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
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”
www.ncbi.nlm.nih.gov/pubmed/22520989
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“
http://www.ncbi.nlm.nih.gov/pubmed/22808962
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”
http://www.ncbi.nlm.nih.gov/pubmed/21993424
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'”
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”
http://www.ncbi.nlm.nih.gov/pubmed/22653461
It’s Nothing Like “ER”
This is a fun little article regarding the realism of the Emergency Medicine environment showcased on the popular U.S. television show “ER”. As the authors state in their introduction, the viewers of the show have been surveyed, and a significant portion of the viewers believe the content of the show to be valid clinical information. However, the televised outcomes are frequently unrealistic (CPR success rates, patients emerging from comas, etc.), and lead to inaccurate public perceptions.
This team of authors watched all 22 episodes from a single season of “ER” to evaluate the types of patient encounters depicted, and then compared their findings with representative data from the NHAMCS dataset. Overall, there were 192 patients during the 22 episodes, and they differed from the real-world by:
– Weighted heavily towards 25-44 years of age, rather than infants and elderly.
– More male and white, rather than black and female.
– Depictions of lower pain levels.
– Far more traumatic injuries.
And, this analysis only observed the patients – the responsibilities and skills of the treating medical students, residents, and attendings are also wildly dramatized, of course.
So, it’s nothing like “ER”. It’s really more like “Scrubs”….
“ER vs. ED: A comparison of televised and real-life emergency medicine.”
http://www.ncbi.nlm.nih.gov/pubmed/22766407
Flumazenil – Seizures, But Not Frequently
It seems as though, when teaching trainees about benzodiazepine overdose, flumazenil is discussed – and in the same breath, the commandment to use it never or with extraordinary caution. The fundamental issue is whether an underlying pro-convulsant state can be unmasked if the protective effect of benzodiazepines is removed.
The answer from this study, a retrospective review of a decade of flumazenil use in California, is clearly yes. However, the “yes” is only 13 seizures out of 904 reviewed cases, most of whom had some sort of co-ingestant that contributed to the pro-convulsant state. The authors also note, for the cases in which data was available, flumazenil was therapeutic (and potentially diagnostic as well) in 53% of administrations, with return of alertness from unresponsiveness or drowsiness.
So, the answer to the clinical question – whether flumazenil use should be as taboo as current dogma – is more complex, and, unfortunately, descends into that dark area where risks must be weighed against benefits. Is the risk of poor clinical outcome secondary to resuscitative efforts in the field, delayed/missed intubations, etc. greater than the 1-2% risk of seizures? Or can the patient be safely observed with minimal intervention in a monitored setting? Or, if flumazenil is effective, how much money was saved by reducing the need for the expansive medical testing performed on unresponsive individuals? I don’t believe a single blanket answer suffices to cover each individual clinical situation.
“A poison center’s ten-year experience with flumazenil administration to acutely poisoned adults.”
NICE Agrees – No PPI in UGIB
It’s hard to fight this battle in the United States. It’s like hyperkalemia – where you carefully talk down the rotating IM intern from giving albuterol, terbutaline, bicarbonate, insulin, Kayexalate, and calcium to the K+ of 5.7 in your dialysis patient – and then the nephrology fellow on-call tells ’em to give it anyway. Sigh.
But, in any event, despite the lack of evidence for benefit in patient-oriented outcomes for intravenous proton-pump inhibitors in UGIB, invariably the GI fellow wants it. There’s even a suggestion of harms associated with IV PPIs in some of these studies – in addition to everything we’re learning about how gastric acidity contributes to the total body immune defense. For all its criticisms, I think NICE – the clinical effectiveness consensus group in the United Kingdom – has gotten it right for UGIB. Terlipressin, which isn’t available in the United States, appears to be beneficial in variceal bleeding. Somatostatin analogues, not included in this guideline, may or may not be beneficial, and I agree that it was appropriate for them to be excluded.
In the meantime, I’ll keep fighting the inanity, one patient and one resident at a time….
“NICE clinical guideline 141 – Acute upper gastrointestinal bleeding: management”
Put Hydroxyethyl Starch Away
The use of colloid solutions as volume expanders is tempting – massive crystalloid resuscitation suffers from third-spacing, limiting the practical intravascular volume provided. Colloid resuscitation, in theory, uses the oncotic pressure of the solute to favor intravascular expansion. One of the alternatives that I’d seen use, but was unaware it was widely used, are hydroxyethyl starches. Earlier studies, at least, the ones I was familiar with, linked the high-molecular weight HES to renal failure.
This trial, from Denmark, evaluated a low-molecular weight HES (Tetraspan) with Ringer’s acetate resuscitation in an intensive care setting, enrolling patients diagnosed with sepsis in need of fluid resuscitation. The trial was randomized and blinded, with the resuscitation fluids being hung in identical black bags. Each enrolled patient could receive up to 33 mL per kg ideal body weight of the trial fluid, and additional fluid was unmasked Ringer’s acetate.
With 800 well-matched patients between groups, 51% of the HES group was dead at 90 days, compared with 43% in the Ringer’s acetate group (RR 1.17, CI 1.01 to 1.36). Renal replacement therapy was needed in 22% of the HES group, compared with 16% of Ringer’s acetate group – and was a predictor of death.
Investigators did not see any particular fluid volume advantage to the HES solution, and the toxic effects of the hydroxyethyl starch molecules, unfortunately, were associated with greater morbidity and mortality.
Seems like another great-sounding idea that needs to be rapidly curtailed until a better safety profile and outcome benefit can be demonstrated.
“Hydroxyethyl Starch 130/0.4 versus Ringer’s Acetate in Severe Sepsis”
http://www.nejm.org/doi/full/10.1056/NEJMoa1204242