Endovascular Sans tPA in Bern

The first hints of a rollback in tPA use are starting to emerge – not unexpectedly, from those working to improve the outcomes of their endovascular programs.

This is a retrospective evaluation of patients from Bern, Switzerland, all treated with endovascular therapy.  Their registry includes 372 patients since 2004, all treated for MCA or ICA occlusions and with DWI measurements pre-treatment.  As with any data dredge, any findings are just hypotheticals – but, there’s a couple interesting tidbits:
  • Smaller lesions did much, much better – 54.5% achieved mRS 0-2 if lesion volume was <70mL, compared with 21.2% with lesion volume >70mL.
  • If you failed to reperfuse a lesion volume >70mL, mRS 0-2 outcomes sank to 8.6%.
  • Symptomatic intracranial hemorrhage jumped to 19.7% for lesion volume >70mL.
  • There were only 66 patients over >70mL lesion volume, but the best outcomes?  The 19 with mechanical therapy only – balancing 21.1% mRS 0-2 with only 5.3% SICH.
The authors ultimately conclude endovascular therapy for large lesion volumes might be best without any thrombolytic involved.

Wasn’t it lovely how fashionable tPA was – until endovascular therapy finally reached a tipping point in terms of efficacy?

“Younger Stroke Patients With Large Pretreatment Diffusion-Weighted Imaging Lesions May Benefit From Endovascular Treatment”

Clinicians or Statistics for Pediatric Abdominal Injury

PECARN is a wonderful thing.  Any individual pediatric facility sees a handful of children.  A handful, however, multiplied by 20, becomes potentially practice-changing.

And, this is an article further exploring the PECARN pediatric abdominal trauma prediction instrument, comparing its utility to typical clinician judgment.  As part of the initial derivation study, the surveyors asked each clinician to rate the likelihood of intra-abdominal injury, stratified <1%, 1-5%, 6-10%, 11-50%, or >50%.  Turns out, clinician judgement wasn’t too bad.

  • Of 9,252 children with <1% chance of injury requiring intervention, 35 (0.4%) had injuries identified.
  • Of 1,793 between 1-5% chance, 40 (2.2%).
  • Of 506 between 6-10% chance, 33 (6.5%).
  • Of 281 between 11-50% chance, 59 (21.0%).
  • Of 81 greater 50% chance, 36 (41.4%).

The problem with these data?  5,318 CTs were performed to identify 203 significant injuries, including 3,016 in those with <1% chance.

The prediction rule was both better and worse.  It was more sensitive than clinician judgment, but also less specific.  For an endeavor attempting to decrease CT utilization in children, it’s still not quite clear where this fits in – and whether using it in a fashion similar to PERC or D-dimer wouldn’t necessarily increase imaging.  It may, as these authors discuss, have more value in Emergency Departments without the same level of comfort managing traumatically injured children, as it may yet in face reduce imaging in that context.

“Comparison of Clinician Suspicion Versus a Clinical Prediction Rule in Identifying Children at Risk for Intra-abdominal Injuries After Blunt Torso Trauma”

Risk Stratification Cage Match & The Return of TIMI

Sending home chest pain has completely jumped the shark from frankly illegal to fashionably vogue.  Every day, another stick is shaken, and a mess of monkeys and new studies evaluating discharge strategies fall from the trees.

Today in the Octagon, five “established” risk scores for patients with acute coronary syndrome are pitted against each other in a prospective, observational study in Britain:  TIMI, GRACE, HEART, the Vancouver Chest Pain Rule (sure, OK), and the modified Goldman (???).  Each of these risk scores were paired with non-ischemic EKGs, and single initial blood samples for high-sensitivity troponin T (14 ng/L) and high-sensitivity troponin I (26.2 ng/L).  The authors’ stated goal: a negative predictive value of 99.5% for myocardial infarction within 30 days, and a capability of discharging at least 30% of patients at the initial presentation.

Oddly, it’s unexpectedly difficult to pick a winner.  The decision instrument with the greatest ability to discharge patients was TIMI ≤1, over 50% home from the ED, but it just barely missed the NPV threshold.  The modified Goldman ≤1, when paired with the troponin T, was capable of discharging 39.8% of patients with a sensitivity of 98.7%.  Then, the HEART score ≤3 was the most clinically acceptable when used with the troponin I assay, as it was the only decision-instrument taking into account small variations in serum troponin.  However, it just failed to meet the authors' NPV threshold, as well.

So, what has changed since we last crowned HEART the new gnat’s pajamas?  Mostly the troponin assays, although this study also focuses more on NPV than sensitivity.  Indeed, a single hs-cTnT <14 ng/L had an NPV of 98.3% in this study, regardless of all other clinical features.  The implication, potentially, may be that the ideal risk-stratification decision-instrument can be designed for greater specificity, rather than sensitivity.  Other methods to increase sensitivity, such as paired troponins in certain situations, may allow for even further decision-instrument specificity, depending, of course, on the acceptable miss rate.

Despite its performance here, I’m not advocating for a return to TIMI – or to the modified Goldman – because I’m not quite so keen on their sensibility in the ED.  However, the interaction of HEART with different assays is intriguing, and perhaps a venue for further investigation and refinement.  It's probably also worth mentioning an additional overlooked aspect – it is still OK to discharge a patient with a higher risk of AMI or death within 30 days if there is no additive survival benefit associated with acute hospitalization.

“Identifying Patients Suitable for Discharge After a Single-Presentation High-Sensitivity Troponin Result: A Comparison of Five Established Risk Scores and Two High-Sensitivity Assays”

Your CTPA is Lies

There are a few moments you pat yourself on the back in Emergency Medicine.  The good save.  Shared decision-making that goes well.  And, the small victory when you've utilized an evidence-based pathway for pulmonary embolism, and received positive results for the leviathan of over-utilization and over-diagnosis: the CT pulmonary angiogram.

Well, it’s time to deduct about 1.25 fingers from that pat on the back you give yourself, because, unfortunately, radiology PE overcalls may be more rampant than initially thought.

This is a retrospective, single-center study reviewing a year’s worth of CTPA for pulmonary embolism, a total of 937 studies.  Of the studies included, 174 (18.6%) were initially read as positive.  Then, each positive study was reviewed by a panel of three, specially trained chest radiologists, with their consensus read used as the gold standard for diagnosis.  And so: 45 (25.9%) were subsequently judged to be incorrectly read by the original radiologist – a quarter of positive studies! – with those patients almost certainly consigned to at least short-term anticoagulation as a result.

In a light moment in the discussion, the authors helpfully contribute the following commentary:
Furthermore, many pulmonary CTA examinations in our institution are ordered by the emergency department before assessment by the admitting medical team.
My heart goes out to the poor Scottish EM physicians, for whom their radiology colleagues apparently have quite the low opinion for appropriate testing.  However, the authors' attention may be better spent further discussing their own false-positive rate, which is double the ~11% rate of other similar reviews.  They also do not provide any accompanying data on the rate of false-negatives, although, in theory, these should be less clinically important.

So, think twice about doing your little happy dance for a positive CT – if your pretest likelihood was low, and the PE is subsegmental, there’s a substantial chance the stars have aligned in just the wrong constellation.

“Overdiagnosis of Pulmonary Embolism by Pulmonary CT Angiography”

Better Less than More for tPA

Ah, but this is not one of those rants about the inefficacy of tPA.  This is just an amuse-bouche of a mention of an article from Stroke, regarding a line of investigation in Asian countries.

In these countries, particularly Korea and Japan, there is some substantial thought given to “low dose” tPA being just as effective, with a lower risk of intracranial hemorrhage.  Interestingly, approximately 40% of acute stroke patients in Asian countries is at this lower dose, 0.6 mg/kg compared with the typical 0.9 mg/kg.  This study is a retrospective evaluation of registry data from 13 academic stroke centers, comparing 3-month outcomes on the modified Rankin Scale.

There were, essentially, two entertaining bits from this article:
  • The rate of symptomatic ICH in centers contributing at least 100 patients during the study period ranges from 3.7% on the low side up to 13.0% on the high.
  • Given the constraints of the study, they were unable to demonstrate any reliable difference between the two doses.  In fact, as you can see from the figure below, retrospective data can be adjusted, propensity matched, or essentially tortured to show whatever advantage preferred:

Should we be using low-dose?  And why stop at 0.6 mg/kg – why not 0.3 mg/kg?  And, further down the rabbit hole, back to the ideal dose of … none.  Ah, but I kid, I kid ….

“Low-Versus Standard-Dose Alteplase for Ischemic Strokes Within 4.5 Hours: A Comparative Effectiveness and Safety Study”