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"

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"

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.


And certainly not just the Pediatricians.

"Antibiotic and bronchodilator prescribing for acute bronchitis in the Emergency Department."

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"

Friday, March 16, 2012

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:

And my West JEM article is open access, available here:

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"

Wednesday, March 14, 2012

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"

Monday, March 12, 2012

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"

Saturday, March 10, 2012

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"

Thursday, March 8, 2012

The Future of Defensive

At Northwestern University in Chicago, anyway - and probably externally valid to other institutions, as well.

This is a survey of 194 fourth-year medical students and 141 third-year residents regarding whether they observed or encountered "assurance" practice (extra testing of minimal clinical value) or "avoidance" practice (withholding services from patients perceived as high risk).  65% of medical students and 54% of residents completed the survey - decent numbers, but low enough to introduce sampling bias.

The numbers, of course, are grim - 92% of medical students and 96% of residents reported encountering "assurance" practice at least "sometimes" or "often", while 34% of medical students and 43% of residents had encountered "avoidance" practice at least "sometimes" or "often" - nearly all of those being "sometimes".  These behaviors are apparently learned from their superiors - approximately 40% of medical students and 55% of residents were explicitly taught to consider practicing defensive medicine.

Interestingly, medical students, internal medicine residents, and surgical residents all reported nearly identical levels of "often"/"sometimes"/"rarely" regardless of the behavior sampled - although surgical residents were more frequently taught to be defensive than medicine residents.

Must be a tough legal quagmire up in Chicago.

"Medical Students’ and Residents’ Clinical and Educational Experiences With Defensive Medicine"

Tuesday, March 6, 2012

Zolpidem and Benzodiazepines Will Kill You


Especially if you're elderly.

It's an interesting observational, statistically matched-control study using Electronic Health Records to monitor prescriptions of zolpidem (Ambien) and other benzodiazepines (Temazepam), commonly used as sleep aids, particularly in the shift-work population.

I think this graph pretty well sums up their results:

Blue lines are hypnotic-free, orange lines are patients taking hypnotics.  Downward slopes - exaggerated by the vertical scale - are bad.  An increased hazard for cancer was also found in patients prescribed hypnotics.

There are, of course, flaws with this study - but it is consistent with other published literature suggesting harms associated with hypnotic use.  The huge limitation of a study like this is controlling retrospectively for all the comorbid cofounders.  They attempt to do this statistically with a small set of comorbid disease, but it remains a limitation.

"Hypnoticsassociation with mortality or cancer: a matched cohort study"

Sunday, March 4, 2012

One-Man Crusade For Steroids In Spinal Trauma

The Cochrane Review regarding the efficacy of steroids in acute spinal cord injury, first published in 2002, has been updated for 2012.  The author's conclusions: "Methylprednisolone sodium succinate has been shown to enhance sustained neurologic recovery in a phase three randomized trial, and to have been replicated in a second trial."

This is an interesting conclusion to draw from an analysis of, essentially, only negative studies.  NASCIS 1 (1984) was statistically negative - but was discounted because the dosing was possibly too low.  NASCIS 2 (1990) was also statistically negative, except for pinprick and light touch at six months, which disappeared at one year.  The supposed positive outcome comes from a post-hoc analysis in which the patients who received their steroids between 3 and 8 hours after injury shook out to have a statistically significant improvements in motor score at six months and one year.  However, post-hoc subgroup analysis cannot be considered practice-changing evidence until confirmed in subsequent studies.  Otani (1994) was statistically negative for the primary outcome, but post-hoc analysis identified greater sensory improvement in the steroid group - which therefore implies greater motor improvement in the control group, as the overall combined neurologic scores were not different.  NASCIS 3 is not placebo-controlled.

There is also no mention in the Cochrane Review of adverse events - the only mention of the safety profile of high-dose steroids in the discussion section references a systematic review of high-dose steroids given to general surgical patients, both elective and trauma.  This is rigorously invalid, as the correct assessment of the safety profile of an intervention should be derived from the safety outcomes of the studies included in the analysis - nearly all of which had consistent, non-significant (underpowered) trends towards increased infectious complications.

Would it surprise you to discover that the author of the 2000, 2002 and 2012 Cochrane Review articles is the same first author of NASCIS 1, 2, and 3?

"Steroids for acute spinal cord injury."

Friday, March 2, 2012

Discharging Bronchiolitis on Home Oxygen

This is another one of those window-to-the-future articles, where an enterprising department has taken a commonplace disease with a relatively high admission rate and tried to change the status quo.

As they note, bronchiolitis is the #1 cause of admission for children < 1 year, it accounts for 150,000 admissions annually, and costs $500 million.  One of the key clinical features that keeps otherwise well-appearing children in the hospital is hypoxia, specifically < 90% saturation by pulse oximetry as recommended by the American Academy of Pediatrics.

This is a retrospective chart review that essentially says "we did this and we like it."  4,194 relevant charts were reviewed, 57% of which were discharged without home oxygen, 15% were discharged on oxygen, and 28% were admitted.  Of the discharged patients, 4% of the no-home-oxygen patients returned for eventual admission compared with 6% of the discharge-on-oxygen patients.  Overall, this led to a 25% relative decrease in admissions for bronchiolitis at their institution, compared to historical controls.

More confirmatory study is needed - it's a little different at mile-high Denver than the rest of the U.S. - but this may be a promising way to reduce admissions for bronchiolitis.  It is also suggestive of what is likely the new future of cost-containment medicine, at least where the malpractice environment will tolerate it - an increasing proportion of higher-risk discharges with, in theory, closer follow-up that saves money in the long run.

"Discharged on Supplemental Oxygen From an Emergency Department in Patients With Bronchiolitis"

Wednesday, February 29, 2012

Ciprofloxacin is Better Than Cefpodoxime for UTI

...but don't use either of them first-line.  And, of course, your mileage may vary based on local resistance patterns.

This study, in JAMA, is from Seattle, where their ciprofloxacin resistance in e. coli is extraordinarily low - only 4%.  Their e. coli resistance to cefpodoxime, a third-generation cephalosporin, was 8%.  They randomized 300 women with uncomplicated cystitis into, luckily, two rather similar groups - and found a 93% clinical cure rate for ciprofloxacin and an 82% cure rate with cefpodoxime.  Microbiologic cure rate at 5 days was 96% in the ciprofloxacin group and 81% in the cefpodoxime group.  And, then, there are a bunch of minor details in laborious text regarding the microbiology of the non-responders, but I'm not sure any of it's actually relevant.  Seven women in the ciprofloxacin group required treatment for an "adverse effect" (nausea, headache, vaginal discomfort), compared with three in the cefpodoxime group.

However, neither of these agents should be considered first-line for uncomplicated cystitis.  Nitrofurantoin and fosfomycin are recommended as first-line therapy in the most recent guidelines, along with trimethoprim-sulfamethoxazole depending on local resistance.  After that, consult your local antibiogram to determine whether beta-lactams are viable, or whether a fluroquinolone or a third-generation cephalosporin should be your next option.

"Cefpodoxime vs ciprofloxacin for short-course treatment of acute uncomplicated cystitis: a randomized trial."

Monday, February 27, 2012

Everyone Loves "Art"

Apparently, rather than spend a lot of money on the back-end with patient satisfaction initiatives, all you really need is soothing artwork in your ED waiting room.

This is a rather simple, prospective cohort study in which research associates observed the waiting room behaviors of waiting patients.  They observed several different behaviors, but mostly were interested in "disruptive" behaviors - fidgeting, aggressive behavior, pacing, getting out of seat, etc.  After initial observation, artwork of "natural beauty" along with a DVD of soothing nature scenes was introduced into the waiting room of the two EDs in the study.

And, essentially, the ED waiting experience appeared more pleasant, according to their surrogate measures of patient disruptive behaviors - significant improvements in reducing out of seat behavior, fidgeting, front desk inquiries.

So, art?  Probably good, although this is a relatively methodologically weak study.

"Impact of Visual Art on Patient Behavior in the Emergency Department Waiting Room."