Monday, August 13, 2012

Mistakes Were Made

This is a fascinating series in Pediatric Emergency Care in which interesting cases from published medical malpractice verdicts are featured.  Each case – typically ending poorly – is followed by a short editorial on the underlying disease processes, with pearls regarding treatment, diagnosis, and the case outcome.  Reading these cases, hopefully, will not contribute to recency bias, and ideally serve simply as brief reminders of clinical features of the rare sick children lurking in the haystack of walking well.

Medicine – as much as or greater than any other profession – is a delicate mix of confidence, humility, and the recognition of the underlying biases in our cognition and practice.  Most of this blog focuses on practicing based on evidence, applying the rules and probabilities of populations as guides towards the diagnosis and treatment of individual patients.  Therefore, when reading these Legal Briefs, I simply want to reinforce the dangers of anecdote-based medicine.

"Pediatric Emergency Medicine:  Legal Briefs"

Friday, August 10, 2012

Here Comes Gonorrhea (Again)

Good news for the monogamous – bad news for the rest – Neiserria gonorrhoeae is rapidly becoming resistant to cefixime, an oral third-generation cephalosporin.  The resistance rates are low – a maximum of 17% in Honolulu – but the fear is that continued cefixime use will carry-over into an increased resistance for ceftriaxone.

This follows the 2007 declaration that fluoroquinolone resistance had obviated their use.

For now, the CDC recommendations have narrowed to 250mg IM/IV ceftriaxone plus 1g oral azithromycin once or 100mg oral doxycycline BID for seven days.

"Update to CDC's Sexually Transmitted Diseases Treatment Guidelines, 2010: Oral Cephalosporins No Longer a Recommended Treatment for Gonococcal Infections"

Thursday, August 9, 2012

Cited in Journal Watch

My dabigatran article from Annals of Internal Medicine has been cited in Journal Watch.  Huzzah!

"Within 12 weeks of marketing approval, dabigatran was found to be 
responsible for more adverse events than nearly all other medications.
   By David Green, MD, PhD"

Dabigatran:  How Safe?

Wednesday, August 8, 2012

Ketamine - Cure For Everything

There aren't many medications I love using more than ketamine.  I use it for adjunctive pain control, to control agitation, and for induction prior to intubation.  Now, chances are, it's probably useful in seizures.

This is a case report and review of the literature for the use of ketamine in the control of refractory status epilepticus.  The literature is profoundly weak – the "review" is essentially a review of case reports.  And, the patient outcomes describe in the case reports are replete with "All died" or "Survived but severely disabled."  However, this is primarily due to the serious cause of the underlying disorders – encephalitis, neurosyphilis, meningitis, anoxic brain injury – and less likely the ketamine, although this does not provide the evidence to that effect.  The proposed mechanism is via NMDA receptor antagonism, which the author proposes works better by synergy with GABA antagonism, rather than either as monotherapy.

Seems like a fair physiologic mechanism, and it's nice to have something additional to consider in refractory disease.  Ketamine also was noted in this case report to counteract the hypotensive effects of midazolam and propofol, consistent with prior literature describing its beneficial effect on cerebral perfusion pressure.  It's pretty much a "I tried this and I like it" article, but I think it's probably likable and not the last we've heard about ketamine for status.

"Early Ketamine to Treat Refractory Status Epilepticus"

Monday, August 6, 2012

When Do Patients Need Blood Cultures?

Another lovely JAMA Rational Clinical Examination article relevant to the Emergency Department – this time regarding the utility of blood cultures.  Blood cultures are frequently requested for febrile inpatients, however, the incidence of false positive ranges between 2.5% and 8%.  This leads, unfortunately, to additional patient harms from additional treatment or observation.

This article is a systematic review of several studies gathering clinical features of patients for whom blood cultures were requested, as well as the clinical outcomes of the cultures, in an attempt to identify features predictive of positive or negative cultures.  They also examine a couple validated clinical decision instruments to determine their potential utility in stratifying the appropriateness of cultures.

Essentially, based on a few pieces of decent evidence and a few pieces of poor evidence, the authors determine a few general categories of infectious etiology with varying pretest probability for bacteremia.  These are:
 • Cellulitis, community-acquired pneumonia, community-acquired fever: low (<14%) probability
 • Pyelonephritis: mid (19-25%)
 • Severe sepsis, septic shock, bacterial meningitis: high (38-69%)

In general, however, no individual clinical feature had a positive or negative likelihood ratio of sufficient magnitude to guide testing.  Combinations of clinical features – such as patients with SIRS – were capable of excellent sensitivity & negative likelihood ratios, but only had specificities of 0.27 to 0.47.

However, the more important clinical aspect of blood cultures and bacteremia is not addressed in this article, which is how frequently the true positives even change clinical management.

"Does This Adult Patient With Suspected Bacteremia Require Blood Cultures?"

Friday, August 3, 2012

Vancouver Chest Pain Rule in Tehran

Iran and Canada would be considered by most to be very different places.  However, from a cardiovascular standpoint, it seems they're not so disparate.

This is a prospective, validation study of the Vancouver Chest Pain Rule.  The Vancouver rule is one of many 2-hour accelerated rule-outs operating under the presumption that all disease can never be detected – sensitivity will never be 100%, but this assumes a context in which a discussion may be had with the patient about outpatient disposition.  Essentially, any patient under 40 years without a history of coronary artery disease and a normal EKG simply gets discharged.  Older than 40 and atypical chest pain is discharged either immediately after a CK-MB < 3.0 µg/L, or receives a 2-hour delta + repeat EKG if > 3.0 µg/L.  Essentially, the rule is designed only to ensure all unusual NSTEMIs are picked up.

In the initial study, the 30-day ACS rate for the discharged group was 1.2%.  In this Iranian study, the 30-day ACS rate of 292 very-low-risk patients is 1.3%.  Two of the four patients meeting criteria for discharge by CK-MB had positive troponins.  Considering CK-MB is nearly considered anachronistic now, most modern EDs would have not have discharged these patients based on troponin testing.  A third patient had EKG changes on the second EKG – which should fail the Vancouver rule, so I'm uncertain why it was included in their very-low-risk group.  Finally, the last patient had an entirely normal evaluation and a subsequent 70% lesion discovered on angiography a week later.  No mention of the hemodynamic significance/relation to ischemia of this lesion is noted.

A few hundred patients is hardly a definitive validation, but it's a nice demonstration that 50% of their cohort could have been discharged in two hours – and with the same 30-day event rate as the poor people being made to glow in the CCTA studies.

"Validation of the Vancouver Chest Pain Rule: A Prospective Cohort Study"

Wednesday, August 1, 2012

Tramadol: A Myth of Safety

For me, tramadol lands squarely in the gap between oral analgesics I might use for "no pain" – ibuprofen, acetaminophen – and analgesics I might use for "real pain" – hydrocodone derivatives.  The literature describing the analgesic properties of tramadol is bizarre, with multiple comparisons with placebo, nerve blocks, adjunctive epidural anesthesia, etc., and very few head-to-head comparisons to the sorts of medications we routinely use.  When there are comparative efficacy reports, they typically conclude that tramadol is effective...just as effective as the NSAIDs its being compared with.

The theory I've heard people use when considering use of tramadol is that it has a better safety profile than hydrocodone and is less dependence-forming.  These claims may be true, but I do not believe they are true to the extent that it is clinically relevant.  Tramadol still generates an opioid withdrawal syndrome and, as this article describes, overdose/abuse still results in apnea with need for ventilatory support.

Additionally, tramadol is a GABA antagonist, lowering seizure threshold.  Of the 525 patients overdosing primarily on tramadol retrospectively identified at this Iranian hospital, 19 experienced apnea and 242 (46.1%) experienced seizures.  This is retrospective and co-ingestants cannot be fully ruled out, but the propensity for seizure is far more surprising than the incidence of apnea.

Tramadol has a role in pain control prescribing, but, in my practice, that role is tiny.

"Tramadol-induced apnea"

Tuesday, July 31, 2012

The "Peripheral" IJ

Some patients just have no IV access – no superficial peripherals, no deep peripherals, no external jugular veins.  In a critical emergency, this is the perfect time for an intraosseous line.  But, what about the situation where IV access is simply necessary, but not urgent?  Placing a central line is the last thing we're interested in doing – draping, opening a costly central line kit, billing for an expensive procedure, exposing them to risks of over-the-wire techniques in the central circulation.

This technique, described formally here by folks from Highland Hospital, involves placing a standard, peripheral catheter into the internal jugular vein under ultrasound guidance.  While I think this is a fantastic idea – much faster and less expensive than a full multi-lumen central line set-up – I wouldn't characterize it as "risk-free", either.  The nine cases in this year-long review all demonstrated a lack of complications, but more data would help refine the procedural risks.

"The ultrasound-guided 'peripheral IJ': internal jugular vein catheterization using a standard intravenous catheter."

Monday, July 30, 2012

Excitement For/Failure of CCTA

The third of the big CT coronary angiography studies from the last year – and, yet again, this is positive for its primary endpoint.

However, that value of that endpoint is another matter – mean length of stay in the hospital.  For the CCTA cohort, that mean was 23.2 hours and the "standard evaluation" was 30.8 hours.  However, more illuminating – and further favoring CCTA – is that the median CCTA evaluation time was 8.6 hours compared with 26.7 hours in the "standard evaluation" group.  Just like in the previous studies, CCTA is faster, and, for some patients, much, much faster.

But, as you can probably gather from that mean/median discrepancy, a substantial cohort in the CCTA group went on to have some pretty extensive downstream testing and prolonged hospital stays.  This means, from a costs standpoint, the two strategies eventually even out.  No significant safety differences were detected between the two strategies.

Now that we've seen the full results of ROMICAT II, CT-STAT, and ACRIN-PA, we have a pretty good idea of what this test does.  If you must evaluate these low-risk chest pain patients with imaging of some sort, need to clear them out of your Emergency Department quickly, your cardiology team is excited to take on the false positives, and you're unconcerned about the downstream harms – then CCTA is the test for you.  If the potential harms, the poor specificity, and the non-functional nature of the test concerns you – then no one will fault you for dragging your feet.

The accompanying editorial gets it right - this is still a test looking for the correct application.  However, we don't just need a better test – we need a better consensus for whom we're simply not going to test.

"Coronary CT Angiography versus Standard Evaluation in Acute Chest Pain"

Friday, July 27, 2012

Predicting sICH in Thrombolysis

In contrast to the lunacy of IST-3, this is another piece of work that at least in the right direction – helping us avoid harming patients with thrombolysis.  

These authors use the Get With The Guidelines registry as their derivation and validation group to develop a prediction rule for sICH in the setting of thrombolytic use for acute ischemic stroke with in 3 hours of symptom onset.  Subsequently, they "externally validate" their rule by applying it retrospectively to the NINDS data set.  At the end of it, they come up with a not-so-handy point scale with six clinical features and twenty discrete elements, but basically, these things are bad:
 - Older patients
 - More severe strokes
 - Higher systolic blood pressure
 - Elevated blood glucose
 - Asian ethnicity
 - Male gender

The C-statistic was .71 on their derivation cohort, .70 on their validation cohort, and .68 on the NINDS cohort - which is more or less just OK.  In practical, clinical terms, their tool more or less discriminates between folks who are at 1-3% risk of ICH, and then 6-10% risk of ICH.  And, I think it's extremely valuable when discussing risks with our patients to not use blanket generalities, and attempt to tailor the discussion to the individual.

"Risk Score for Intracranial Hemorrhage in Patients With Acute Ischemic Stroke Treated
With Intravenous Tissue-Type Plasminogen Activator" 

Wednesday, July 25, 2012

Anterior STEMI or Benign Repolarization?

As requested by @jord7an, this covers Dr. Smith's recent Annals publication regarding the differentiation of anterior STEMI from early repolarization abnormalities.  Classically, early repolarization abnormalities manifest with prominent R waves, J-point elevation, ST-segment elevation, and a concave ST-segment morphology in the precordial leads.  However, physician performance in practice at differentiating this pattern from true STEMI could be better, with benign repolarization making up about 10% of anterior STEMI cath lab activations.

In short, this is a retrospective evaluation of electrocardiographic features of anterior STEMI, trying to find an accurate, reliable rule to diagnose STEMI rather than a similar "pseudoinfarction" pattern.  After doing objective measurements of several possible criteria between their comparison sets of "subtle" anterior STEMI and early repolarization, they come up with this rule:

            (1.196 x STE60 V3) + (0.059 x QTc) – (0.326 x RA V4)

If the result of that equation is calculated as >23.4, there's a +LR of 9.2 for STEMI, and a -LR of 0.1 if negative.  And, those are useful LRs.

So, this is probably helpful.  The authors suggest this could be easily programmed into the automatic rhythm analysis software of ECG machines, which is plausible.  However, both the derivation and validation of this rule were performed retrospectively.  The next step, ideally, would be a prospective comparison between rule-augmented clinical decision-making and non-augmented decision-making.  Unfortunately, detecting small differences in clinical performance may require large samples, and these clinical dilemmas are not common at single centers.

"Electrocardiographic Differentiation of Early Repolarization From Subtle Anterior ST-Segment Elevation Myocardial Infarction"

Monday, July 23, 2012

The Wrong Way To Quit Drinking

This week's NEJM Case Records is an Emergency Department & Toxicology patient – I won't ruin the final diagnosis for you – who uses a mysterious South American alcoholism cure to attempt to rehabilitate himself after a night of heavy drinking.

Obviously, it wouldn't be a case report if the patient in question didn't end up in the ICU!  There are nice, educational discussions of several toxodromes, antidotes, and various options for preventing end-organ damage in a subset of uncommonly seen poisonings.

"Case 22-2012: A 34-Year-Old Man with Intractable Vomiting after Ingestion of an Unknown Substance"

Friday, July 20, 2012

Empiric Measurement of Bias in Unblinded Trials

This lovely article was passed along to me by David Newman during a discussion of IST-3 – the recently infamous, massive randomized trial of thrombolysis for acute stroke.  There are two ways of thinking about IST-3, and how the results are viewed in the literature seems to depend how much funding you receive from Boehringer or Genentech.  The first way of thinking seems to be accept the results as published, pick apart the subgroups, do statistical contortions, and then either come out in the "pro" camp (Boehringer) or the "con" camp.

The second way of thinking, supported by this article, is "garbage-in, garbage-out".  The key issue for this approach is that IST-3 is an unblinded, open trial, which introduces bias - treating clinicians and patients who believe TPA is a "promising, yet unproven" treatment (from the uncertainty principle of the study) are perceived as more likely to contribute to favorable reported outcomes when receiving the experimental intervention.  This effect is probably even more pronounced given that much of the follow-up scoring for the Oxford Handicap Scale was performed by mail-in questionnaire, rather than standardized expert evaluation – which has rather poor kappa to begin with.

Page three of this article delves into the empiric analysis of the impact of blinding, and the relative likelihood of unblinded trials to report favorable outcomes.  Essentially, the relative chance of reporting both favorable and unfavorable outcomes are significantly affected.  In clinical terms, this leads to presentation of results in which the benefits are exaggerated and the harms are minimized.  In the context of IST-3, this essentially means the likelihood of any hidden positive effects vanishes, while the poor outcomes are underreported – and it's more "negative" than "neutral".

The authors also note they are preparing a systematic review of trials with blind and non-blind outcome assessors, which would be particularly apt to IST-3, as well.

"Blinding in Randomized Clinical Trials: Imposed Impartiality"

Wednesday, July 18, 2012

Keeping Children Happy

When I started in medicine – hardly long ago – Child Life, if it existed at all in the Emergency Department, might have consisted of a few plastic toys and perhaps a Nintendo Entertainment System.  Now, the staple of every department is an iPad, filled with apps and distractions for children.

This is a short article from the Pediatric literature reviewing a few cases in which tablet computers proved useful, along with a review of several apps worth loading on for distraction during potentially troubling procedures.  Most of the apps reviewed are for iPad, but equivalent exist for Android devices and iPhone.

I've definitely gotten mileage out of the movie "Toy Story 3" on my iPhone – perfect for the 3 AM laceration repair when Child Life has gone home for the night.

"Using a Tablet Computer During Pediatric Procedures - 
A Case Series and Review of the 'Apps'"

Monday, July 16, 2012

Massive Overtesting for Febrile Seizures

Frightening, yet benign, febrile seizures are seen frequently in the Emergency Department.  The American Academy of Pediatrics recommends minimal evaluation for uncomplicated febrile seizures, and invasive testing only in complex cases or those with other indications for testing.

Despite this, the real-world experience documented by these authors at a community hospital in New York is slightly different.  Rather than minimal testing, 100% of patients - mostly aged greater than 12 months - received a CBC and Chem7.  94% received a blood culture, 94% received a urine culture, and 85% had a chest x-ray.  24% had CSF cultures and 21% had CT scans - mostly the complex febrile seizures.

The yield of all this testing - they diagnosed a few UTIs, and one blood culture grew out salmonella.  The authors appropriately feel this testing strategy is excessively wasteful - and confirms the AAP recommendations.

"Current Role of the Laboratory Investigation and Source of the Fever in the Diagnostic Approach"