July 2015 – Page 2 – Emergency Medicine Literature of Note

High-Dose Oral Steroids for Multiple Sclerosis Flare

I am always a fan of evidence supporting treatments that are safe, efficacious, and massively less expensive than conventional care. Even if multiple sclerosis flares are infrequently seen in the Emergency Department setting compared with, say, sepsis or chest pain, their care is part of the spectrum of our purview.

We’ve known all along oral steroids are just as useful as intravenous steroids for asthma. However, multiple sclerosis flares are typically treated with 1000mg of intravenous methylprednisolone. When’s the last time you gave that dose – or equivalent with another steroid – orally?

So, this is the COPOUSEP trial, and it is a non-inferiority investigation comparing three days of high-dose oral administration of methylprednisolone with intravenous. Enrolling 199, and reporting outcomes on 90 and 93 patients in the oral and IV groups, respectively, the authors find functional improvement in the most disabling aspect persisting at 28 days in 81% for oral and 80% of IV. Adverse effects tended to favor the intravenous cohort, with agitation and insomnia troubling the oral cohort in greater fashion than IV. Despite these adverse effects, given the costs and inconvenience of inpatient or infusion center treatment, it is certainly reasonable to encourage patients to pursue the oral option.

Oddly, the authors omit their intention-to-treat results from the paper, and provide only the per-protocol. The ITT results, supposedly, are available in a supplementary appendix – not yet available, apparently – and are similar to the per-protocol outcomes. Thus, I see no particular reason to omit the ITT, as such better reflects the efficacy and safety profile of pragmatic use; the authors should either present both together, or defer the per-protocol analysis to the appendix.

Nearly all individuals involved in the study declared conflicts of interest with multiple pharmaceutical companies, although I do not see how any would have untoward effect on the work in question.

“Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): a randomised, controlled, double-blind, non-inferiority trial”
http://www.ncbi.nlm.nih.gov/pubmed/26135706

Get on the Haloperidol Wagon

For many years, droperidol has been a valuable tool for nausea, vomiting, headache, and termination of psychosomatic contributors to patient distress. Alas, droperidol availability has been markedly diminished in the U.S. in recent years, depriving us of one of our most efficacious management tools.

But, we still have plenty of haloperidol. So, let’s use it for the same purposes.

What’s the difference between droperidol and haloperidol? From a pharmacologic standpoint, the metabolism of haloperidol to active and toxic metabolites is far more complex than droperidol. But, from a clinical standpoint, there is very little difference – they are both butyrophenones with similar receptor antagonism.

This paper is not terribly robust, but compares the use of haloperidol against metoclopramide for acute headache in the Emergency Department. After pre-treatment with 25mg of IV diphenhydramine, either 10mg of IV metoclopromide or 5mg IV haloperidol was administered in double-blinded fashion. Owing to the small sample size of 64 patients, all measures of pain reduction, nausea, restlessness, and sedation were statistically equivalent between groups, although 8 of 33 of the metoclopromide cohort required rescue medications, compared with just 1 of 31 in the haloperidol cohort. However, telephone follow-up of patients following discharge also found the sedation and restlessness symptoms were more persistent in the haloperidol group compared with metoclopramide.

But, regardless, most of these differences – or lack thereof – is all small sample-size theatre. However, in addition to anachronistic anesthesia research into post-operative nausea and vomiting, this reasonably reinforces what we already know: if you’ve been suffering the loss of droperidol, you ought now be using haloperidol.

“A Randomized Controlled Trial of Intravenous Haloperidol vs. Intravenous Metoclopramide for Acute Migraine Therapy in the Emergency Department.”
http://www.ncbi.nlm.nih.gov/pubmed/26048068

What Does EAST Say About ED Thoracotomy?

The resuscitative emergency thoracotomy in trauma – rarely used and rarely successful. However, for appropriately selected patients in extremis, such timely intervention may be literally life-saving.

The downside: resource utilization associated with saving the neurologically unsalvageable and the risks to providers associated with the procedure.

This is an evidence synthesis performed by a group of authors affiliated with the Eastern Association for the Surgery of Trauma, addressing the topic of patient selection for Emergency Department thoracotomy. Screening 2,152 studies to review, ultimately, 72, these authors review a total of 10,238 patient encounters in which patients underwent ED thoracotomy. This results in six recommendations for patients presenting pulseless to the Emergency Department after trauma:

In patients with signs of life after penetrating thoracic injury: strongly recommend EDT.
In patients without signs of life after penetrating thoracic injury: conditionally recommend EDT.
In patients with signs of life after penetrating extra-thoracic injury: conditionally recommend EDT.
In patients without signs of life after penetrating extra-thoracic injury: conditionally recommend EDT.
In patients with signs of life after blunt injury: conditionally recommend EDT.
In patients without signs of life after blunt injury: conditionally recommend against EDT.

However, before you start rummaging around in your toolbox for the rib spreaders, it should be recognized the conditional recommendations – except in penetrating thoracic injury – result in absolute intact survival increases only in the range of 20-40 patients per 1000. Therefore, unless you’re working in a setting of maximal effectiveness and experience, it is unlikely you’ll see even this small absolute benefit. And, even in the setting with the strong recommendations and excess intact survival benefits of 100 patients per 1000 – your individual hospital system, based on institutional support and experience level of the providers involved, will need to develop specific policies for these situations. Even though many ED physicians are capable of performing these heroic procedures based on their training, the remaining ED staff and systems in place may not be adequate to support the intervention.

“An evidence-based approach to patient selection for emergency department thoracotomy: A practice management guideline from the Eastern Association for the Surgery of Trauma”
http://www.ncbi.nlm.nih.gov/pubmed/26091330

New AHA/ASA Endovascular Guidelines

How did I find out about the final publication of the new AHA/ASA Guidelines regarding endovascular intervention in acute ischemic stroke? I received unsolicited e-mail spam from their representative at a public relations firm, gushing about the technology and offering to put me in touch with their generously available expert.

Before getting into the content, the standard housekeeping exercise regarding declared financial conflicts of interest:

Dr. Powers: None
Dr. Derdeyn: Microvention, Penumbra, SILK Road, Pulse Therapeutics
Dr. Biller: None
Dr. Coffey: None
Dr. Hoh: None
Dr. Jauch: Covidien, Genentech, Penumbra, Stryker
Dr. K. Johnston: Roche/Genentech
Dr. S. Johnston: None
Dr. Khalessi: Covidien, Microvention, Penumbra, Sequent, Codman, Stryker
Dr. Kidwell: None
Dr. Meschia: None
Dr. Ovbiagele: None
Dr. Yavagal: Covidien/Medtronic, Penumbra

Yes, Virginia, despite the worldwide availability of methodologists and clinicians to review evidence for guidelines, the AHA/ASA were unable to compose such content absent individuals with professional and financial relationships to the manufacturers of the products involved. Another sad failure regarding the Institute of Medicine’s Guidelines We Can Trust.

So, what’s wrong with these guidelines? I’ve written and published multiple times regarding endovascular intervention, and it’s a therapy I’m excited about. For once, the theory and the practice seem to demonstrably align. The new stent retrievers seem to substantially benefit patients with viable tissue behind a clot – whether because of collateral circulation, retrograde flow, or semi-permeable occlusion – and have the clot safely removed in a timely fashion.

But, that isn’t everyone. The most successful trials – ESCAPE, EXTEND-IA, and SWIFT-PRIME – were all designed to intervene on a narrow population with salvageable tissue. The less successful, but still positive, trials – REVASCAT and MR-CLEAN – generally intervened based only on broadly eligible angiographic occlusions. Such a strategy will definitely catch the few patients with salvageable tissue, but also involves significant resource utilization and procedural risk conferred upon those without the possibility of benefit.

However, that’s what these guidelines suggest – to treat all-comers presenting within six hours, discarding the use of tissue-based criteria for intervention. The benefit to the corporations involved is obvious, as routine angiography – let alone rapid perfusion calculation – is not widespread. Without the broadest possible criteria, many centers might not refer patients for intervention. Given the choice between maximizing yield of this intervention and generating profits for their financial and professional affiliates, the authors of this guideline have chosen the latter.

Not only that, these authors give this recommendation the strongest possible Class I and Level A qualifiers. The body of the text states this is a result of the findings of the five aforementioned trials published at the time this was drafted. Unfortunately, from just a simple methodologic standpoint, the authors have developed complete amnesia regarding the entire prior body of negative evidence regarding endovascular intervention – nor acknowledged the open-label nature of these trials stopped early, nor other threats to bias.

So, yet again – from the folks who gave us flawed tPA guidelines and “quality measures” – a guideline we can’t trust. The Society for Academic Emergency Medicine was solicited to endorse this guideline several months ago, and I was involved in the review process at that time. Unfortunately, none of the concerns expressed at that time appear to have been addressed – and as such, SAEM is not included among the professional societies endorsing this guideline.

Endovascular therapy is coming. And, unfortunately, it is certainly going to be coming to many more than for whom appropriate.

“2015 AHA/ASA Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment”
http://m.stroke.ahajournals.org/content/early/2015/06/26/STR.0000000000000074.full.pdf