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."

Saturday, February 25, 2012

An Overblown Critique of CMS OP-15

OP-15 for imaging effectiveness in atraumatic headache is coming, vigorously opposed by many.  To date, most of the opposition has been in principle, or with specific clinical concerns.

This is a different approach to the problem - looking at whether the patients that CMS identified as "inappropriate" were actually appropriate exceptions.  This was a retrospective chart review of 748 charts that were referred back to 21 hospitals as "inappropriate" following a "dry run" of OP-15.  Based on individual chart review, the authors found documentation of one of the exclusion criteria in 489 of them - 479 based on the clinical criteria, and 35 based on administrative criteria (some met both).  They then look at those 259 patients for whom there is no CMS exception for their CT, and they claim that 136 of those were clinically warranted.  They therefore conclude that only 125 of the original 748 were accurately identified by this quality measure as inappropriate use of CT in atraumatic headache, and that this measure is garbage.

And, a quick Google News search finds an extensive parade of indignant headlines pulled from ACEP's press release, condemning the measure.

But, this study misses the point.  It's not CMS' responsibility to comb through individual charts to find these exclusion criteria.  The onus is on clinicians and hospitals to ensure their documentation clearly expresses the indications for CT in those cases that meet the exclusion criteria, and the purpose of this dry run is to help hospitals identify where the information they are supplying to CMS is deficient.

Then, I expect CMS to take a low opinion of the additional patients in whom these authors felt the imaging was clinically warranted.  Of the 78 patients for whom the authors felt ACEP guidelines for imaging were met, 73 of them met only the Level C recommendation: >50 years of age with a new type of headache and a normal neurologic examination.  Then, there is another set of patients with headaches on warfarin, who had recent neurosurgery, or had known hydrocephalus that they claim are misclassified by CMS - but I can't see how the misclassification isn't on the documentation end, as headaches in all those patients should meet ICD-9 339.44 "Other complicated headache syndrome," which is an exclusion to the rule as well.

So, even just on first pass, I'm not sure this is an effective tool with which to influence revision of OP-15.  I expect this measure to go into effect as planned - and it will be up to us to document appropriately and thoroughly, and then to monitor and demonstrate that compliance results in measurable patient harms.

"Assessment of Medicare’s Imaging Efficiency Measure for Emergency Department Patients With Atraumatic Headache"

Thursday, February 23, 2012

Unneeded Stents Are Bad And Bad For You

Well past a decade into the stent era, there's finally a growing recognition and furor over the costs and potential harms of unnecessary stenting.  While interventional cardiologists are great for the bottom line of hospitals, a few high profile cases have demonstrated that PCI and stenting might be performed more than indicated.

And, not only is it costing those patients more in procedural billing, it's likely harmful to them as well.

This concept of "Fractional Flow Reserve" has been developing in cardiology literature to better evaluate whether a stenotic lesion is actually significantly impairing the perfusion of myocardium.  These authors, part of a French cohort study called "DEFER," are following up prior studies showing FFR-guided selective stenting for left main disease is reasonable, and looking back at what they call "small vessel" coronary disease - LAD, RCA, and LCx.

This is, unfortunately, a retrospective analysis, and there are huge differences between the groups that underwent angiography-guided PCI and the group that underwent FFR-guided PCI - but not enough difference to account for the additional hazard ratio acquired by the angiography-guided PCI.  Angiography-guided PCI, in their propensity-score adjusted hazard ratio, still had significant associations with increased non-fatal MI and future revascularizations during their five-year follow-up period.  Indeed, the FFR-guided PCI group that did not find any vessels requiring intervention did outstanding - suggesting this perfusion-based strategy might be better for ensuring the benefits of stents do not outweigh the risks.

"Long-Term Clinical Outcome After Fractional Flow ReserveGuided Percutaneous Coronary Revascularization in Patients With Small-Vessel Disease"

Tuesday, February 21, 2012

Is Midazolam Really Superior to Lorazepam?

Or, more accurately, is it reasonable to perform an intramuscular injection of midazolam rather than an intravenous injection of lorazepam for seizure-like activity in the prehospital setting?

Almost certainly.

In fact, some folks are taking this article and claiming that intramuscular midazolam is superior to intravenous lorazepam, that it's a "game changer."

Well, let's not go crazy here.

As with any piece of literature, the more vocal the giddiness I see perpetuated about the internet, the more cautious I am with rushing to judgement.  It is, of course, a very well-designed, prospective, double-dummy, randomized, non-inferiority comparison between midazolam and lorazepam.  The aim of the study is, essentially, to show that, even though midazolam is not typically as rapidly effective at terminating seizures, the time difference is made up by intramuscular route versus the time required for an IV start.

What's kind of odd that I see in this article is that nearly a third of the lorazepam group did not receive the benzodiazepine portion of the intervention - and they compare it to the midazolam group in which all but 5 patients received the intervention.  When their primary outcome is the number of folks who arrived seizure-free in the Emergency Department - it seems as though the 7% absolute difference between the two groups could be easily explained by the fact that a third of the lorazepam group didn't receive an intervention.  Most of the lorazepam group had the intervention withheld because they stopped seizing of their own accord at the time of enrollment, with a minority having the intervention withheld because IV access could not be obtained.

And, the differences favoring midazolam are hard to pin down whether it's actually medication superiority, or something different about the seizures.  42 patients in the lorazepam group failed to stop seizing after additional therapy, compared with only 22 in the midazolam group - is this a difference in efficacy, or a difference in the underlying disease process - which appears to be more resistant to any therapy, including rescue, in the lorazepam group?

But, in any event, this just nitpicking against the superiority argument, and not the non-inferiority argument.  From a clinical standpoint, it is clearly safe and effective to use intramuscular midazolam for seizures in the prehospital setting.  However, what I'd prefer to see is a similarly powered trial of intranasal midazolam, which takes all the injection risks for patient and provider out of the equation during the seizure.  This is a good first step, but I think we can make effective treatment even safer if intranasal can be shown non-inferior as well.

"Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus"

Sunday, February 19, 2012

No One Knows How To Diagnose CAD

And, once they diagnose it - it doesn't seem like anyone knows what to do with it, considering all the brouhaha these days about potentially unnecessary PCI and stenting.

But, this is a prospective coronary CT angiography registry that was reviewed to determine whether any value was added with the CCTA over conventional stress testing in patients without known CAD.  They reviewed 22,551 patient records, excluded patients with known CAD, incomplete data, and patients who hadn't undergone a recent (<3 months) cardiac stress test, and ended up with 6,198 patients.

The point the authors seem to be trying to make is that CCTA is a better test than stress testing, but that's only part of the story.  What they note that is interesting along the way is that there is absolutely no correlation between stress testing results and CCTA results.  Patients with normal, equivocal, and abnormal stress results had, essentially, the same incidence of normal, <50%, and >50% coronary stenosis.  And, the hidden story about how CCTA is being used in their patient cohort is fascinating - a younger group with typical chest pain and normal stress tests referred to CCTA vs. an older group with less typical symptoms and abnormal stress tests referred to CCTA.

But, then, finally they compare both of their disparate tests to the "gold standard" of invasive angiography, and they find that both tests are awful at predicting >50% coronary stenosis.  Stress testing was 60.4% sensitive and 34% specific, while CCTA was 94% sensitive and 37% specific.  So, we have two tests that are wrong about the presence of disease twice as often as they're right - and these authors are using a clinically irrelevant 50% stenosis as their "gold standard".

Rather entertaining to observe the difficulty the cardiology literature is having reconciling all their different imaging options with clinically relevant stenoses, much less outcomes.  Good thing all these inadequate tests are cheap and harmless....

"Coronary Computed Tomography Angiography After Stress Testing"