Blood Cultures Save Lives and Other Pearls of Wisdom

It’s been sixteen years since the introduction of Early Goal-Directed Therapy in the Emergency Department. For the past decade and a half, our lives have been turned upside-down by quality measures tied to the elements of this bundle. Remember when every patient with sepsis was mandated to receive a central line? How great were the costs – in real, in time, and in actual harms from these well-intentioned yet erroneous directives based off a single trial?

Regardless, thanks to the various follow-ups testing strict protocolization against the spectrum of timely recognition and aggressive intervention, we’ve come a long way. However, there are still mandates incorporating the vestiges of such elements of care –such as those introduced by the New York State Department of Health. Patients diagnosed with severe sepsis or septic shock are required to complete protocols consisting of 3-hour and 6-hour bundles including blood cultures, antibiotics, and intravenous fluids, among others.

This article, from the New England Journal, looks retrospectively at the mortality rates associated with completion of these various elements. Stratified by time-to-completion following initiation of the 3-hour bundle within 6 hours of arrival to the Emergency Department, these authors looked at the mortality associations of the bundle elements.

Winners: obtaining blood cultures, administering antibiotics, and measuring serum lactate
Losers: time to completion of a bolus of intravenous fluids

Of course, since blood cultures are obtained prior to antibiotic administration, these outcomes are co-linear – and they don’t actually save lives, as facetiously suggested in the post heading. But, antibiotic administration was associated with a fraction of a percent of increased mortality per hour delay over the first 12 hours after initiation of the bundle. Intravenous fluid administration, however, showed no apparent association with mortality.

These data are fraught with issues, of course, relating to their retrospective nature and the limitations of the underlying data collection. Their adjusted model accounts for a handful of features, but there are still potential confounders influencing mortality of those who received their bundle completion within 3 hours as compared to those who did not. The authors are appropriately reserved with their conclusions, however, only stating these observational data support associations between mortality and antibiotic administration, and do not extend to any causal inferences.

The lack of an association between intravenous fluids and mortality, however, raises significant questions requiring further prospective investigation. Could it be, after these years wandering in the wilderness with such aggressive protocols, the only universally key feature is the initiation of appropriate antibiotics? Do our intravenous fluids, given without regard to individual patient factors, simply harm as many as they help, resulting in no net benefit?

These questions will need to be addressed in randomized controlled trials before the next level of evolution in our approach to sepsis, but the equipoise for such trials may now exist – to complete our journey from Early Goal-Directed to Source Control and Patient-Centered.

“Time to Treatment and Mortality during Mandated Emergency Care for Sepsis”

http://www.nejm.org/doi/full/10.1056/NEJMoa1703058

More Coverage of Inappropriate Antibiotic Prescribing

If this feels like déjà vu, it might be because it is.

This short research letter in JAMA Internal Medicine describes patterns of antibiotic prescribing for three common conditions: otitis media, sinusitis, and pharyngitis. In all of these cases – in the infrequent occasion antibiotics are necessary – the appropriate first-line antibiotic is amoxicillin/penicillin. These authors estimate, based on treatment failures, allergies, and complicated disease, approximately 80% of antibiotic prescriptions for these conditions should be the first-line agents.

How did we do? Well, better in pediatrics than adults, but first-line prescribing ranged from a low of 37% to a high of 67%. The most commonly used inappropriate antibiotics were macrolides (invariably azithromycin) and fluoroquinolones. Macrolides are usually inappropriate due to high levels of resistance among common pathogens, and fluroquinolones are simply too broad-spectrum to be appropriate.

The catch, unfortunately, is the data source: the National Ambulatory Medical Care Survey, warts and all, from 2010 to 2011. The authors state they expect practice patterns have not changed much in the last five years, but it’s still a little challenging to generalize this to current practice.

Finally, as a nice corollary, this Medical Letter article was featured in JAMA regarding fluoroquinolones and their increasingly detected serious adverse effects. When antibiotics are truly necessary, physicians should try and choose one of the many alternatives presented in the article.

“Frequency of First-line Antibiotic Selection Among US Ambulatory Care Visits for Otitis Media, Sinusitis, and Pharyngitis”
http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2571613

Choosing Wisely – Invisible, Impractical

There are two parts to Choosing Wisely – the “Five Things” and then the bit where “Physicians and Patients Should Question” them.  Most specialities – for better or worse – have generated lists of five things.  Some go beautifully against the grain, like Pediatric Hospital Medicine.  Others are criticized for mostly what is lacking.

Regardless, these suggestions work only when physicians are aware of them, and their suggestions are practical.  This survey of outpatient physicians in a group in the state of Massachusetts, unfortunately, is rather bleak.  At best, 47.2% of primary care physicians were aware of Choosing Wisely, compared with a mere 27% of surgical specialists.  In a similar pattern, less than half and then less than a quarter of PCPs and surgeons felt Choosing Wisely was “Yes, absolutely” a legitimate source of guidance.  Finally, just over half of all physicians surveyed felt the Choosing Wisely campaign had empowered them to reduce testing and procedures.

This is, of course, better than zero – which was effectively the base case.  That said, these authors identified many barriers to their use.  Physicians preferred to serve their patients desires and interests over the guidelines and recommendations made based on medical evidence.  Further, most all physicians expressed a fear of malpractice and legal difficulties.

Awareness, certainly, would be a start.  Then, making these recommendations usable in practice – moreso than then currently are – might be the next step in helping physicians bring them into the conversation.

“Physician Perceptions of Choosing Wisely and Drivers of Overuse”
http://www.ajmc.com/journals/issue/2016/2016-vol22-n5/physician-perceptions-of-choosing-wisely-and-drivers-of-overuse

Let’s Get Inappropriate With AHA Guidelines

How do you hide bad science?  With meta-analyses, systematic reviews, and, the granddaddy of the them all, guidelines.  Guidelines have become so twisted over the recent history of medicine the Institute of Medicine had to release a statement on how to properly create them, and a handful of folks have even gone so far as to imply guidelines have become so untrustworthy a checklist is required for evaluation in order to protect patients.

Regardless, despite this new modern era, we have yet another guideline – this time from the American Heart Association – that deviates from our dignified ideals.  This guideline is meant to rate appropriate use of advanced imaging in all patients presenting to the Emergency Department with chest pain.  This includes, for their purposes, imaging to evaluate nSTEMI/ACS, suspected PE, suspected syndromes of the aorta, and “patients for whom a leading diagnosis is problematic or not possible”.

My irritation, as you might expect, comes at the expense of ACS and “leading diagnosis is problematic or not possible”.  The guidelines weighing the pros and cons of the various options for imaging PE and the aorta are inoffensive.  However, their evaluation of chest pain has one big winner: coronary CT angiograms.  The only time this test is not appropriate in a patient with potential ACS is when the patient has a STEMI.  They provide a wide range of broad clinical scenarios to assist the dutiful reader – all of which are CCTA territory – including as every low/intermediate risk nonischemic EKG and troponin-negative syndrome, explicitly even TIMI 0 patients.

Their justification of such includes citation of the big three – ACRIN-PA, ROMICAT II, and CT-STAT – showing the excellent negative predictive value of the test.  Indeed, the issues with the test – middling specificity inflicted upon low disease prevalence, increased downstream invasive angiography and revascularization of questionable value – are basically muttered under the breath of the authors.  Such dismissive treatment of the downsides of the test are of no surprise, considering Harold Litt, of ACRIN-PA and Siemens, is part of the writing panel for the guideline.  I will, again, point you to Rita Redberg’s excellent editorial in the New England Journal of Medicine, refuting the foundation of such wanton use of CCTA in the emergency evaluation of low-risk chest pain.

The “leading diagnosis is problematic or not possible” category is just baffling.  Are we really trying to enable clinicians to be so helpless as to say, “I don’t know!  Why think when I can scan?”  The so-called “triple rule-out” is endorsed in this document for this exact scenario – so you can use a test whose characteristics for detection of each entity under consideration are just as degraded as your clinical acumen.

Fantastically, both the Society of Academic Emergency Medicine and the American College of Emergency Physicians are somehow co-signatories to this document.  How can we possibly endorse such fragrant literature?

“2015 ACR/ACC/AHA/AATS/ACEP/ ASNC/NASCI/SAEM/SCCT/SCMR/ SCPC/SNMMI/STR/STS Appropriate Utilization of Cardiovascular Imaging in Emergency Department Patients With Chest Pain”
http://www.ncbi.nlm.nih.gov/pubmed/26809772

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

The New, Improved, ACEP Clinical Policy for tPA in Stroke

Released with minimal fanfare, approved by the ACEP Board of Directors on June 24th, the revised ACEP Clinical Policy regarding the use of TPA for acute ischemic stroke has gone final.

It is, of course, a vast improvement over the 2012 version – but has, unfortunately, changed for the worse since the draft was posted.

The highlights:

  • The Level A suggestion to consider the risk of ICH with tPA administration has been eliminated.  It has been moved, nonsensically into the Level B recommendations for offering tPA – when, frankly, it’s the only consistent finding across all the evidence.
  • The Level B recommendation in which tPA “may be given” within 3 hours has been strengthened to “should be offered and may be given”.  Obviously, a profound difference.
  • The Level B recommendation for 3-4.5 hours remains unchanged, based on only one flawed piece of Class II evidence (ECASS III), and conflicting Class III evidence (ATLANTIS, IST-3, meta-analyses).
  • The Level C recommendation to engage in shared decision-making now states “when feasible”, which is obviously open to interpretation.
  • No further clarification of “carefully selected patients” or “systems … in place to safely administer the medication” is provided.

Some wins, some losses.  Obviously, the shared decision-making supporting any “offer” of tPA can be very different, depending on an individual clinicians’ interpretation of the evidence – and it is nice to see the prior COI-infested husk of rotten guidelines finally, officially, tossed on the compost heap.  Let us hope (irrationally, of course) the efforts underway in the United Kingdom spur further, independent, investigation with which to better understand and individualize the risks and benefits of treatment with tPA.

“Clinical Policy: Use of Intravenous Tissue Plasminogen Activator for the Management of Acute Ischemic Stroke in the Emergency Department”
http://www.acep.org/workarea/DownloadAsset.aspx?id=102373

Guideline Recommendations Are Written in Dry Erase Marker, Not Stone.

A guest post by Anand Swaminathan (@EMSwami) of EM Lyceum and Essentials of EM fame.

Medicine is filled with guidelines, professional recommendations and expert consensus statements. These documents guide clinical practice. In Emergency Medicine, we often rely on non-EM specialty guidelines. For instance, we often state that a patient in whom you consider ACS should get evocative testing (i.e. stress test) within 72 hours of presentation according to the American College of Cardiology/American Heart Association (ACC/AHA) guidelines. As more guidelines and subsequent revisions are released a number of questions arise. Should we adopt the guidelines immediately? If so, which pieces are ready for immediate incorporation into clinical care? At the heart of these questions is the strength and durability of the recommendations.
This article is unique in the question it asked: what is the durability of class I recommendations from the ACC/AHA? The looked at 11 guidelines published between 1998 and 2007 along with revisions to these guidelines from 2006 to 2013. What they found was surprising. Out of 619 original class 1 recommendations, about 80% were retained in subsequent revisions. About 9% were downgraded or reversed and about 11% were omitted.  Not surprisingly, recommendations with multiple randomized studies backing them up tended to stick around (90.5%) but those recommendations supported by opinion only did not (73.7%).
What can we take away from this? First, we shouldn’t adopt recommendations (even level 1) that don’t have good evidence backing them up. Secondly, guidelines should be updated frequently (these authors suggest every 3 to 5 years) to incorporate new evidence that may up or downgrade recommendations. Guideline adherence shouldn’t be used as a performance measure since the recommendations are anything but written in stone. Lastly, this is a further call for our specialty to take the reigns and start writing our own, high-quality guidelines from which we can base clinical practice.
“Durability of Class 1 American College of Cardiology/American Heart Association Clinical Practice Guideline Recommendations”