Some Old News About Thrombolysis Before Endovascular Therapy

We’ve spent a little bit of energy on this blog teasing out the appropriate indications for endovascular therapy, and and we’ve used a few of those words to discuss whether thrombolysis prior to is necessary. I am of the opinion: probably not.

It turns out, there are many other prominent neurologists who share that same opinion. Unfortunately, this article is just a rehash of prior data without any new specific insight. Of course, the lay medical press does their typical job of creating definitive, misleading headlines:
Stroke: No Benefit from Adding tPA to Thrombectomy
No Benefit for IV tPA Before Mechanical Thrombectomy in Ischemic Stroke

This is a small post-hoc analysis of the 291 patients undergoing treatment in the SWIFT and STAR trials. Of these, 131 did not receive thrombolysis prior to intervention, with the most common exclusion being either presence of an elevated INR and oral anticoagulation or symptom onset being >4 hours prior to hospital arrival. Other, less common exclusions included blood pressure exclusions, hypoglycemia, and prior strokes. Some patients also received bridging tPA or reduced-dose tPA, as determined appropriate by the interventionalist.

In such a small analysis such as this, little reliable can be made of the results – except to generally say there was no obvious signal confirming nor refuting the appropriateness of thrombolysis prior to intervention. Hemorrhagic complications were similar between groups, as were patient-oriented outcomes. At the least, they offer the appropriate weak conclusion supported by these data: prospective trials are reasonable.

“Combined Intravenous Thrombolysis and Thrombectomy vs Thrombectomy Alone for Acute Ischemic Stroke: A Pooled Analysis of the SWIFT and STAR Studies”
http://jamanetwork.com/journals/jamaneurology/article-abstract/2596239

Does FEIBA Work for NOACs?

“Maybe”?

The novel oral anticoagulants – dabigatran, rivaroxaban, apixaban, edoxaban – have spread in use quite rapidly. There is weak evidence supporting the use of idarucizumab for emergency reversal of dabigatran, and even weaker evidence regarding the use of adenxanet alfa. Prothrombin concentrate complexes seem to be efficacious for the Factor Xa inhibitors – but what about factor eight inhibitor bypassing agent?

This small case series from Pittsburgh addresses this question in the least helpful fashion: 11 patients and no comparison group. These 11 patients, most of whom were on rivaroxaban, received 20mg/kg of FEIBA for emergency reversal of anticoagulation in the setting of traumatic intracranial hemorrhage. The authors report 6 of these 11 had stable ICH on repeat CT following initial diagnosis, and, therefore, FEIBA is a potentially safe reversal option.

Of course, the full accounting requires us to mention the remainder of patients had radiographic progression of their injuries despite FEIBA. Most injuries were minor and not expected to have elevated 30-day mortality – and, unsurprisingly then, most survived. In the patients demonstrating substantial derangement of laboratory measures of coagulation, most showed profound improvement of the PT following FEIBA administration. Two patients also suffered subsequent thromboembolic events.

So, yes, FEIBA may be a treatment option for the Factor Xa inhibitors – but this hardly supports routine use outside a study setting as these authors seem to be doing.

“Factor Eight Inhibitor Bypassing Agent (FEIBA) for Reversal of Target-Specific Oral Anticoagulants in Life-Threatening Intracranial Bleeding”

https://www.ncbi.nlm.nih.gov/pubmed/28007364

Insight Is Insufficient

In this depressing trial, we witness a disheartening truth – physicians won’t necessarily do better, even if they know they’re not doing well.

This study tested a mixed educational and peer comparison intervention on primary care physicians in Switzerland, with an end goal of improving antibiotic stewardship for common ambulatory complaints. The “worst-performing” 2,900 physicians with respect to antibiotic prescribing rates were enrolled and randomized to the study intervention or none. The study intervention consisted of materials regarding appropriate prescribing, along with personalized feedback regarding where their prescribing rate ranked compared to the entire national cohort. The core of their hypothesis involved whether just this passive knowledge regarding their peer performance would exert normalizing influence over their practice.

Unfortunately, despite providing these physicians with this insight, as well as tools for improvement, the net effect of their intervention was effectively zero. There were some observations regarding changes in prescribing rates for certain age groups, and for certain types of antibiotics, but dredging through these secondary outcomes leads to only unreliable conclusions.

This is not particularly surprising data. These sorts of passive feedback mechanisms unhitched from material consequences have never previously been shown to be effective. There are other, more effective mechanisms – focused education, decision-support interventions, and shared decision-making – but, for a fragmented, national health system, this represented a relatively inexpensive model to test.

Try again!

“Personalized Prescription Feedback Using Routinely Collected Data to Reduce Antibiotic Use in Primary Care”

https://www.ncbi.nlm.nih.gov/pubmed/28027333

No Mandate for Hyperbaric Therapy in CO Poisoning

The new year – actually, the end of the old year – brings us a new update on the management of carbon monoxide poisoning, as distilled into an ACEP Clinical Policy statement. There are three elements to their update, addressing specific management questions in the context of carbon monoxide toxicity:

  • Don’t rely exclusively on non-invasive means for CO measurement.
  • Hyperbaric oxygen therapy is neither proven nor disproven of benefit.
  • Cardiac testing provides useful prognostic information.

The most impactful recommendation of the three is the one for HBO therapy, which is either dismissed out-of-hand or pursued with such zealotry that eligible patients are airlifted to far-flung dive chambers for treatment. In theory, HBO therapy helps reduce the delayed neuropathology and cognitive burden related to lipid peroxidation and other toxic metabolites. However, these authors appropriately synthesize the low-quality evidence into a conclusion that HBO therapy has no proven advantage to high-flow oxygen.

As with any therapy for which the evidence is poor, there are proponents on both sides and substantial practice variation. This Clinical Policy does not state HBO is inappropriate or not beneficial for carbon monoxide poisoning, merely the evidence is inconclusive. Sometimes, when the evidence is insufficient to provide an answer, the magnitude of benefit is small or clinically unimportant. In this case, I’m not even sure such a conclusion regarding the scope of benefit can be made – the foundational evidence is simply too unreliable to make any practice-influencing recommendations.

“Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Acute Carbon Monoxide Poisoning”
https://www.ncbi.nlm.nih.gov/pubmed/27993310