Saturday, March 24, 2012

More Nails In the Coffin For Epinephrine

The news for epinephrine in cardiac arrest keeps getting worse - it restarts the heart, but at what cost, and with what outcomes?

This is a study, published in JAMA, of 417,188 out-of-hospital cardiac arrest patients in Japan - only 15,030 of which received epinephrine during prehospital transport - a far cry from the U.S., where the toolbox has typically already been emptied prior to the ED.  Nearly every baseline characteristic favored the epinephrine group - more witnessed arrests, more received bystander CPR, a physician was more frequently in the ambulance, more patients in ventricular fibrillation/PEA.  However, more of these patients also received an advanced airway, which has also been associated with worse outcomes.

In their unadjusted analysis, the epinephrine cohort was three times as likely to have ROSC, and had an OR of 1.15 to be alive at one month.  However, they were half as likely to be functional as the non-epinephrine survivors.  Then, when they do all their statistical adjustments for all the favorable baseline factors in the epinephrine cohort, all these numbers become less favorable for epinephrine.  They also do a propensity-matched cohort of 26,802 patients that has favorable ROSC with epinephrine, but dismal 1 month and functional outcomes.

This data is from before the era of routine hypothermia - which may be beneficial - but it certainly supports what we already expected regarding the damaging physiologic effects of epinephrine while senselessly flogging the heart back into action.

"Prehospital Epinephrine Use and Survival Among Patients With Out-of-Hospital Cardiac Arrest"
http://jama.ama-assn.org/content/307/11/1161.short

Thursday, March 22, 2012

TPA is Dead, Long Live TPA

I'm sure this saturating the medical airwaves this morning, but yesterday's NEJM published a study which they succinctly summarize on Twitter as "In trial of 75 pts w/ acute ischemic , tenecteplase assoc w/ better reperfusion, clin outcomes than alteplase."


Well, that's very exciting!  It's still smashing a teacup with a sledgehammer, but it does appear to be a more functional sledgehammer.  Particularly encouraging were the rates of sustained complete recanalization - which were 36% at 24 hours for alteplase and 58% for tenecteplase - and the rates of intracranial hemorrhage - which were 20% for alteplase and 6% for tenecteplase.


However, the enthusiasm promoted by NEJM, and likely the rest of the internet, should be tempered by the fact that there were only 25 patients in each arm, and there is enough clinical variability between groups that it is not yet practice changing.  This was a phase 2B trial, and it is certainly reasonable evidence to proceed with a phase III trial.


Unfortunately, in a replay of prior literature, the authors are all affiliated with Boehringer Ingelheim, the manufacturer of tenecteplase.


"A Randomized Trial of Tenecteplase versus Alteplase for Acute Ischemic Stroke"
http://www.nejm.org/doi/full/10.1056/NEJMoa1109842

Addendum:  As Andy Neil appropriately points out, tenecteplase has been studied before - 112 patients over several years, terminated early due to slow enrollment - without seeing a significant advantage.

Tuesday, March 20, 2012

Over-Prescribing of Antibiotics Happens Everywhere

On Twitter a couple weeks back, in response to my plea to reduce empiric macrolide use for benign clinical syndromes, there was an allusion suggesting Pediatricians were the culprits of a poor antibiotic stewardship.

Of course, that's clearly not the case.  And, while we all envision Urgent Cares and customer-service medicine contributing to the over-prescription of antibiotics, it's happening in our academic medical centers, as this article indicates.  This is a retrospective chart review from San Diego that evaluated 836 patients receiving a diagnosis of "acute bronchitis", a typically self-limited disease that evolves into pneumonia only in a minority of cases in elderly patients or patients with significant pulmonary comorbidities.

The average age was 46, 10% had comorbid COPD noted, 17% asthma, 8% diabetes, and 4% HIV/AIDS.  All told, 74% were prescribed antibiotics - 50% received a macrolide, 15% a tetracycline, 6% a fluoroquinolone, along with a few others.

Unfortunate.

And certainly not just the Pediatricians.

"Antibiotic and bronchodilator prescribing for acute bronchitis in the Emergency Department."
http://www.ncbi.nlm.nih.gov/pubmed/22341759

Sunday, March 18, 2012

Is It Reasonable to Keep Using Vasopressin in Shock?

The authors of this meta-analysis seem to think so.

Unfortunately, they identify a very heterogenous set of evidence for analysis, which reduces the statistical power of every comparison.  They identify only a couple studies of vasopressin vs. placebo, and most of their studies are vasopressin vs. an increased dose of norepinephrine.

It's hard to generate any unreasonable conclusion from this data - the error bars cross one, so you can either take this as permission to drop vasopressin from your usage patterns because its use has no measurable mortality benefit, or you can continue to use vasopressin because it doesn't seem to be harmful, and allows you to reduce the dose of norepinephrine.

I'd really like to see more vasopressin vs. control - there's only one reasonably sized vasopressin vs. placebo trial - and it heavily, but non-significantly, favors control with a risk ratio for mortality of 1.94 (0.74 to 5.10).

More to be done!

"Vasopressin for treatment of vasodilatory shock: an ESICM systematic review and meta-analysis"