Monday, July 21, 2014

The Return of Metoprolol – for Anterior STEMI

Beta-blockade early in the course of myocardial infarction was once fashionable – until COMMIT demonstrated an excess of early cardiogenic shock detracting from subsequent late, favorable effects.  This led to beta-blockade initiation being deferred until after hemodynamic stability established.

This study, METOCARD-CNIC, is a trial of early intravenous metoprolol prior to primary PCI in patients with anterior STEMI.  270 patients were randomized over two years to receive IV metoprolol pre-reperfusion versus standard initiation following PCI.  These two publications describe a surrogate outcome based on infarct size seen in follow-up MRI, and patient-oriented outcomes of 2-year MACE and heart failure progression.  And, overall, it’s a good thing – infarct size at 1 week was reduced from 32.0 to 25.6 grams, and long-term MACE at median 2-year follow up was reduced from 18.3% to 10.8%.

However, long-term MRI follow-up at twelve months showed infarcted myocardium measured at 15.7 grams in the intervention group versus 18.2 grams in the control – no longer statistically significant.  And, the patient-oriented outcome of MACE is a combined endpoint of death, heart failure admission, reinfarction, and malignant arrhythmias – with most of the separation in groups coming from heart failure admissions and malignant arrhythmias, as opposed to hard endpoints.

But, at the minimum, this is worth continuing to investigate.  There are likely patients, such as this anterior STEMI cohort, with Killip Class II or lower at presentation, that reasonably have a greater chance of benefit than harm from early metoprolol.  This is also quite small study – but taken in the context of the prior evidence, an argument could be made to cautiously re-introduce this treatment strategy, ideally as part of prospective investigation.

“Effect of Early Metoprolol on Infarct Size in ST-Segment−Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention”
http://www.ncbi.nlm.nih.gov/pubmed/24002794

“Long-Term Benefit of Early Pre-Reperfusion Metoprolol Administration in Patients With Acute Myocardial Infarction”
http://www.ncbi.nlm.nih.gov/pubmed/24694530

Friday, July 18, 2014

Should We Keep Patients in the Dark on Costs?

That seems to be the overwhelming opinion of folks interviewed for this recent News & Perspective from Annals of Emergency Medicine.

Citing everything from ignorance, to the Emergency Medical Treatment and Labor Act, several clinicians in this vignette make the case discussions of cost have no role in Emergency Department care.  Victor Friedman, of the ACEP board of directors says costs are “irrelevant to me as a provider …. The billing and all that stuff comes later.”  Ellis Weeker from CEP America is concerned any discussion of costs might influence decisions regarding whether patients are seen, and potentially represent an EMTALA violation.

On the other hand, Neal Shah of Costs of Care points out there are real patient harms secondary to the financial burdens of healthcare, in no small part because of the astounding charges meted out from the Emergency Department.  While patients rarely see (or pay) the fantasy prices on the chargemaster, the burdens of even a fraction of these costs may mean choosing between food and insulin, or heat and clopidogrel.

If you’ve seen my writing to this effect, I fall squarely on the side of “costs should be communicated”, within reason.  I agree with Dr. Shah, that many Emergency Department interactions are “urgent” rather than “emergent”, and there is time to include costs as an adverse effect of a test or therapy.  I look forward to the communication instrument his team is developing.

“Price Transparency in the Emergency Department”
http://www.sciencedirect.com/science/article/pii/S0196064414004211

Thursday, July 17, 2014

ED Hocus POCUS ... or Just a Hoax?

A guest post by Rory Spiegel (@EMNerd_) who blogs on nihilism and the art of doing nothing at emnerd.com.

A landmark paper recently published in Lancet Respiratory Medicine is certainly destined to send the ED Ultrasound world into a tizzy. This is the first RCT examining the utility of Emergency Department based Point of Care ultrasound (POCUS) for patients presenting with undifferentiated respiratory complaints. Authors randomized patients presenting to the ED with signs or symptoms concerning for a respiratory etiology to either a standard work up as determined by the treating physician or the addition of POCUS performed by a single experienced operator. The US protocol consisted of sonographic examination of the heart, lungs and lower extremity deep veins to identify possible causes of patients' symptoms. The authors' primary outcome was the percentage of patients with a correct presumptive diagnosis 4 hours after presentation to the Emergency Department as determined by two physicians blinded to ED POCUS findings, but with access to the records of the entire hospital stay.

Using this POCUS protocol the authors found stunning success in their primary endpoint. Specifically, the rate of correct diagnoses made at 4-hours in the POCUS group was 88% compared to 63.7% in the standard work up group. Furthermore 78% of the patients in the POCUS group received "appropriate" treatment in the Emergency Department compared to 56.7% in the standard work up group.

Though promising, these benefits did not translate into improvements in true patient oriented benefits. Though not statistically significant, the observed in-hospital and 30-day mortality trended towards harm in the POCUS arm ( 8.2% vs 5.1% and 12% vs 7% respectively). Nor was there any meaningful difference in length of stay or hospital-free days between those in the POCUS group and those in the control group. Even more concerning, was the significant increase in downstream testing that occurred in patients randomized to the POCUS group. Specifically the amount of chest CTs (8.2% vs 1.9%), echocardiograms (10.1% vs 3.8%) and diagnostic thoracocenthesis (5.7% vs 0%). This, of course, may be statistical whimsy, but these findings are concerning for a certain degree of overdiagnosis. Unless detected pathology results in improved patient outcomes secondary to treatment, are we truly helping, or just piling on potential costs of increased vigilance?

I’m sure we all have experienced firsthand the utility of bedside US and this is by no means a call to abandon our probes, but rather an acknowledgement of the possibility of subtle harms. We must keep in mind, all testing comes at a price no matter how non-invasive and radiation-free it appears. The cost in this case is information and how we choose to act on it. This would certainly not be the first time increased access to medical technology has lead to such unintended consequences.

"Point-of-Care Ultrasonography in Patients Admitted With Respiratory Symptoms: a Single-Blind, Randomised Controlled Trial"
http://www.ncbi.nlm.nih.gov/pubmed/24998674

Wednesday, July 16, 2014

You Can Use Absorbable Sutures Anywhere

Although, can and should are entirely different interpretations of these data.

There have been many studies showing facial lacerations can be repaired with absorbable sutures with similar cosmetic and adverse outcomes compared with non-absorable sutures.  The same principles, presumably, hold for the trunk and extremities – although, there are significant differences in blood supply and healing time.

This study aimed to demonstrate the non-inferiority of absorbable sutures – specifically, Vicryl Rapide – compared with non-absorbable monofilament.  All lacerations were simple, superficial, and repaired using identical interrupted technique.  At plastic surgery 3-month follow-up, although the absorbable sutures were judged to have generated increased “train tracking” of wounds, cosmesis on the visual analog scale was identical.

However, of the 113 patients they enrolled, they lost 40 to follow-up at 3 months – 20 in each group.  There was no wound dehiscence in either group, but 4/35 developed wound infectious in the Vicryl cohort versus 1/38 in the Prolene cohort.  Given the small sample sizes, this did not reach statistical significance, but increased infection cannot be ruled out.

So – yes, you can use absorbable sutures anywhere.  However, given the attrition in this study and the confidence intervals around infection rates, this study does not represent strong evidence in support.

“A Comparison of Cosmetic Outcomes of Lacerations on the Extremities and Trunk Using Absorbable Versus Nonabsorbable Sutures”
http://onlinelibrary.wiley.com/doi/10.1111/acem.12387/abstract

Monday, July 14, 2014

The Broken ED Sepsis Quality Measure

Are there yet sufficient mandates in the Emergency Department?  Door-to-physician times, door-to-CT time in acute ischemic stroke, door-to-analgesia for long bone fractures – and, on the horizon, National Quality Forum proposed measures for delivery of sepsis bundle components within 3 and 6 hours.

The problem? As these authors discover, even for patients ultimately receiving a diagnosis of severe sepsis and septic shock, many do not meet those criteria within 3 hours, or in the Emergency Department.  These authors perform a retrospective review of 113 patients from a public Level 1 trauma center and 372 from a university teaching hospital who received who received at least a provisional diagnosis of severe sepsis or septic shock.  According to their review, 9.8% of patients at the trauma center and 15.3% of patients did not meet criteria for severe sepsis or septic shock within 3 hours of arrival.

No one disputes early recognition and treatment of sepsis is a cornerstone of quality Emergency Department care.  However, retrospective application of sepsis definitions to the initial time period of presentation is clearly a Quixotic quest.  Chasing every last potential severe sepsis patient will only lead to further unintended consequences, inappropriate care, and resource over-utilization – particularly because most patients with SIRS in the Emergency Department are never diagnosed with an infection.

Just as with OP-15, we should continue to work against implementation of this measure.

“Many Emergency Department Patients With Severe Sepsis and Septic Shock Do Not Meet Diagnostic Criteria Within 3 Hours of Arrival”
http://www.ncbi.nlm.nih.gov/pubmed/24680548

Friday, July 11, 2014

End-Tidal CO2 Monitoring Unhelpful in Sedation

Capnography during procedural sedation has rapidly become standard practice in the interests of “safety” – despite decades of Emergency Medicine experience safely performing sedation without.  The theory: earlier detection of inadequate ventilation allows for intervention and prevention of hypoxemic episodes.  In the most prominent randomized trial, there was a 17% absolute reduction in transient hypoxemic events.  Critics appropriately point out, however, that transient events are hardly a meaningful patient-oriented outcome.

This trial, in which sedation was performed by nurses in an outpatient gynecology setting in the Netherlands, describes 427 patients randomized either to capnography or “routine monitoring”.  Supplemental oxygen was not used in this setting, as these practioners considered it to obscure the additive value of pulse oximetry.  Essentially by definition, all patients were female, and the median age was 24 with few co-morbidities.

Overall, 25.7% of patients in the capnography group developed hypoxemic episodes versus 24.9% of patients in the control group.  There were also no differences in numbers of patients with profound hypoxemia (<81%) or prolonged hypoxemia (>60 seconds), although patients with hypoxemia in the capnography group had more frequent prolonged episodes than the control group (14.0% vs. 3.7%).  Likely as a result, patients in the capnography group underwent airway positioning maneuvers more frequently (49.5% vs. 32.1%).

It’s a stretch to say this is information is generalizable to Emergency Department sedation.  It is, at least, a useful window into what many skeptics have been saying all along – the additive value of capnography in sedation is low, and, rather, the extra information leads to additional interventions and procedural interruptions without measurable benefit.  Procedural success in this setting was not adversely impacted by the frequent interruptions, however.

“Capnography During Deep Sedation with Propofol by Nonanesthesiologists: A Randomized Controlled Trial”
http://www.ncbi.nlm.nih.gov/pubmed/24836471

Wednesday, July 9, 2014

Build a New EDIS, Advertise it in Annals for Free

As everyone who has switched from paper to electronic charting and ordering has witnessed, despite some improvements, many processes became greatly more inefficient.  And – it doesn’t matter which Emergency Department information system you use.  Each vendor has its own special liabilities.  Standalone vendors have interoperability issues.  Integrated systems appear to have been designed as an afterthought to the inpatient system.  We have, begrudgingly, learned to tolerate our new electronic masters.

This study, in Annals of Emergency Medicine, describes the efforts of three authors to design an alternative to one of the vendor systems:  Cerner’s FirstNet product.  I have used this product.  I feel their pain.  And, I am in no way surprised these authors are able to design alternative, custom workflows that are faster (as measured in seconds) and more efficient (as measured in clicks) for their prototype system.  It is, essentially, a straw man comparator – as any thoughtful, user-centric, iterative design process could improve upon the current state of most EDIS.

With the outcome never in doubt, the results demonstrated are fundamentally unremarkable and of little scientific value.  And, it finally all makes sense as the recurrent same sad refrain rears its ugly head in the conflict-of-interest declaration:
Dr. Patrick and Mr. Besiso are employees of iCIMS, which is marketing the methodology described in this article.
Cheers to Annals for enabling these authors to use the pages of this journal as a vehicle to sell their consulting service.

"Efficiency Achievements From a User-Developed Real-Time Modifiable Clinical Information System"
http://www.ncbi.nlm.nih.gov/pubmed/24997563


Tuesday, July 8, 2014

Dueling PE Meta-Analyses

A guest post by Rory Spiegel (@EMNerd_) who blogs on nihilism and the art of doing nothing at emnerd.com.

Nothing sparks controversy quite like a discussion on the utility of thrombolytics. No sooner had the wave of debate brought on by the publication of the PEITHO trial and its finding of no overall mortality benefit died down, did JAMA stoke these flames with the publication of a meta-analysis including the entirety of the literature on thrombolytic use for pulmonary embolism. Examining 16 trials, the authors found a statistically significant absolute mortality benefit of 1.12% or an NNT of 59 patients. This benefit was offset by the increase in major bleeding events observed in those given thrombolytics (9.24% vs 3.42%) with a 1.27% absolute increase in ICH.



The cascade of incendiary events continued when one week later a second meta-analysis examining the very same question was published in Journal of Thrombosis and Haemostasis. Only these authors claimed to find the exact opposite of their JAMA counterparts. In this case the authors found no statistical improvement in mortality in the patients given thrombolytics when compared to those given a placebo. Despite these contradictory claims, a more comprehensive inspection reveals these meta-analyses are extensively saying the same thing. A comparison of the two serves as a timely reminder that conclusions reached from any meta-analysis is primarily dependent on the trials selected for inclusion.  The JAMA meta-analysis included 2115 patients in 16 trials, while the Journal of Thrombosis and Haemostasis examined only 1510 patients in 6 trials. Interestingly, the absolute risk reduction in mortality was 1.12% in the JAMA publication vs 1.4% in the Journal of Thrombosis and Haemostasis publication. Though the JAMA analysis had an overall smaller absolute risk reduction, the result reached statistical significance due to the larger sample size.



More importantly the results of these publications should not come as a surprise. Before the publication of PEITHO the data on thrombolytics for PE was sparse. Most of the trials suffered from small sample sizes and questionable methodology. It is the amalgamation of these small trials that accounts for the mortality benefit in both meta-analyses. In the JAMA publication the mortality difference consisted of 17 fewer deaths in the thrombolytic arm compared to the placebo. All of which originated from these small underpowered studies. Conversely, the two large high quality trials (PEITHO and MSPPE) consisting of 1005 and 256 patients respectively made up the majority of patients meta-analyzed, neither of which found a mortality benefit with the use of thrombolytics. Moreover the 2% absolute increase in ICH seen in the PEITHO cohort is only diluted by the inclusion of these small trials, whose sample sizes were not powered to detect such rare events. A more elegant design would be to utilize a weighted average or one of the various statistical methods that takes into account each study's sample size and event rate, allocating a greater weight to the hardier cohorts. Though one might argue an equally elegant solution would be to not include such flawed trials in the first place.

The publication of these dueling meta-analyses highlights the flaws of such statistical endeavors. Small trials with flawed methodological designs are prone to fall victim to publication bias and the fluctuating whims of chance. Collecting this data and attaching a statistical judgment to it does not correct these imperfections, it augments them. The overall benefit of thrombolytics in PE is yet undetermined, but the answer will not be elucidated in such analysis. We require further large randomized controlled trials like the PEITHO trial. Adding small flawed cohorts to this robust dataset does nothing but muddy the already murky waters.

"Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis."
http://www.ncbi.nlm.nih.gov/pubmed/24938564

"Impact of the efficacy of thrombolytic therapy on the mortality of patients with acute submassive pulmonary embolism: a meta-analysis."
http://www.ncbi.nlm.nih.gov/pubmed/24829097

Monday, July 7, 2014

Lives Saved … or Profiteering by Overdiagnosis?

Following an initial acute ischemic stroke, a search for the cause must be undertaken – for small vessel vasculitis, atherosclerotic emboli, thrombi from the systemic circulation, and so forth, beyond the domain of the Emergency Physician.  However, what the Emergency Physician does encounter is the sequelae of this search, in the form of oral anticoagulants.

These two articles from the New England Journal of Medicine, on their own, seem to reflect advances in diagnostic yield following acute ischemic stroke or transient ischemic attack.  The authors point out approximately 25% of patients suffering AIS and half of those suffering TIA never receive an ultimate identified etiology for stroke – and are classified as “cryptogenic”.  The authors in each of these studies suppose this may be due to the paroxysmal nature of atrial fibrillation, and that short-term electrocardiographic monitoring is missing this diagnosis.  In each study, some type of long-term monitoring technology is utilized, and, ultimately, the rate of diagnosis for paroxysmal atrial fibrillation jumps from 1-3% in each cohort to 8-12% in each cohort.

The catch – scads of authors for each report conflict-of-interest with both manufacturers of novel oral anticoagulants, or device manufacturers likely related to continuous ambulatory monitoring.  There is clear benefit to each of these parties, considering potential expanded indication for both monitoring and for anticoagulation.  These articles will likely be used to support both activities, despite not measuring any patient-oriented benefit.  How much of a primary or recurrent stroke risk is attributable to these very-infrequent paroxysms of atrial fibrillation?  Do they benefit equally from anticoagulation?

Given the conflict-of-interest enshrined in these articles, I am certain the advertised presumption will be they do.  They may, of course, be right – or, this may turn into yet another example of overdiagnosis and high-cost, low-yield medicine.

“Atrial Fibrillation in Patients with Cryptogenic Stroke”
http://www.nejm.org/doi/full/10.1056/NEJMoa1311376

“Cryptogenic Stroke and Underlying Atrial Fibrillation”
http://www.nejm.org/doi/full/10.1056/NEJMoa1313600

Friday, July 4, 2014

Independence Day History Lesson

July 4th, for our worldwide readers, is Independence Day in the United States.  This means the trauma centers fill up with all manner of traumatic and alcohol-related injuries.  Just as the Founding Fathers intended.

However, for your reading enjoyment today, I give you the medical biography of John Jones, the first Professor and Chair of Surgery in the American Colonies – as part of the group establishing the Columbia University College of Physician and Surgeons in 1767.

“John Jones, M.D.: pioneer, patriot, and founder of American surgery.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860285/ (free full text in PubMed Central)