A turn for the best? Prone positioning saves lives in ARDS trial
Prone Positioning Saves Lives in Severe ARDS Patients: NEJM
It's long been known that positioning patients with ARDS on mechanical ventilation face-down (prone) improves their oxygenation. (There are various theories why prone positioning helps, such as by reducing ARDS's injurious heterogeneous alveolar overdistension.) The improved oxygen levels have never translated into improved outcomes in ARDS patients treated with prone positioning in individual multicenter randomized trials, but meta-analyses have concluded prone positioning improves survival from ARDS, especially in the most hypoxemic patients.
Claude Guérin et al's PROSEVA study in the online May 20, 2013 New England Journal of Medicine will make everyone treating ARDS turn their heads, if not their patients. It shows an almost unbelievable benefit of more than a 50% reduction in mortality from ARDS, simply from positioning patients prone for most of the day while otherwise delivering normal ARDS care.
What They Did
Investigators randomized 474 patients at 26 French ICUs (and one in Spain) with severe ARDS (PaO2:FiO2 ratio of <150 mm Hg, PEEP >5, FiO2 > 0.60) to receive standard care, or to also be "proned" (turned face-down) for 16 hours a day, every day for up to 28 days (or longer if their doctors so chose).
The patients were well matched statistically, but the control group (supine, face-up) were slightly sicker, with SOFA scores of 10.4 vs 9.6, and greater use of vasopressors (83% vs 73%). They also had reduced use of neuromuscular blockers (82% vs 91%) than the prone-positioned patients (the use of such paralytics may possibly help in ARDS). Control (supine) patients' greater need for dialysis was large (17% vs 11%) but not statistically significant.
Of course, and importantly, the patients' physicians were unblinded to study allocation.
What They Found
Far more prone-positioned patients survived their ARDS: 16% mortality at 28 days (38 deaths in 237 patients) vs. 33% in the supine group (75 of 229 patients), with a very low p-value, < 0.001. That's a staggering 17% absolute risk reduction. The benefit was only slightly smaller at 90 days.
There was a clear mechanism of benefit, with prone-positioned patients having higher paO2:FiO2 ratios, lower plateau pressures (average 2 cm H2O), and lower required PEEP.
There were no excess adverse events -- such as unplanned extubations -- in the prone-positioning group. After adjusting for the imbalance in SOFA scores, pressors and neuromuscular blockade at randomization, the benefits of prone positioning persisted.
What It Means
Whether this study heralds the coming of a new standard of care, or yet another boom-bust cycle in the critical care collective consciousness (see our previous love affairs with Xigris and intensive glucose therapy, ending in disillusionment), only time will tell. The question now is, who will rush to be the early adopters, and how will prone positioning disseminate and be evaluated over time?
Prone positioning is not brain surgery, but it's not a practice change you make overnight (see the videos linked from the article). Someone has to teach staff how to do it, and it takes time for everyone to get familiar and comfortable with the new routines. Most or all the centers in this study have been doing it for years, with the requisite staff training and culture in place to avoid uncommon but serious complications (such as pressure necrosis and endotracheal tube displacement). Remember this baked-in publication bias when admiring their negligible complication rate; no one publishes the paper that says, "Here at St. Elsewhere, we held a training meeting, then proned 200 people, accidentally dislodged 20 ET tubes, and increased our mortality rate by 10%. Be careful, everybody!"
The NEJM editorialist announced, "There can no longer be any doubt. Prone ventilation in selected patients with severe ARDS has arrived and is ready for its turn in the management of the disease."
No question, these findings are exciting. Early adoption is fully appropriate -- maybe ethically imperative -- by motivated centers with the resources to do so. Observational studies can help us ascertain the real world benefit over time. But ... "no longer any doubt?" After previous negative trials of prone positioning, including by this same group? And notwithstanding the boulevard of broken dreams paved by previous blockbuster, too-good-to-be-true treatments in critical care that turned out to be just that? Scott Aberegg expounds on this latter theme compellingly at his Medical Evidence Blog, well worth reading.
Practically speaking, if this finding is real, we in the U.S. are way behind the curve. Few U.S. ICU's have institutional experience "proning" patients, and we will need to learn how. Suctioning, wound care, tube feedings, ventilator circuit maintenance -- all these little ICU tasks are slightly different on prone patients. Maybe some of our overseas colleagues can hop over for visits to get us up to speed.
I hope that the positive finding here is because these centers (as authors basically argue) finally got really good at proning, and did it for a really long time (17 hours daily) on the right patients (severe ARDS early in their disease course). That would make this the most important new therapy in critical care since low-tidal volume ventilation (which isn't a therapy, just the cessation of a harmful practice) -- and tens of thousands of lives could be saved.
But the underlying culture changes and accumulated experience that culminated in this positive study took place at those centers over more than a decade, during which their previous randomized trial failed to show a benefit. For me heading into work tomorrow, it's hard to ask untrained ICU staff to start turning patients over, leave them there all day and half the night, and trust that we will do it well enough to help them without occasionally scraping off their corneas due to inexperience. The prone-bed-sellers, experienced physicians, and professional societies like SCCM will likely step in with the needed training and guidance to our proning-naive centers on how to successfully implement prone positioning. Bottom line: expect to see more of your ARDS patients backside-up.
Clinical Takeaway: If this study is replicated on any scale in U.S. centers, or if anecdotal reports describe safe, successful roll-outs of the intervention by previously untrained staff, I'd eagerly flip my practice in the hope of saving more people with severe ARDS.