Etomidate Succs: Preventing Dogma from Becoming Practice in RSI

The editorial about the PreVent trial in the NEJM a few months back is entitled "Preventing Dogma from Driving Practice".  If we are not careful, we will let the newest dogma replace the old dogma and become practice.

The PreVent trial compared bagging versus no bagging after induction of anesthesia for rapid sequence intubation (RSI).  Careful readers of this and another recent trial testing the dogma of videolaryngoscopy will notice several things that may significantly limit the external validity of the results.

• The median time from induction to intubation was 130 seconds in the no bag ventilation group, and 158 seconds in the bag ventilation group (NS).  That's 2 to 2.5 minutes.  In the Lascarrou 2017 JAMA trial of direct versus video laryngoscopy, it was three minutes.  Speed matters.  The time that a patient is paralyzed and non-intubated is a very dangerous time and it ought to be as short as possible
• The induction agent was Etomidate (Amidate) in 80% of the patients in the PreVent trial and 90% of patients in the Larascarrou trial (see supplementary appendix of PreVent trial)
• The intubations were performed by trainees in approximately 80% of intubations in both trials (see supplementary appendix of PreVent trial)

I don't think these trials are directly relevant to my practice.  Like surgeon Robert Liston who operated in the pre-anesthesia era and learned that speed matters (he could amputate a leg in 2.5 minutes), I have learned that the shorter the time from induction to intubation, the better - it is a vulnerable time and badness occurs during it:  atelectasis, hypoxemia, aspiration, hypotension, secretion accumulation, etc.

Does Investigating Delirium Make You Delirious? A Sober Look at Sedation and Analgesia in the ICU

Michael's Milk

I rarely use the Medical Evidence Blog to discuss review articles, but today's NEJM has one that I can't pass up about Sedation and Delirium in the Intensive Care Unit.  It is my opinion that we have gotten carried away by the torrent of articles, many in prominent journals, about delirium in the ICU and that while this is an important topic for research, it is extremely premature to try to translate the findings into practice, and moreover, that the approach to sedation suggested by the article is lacking in common sense.

As chronicled in the accompanying perspective article by D.S. Jones, delirium has been around as long as ICUs have, and the longer you're there, the more likely you will become delirious.  It's an exposure thing.  Thus, until somebody reports the results of a trial of delirium treatment or prevention that has important and undeniable effects on clinically relevant outcomes, I will continue to approach delirium as I always have - by going to great lengths to get patients out of bed, off the vent, and out of the ICU as fast as I possibly can - because these things benefit all patients regardless of whether they have an impact on delirium.

More Data on Dexmedetomidine - moving in the direction of a new standard

A follow-up study of dexmedetomidine (see previous blog: http://medicalevidence.blogspot.com/2007/12/dexmedetomidine-new-standard-in_16.html )
was published in last week's JAMA (http://jama.ama-assn.org/cgi/content/abstract/301/5/489 ) and hopefully serves as a prelude to future studies of this agent and indeed all studies in critical care. The recent study addresses one of my biggest concerns of the previous one, namely that routine interruptions of sedatives were not employed.

Ironically, it may be this difference between the studies that led to the failure to show a difference in the primary endpoint in the current study. The primary endpoint, namely the percentage of time within the target RASS, was presumably chosen not only on the basis of its pragmatic utility, but also because it was one of the most statistically significant differences found among secondary analyses in the previous study (percent of patients with a RASS [Richmond Agitation and Sedation Scale] score within one point of the physician goal; 67% versus 55%, p=0.008). It is possible, and I reason likely, that daily interruptions in the current study obliterated that difference which was found in the previous study.


But that failure does not undermine the usefulness of the current study which showed that sedation comparable to routinely used benzos can be achieved with dexmed, probably with less delirium, and perhaps with shorter time on the ventilator and fewer infections. What I would like to see now, and what is probably in the works, is a study of dexmed which shows shorter time on the ventilator and/or reductions in nosocomial infections as primary study endpoints.

But to show endpoints such as these, we are going to need to carefully standardize our ascertainment of infections (difficult to say the least) and also to standardize our approach to discontinuation of mechanical ventilation. In regard to the latter, I propose that we challenge some of our current assumptions about liberation from mechanical ventilation - namely, that a patient must be fully awake and following commands prior to extubation. I think that a status quo bias is at work here. We have many a patient with delirium in the ICU who is not already intubated and we do not intubate them for delirium alone. Why, then, should we fail to extubate a patient in whom all indicators show reaolution of critical illness, but who remains delirious? Is it possible that this is the main player in the causal pathway between sedation and extubation and perhaps even nosocomial infections and mortality? (The protocols or lack thereof for assessing extubation readiness were not described in the current study, unless I missed them.) It would certainly be interesting and perhaps mandatory to know the extubation practices in the centers involved in this study, especially if we are going to take great stock in this secondary outcome of this study.

Another thing I am interested in knowing is what PATIENT experiences are like in each group - whether there is greater recall or other differences in psychological outcomes between patients who receive different sedatives during their ICU experience.

I hope this study and others like it serve as a wake-up call to the critical care research community which has heretofore been brainwashed into thinking that a therapy is only worthwhile if it improves mortality, a feat that is difficult to achieve not only because it is often unrealistic and because absurd power calculations and delta inflation run rampant in trial design, but because of limitations in funding and logistical difficulties. This group has shown us repeatedly that useful therapies in critical care need not be predicated upon a mortality reduction. It's past time to start buying some stock in shorter times on the blower and in the ICU.