Monday, July 28, 2014

The Glucose-Insulin-Potassium in ACS (IMMEDIATE) Revisited

There are a few folks persistently enamored with the use of glucose-insulin-potassium cocktails in the setting of acute coronary syndrome.  Two years ago, I reported on the initial results of the IMMEDIATE trial, published in JAMA.  At the time, I boggled that such a small, underpowered study – and one that changed their enrollment target and primary endpoint during the trial – would ultimately be accepted into JAMA.  It was also subsequently picked up and promoted by ACEPNow as a "promising therapy" that "slashes death risk" (Tweet still visible, site content since deleted).

As I noted last time, the authors reported 30-day outcomes.  Now, they’re back, as promised, with 1-year outcomes – hoping to build on the “trends” previously observed.

Did it work?  Did a longer follow-up period help?  I’ll let the authors answer in their own words:
“The 1-year outcomes (Table 2) generally demonstrate point estimates favoring GIK for individual events and for composites, but CIs overlap 1.0 in most analyses.”
Which is to say, no.  Trends stayed trends, for the most part.  And, considering the neutral pre-study evidence from such studies as CREATE-ECLA, which enrolled 20,201 patients, even such hopeful interpretations of these data should not inspire a change in practice.

It is still reasonable, however, as these authors suggest, to continue studying this treatment.  There are small differences in important patient-oriented outcomes (10.9% vs. 13.0% in 1-year mortality) favoring the intervention.  These effects were even more pronounced in the subgroup of patients for whom ST-elevation was present on the pre-hospital ECG.  Considering there’s not much room left in acute medical management of STEMI offering a survival advantage – if there is, in fact, a 4.3% absolute 1-year survival attributable to GIK, it is worth continuing to investigate and tailor trials to the subgroup most likely to benefit.

“One-Year Outcomes of Out-of-Hospital Administration of Intravenous Glucose, Insulin, and Potassium (GIK) in Patients With Suspected Acute Coronary Syndromes”
http://www.ncbi.nlm.nih.gov/pubmed/24792735

Friday, July 25, 2014

The Scandal of Dabigatran – A Summary

We’ve been desperate for a more elegant solution to anticoagulation than rat poison for seemingly an eternity.  Now, we have them: direct thrombin and factor Xa inhibitors.  The studies supporting their use seem favorable.

But, as the old story goes – and as previously reported on this blog many times – Boehringer Ingelheim has been selectively reporting only the most favorable aspects of their flagship drug, dabigatran.  Increased cardiovascular events have been downplayed through study design not powered to detect a difference.  Issues with fixed dose therapy – and lack of a range of options for patients with renal impairment – rear their ugly head in multiple case reports.

Then, the most damning – the recent legal action reveals Boehringer Ingelheim, after selling dabigatran as not requiring monitoring nor having a reliable assay to monitor its effects, was hiding information on both counts.  There is, in fact, substantial individual-patient variability in dabigatran efficacy and bleeding risk, and the HEMOCLOT test is, in fact, a reliable method of measuring activity.  Review of internal documents shows employees were aware many patients might benefit from routine monitoring of levels – but this would eliminate one of its selling points (and cost savings) over warfarin.  These e-mails also specifically address the potential damaging effect on sales if said information were released in the scientific literature.

Clearly, yet another case where first-mover status into a lucrative market trumped patient-safety concerns.  If you wonder where the rampant skepticism regarding conflict-of-interest comes from on this blog – this is a beautifully flagrant example.

“Dabigatran: how the drug company withheld important analyses”
http://www.bmj.com/content/349/bmj.g4670 (free fulltext)

Previous EM Lit of Note Posts:
Rivaroxaban Can Be Reversed, But Not Dabigatran” - Sept 2011
Scattering Tacks In The Road” - Jan 2012
Dabigatran — Uncharted Waters and Potential Harms” (Annals of Internal Medicine) - May 2012
Dabigatran - It's Everywhere!” - Sept 2012
Not-So Routine Surgery on Dabigatran” - Sept 2012
Dabigatran: Hidden Danger in the Home” - Nov 2012
Dabigatran & CES1 SNP rs2244613” - Mar 2013

Wednesday, July 23, 2014

How Electronic Health Records Sabotage Care

Our new information overlords bring many benefits to patient care.  No, really, they do.  I’m sure you can come up with one or two aspects of patient  safety improved by modern health information technology.  However, it’s been difficult to demonstrate benefits associated with electronic health records in terms of patient-oriented outcomes because, as we are all well aware, many EHRs inadvertently detract from efficient processes of care.

However, while we intuitively recognize the failings of EHRs, there is still work to be done in cataloguing these errors.  To that end, this study is a review of 100 consecutive closed patient safety investigations in the Veterans Health Administration relating to information technology.  The authors reviewed each case narrative in detail, and divided the errors up into sociotechnical classification of EHR implementation and use.  Unsurprisingly, the most common failures of EHRs are related to failures to provide the correct information in the correct context.  Following that, again, unsurprisingly, were simple software malfunctions and misbehaviors.  Full accounting and examples are provided in Table 2:


Yes, EHRs – the solution to, and cause of, all our problems.

“An analysis of electronic health record-related patient safety concerns”
http://jamia.bmj.com/content/early/2014/05/20/amiajnl-2013-002578.full

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