Monday, April 20, 2015

It's Stroke Week Again!

Discovery Channel had Shark Week.  Around Emergency Literature of Note Headquarters, we do Stroke Week.

Why?  Because, from a methodologic standpoint, acute stroke care is the gift that keeps on giving.  This week, we will see randomized-controlled trials stopped for “loss of equipoise”, a few authors who are still working out how to conduct a systematic review, and more practice-changing conclusions drawn from retrospective registry data.

As we noted a couple weeks ago, there were three major endovascular trials presented in early February – ESCAPE, EXTEND-IA, and SWIFT-PRIME.  ESCAPE and EXTEND-IA were simultaneously published in the New England Journal of Medicine.  Now, SWIFT-PRIME has reached final publication.  These trials are hailed as a sort of second-coming of the messiah for the exiles wandering in the wilderness since PROACT-II.

And, now, interestingly, a fourth trial is presented – simultaneously published along with presentation at the European Stroke conference.  This is REVASCAT, yet another stent retriever trial funded by an unrestricted grant from Covidien, the manufacturers of the Solitaire device.  And, I can tell you Covidien saved themselves a lot of money in this trial – because it was planned to enroll 692 patients, and was terminated after 206.

Why was it terminated?  Not, as the other trials were, due to having met pre-specified efficacy criteria.  This trial was stopped because of “loss of equipoise”, following presentation of the other trials.  This is, effectively, the equivalent of stopping your moon landing program because the other side got there first, sitting around glumly shuffling papers.  But, more data is still important – and this data is important because it throws a little bit of cold water on the other trials.

SWIFT-PRIME, for example – mRS 0-2 in 60% of the endovascular intervention cohort, compared with 35% of the tPA-only cohort.  REVASCAT – mRS 0-2 in 44% of the endovascular cohort, compared with 28% of the tPA-only cohort.  25% treatment difference versus 16% treatment difference.  SWIFT-PRIME – 12% mortality in the endovascular cohort, compared with 26% mortality with usual care.  REVASCAT – 18% mortality in the endovascular cohort compared with 15%.

What’s different?  Where the previously presented trials used strict imaging criteria for small infarct cores and good collateral circulation, REVASCAT simply included all patients with low ASPECTS scores and proximal vascular occlusions.  This is, then, more akin to MR-CLEAN or ICARO-3, in which the benefit is attenuated substantially if the status of the underlying tissue is not fully appreciated.

The lesson from this should be clear – imaging criteria requiring salvageable tissue as result of collateral flow provide maximum yield in reducing the number of endovascular procedures performed with low or no chance of benefit.  Whether these lessons are heeded, I remain highly skeptical.

The other lesson: when you're hot, you're hot, and even lukewarm half-raw results can still get you into NEJM.

“Thrombectomy within 8 Hours after Symptom Onset in Ischemic Stroke”

“Stent-Retriever Thrombectomy after Intravenous t-PA vs. t-PA Alone in Stroke”

Friday, April 17, 2015

Blunt Trauma Thoracotomy: Probably Still Not Time for Heroics

A guest post by Matthew DeLaney, Assistant Program Director of the University of Alabama at Birmingham Emergency Medicine residency. 

For most providers, there is a limited but well delineated role for emergency department thoracotomy (EDT) in patients with penetrating trauma. The potential role for EDT in blunt trauma patients is much less clear. In a recent meta-analysis, Slessor et al. included 13 studies consisting of 1369 patients who underwent EDT after blunt trauma.

Overall most of the patients who underwent a thoracotomy did poorly, with only 21(1.5%) patients having a good neurologic outcome. The highest rate of survival was found in patients who had vital signs either in the field or in the emergency department. All patients who experienced good neurologic outcomes had vital signs in the emergency department. Patients who have vital signs in the field but he did not have vital signs in the emergency department had lower rates of survival and worse neurologic outcomes compared to the patients who had signs of life in the ED.

Time to EDT seemed to play a role in terms of improving patient outcomes. The authors note one instance where an EDT was performed after 136 minutes of CPR, not surprisingly this patient did not have a good outcome. When looking at patient’s who underwent CPR, all patients who experienced good outcomes received less than 15 minutes of CPR before undergoing an EDT. Patients with no signs of life at any point did poorly with a reported survival rate of 0.4% with a 100% rate of bad neurologic outcomes.

While authors of the study concluded that the chances of survival with a good outcome were approximate 1.5%, this may not be applicable to most emergency medicine trained providers. Most of the included studies involved procedures performed by surgeons at large trauma centers, in fact only 1 study included EDT performed by emergency medicine providers. Unfortunately this study included a small number of cases with no reported survivors. Even under ideal circumstances if we look at cases where we as emergency department providers could be expected to make a critical intervention, (cardiac tamponade / penetrating cardiac injury) the rate of survival with good outcomes is closer to 0.07% (4/1369).

When performed by surgeons in large trauma centers, the EDT may be a reasonable “hail-mary” for a blunt trauma patient who is actively dying. Despite being the largest study to date on this subject, this study provides essentially no evidence to support the use of EDT by emergency trained providers.  Given the invasive nature of the EDT, there is a very real risk of harm to the providers and staff from needle/scalpel injuries and exposure to broken ribs and blood. As with other seldom performed heroic procedures, there may be a clinical scenario where EDT by an emergency medicine provider is effective.When treating a patient in cardiac arrest from a blunt trauma, providers need to balance the potential risk of harm to provider and staff before performing an invasive procedure with a very low chance of success.

“To be blunt: are we wasting our time? Emergency department thoracotomy following blunt trauma: a systematic review and meta-analysis.”

Wednesday, April 15, 2015

The 1-Hour Rule-Out

All of a sudden, it’s become vogue to send home chest pain.  After a decade of horror stories regarding the diagnostic errors and medicolegal consequences of discharging chest pain, there is no shortage now of strategies for rapid disposition.  Do you like HEART?  Go ahead and use it.  Do you like CCTA?  Please, no – but, OK.  Do you like high-sensitivity troponin?  Then this is for you.

From Switzerland, Spain and Italy, these authors prospectively evaluated the sensitivity and area under the receiving operator curve for a 1-hour rule-out.  Analyzing 1,320 patients with acute chest pain of onset within 12 hours, after excluding STEMI and those with missing data.  Final adjudication of MI was performed by two independent cardiologists and based additionally on 3- and 6-hour conventional troponins for each patient.  3, 12, and 24-month follow-up was attempted on each patient.  As with each of these new studies, the devil is in the assay – in this case, the Roche Elecsys 2010 hsTnT with a 99th percentile healthy reference cut-off of 14ng/L.

The algorithm for rule-in and rule-out entailed the following:
  • Out: hsTnT less than 12 ng/L and a less than 3 ng/L 1-hour delta.
  • In:  hsTnT greater than 52 ng/L or a greater than 5 ng/L 1-hour delta.
  • Who knows (the “observation zone”):  Everyone else!
This resulted in 786 (59.5%) patients classified as “rule out”, with 1 patient ultimately falling out with a diagnosis of acute MI.  “Rule in” occurred in 216 (16.4%) of cases, with 169 (78.2%) true positives.  318 (24.1%) remained in the Danger Zone, where 59 (18.6%) ultimately ruled-in.  The AUC of the algorithm – based on the rule in/rule out – was 0.96 for the 1-hour strategy, as compared to 0.93 for just an initial measurement, or 0.96 for a 2-hour delta.  30-day follow-up showed zero mortality for the “rule out” patients, and even 24-month follow-up with less than 1% all-cause mortality.

These results are fairly consistent with prior strategies incorporating the use of high-sensitivity troponins, which inevitably produce a “gray area” of sorts between the rule-in and rule-out requiring further observation.  An area of continued concern, as well, remains the false-positives – nearly a quarter of the “rule in” cohort.  The authors provide a small breakdown of these patients, and most were suffering from some acute cardiopulmonary condition – heart failure, myocarditis, acute pulmonary embolism, etc.

However, not mentioned in the paper, but noted on the last page of the appendix, is the full accounting of final adjudicated diagnoses.  In addition to the 229 with a final diagnosis of acute MI, another 109 received a diagnosis of unstable angina and 194 “cardiac but non-coronary disease”.  Unstable angina, per the authors definition, was a bit of a catch-all category, including those with positive functional testing, cardiac catheterization, and acute MI within 60 days.  More detailed information on this heterogeneous endpoint, and their distribution within the “rule out”/“observation zone”/“rule in” cohorts would be helpful.

From a pragmatic standpoint, I think most groups will have success with these accelerated rule-out strategies.  The key, as always, is intelligent disposition and management of those in the ambiguous range – in which additional resource utilization associated with troponin measurements above the 99th percentile can torpedo any advantages to this strategy.  Regardless, these assays are certainly proliferating, and clinicians need be familiar with their advantages and disadvantages.

Naturally, there were diverse conflicts-of-interest with the makers of the assay involved.

“Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity cardiac troponin T assay”

Monday, April 13, 2015

Flank Pain – Ureterolithiasis or Nothin’?

There is a school of practice in which patients are evaluated for potential ureterolithiasis primarily by history, physical, and urinalysis.  If the stars align, it’s ureterolithiasis.  Simple.

But, how do you know?  What if it isn’t?  Then you have a misdiagnosis, diagnostic inertia, and the patient will obviously go wander off and expire somewhere inconvenient.

I fall into the minimalist category for advanced imaging, and I do quite prefer to manage ureterolithiasis with as little fuss as possible.  So, an article like this one – clearly stating in the title the conclusion I want to hear – ought to be precisely my cup of tea.

But, it’s a retrospective chart review.  And, over half of the 291 patients identified as having “flank pain” didn’t receive any documented imaging.  And, finally, even though the ultimate conclusion addresses the benign outcomes of patients with suspected renal colic – any sort of follow-up occurred only if patients re-presented to the same ED.  So, yes, based on initial evaluation, few patients required urologic intervention and no critical alternative diagnoses were on advanced imaging.  But, beyond the initial visit, there’s simply completely inadequate capture of any downstream adverse outcomes.  No vital records, no telephone contact – nothing.

Their title is still probably correct.  However, their study design only weakly supports said conclusion.

“Young Patients with Suspected Uncomplicated Renal Colic are Unlikely to Have Dangerous Alternative Diagnoses or Need Emergent Intervention”

Friday, April 10, 2015

The Golden Hour, Revisited

Medicine is full of “golden” times.  tPA, door-to-balloon time, sepsis bundles, and more – as the various time-dependent mandates pile up and resources remain static, it is important to revisit each and prioritize.

These authors are making an observational comment on the “golden hour” as it applies to seriously injured trauma patients.  Modern trauma systems have evolved to rapidly funnel patients through the system to the best-equipped facility.  This has involved significant investment and resource utilization by aeromedical transport.  While glamorous and heroic, unfortunately many patients transported by this inefficient and dangerous method are either too lightly or badly damaged to demonstrate any benefit from alacrity.

These authors, looking at data from a clinical trial concerning early resuscitation fluids, analyze 778 patients with hemorrhagic shock and 1,239 patients with traumatic brain injury.  Patients whose pre-hospital time exceeded 60 minutes – the “golden hour” – were no more likely to be dead or neurologically devastated than those who reached the hospital within 60 minutes.  Thus, questioning the "golden hour" of trauma.

However, at least, within the hemorrhagic shock group, the subset of 484 patients in which a “critical intervention” was performed within 24 hours of arrival did show a survival advantage – OR 2.37 (95% CI 1.05 to 5.37).  It is probably still reasonable to continue transporting those in hypovolemic shock until validated criteria for non-survivability or lack of intervention exist.  Traumatic brain injury patients, however, may urgently need to be revisited for the necessity of resource-intensive transport.

This is, additionally, a lovely example of secondary use of clinical trial data.  Even though the original trial was stopped early due to futility regarding the primary efficacy endpoint, the re-use of the rigorously collected data redeems the invested resources.  High-quality clinical trial data is accumulating rapidly – and perhaps the greatest tragedy in medicine is how much it is locked away as proprietary intellectual property.  Share!  Share!

“Revisiting the ‘Golden Hour’: An Evaluation of Out-of-Hospital Time in Shock and Traumatic Brain Injury”

Wednesday, April 8, 2015

Ketamine vs. Morphine – Again

Everyone loves ketamine.  It’s a floor wax and a dessert topping.  Traditionally, however, it has primarily been used in procedural sedation and the pre-hospital setting.  In the Emergency Department, severe pain is almost universally the domain of intravenous opiates.  Of course, opiates tend to disagree with some patients and cause others to be yet more disagreeable, so the search for alternatives continues.

This trial, similar to prior work, randomized severe, acute pain to an intravenous dose of 0.3 mg/kg of ketamine or 0.1 mg/kg of morphine.  And, again, pain relief between two groups was statistically similar – and probably clinically similar, as well.  The main difference, unsurprisingly, was adverse effects.  The ketamine cohort was associated with an absolute surplus of 20% of patients complaining of dizziness, a surplus of 27% complaining of disorientation, and a few extra complaining of mood changes.  However, all the extra adverse effects regressed to the level of the morphine group within 30 minutes.

We should be entirely settled by now regarding the safety and efficacy of ketamine.  It works, and it works well – but some patients clearly find it unpleasant.  I don’t foresee ketamine displacing opiates as typical first-line therapy for the majority, but there are certain types of patients and pain for which this would be a lovely option.  If your hospital does not yet support its use for acute pain, they are falling behind and doing their patients a disservice.

“Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial”

Monday, April 6, 2015

No Additive Value for Macrolides?

As we’ve been repeatedly drilled by our quality groups – and in part to pneumonia core measures – appropriate empiric treatment for hospitalized community-acquired pneumonia is: 1) a beta-lactam plus a macrolide, or 2) respiratory fluoroquinolone monotherapy.

Or is it?

This cluster-randomized trial across seven hospitals in the Netherlands questioned the additive value of the macrolide, in the name of antibiotic resistance, and appear to have come out ahead.

Participants admitted to non-ICU settings with a clinical diagnosis of CAP received either beta-lactam monotherapy, beta-lactam plus macrolide, or respiratory fluoroquinolone monotherapy.  With between ~650 and ~890 patients enrolled during the time periods assigned to each arm, the final outcome was: no difference.  In fact, across nearly all intention-to-treat, radiographically-confirmed, and strategy-adherent analyses, beta-lactam monotherapy was solidly on the “better than” side of the confidence intervals versus added macrolide therapy.  There was no detectable trend with regard to the fluoroquinolone group – excepting the notable advantage of oral administration.  Nearly 30% of the fluoroquinolone group received their entire therapy by the oral route alone – an appreciable resource savings, at the least.

The authors do note the low seasonal prevalence of atypical pathogens during the time of the trial.  And, as with nearly all topics in medicine, the ultimate conclusion is not an “always” or “never” proposition.  However, in the patients selected for this trial, it certainly did not appear harmful to withhold a macrolide when treating with a beta-lactam.

“Antibiotic Treatment Strategies for Community-Acquired Pneumonia in Adults”

Friday, April 3, 2015

Too Many Tests! Or, So We Believe ….

Yes, Virginia, we order too many tests.  And, we know it – as evidenced by such conferences on overdiagnosis and costs of care.  And, even more relevant than such academic exercises, as this study indicates, even the general clinician seems to have a fair bit of self-awareness.

In this survey consisting of 435 respondents, 85% of emergency physicians believed excessive testing occurred in their Emergency Department.  Most frequently, such testing was motived by fear of missing even rare diagnoses, but defensive medicine and malpractice came a close second.  Patient expectations, local practice patterns, and time saving were also substantially cited as motivators for ordering.  Thankfully, administrative and personal motivations to increase reimbursement were rarely reported as reasons.

Despite the protestations of some policy-makers, the clinicians surveyed believed the most helpful change to the system would be malpractice reform.  Interestingly, the next ranked helpful interventions included educating patients and increasing shared decision-making.  While the first item may be logistically (or politically) unachievable, there are no obstacles to integrating improved communication behaviors into routine practice.  It does, however, show a need for increased availability of tools for clinicians to use at the point of care.

There are flaws in these sorts of perception-based surveys with regard to the accuracy of such anecdotal self-assessment.  Physician assessment of their own practice and that of others can certainly be questioned.  It must be admitted, however, a more intensive just-in-time surveying method would likely impact the variables measured.

There are also some highly entertaining outliers in Figure 2, of course, the perception of self vs. colleague ordering.  There is a handful of physicians who believe they, themselves, order over 80% of their CTs and MRIs unnecessarily – but that no one else in their group does.  Likewise, there is a handful with just the opposite perception – that their colleagues over-order, while they, themselves rarely do.  I wonder if they work in the same department?

Regardless, first step is admitting you have a problem.  We have many steps yet to go.

“Emergency Physician Perceptions of Medically Unnecessary Advanced Diagnostic Imaging”

Wednesday, April 1, 2015

All Hail n-tPA! [April Fools]

As much of a naysayer I’ve been over the past few years, holding out as a skeptic, waiting for a study to finally settle the issue on thrombolytics in acute ischemic stroke – that day has come.

Except, it’s not tPA.  It’s a novel isoform of tPA, dissimilar to all of the versions we’re familiar with – alteplase, desmoteplase, tenecteplase, etc.  The novel effect seems to be, according to these authors, related to cross-linking between n-tPA molecules rather than the intrinsic structure of the molecule itself, in which the n-tPA forms a sort of fibrinolytic meshwork.  The best conceptual physiologic analogy is probably phagocytosis, in which the intracerebral obstruction is more devoured than lysed.  As a result, outcomes appear to be dramatically improved – both in terms of efficacy and safety.

These authors describe the first phase of a single-center dose-finding study in which ischemic stroke patients otherwise meeting criteria for tPA were given 0.8 mg/kg, 1.2 mg/kg, or 1.6 mg/kg of n-tPA.  All patients had demonstrable arterial occlusion on CT angiography prior to administration.  Recanalization, as measured by repeat angiography, was 40%, 70%, and 70% in each cohort – with zero cases of intracranial hemorrhage or neurologic deterioration.

In the second phase, the authors expanded the protocol to randomize 200 patients either to tPA or n-tPA at the 1.6 mg/kg dose.  Unfortunately, they only report functional outcomes at hospital discharge, rather than the typical long-term follow-up of contemporary stroke studies.  That said, at discharge, 59% of n-tPA patients achieved favorable outcome, mRS 0-1, compared with 28% of the usual care group.  Rates of sICH were 1% in the n-tPA cohort compared with 4.5% in usual care.

As with all relatively preliminary data – and coming from a single-center – these results should be treated with caution.  But, has the impossible happened?  Has the day finally come where I can enthusiastically support the use of thrombolytics in stroke?

“Dose-Ranging and Outcomes Using a Novel Tissue Recombinant Activator in Acute Ischemic Stroke”

Monday, March 30, 2015

Sometimes, The Stick Doesn’t Work

Pressure ulcers, catheter-associated UTIs, central-line infections, and injuries from falls are all iatrogenic injuries associated with healthcare and hospitalization.  Fewer of all these events would be ideal.

Of course, since asking nicely isn’t much of a motivation for healthcare delivery systems to improve practice, Medicare had a different solution – non-payment.  In 2008, Medicare ceased allowing hospitals to claim higher severity diagnosis related group codes to account for costs incurred by eight “never event” complications.  Money, on the other hand, is a strong motivator for change.  This study tries to evaluate just how successful such a heavy stick is at influencing care delivery.

These authors looked at the National Database of Nursing Quality Indicators, counting reported ulcers, falls, CLABSI, and CAUTI occurring between 2006 and 2010.  The trends reported for each differ starkly.  For CLABSI and CAUTI, in the quarters leading up to CMS policy change, the prevalence of each was gradually increasing.  After 2008, however, both trends show abrupt and consistent reversal and downward movement.  For pressure ulcers and injurious falls, however, the prevalence was gradually decreasing at the time of CMS policy implementation, and the slope of the line after 2008 is consistent with that same gradual decline.

The authors go into the limitations of each data source, but, the general takeaway is likely still valid – some “never events” just aren’t consistently, systematically preventable.  There are concerted, teachable best-practices involved with decreasing CLASBI and CAUTI.  Fall prevention and pressure ulcer prevention, on the other hand, are less amenable to care bundles, and seem to depend on gradual cultural changes and vigilance.  Thus, while outcomes-focused quality improvement using a financial motivator, while a reasonable method to try, will probably have the greatest impact and yield where a validated, evidence-based strategy can be implemented.

“Effect of Medicare’s Nonpayment for Hospital-Acquired Conditions Lessons for Future Policy”