In the most recent issue of JAMA, Terragni et al report the results of an Italian multicenter trial of early (6-8 days) versus delayed (13-15 days) tracheostomy for patients requiring mechanical ventilation (http://jama.ama-assn.org/cgi/content/short/303/15/1483 ). This research complements and continues a line of investigation of early tracheostomy in RCTs by Rumbak et al in 2004. In that earlier trial (http://journals.lww.com/ccmjournal/Abstract/2004/08000/A_prospective,_randomized,_study_comparing_early.9.aspx ) the authors showed that [very] early tracheostomy (at 48 hours into a patient's illness) compared to delayed tracheostomy (after 14 days of illness) let to reduced mortality, pneumonia, sepsis, and other complications of critical illness. The mediators of this effect are not known with certainty, but may be related to the effects of reduced sedation requirements with tracheostomy, reduced dead space, facilitation of weaning from mechanical ventilation, or psychological effects on the patients or the physicians caring for them. Regardless of the mediators of the effect, I can say confidently from an anecdotal perspective that the effects appear to be robust. Almost as if by magic, something changes after a patient gets a tracheostomy, and recovery appears to accelerate - patients just "look better" and they appear to get better faster. (Removal of the endotracheal tube (ETT) allows spitting and swallowing, activities which will be required to protect the airway when all artificial airways are removed; it allows lip-reading by families and providers and in some cases speech; it allows sedation to be reduced expeditiously; it facilitates weaning; it allows easier positioning out of bed in a chair and working with physical therapy during weaning; the list goes on...)
What are the drawbacks to such an approach? Traditionally, a tracheostomy has been viewed by practitioners as the admission of a failure of medical care - we couldn't get you better fast, with a temporary airway, so we had to "resort" to a semi-permanent or permanent [surgical] airway. Moreover, a tracheostomy was traditionally a surgical procedure requiring transportation to the operating suite, although that has changed with the advent of the percutaneous dilitational approach. Nonetheless, whichever route is used to establish the tracheostomy, certain immediate and delayed risks are inherent in the procedure, and the costs are greater. So, the basic question we would like to answer is "are there benefits of tracheostomy that outweigh these risks?"
There were several criticisms of the Rumbak study which I will not elaborate upon here, but suffice it to say that the study did not lead to a sweeping change in practice with regard to the timing of tracheostomies and thus additional studies were planned and performed. One such study, referenced by last week's JAMA article, only enrolled 25% of the anticipated sample of patients with resulting wide confidence intervals. As a result, few conclusions can be drawn from that study, but it did not appear to show a benefit to earlier tracheostomy (http://journals.lww.com/ccmjournal/Abstract/2004/08000/A_prospective,_randomized,_study_comparing_early.9.aspx ) A meta-analysis which included "quasi-randomized" studies (GIGO: Garbage In, Garbage Out) concluded that while not reducing mortality or pneumonia, early tracheostomy reduced the duration of mechanical ventilation and ICU stay. (It seems likely to me that if you stay on the ventilator and in the ICU for a shorter period, since there is a time/dose-dependent effect of these things on complications such as catheter-related blood stream infections and ventilator-associated pneumonia (VAP), that these outcomes and outcomes further downstream such as mortality WOULD be affected by early tracheostomy - but, the further downstream an outcome is, the more it gets diluted out, and the larger a study you need to demonstrate a significant effect.)
Thus, to try to resolve these uncertainties, we have the JAMA study from last week. This study was technically "negative." But in it, every single pre-specified outcome (VAP, ventilator-free days, ICU-free days, mortality) trended (some significantly) in favor of early tracheostomy. The choice of VAP as a primary outcome (P-value for early versus delayed trach 0.07) is both curious and unfortunate. VAP is notoriously difficult to diagnose and differentiate from other causes of infection and pulmonary abnormalities in mechanically ventilated ICU patients (see http://content.nejm.org/cgi/content/abstract/355/25/2619 ) - it is a "soft" outcome for which no gold standard exists. Therefore, the signal-to-noise ratio for this outcome is liable to be low. What's perhaps worse, the authors used the Clinical Pulmonary Infection Score (CPIS, or Pugin Score: see Pugin et al, AJRCCM, 1991, Volume 143, 1121-1129) as the sole means of diagnosing VAP. This score, while conceptually appealing, has never been validated in such a way that its positive and negative predictive values are acceptable for routine use in clinical practice (it is not widely used), or for a randomized controlled trial (see http://ajrccm.atsjournals.org/cgi/content/abstract/168/2/173 ). Given this, and the other strong trends and significant secondary endpoints in this study, I don't think we can dichotomize it as "negative" - reality is just more complicated than that.
I feel about this trial, which failed its primary endpoint, much the same as I felt about the Levo versus Dopa article a few weeks back. Multiple comparisons, secondary endpoints, and marginal P-values notwithstanding, I think that from the perspective of a seriously ill patient or a provider, especially a provider with strong anecdotal experience that appears to favor earl(ier) tracheostomy, the choice appears to be clear: "If you want a fair shake, you gotta get a trach."
This is discussion forum for physicians, researchers, and other healthcare professionals interested in the epistemology of medical knowledge, the limitations of the evidence, how clinical trials evidence is generated, disseminated, and incorporated into clinical practice, how the evidence should optimally be incorporated into practice, and what the value of the evidence is to science, individual patients, and society.
Saturday, May 1, 2010
If you want a fair shake, you gotta get a trach (and the sooner the better)
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Might this be the ideal study to sue an outcome like cost per QALY?ReplyDelete
Dr. Jim - that is the kind of complicated and interesting analysis that only a person with your talents would dare to conduct.ReplyDelete
A simpleton like me would just design a study with a composite endpoint: at 28 or 60 days, it would be comprised of mortality, non-ambulatory status, requiring nutritional support, non-verbal, requiring vent support, requiring intravenous access, perhaps others. Those are the things that burden critically ill patients who survive the initial critical illness but remain "professional patients" for weeks or months after the acute storm has passed....