Our EM Journal Club group down here at UT-Houston collaborated to write the Annals of Emergency Medicine monthly Journal Club installment, published in the November issue.
You get the questions now – at least, they’re available online starting today – but you’ll have to wait in suspense for months to hear our “answers”.
I don’t know if it was an editorial decision to put our thinly veiled IST-3 critique on page 666 of this year’s volume, but I can’t imagine it’s just a coincidence….
“rt-PA and Stroke: Does IST-3 Make It All Clear or Muddy the Waters?”
http://www.ncbi.nlm.nih.gov/pubmed/23089093
Category: Medication Safety
Normal Procalcitonin Rules-Out Line Sepsis
The use of procalcitonin in sepsis has been evolving rapidly in the recent literature. The theory behind procalcitonin is that, typically, it is rapidly converted to calcitonin. However, in the presence of gram-positive and gram-negative sepsis, circulating endotoxin results in a rapid rise in procalcitonin levels not seen during viral infection. There’s a nice study showing use of procalcitonin levels allows for reductions in antibiotic use in the ICU, without a corresponding increase in mortality – which makes it a promising test to assist in antibiotic stewardship.
This is a little bit different spin on the question addressing the use of procalcitonin levels in a population that is febrile all the time – pediatrics. Most of the time, when children are febrile, the infectious etiology is either readily identifiable as bacterial or presumed to be viral. However, in the subset of children with indwelling central venous catheters – they’re treated presumptively as line sepsis until proven otherwise, despite the preponderance of viral etiologies.
This is a small case series of 62 children with indwelling lines, 14 of whom eventually grew positive blood cultures. Using procalcitonin levels drawn in the Emergency Department to rule out bacteremia gave an AUC of 0.82 (0.70 to 0.93) with the “optimal” cutoff at 0.3 ng/mL giving a sensitivity of 93% and specificity of 63%. I’m not sure I’d settle for anything less than 100% sensitivity for line sepsis, but there is a point at which the risks associated with healthcare delivery are equivalent to the risks of bloodstream infection. This is a nice idea I wasn’t previously familiar with that hopefully will be confirmed in subsequent evaluation.
“Procalcitonin as a Marker of Bacteremia in Children With Fever and a Central Venous Catheter Presenting to the Emergency Department”
www.ncbi.nlm.nih.gov/pubmed/23023470
A Month’s Supply of Ketamine
This is a highly entertaining, short, qualitative survey of ketamine use in April 2011 at U.C. Davis. Ketamine is quite popular outside the United States – but hasn’t reached widespread, routine use here.
Specifically, this study looks at “low-dose ketamine” a supplementary analgesia in the Emergency Department. Usually defined in the range of 0.1mg/kg to 0.3mg/kg, the authors use 0.2mg/kg. Ketamine was generally efficacious, and adverse events were mild – highly limited by the size of their cohort, a mere 24 patients. But the entertaining bit are the qualitative patient comments, including:
“I was in a science fiction movie.”
“I was on TV.”
“I was a hippie.”
“It was pure euphoria.”
“I was scared.”
“I was hot.”
“I was on TV.”
“I was a hippie.”
“It was pure euphoria.”
“I was scared.”
“I was hot.”
“It made me sleepy.”
“I was itchy.”
…and many others.
“Low-dose ketamine analgesia: patient and physician experience in the ED”
www.ncbi.nlm.nih.gov/pubmed/23041484
tPA of The Future
“The potential benefits associated with this approach are faster reperfusion, lower risk of hemorrhage, and earlier initiation of fibrinolytic therapy, possibly by first responders.”
Sounds lovely, yes? This is the pie-in-the-sky version of tPA, complete with flying cars and hoverbuses. It’s a “Clinical Implications of Basic Research” article from NEJM covering a Science article about shear-activated nanoparticles.
Essentially, in a mouse model of acute arterial thrombosis and pulmonary embolism, researchers bound tPA to aggregated nanoparticles. In normal vasculature, these aggregates remain unaffected. However, in regions of turbulence and shear associated with stenosis, the aggregates break apart, exposing the biochemically active tPA in greater quantities. The authors, taking cue from the current political season, promise potential 100-fold reductions in dosing of tPA associated with this serendipitously targeted approach rather than standard systemic therapy.
So, someday, instead of taking an aspirin and calling 911 – home thrombolytics?
“The Shear Stress of Busting Blood Clots”
www.ncbi.nlm.nih.gov/pubmed/23034026
“Say Anything”, Regardless of the Data
As we’ve learned from prior publications, the conclusions section of the abstract is the ideal location to “spin” your article to generate news releases. This article, from JAMA Neurology, compares thrombolysis to endovascular intervention for acute carotid artery occlusions and states “Intravenous thrombolysis should be administered as first-line treatment in patients with early cervical ICA occlusion.”
That’s a pretty strong statement, without qualifiers. And, it means it received press coverage from MedPage Today, the ACEP News network, etc.
And, they base that statement on retrospective review of a cohort of 21 patients, 13 of whom received thrombolysis and 8 of whom received endovascular intervention. The tPA patients did better, done and done, OR for early neurologic recovery 77 (95% CI 3 to 500). But, then, Table 2 is a mini-systematic review of prior studies – and it turns out the rate of neurologic recovery is more like 40-50% with endovascular treatment, not the 1 in 8 they found in their retrospective cohort. Indeed, the authors go on to state in the article “These findings are in contrast to the results of previous studies”, and have an entirely reasonable, non-conclusive discussion of their findings in context of the other daa.
But, if you want news coverage, say something “interesting” in your abstract.
“Stroke From Acute Cervical Internal Carotid Artery Occlusion”
http://www.ncbi.nlm.nih.gov/pubmed/23007611
Acetaminophen and Asthma
If this article strikes your fancy – then you’ll never look at acetaminophen the same way again.
Published in Pediatrics, this is a bit of a commentary summarizing epidemiological data in both children and adults related to the association between acetaminophen (paracetamol) use and asthma. Specifically, that there is one, based on the studies he reviews, including:
• A prospective childhood asthma study of 520,000 subjects suggesting a dose-response effect between acetaminophen and asthma in children, up to an increased OR for wheezing of 3.25 for children taking acetaminophen at least once a month.
• A meta-analysis of six pediatric studies with a pooled increased OR for wheezing of 1.95 related to acetaminophen use.
• A meta-analysis of six adult studies with up to an increased OR for asthma of 2.87 for adults taking acetaminophen weekly.
…and several others. The author does not suggest any specific mechanism through which acetaminophen increases airway reactivity, but he has changed his practice to reduce acetaminophen usage to the minimum. I can’t say I disagree with his hypothesis, and there does appear to be a preponderance of mounting evidence, although I wouldn’t say this is an area where I am intimately familiar with the literature.
“The Association of Acetaminophen and Asthma Prevalence and Severity”
www.ncbi.nlm.nih.gov/pubmed/22065272
Don’t Believe The Data
This NEJM study published a couple days ago addresses the effect of funding and methodological rigor on physicians’ confidence in the results. It’s a prospective, mailed and online survey of board-certified Internal Medicine physicians, in which three studies of low, medium, and high rigor were presented with three different funding sources: none, NIH award, or industry funding.
Thankfully, physicians were less confident and less likely to prescribe the study drug for studies that were of low methodological quality and were funded by industry. Or, so I think. The study authors – and the accompanying editorial – take issue with the harshness with which physicians judge industry funded trials. They feel that, if a study is of high methodological quality, the funding source should not be relevant, and we should “Believe the Data“. Considering how easy it is to exert favorable effects on study outcomes otherwise invisible to ClincalTrials.gov and the “data”, I don’t think it is safe or responsible to be less skeptical of industry-funded trials.
Entertainingly, their study probably doesn’t even meet their definition of high rigor, considering the 50% response rate and small sample size….
“A Randomized Study of How Physicians Interpret Research Funding Disclosures”
www.ncbi.nlm.nih.gov/pubmed/22992075
Not-So Routine Surgery on Dabigatran
This correspondence, published in Blood in March, was probably pretty easy to overlook.
A patient enrolled in RE-LY, the trial comparing dabigatran and warfarin for non-valvular atrial fibrillation, underwent open aortic valve replacement surgery. As instructed, he discontinued his dabigatran two days prior to the surgery.
Had a little bit of a bleeding problem.
After 26 units of RBCs, 5 packs of platelets, 22 units of FFP, 5 x 10 units of cryoprecipitate, two doses of protamine, two doses of tranexamic acid, and five doses of Factor VIIa, the patient was finally stable enough to be evacuated to the ICU for dialysis to remove the remaining dabigatran.
What’s most fabulously ironic about this correspondence is that the authors use this horrifying case to sprightly conclude Factor VIIa and hemodialysis are viable and effective reversal strategies for dabigatran-associated bleeding.
The patient – “The postoperative course was complicated by prolonged ventilation/Enterobacter pneumonia, asymptomatic nonocclusive femoral DVT (by surveillance ultrasonography [postoperative day (POD 7)]), and acute-on-chronic renal failure. Discharge to a rehabilitation facility occurred on POD56.” – probably disagrees.
Would you be surprised if I mentioned there’s a COI issue involving the authors and the manufacturer?
“Recombinant factor VIIa (rFVIIa) and hemodialysis to manage massive dabigatran-associated postcardiac surgery bleeding”
www.ncbi.nlm.nih.gov/pubmed/22383791
Dabigatran – It’s Everywhere!
Dabigatran, you may know it at Pradaxa, the first in a string of potential blockbuster oral anticoagulants, has a few problems. Lack of effective reversal options, poor prescriber understanding of drug-drug and GFR interactions, and reduced dosing options should make physicians wary of this medication.
Well, it’s not.
This is a dataset gleaned by an ongoing physician audit covering ~4800 U.S. practioners between 2007 and 2011, used to estimate prescription trends for the U.S. Warfarin prescriptions were reasonably stable between 2007 and 2010, but then have dropped approximately 20% over the course of 2011. The medication taking up the slack? Dabigatran.
If you accept the findings from RE-LY, then you’re probably OK with its use in non-valvular atrial fibrillation. Unfortunately, 37% of the prescriptions were off-label, outside the FDA approved indications. Then, within the remaining 63%, there’s no breakdown for whether it was valvular or non-valvular atrial fibrillation. So, the percentage of off-label use is probably even higher than found in the data.
It would seem to be prudent to be cautious with a new medication that’s already being investigated by the FDA for serious bleeding complications. Luckily for the manufacturer, that’s not happening, and prescription expenditures for dabigatran already exceed those for warfarin – over $160 million per quarter.
“National Trends in Oral Anticoagulant Use in the United States, 2007 to 2011”
http://www.ncbi.nlm.nih.gov/pubmed/22949490
“Propoven”
Medication shortages are affecting many hospitals – we’re low/out of prochlorperazine, injectable metaclopromide, etomidate, propofol, brevital – and one of the replacements we’ve recently been introduced to is “Propoven”, a European manufacture of propofol.
It has only minor differences from propofol, but it should be noted it requires strict sterile technique when handling and has more medium-chain fatty acids. An informational letter from Kabi describing a few of the differences is here: