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To Prone or not to Prone ... That Is the Question
Abstract & Commentary
By Andrew M. Luks, MD, Pulmonary and Critical Care Medicine, University of Washington, Seattle. Dr. Luks reports no financial relationship to this field of study. This article originally appeared in the January 2010 issue of Critical Care Alert. It was edited by David J. Pierson, MD and peer reviewed by William Thompson, MD.
Synopsis: This multicenter, unblinded, randomized trial demonstrated that prone positioning was not associated with a mortality benefit in patients with ARDS, including subgroups with moderate and severe hypoxemia.
Source: Taccone P, et al. Prone positioning in patients with moderate and severe acute respiratory distress syndrome: A randomized controlled trial. JAMA. 2009;302:1977-1984.
Prone positioning has been advocated as a management strategy for patients with acute respiratory distress syndrome (ARDS), but despite evidence of improved oxygenation with the technique, numerous studies have yet to establish a mortality benefit from the practice. Post-hoc analysis of data from an earlier trial did suggest, however, that a mortality benefit might be present in patients with the most severe hypoxemia.1 Taccone et al sought to test this finding in a prospective manner by applying prone positioning to ARDS patients with moderate and severe hypoxemia and evaluating whether the practice led to improvement in survival for these patients.
To test their hypothesis, Taccone et al conducted a multicenter, unblinded, randomized controlled trial in 23 centers in two countries. Eligible patients included those 17 years and older, receiving mechanical ventilation and meeting accepted diagnostic criteria for ARDS. Patients were excluded from the study if more than 72 hours had elapsed since the diagnosis of ARDS, or if they had a history of solid-organ or bone-marrow transplantation or had any condition precluding prone positioning (e.g., intracranial hypertension, spine or pelvic fractures). Included patients were randomly assigned to the control (supine positioning) or intervention (prone positioning using a Rotoprone rotational bed for > 20 hours per day until resolution of acute respiratory failure or the end of the 28-day study period) group, and were stratified into two groups based on the severity of their hypoxemia at the time of enrollment: moderate hypoxemia (PaO2/FIO2 ratio, 100-200 mm Hg) and severe hypoxemia (PaO2/FIO2 ratio < 100 mm Hg). Patients in both groups were ventilated using a standard protocol requiring tidal volume ≤ 8 mL/kg, plateau pressure ≤ 30 cm H2O, and standardized adjustments in positive end-expiratory pressure (PEEP) and FIO2 to maintain PaO2 at 70-90 mm Hg. All other therapeutic decisions (e.g., antibiotics, sedation) were at the discretion of the treating physician. The primary outcome measure was 28-day mortality, while secondary outcome measures included mortality at ICU discharge and six months, Sequential Organ Failure Assessment (SOFA) scores at 28 days, and ventilator-free days during the 28-day study period.
A total of 342 patients were included in the final analysis (168 prone, 174 supine). Of these patients, 192 were classified as having "moderate" hypoxemia (94 prone, 98 supine), while the remaining 150 had severe hypoxemia (74 prone, 76 supine). Patients in the intervention group were prone a mean of 8.4 ± 6.3 sessions lasting on average 18 ± 4 hours per day. Twenty percent of patients in the prone group missed at least one proning session due to factors such as hemodynamic instability, facial edema, or malfunction of continuous renal replacement therapy. Twenty patients in the supine group (11.5%) received prone positioning as a rescue procedure. Across the entire study population, the PaO2/FIO2 ratio was higher in the prone group compared to the supine group. Mortality at 28 days was the same in the prone and supine groups (31% vs. 32.8%) and there were also no statistically significant differences in mortality between patients with moderate (prone, 25.5% vs. supine, 22.5%) or severe hypoxemia (prone, 37.8% vs. supine, 46.1%).
There were no differences in secondary outcomes between the prone and supine groups across the entire study population or within the predefined subgroups. The complication rate was significantly higher in the prone group (95% with at least one complication compared to 76% in the supine group), with the prone patients having a higher incidence of need for increased sedation or paralysis (80% vs. 56%), airway obstruction (51% vs. 34%), vomiting (29% vs. 13%), loss of venous access (16% vs. 4%), hypotension or need for pressors (72% vs. 55%), and endotracheal tube displacement (11% vs. 5%).
This paper is yet another entry in a line of studies that shows the same pattern of results with regard to the effect of prone positioning in patients with ARDS improvements in oxygenation that do not translate to improvements in important patient outcomes. By looking specifically at patients with severe hypoxemia (PaO2/FIO2 < 100 mm Hg), the study by Taccone et al was supposed to address an important limitation of previous studies their inclusion of patients with a wide range of abnormalities in oxygenation that was purported by proning proponents to be masking a survival benefit that would otherwise be seen in the more severely ill patients. As we see now, however, even within the most severely ill ARDS patients, proning has no impact on survival.
In addition to the persistent inability to demonstrate a mortality benefit, there are other data in this paper that should give pause to those considering the utility of this technique. In particular, even though they used a specialty proning bed rather than manual proning techniques, there was a high complication rate in the prone patients, with more than 94% of them experiencing at least one complication such as endotracheal tube dislodgement, loss of venous access, airway obstruction, hypotension, and need for increased sedation and paralysis. This surprisingly high complication rate forces one to step back and wonder whether the use of proning not only doesn't provide benefit to our patients, but may also put them at risk for more harm.
Will the results of this study change practice and decrease the use of this expensive modality? That is probably unlikely to happen. Like a lot of the therapies used in the management of patients with critical hypoxemia, including inhaled vasodilators, extracorporeal membrane oxygenation (ECMO), and alternative modes of mechanical ventilation, this therapy has its proponents, as well as those whose assessment of its utility is affected by anecdotal experiences of patient improvement. It is hard to look at the single patient at the bedside who is experiencing severe, life-threatening hypoxemia and not use a technique that "worked" in a previous patient. At some point, however, the preponderance of the evidence has to win out, and we need to step back and consider whether this therapy is really safe and beneficial.
1. Gattinoni L, et al. Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med 2001;345:568-573.