Getting High, Getting Nauseated

Can you name some of your favorite types of patients in the Emergency Department?  Weak and dizzy?  Syncope?  Low back pain?  How about gastroparesis or cyclic vomiting syndromes?

Well, good news – if drug-induced vomiting is on your list of rewarding patient encounters, then this wave of states with newly legalized marijuana is just for you.

This is a small review of two urban, academic Emergency Departments in Colorado, retrospectively analyzing their diagnoses for encounters involving nausea & vomiting.  The breakpoint in their analysis was the legalization of recreational marijuana in 2009.  Through, frankly, a great number of assumptions involving documentation, drug screens, and other chart review calisthenics, the authors distilled out the patients with multiple ED visits for vomiting associated with drug abuse – clinically, the cyclic vomiting syndrome.  And, if you accept the limitations of their review: the number of visits for cyclic vomiting to their EDs has doubled since the introduction of legalized marijuana.


Interestingly, there is also a small exploratory analysis included in the paper regarding the antiemetic of choice.  They note promethazine use, despite the small sample, was significantly associated with needing admission – with an OR of 5.06 (95% CI 2.01 to 13.63).  Whether this represents unmeasured cofounders or a real effect is uncertain.  Anecdotally, with some evidence to support the practice, I have good experiences with droperidol and haloperidol in these sorts of patients.

“Cyclic Vomiting Presentations Following Marijuana Liberalization in Colorado”

A Window Into Your EHR Sepsis Alert

Hospitals are generally interested in detecting and treating sepsis.  As a result of multiple quality measures, however, now they are deeply in love with detecting and treating sepsis.  And this means: yet another alert in your electronic health record.

One of these alerts, created by the Cerner Corporation, is described in a recent publication in the American Journal of Medical Quality.  Their cloud-based system analyzes patient data in real-time as it enters the EHR and matches the data against the SIRS criteria.  Based on 6200 hospitalizations retrospectively reviewed, the alert fired for 817 (13%) of patients.  Of these, 622 (76%) were either superfluous or erroneous, with the alert occurring either after the clinician had ordered antibiotics or in patients for whom no infection was suspected or treated.  Of the remaining alerts occurring prior to action to treat or diagnose infection, most (89%) occurred in the Emergency Department, and a substantial number (34%) were erroneous.

Therefore, based on the authors’ presented data, 126 of 817 (15%) of SIRS alerts provided accurate, potentially valuable information.  Unfortunately, another 80 patients in the hospitalized cohort received discharge diagnoses of sepsis despite never triggering the tool – meaning false negatives approach nearly 2/3rds the number of potentially useful true positives.  And, finally, these data only describe patients requiring hospitalization – i.e., not including those discharged from the Emergency Department.  We can only speculate regarding the number of alerts triggered on the diverse ED population not requiring hospitalization – every asthmatic, minor trauma, pancreatitis, etc.

The lead author proudly concludes their tool is “an effective approach toward early recognition of sepsis in a hospital setting.”  Of course, the author, employed by Cerner, also declares he has no potential conflicts of interest regarding the publication in question.

So, if the definition of “effective” is lower than probably 10% utility, that is the performance you’re looking it with these SIRS-based tools.  Considering, on one hand, the alert fatigue, and on the other hand, the number of additional interventions and unnecessary tests these sorts of alerts bludgeon physicians into – such unsophisticated SIRS alerts are almost certainly more harm than good.

“Clinical Decision Support for Early Recognition of Sepsis”

Again With the Claim tPA is “Safe” in Mild Strokes

In yet another exercise in asking the wrong questions, these authors put forth a rather great deal of effort to regurgitate a vast quantity of mostly meaningless data.

Neurologists, generally those well-supported by Genentech and Boehringer Ingelheim (as in this article), are keen to expand the use of tPA beyond the license criteria.  One of the easiest targets is the giant cohort of stroke patients excluded from treatment for low NIHSS.  In some respects, it seems reasonable to discard an ordinal cut-off in a measure of stroke severity having a non-linear relationship with disability.  But, when media coverage describes an expansion of tPA to mild stroke patients as “saving hundreds of millions of dollars” or “having no downside”, even the hypothetical best intentions have clearly gone awry.

This is a retrospective review of the Get With the Guidelines-Stroke registry, a voluntary, prospective quality improvement project used by hospitals in the U.S.  Between 2010 and 2012, 7,621 patients were treated with IV tPA for AIS having an NIHSS of 5 or less, with 5,910 having data for analysis.  Ranging from 192 patients with an NIHSS to 0 to 1,800 having NIHSS of 5, treatment complications were fairly consistent: 1.3% died, 1.8% suffered sICH, 0.2% suffered serious systemic hemorrhage, and 1.8% suffered other serious complications (e.g., angioedema).

So, of course, for a treatment with no demonstrated efficacy in this population, the authors conclude a number-needed-to-harm somewhere between 30 and 50 “provide[s] reassurance about the safety of IV rtPA in patients with low NIHSS scores”.

Interestingly, this data is essentially an update of the authors’ prior work, published using the 2003 to 2009 GTWG-Stroke registry data.  That publication provided a helpful data supplement comparing outcomes of tPA-treated patients with non-tPA-treated patients with NIHSS 5 or less.  Within the limitations of such a comparison, tPA treatment was associated with significantly increased odds of death, decreased discharges to home, and decreased ambulation at discharge.  The authors have in no way muddled this article with such negativity, nor did they perform any sort of gross comparison between the ambulatory and independence outcomes in the present study with the prior, non-treated population – as they are essentially identical.

But, when you’re fed free money from your sponsors, including free airfare to Chicago, why report or suggest anything that might disrupt the narrative?

“Outcomes in Mild Acute Ischemic Stroke Treated With Intravenous Thrombolysis: A Retrospective Analysis of the Get With the Guidelines–Stroke Registry”

A Laughable tPA “Systematic Review”

Over 200,000 physicians belong to the American Medical Association.  The Journal, therefore, of this Association has a significant audience and a long tradition.  Continuing Medical Education inserts in JAMA may represent the basic education of many new developments for general practitioners.

Unfortunately, the authors of this most recent CME portion seem to require their own education on the conduct of a “systematic review”.

A properly performed systematic review utilizes a precise, replicable, well-described search strategy with which to canvass the evidence for synthesis.  The assembled evidence is then evaluated based on pre-specified criteria for inclusion or exclusion.  The end-result, hopefully, is a knowledge translation document based on the entire scope of published literature, accounting for controversy and irregularity in the context of a larger summary.

These authors perform a systematic review on “acute stroke intervention”.  They identify and review 145 abstracts utilizing multiple combinations of MeSH terms and synonyms for “brain ischemia/drug therapy, stroke drug/therapy, tissue plasminogen activator, fibrinolytic agents, endovascular procedures, thrombectomy, time factors, emergency service, treatment outcome, multicenter study, and randomized controlled trial”.  A massive undertaking, to be sure – considering these authors are also including intra-arterial and mechanical therapy in their review.

Yet, as indicated in their evidence review chart in the supplement, this strategy managed to identify only 17 RCTs – in the whole of systemic and endovascular therapy.  As an example for comparison, the latest Cochrane Review of thrombolytics for acute ischemic stroke included 27 trials of fibrinolytic agents alone.  And, as covered in their text and cited in their References, the RCT evidence regarding systemic therapy for acute stroke consists of: NINDS and ECASS III.

That’s it.

No MAST-E, MAST-I, or ASK.  No mention of the smaller imaging-guided trials, EPITHET, DEDAS, DIAS, or DIAS II.  Or, even excluding non-tPA trials, no ECASS, ECASS II, ATLANTIS, or, even the largest of flawed acute stroke trials, IST-3.  And, even with such limited coverage, certainly no mention of any of the controversy over imbalances in NINDS, nor flaws in ECASS III pertaining to tPA’s persistent non-approval by the FDA for the 3-4.5 hour time window.

If this were simply a commentary for the lay press regarding the bare minimum highlights of the last 20 years of stroke treatment, perhaps this would suffice.  And, frankly, these authors do much better regarding their reporting on the recent endovascular trials.  But, a CME publication in a prominent medical journal failing to address 90% of the evidence on a particular topic – yet calling itself a “systematic review” – is retraction-worthy.

“Acute Stroke Intervention – A Systematic Review”

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”

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.”

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”

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”

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”

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”