I do not believe the degree of benefit. Seriously? 16% ABSOLUTE reduction? Bs.....
http://medicalevidence.blogspot.com/2013/05/over-easy-recent-history-of-trials-of.html?m=1
Other questions that bug me. In ARMA, which group had the better outcomes? (The Worse pa ratios)
What's the primary cause of death in ARDS PTs? It usually isn't hypoxic induced issues. It's usually the inciting etiology. OR you get barotrauma which leads to a sudden decompensation & death. and does proning decrease barotrauma? Does it reduce GI bleeds? Does it reduces VAP? Does it reduce CLABS?
Hern,
I think there's good reason to consider proning those with very severe ARDS. I just had to give a talk to our division on this topic. We're currently writing a protocol and have started proning patients with pretty good results though our "n" is currently too small to say anything definitively. After a deep dive into the literature, I'd say that my views on proning are:
Physiological basis for proning:
1. Proning leads to more overall alveolar recruitment and is synergistic with PEEP -> a given delivered Vt is dispersed to more alveoli -> minimizing stretch injury (reduced tidal hyperinflation and cyclic recruitment/derecruitment)
--- Cornejo et al, AJRCCM, 2013
2. This is likely due to a combination of mechanisms that include altering the relationship between gravitational forces and size-matching, off-loading the region of the lungs that are posterior to the heart, and minimizing PEEP-associated alveolar hyperinflation.
--- Gattinoni et al, AJRCCM, 2013
--- Albert et al, AJRCCM, 1999
3. But, improvements in oxygenation does not correlate very well with improvements in mortality.
Clinical data for proning:
In looking at the RCTs conducted thus far you can see that over time there's been an improved understanding of which patient population to include (severe ARDS by P/F ratio) as well as how long we should prone these patients for (most of the day). The early trials proned all comers with ARDS including those with mild disease. That would dilute any effect. They also proned patients for a short time period (e.g. 6hrs). Furthermore, they had no understanding of lung protective mechanical ventilation. Given the theoretical basis for proning mentioned above, no understanding person would expect a mortality benefit with proning when applied in this manner to all comers. However, even under these conditions, subgroup analyses on very severe hypoxemia showed hints of a potential mortality benefit.
--- Gattinoni et al, NEJM, 2001
--- Guerin et al, JAMA, 2004
The first trial to look at proning for the majority of the day in severe ARDS (average P/F 105) was Mancebo et al in the blue journal (2006). It was stopped early due to slow enrollment. Meaning, they never had the opportunity to meet statistical power. I wouldn't necessarily call that a negative study.
Taccone et al (JAMA, 2009) then completed a trial of proning for the majority of the day in severe ARDS (P/F 113) and failed to show a mortality benefit. Adherence to lung protective mechanical ventilation in this trial was poor.
There was then was a meta-analysis that looked at all these prior trials (including some others) and found that when you stratify the patient populations (P/F > 100 vs P/F < 100) there's a decreased relative risk of death for proning in patients with severe disease. This set the stage for the recent Guerin paper in the NEJM.
This trial was the first of its kind to prone patients for most of the day and very strictly adhere to lung protective mechanical ventilation. There was also a large amount of paralytic used in both the control and intervention arm so this really was a study where the control arm was the Pappazian study of Cis/Low-stretch (very similar mortality rate to that study as well).
I am also skeptical about the magnitude of the mortality benefit, but it is hard to argue that there is not an added mortality benefit of proning - but this was an excellent that met statistical power and found a very dramatic effect. I'd like another trial to see whether a similar ARR is achieved, but I'm not holding out on changing my practice.
The one thing that is important for all of us to remember is that randomized clinical trials demonstrate efficacy and not effectiveness. Meaning, they include a very specific population and exclude lots of people and are conducted at very experienced high-volume centers. Once it gets rolled out into the real world it will be applied to people who would never been included in the trial and will be done in centers with very limited experience. This is true for proning or any other drug/therapy.
I guess my final take home message on proning would be that:
1. There are data to support that proning helps optimize lung recruitment and may reduce VILI by distributing Vt more homogenously
2. There are no data to suggest that proning is harmful
3. Proning doesn't work in mild/mod ARDS or when used for small fraction of a day
4. A meta-analysis showed that it works in severe ARDS
5. This has been supported in a large multicenter randomized clinical trial
6. There's way more data for proning than there is for flolan and other modes of mech vent like APRV in patients with severe ARDS. And if definitely makes more physiological sense along with supportive outcomes data than esmolol in septic shock. I'll save my critique of the esmolol trial for another day!
Souljah1
Levo at 20mcg/min, so that'd leave lots of people still hypotensive. So then we'd add Neo, then Vaso then epi. Which SSC does not recommend using Neo for sepsis
