Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med. 2001;345:568-573.
2. Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;149(3 pt 1):818-824.
3. Slutsky AS. Consensus conference on mechanical ventilation—January 28-30, 1993 at Northbrook, Illinois, USA: part 2. Intensive Care Med. 1994;20:150-162.

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