Author: Ryan Radecki

Pan-Scan & Zero-Miss

In an interesting contrast to a prior article regarding over-scanning in trauma, this article takes a different perspective.  While the authors do note that there is controversy regarding the impact of “pan scan” on survival, they are rather focused on the sensitivity/specificity of the “pan scan,” rather than the appropriateness.

This is a review of 982 consecutive patients undergoing “pan scan” in Germany.  The indications for scanning were a set of “red flag” criteria, which included impaired patients, patients with obvious injuries, “suspicion of severe trauma” or “high risk mechanism”.  The diagnostic reference standard was chart review by two reviewers of the electronic notes for any injuries missed on the initial scan.

The results are rather interesting in a couple ways:  the prevalence of injuries per organ system is not terribly high, and the sensitivity of scanning was rather low.  The highest prevalence of injuries for an organ system was 37%, for chest, followed by head and neck at 34%.  However, the sensitivities range from a high of only 86.7% for chest down to a low of 79.6% for face – likely because dedicated fine cuts of the face were not part of their protocol.  Regardless, with sensitivities in the mid-80s meant they missed almost one seventh of the total number of injuries.  Of these 70 missed injuries, almost half required surgery or a critical intervention as treatment.

So, pan-scanning: expensive, low yield, yet still misses important injuries.  The authors do not try to fully address whether their yield is reasonable or not, and wisely simply state further research is needed regarding triaging patients into groups likely to benefit from scanning.

“Accuracy of single-pass whole-body computed tomography for detection of injuries in patients with major blunt trauma.”
http://www.ncbi.nlm.nih.gov/pubmed/22392949

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

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 #stroke, 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.

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

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”

Pharmaceutical Bias Article in EM News

Imagine my surprise to be paging through Emergency Medicine News this month and stumble upon an article about TPA in stroke – and find that it’s a review of my Western Journal of Emergency Medicine article from last summer.

The EM News article is here:
http://journals.lww.com/em-news/Fulltext/2012/03000/Journal_Scan__Pharma_Bias_Detected_in_Thrombolytic.6.aspx

And my West JEM article is open access, available here:
http://escholarship.org/uc/item/9504g8md

It Feels Good To Use an iPad

Recently, there has been a great deal of coverage on internet news sites with headlines such as “Study: iPads Increase Residency Efficency.”  These headlines are pulled from a “Research Letter” in Archives of Internal Medicine, reporting from the University of Chicago, regarding the distribution of iPads capable of running Epic via Citrix.

Sounds good, but it’s untrue.

What is true is that residents reported that they used the iPads for work.  The additionally thought that it saved them time, and thought it improved their efficiency on the wards.  This is to say, they liked using the iPad.

The part that isn’t true is where the authors claim an increase in “actual resident efficiency.”  By analyzing the hour of the day in which orders are placed, the authors attempt to extrapolate to a hypothetical reality in which this means iPads are helping their residents place orders more quickly on admitted patients, and to place additional orders while post-call, just before leaving the hospital.  There is, in fact, no specific data that using the iPad makes the residents more efficient, only data showing the hour of the day in which orders are placed has changed from one year to the next.  The iPad has, perhaps, changed their work habits – but without prospectively observing how these iPads are being used, it is impossible to conclude how or why.

But, at least they liked them!  And, considering how addictive Angry Birds is, I’m surprised their productivity isn’t decreased.

“Impact of Mobile Tablet Computers on Internal Medicine Resident Efficiency”

http://archinte.ama-assn.org/cgi/content/extract/172/5/436

Ketamine + Propofol = Ketofol

Combining propofol, a beloved agent for procedural sedation for its rapid onset, quick recovery times, and titratable levels of sedation with ketamine, the world’s safest agent for unmonitored anesthesia, has been shown in case series to be as safe and effective as expected.

This small, randomized trial is a direct comparison between ketofol and propofol, with the primary outcome measure being the proportion of patients experiencing an adverse respiratory event using the standardized Quebec Criteria.  The authors are testing the hypothesis that use of ketofol will result in fewer adverse respiratory events, which they believe to be one of the weaknesses of propofol, and one of the strengths of ketamine.

With ~120 patients in each group, there is essentially no clinical or statistical difference between outcomes of the two groups.  Clinicians provided transient assisted ventilation for three ketofol patients and one propofol patient – which is not statistically different.  Secondary outcomes were similar, although a handful of ketofol patients experienced recovery agitation, some of which required treatment.

It seems odd to me that the authors would be testing the respiratory adverse events of ketofol – both ketamine and propofol are so profoundly safe, with already extremely low rates of assisted ventilation, and unplanned intubation rates of ~1 in 5,000 or more.  Ketofol has been similarly already shown to be extremely safe in terms of respiratory events, primarily in retrospective case series.  They’ve essentially set themselves up to test something that’s almost already conclusively expected to generate insignificant differences.  What is more interesting to clinicians now, when considering agents for sedation, is the secondary effects – hypotension, hypersalivation, vomiting, myoclonus, agitation – and how that affects procedural success and time to disposition.  Ketofol is a great combination – but its value seems to be in the mitigation of the non-airway adverse events.

“Ketamine-Propofol Combination (Ketofol) Versus Propofol Alone for Emergency Department Procedural Sedation and Analgesia:  A Randomized Double-Blind Trial”
http://www.ncbi.nlm.nih.gov/pubmed/22401952

Mechanical Thrombectomy – Promising, But Still Unsafe

This article is just a retrospective, consecutive case series from Spain reporting outcomes and adverse events from mechanical thrombectomy in acute stroke.  Most of their patients are significantly disabled from their strokes, with NIHSS ranging from 12 to 20 – unlikely to have great outcomes – but 14% developed intraparenchymal hemorrhage and 25% were deceased at 90 days.  Six patients had vessel wall perforation from the thrombectomy device.

The key sentence is the last sentence:
“Clinical efficacy of this approach compared with standard medical therapy remains to be demonstrated in prospective, randomized controlled trials.”

When mortality is 25% here, and 33% at 90 days in MERCI, multi-MERCI, and Penumbra trials, I’m still not sure this strategy is quite ready for prime time.  They do report that 54% had a “good outcome”, but it’s interesting to see that “good outcome” in stroke trials has progressed from Rankin Scores of 0 or 1 in NINDS etc. to ≤2 in these new trials.  They  also don’t offer a lot of granularity in their outcomes data.

But, as usual, as long as there are authors out there who “receive consulting and speaker fees from Co-Axia, ev3, Concentric Medical, and Micrus,” we’ll keep seeing reports like this.

“Manual Aspiration Thrombectomy : Adjunctive Endovascular Recanalization Technique in Acute Stroke Interventions”
http://www.ncbi.nlm.nih.gov/pubmed/22382156

Please Stop Using Azithromycin Indiscriminantly

There is a time and a place for a macrolide with a long half-life, and it is not empirically for pharyngitis.

And, it’s even less appropriate empirically for pharyngitis now that it’s been overused to the point where it’s nearly in the drinking water – because it can no longer be considered second-line for group A streptococcus for your penicillin allergic patients.

This is a case report and evidence review from Pediatrics that discusses two cases of rheumatic fever, both of which presented after treatment of GAS pharyngitis with azithromycin.  While rheumatic fever has been almost completely wiped out – there are so few of the RF emm types in circulation, that it’s almost nonexistent in the United States – there are still sporadic cases.  Macrolides are listed as second-line therapy for GAS, but single-institution studies have shown macrolide resistant streptococcus in up to 48% of patients.  Macrolide resistance varies greatly worldwide, from a low of 1.1% in Cyprus to 97.9% in Chinese children.

Why is macrolide resistance so high?  Azithromycin is the culprit; because it has such a long-half life, it spends a long time in the body at just below its mean inhibitory concentration, and preferentially selects for resistant strains.

Please stop using azithromycin.  Use doxycycline, or another alternative, when possible.  There has never been reported resistance to pencillin in GAS.

“Macrolide Treatment Failure in Streptococcal Pharyngitis Resulting in Acute Rheumatic Fever”
http://www.ncbi.nlm.nih.gov/pubmed/22311996