Glucose-Insulin-Potassium For MI?

“Investigators, led by Dr Harry Selker (Tufts Medical Center, Boston, MA), are pleased with the results, believing that after years of futile study, they have finally found some clinical evidence to support the experimental data suggesting that GIK [glucose-insulin-potassium] myocardial metabolic support could protect the heart in the ACS setting.”

…which lead to the press release tweet of “Intravenous GIK Slashes Death Risk in Acute Coronary Syndrome: CHICAGO – Glucose, insulin, and potassium given i…” by @ACEPNews.  That press release can be seen here.

There have been trials enrolling over 20,000 patients to date that have been negative.

Despite all these previous negative trials, the authors believed the problem was timeliness – the critical time in which to provide metabolic support to the infarcting myocardium was in the prehospital setting, upon the earliest recognition of ACS.  The original goal was to enroll 15,450 patients.  They ended up with 880.  Then, after data collection, they changed the primary endpoint from all-cause mortality to progression to myocardial infarction at 30 days and at 1 year.  And they only have the 30 day data right now, they’ll get back to us with the 1 year outcomes.  How this made the cut for publication in JAMA is outside the scope of my speculative powers.

So, they enrolled folks prehospital with signs and symptoms of potential acute coronary syndrome whose prehospital EKG was read as STEMI or met the ACI-TIPI prediction instrument probability threshold of 75%.  They received the GIK solution with 90 minutes, on average.  And, the primary outcome measure was negative for progression to MI, trend favoring GIK with OR 0.88 (CI 0.66-1.13).  Negative for 30 day mortality, OR 0.72 (0.40-1.29).  For STEMI patients, negative for progression to MI, OR 0.74 (0.40-1.38), and negative for 30 day mortality, OR 0.63 (0.27-1.49).
So, yes, there is a trend.  And some subgroups even had significant trends in favor of GIK.  But for JAMA and the rest of the internet to be promoting this as practice-changing at this juncture is absolutely inappropriate.

“Out-of-Hospital Administration of Intravenous Glucose-Insulin-Potassium in Patients With Suspected Acute Coronary Syndromes:  The IMMEDIATE Randomized Controlled Trial”

CCTA Is A Bad Shortcut Around Bad Care

“Although an acute coronary syndrome is ultimately diagnosed in only 10 to 15% of patients who present with chest pain, the majority of these patients are admitted to hospitals, at an estimated cost of over $3 billion annually.”

This is, essentially, the statement of problem from the NEJM article, sponsored by Siemens, regarding the use of coronary CT angiograms in the Emergency Department on low-to-intermediate risk chest pain.  They are clearly huge fans of CCTA up at the University of Pennsylvania, and I hate to think it has something to do with the parade of imaging technology companies and patent applications listed as disclosures by the authors.

In this study, the authors enrolled 1,392 patients with chest pain with the goal of testing the primary hypothesis that “patients without clinically significant coronary disease on CCTA (i.e., no coronary-artery stenosis ≥50%) would have a 30-day rate of cardiac death or myocardial infarction of less than 1%.”

Good news!  They were right.  Bad news:  their entire enrolled cohort had a 30-day death or MI rate of only nearly 1%.  It’s rather incredible, really, that they have this entire article in which they sing the praises of CCTA for identifying low-risk chest pain, when in reality, they gloss over the fact that they simply could have sent home every single patient in the study without doing a single additional test and only nearly 1% would have had death or MI within 30 days.

Going back to their essential statement of problem, it might be true that CCTA were valuable if they were looking to apply it in a population and practice environment in which we were actually hospitalizing patients with a 10-15% rule-in rate.  However, the opposite of what these authors propose is the real truth – clinically identify all the low-risk chest pain and stop doing all these expensive tests!  They claim it expedites discharge from the Emergency Department, which, in theory, saves money – but it isn’t!  Despite 90% of their CCTA being negative for stenosis >50%, they still end up admitting half their CCTA cohort.  Even the negative CCTA cohort, while their length of stay is reduced to 12 hours, still means they’re being placed in observation status and billed an additional separate observation code – which in many places is a protocolized chest pain observation unit run by the Emergency Department.

This is simply a bad solution to bad baseline practice patterns.  The measurable benefit here isn’t to the patient, it’s to the malpractice risk of the physician, to Siemens and other sponsors of the study, and likely to the Emergency Departments whose billing increases for these short stay observation patients.

“CT Angiography for Safe Discharge of Patients with Possible Acute Coronary Syndromes”

Pan-Scan & Zero-Miss

In an interesting contrast to a prior article regarding over-scanning in trauma, this article takes a different perspective.  While the authors do note that there is controversy regarding the impact of “pan scan” on survival, they are rather focused on the sensitivity/specificity of the “pan scan,” rather than the appropriateness.

This is a review of 982 consecutive patients undergoing “pan scan” in Germany.  The indications for scanning were a set of “red flag” criteria, which included impaired patients, patients with obvious injuries, “suspicion of severe trauma” or “high risk mechanism”.  The diagnostic reference standard was chart review by two reviewers of the electronic notes for any injuries missed on the initial scan.

The results are rather interesting in a couple ways:  the prevalence of injuries per organ system is not terribly high, and the sensitivity of scanning was rather low.  The highest prevalence of injuries for an organ system was 37%, for chest, followed by head and neck at 34%.  However, the sensitivities range from a high of only 86.7% for chest down to a low of 79.6% for face – likely because dedicated fine cuts of the face were not part of their protocol.  Regardless, with sensitivities in the mid-80s meant they missed almost one seventh of the total number of injuries.  Of these 70 missed injuries, almost half required surgery or a critical intervention as treatment.

So, pan-scanning: expensive, low yield, yet still misses important injuries.  The authors do not try to fully address whether their yield is reasonable or not, and wisely simply state further research is needed regarding triaging patients into groups likely to benefit from scanning.

“Accuracy of single-pass whole-body computed tomography for detection of injuries in patients with major blunt trauma.”

More Nails In the Coffin For Epinephrine

The news for epinephrine in cardiac arrest keeps getting worse – it restarts the heart, but at what cost, and with what outcomes?

This is a study, published in JAMA, of 417,188 out-of-hospital cardiac arrest patients in Japan – only 15,030 of which received epinephrine during prehospital transport – a far cry from the U.S., where the toolbox has typically already been emptied prior to the ED.  Nearly every baseline characteristic favored the epinephrine group – more witnessed arrests, more received bystander CPR, a physician was more frequently in the ambulance, more patients in ventricular fibrillation/PEA.  However, more of these patients also received an advanced airway, which has also been associated with worse outcomes.

In their unadjusted analysis, the epinephrine cohort was three times as likely to have ROSC, and had an OR of 1.15 to be alive at one month.  However, they were half as likely to be functional as the non-epinephrine survivors.  Then, when they do all their statistical adjustments for all the favorable baseline factors in the epinephrine cohort, all these numbers become less favorable for epinephrine.  They also do a propensity-matched cohort of 26,802 patients that has favorable ROSC with epinephrine, but dismal 1 month and functional outcomes.

This data is from before the era of routine hypothermia – which may be beneficial – but it certainly supports what we already expected regarding the damaging physiologic effects of epinephrine while senselessly flogging the heart back into action.

“Prehospital Epinephrine Use and Survival Among Patients With Out-of-Hospital Cardiac Arrest”

TPA is Dead, Long Live TPA

I’m sure this saturating the medical airwaves this morning, but yesterday’s NEJM published a study which they succinctly summarize on Twitter as “In trial of 75 pts w/ acute ischemic #stroke, tenecteplase assoc w/ better reperfusion, clin outcomes than alteplase.”

Well, that’s very exciting!  It’s still smashing a teacup with a sledgehammer, but it does appear to be a more functional sledgehammer.  Particularly encouraging were the rates of sustained complete recanalization – which were 36% at 24 hours for alteplase and 58% for tenecteplase – and the rates of intracranial hemorrhage – which were 20% for alteplase and 6% for tenecteplase.

However, the enthusiasm promoted by NEJM, and likely the rest of the internet, should be tempered by the fact that there were only 25 patients in each arm, and there is enough clinical variability between groups that it is not yet practice changing.  This was a phase 2B trial, and it is certainly reasonable evidence to proceed with a phase III trial.

Unfortunately, in a replay of prior literature, the authors are all affiliated with Boehringer Ingelheim, the manufacturer of tenecteplase.

A Randomized Trial of Tenecteplase versus Alteplase for Acute Ischemic Stroke”

Addendum:  As Andy Neil appropriately points out, tenecteplase has been studied before – 112 patients over several years, terminated early due to slow enrollment – without seeing a significant advantage.

Over-Prescribing of Antibiotics Happens Everywhere

On Twitter a couple weeks back, in response to my plea to reduce empiric macrolide use for benign clinical syndromes, there was an allusion suggesting Pediatricians were the culprits of a poor antibiotic stewardship.

Of course, that’s clearly not the case.  And, while we all envision Urgent Cares and customer-service medicine contributing to the over-prescription of antibiotics, it’s happening in our academic medical centers, as this article indicates.  This is a retrospective chart review from San Diego that evaluated 836 patients receiving a diagnosis of “acute bronchitis”, a typically self-limited disease that evolves into pneumonia only in a minority of cases in elderly patients or patients with significant pulmonary comorbidities.

The average age was 46, 10% had comorbid COPD noted, 17% asthma, 8% diabetes, and 4% HIV/AIDS.  All told, 74% were prescribed antibiotics – 50% received a macrolide, 15% a tetracycline, 6% a fluoroquinolone, along with a few others.


And certainly not just the Pediatricians.

“Antibiotic and bronchodilator prescribing for acute bronchitis in the Emergency Department.”

Is It Reasonable to Keep Using Vasopressin in Shock?

The authors of this meta-analysis seem to think so.
Unfortunately, they identify a very heterogenous set of evidence for analysis, which reduces the statistical power of every comparison.  They identify only a couple studies of vasopressin vs. placebo, and most of their studies are vasopressin vs. an increased dose of norepinephrine.
It’s hard to generate any unreasonable conclusion from this data – the error bars cross one, so you can either take this as permission to drop vasopressin from your usage patterns because its use has no measurable mortality benefit, or you can continue to use vasopressin because it doesn’t seem to be harmful, and allows you to reduce the dose of norepinephrine.
I’d really like to see more vasopressin vs. control – there’s only one reasonably sized vasopressin vs. placebo trial – and it heavily, but non-significantly, favors control with a risk ratio for mortality of 1.94 (0.74 to 5.10).
More to be done!
“Vasopressin for treatment of vasodilatory shock: an ESICM systematic review and meta-analysis”

Pharmaceutical Bias Article in EM News

Imagine my surprise to be paging through Emergency Medicine News this month and stumble upon an article about TPA in stroke – and find that it’s a review of my Western Journal of Emergency Medicine article from last summer.

The EM News article is here:

And my West JEM article is open access, available here:

It Feels Good To Use an iPad

Recently, there has been a great deal of coverage on internet news sites with headlines such as “Study: iPads Increase Residency Efficency.”  These headlines are pulled from a “Research Letter” in Archives of Internal Medicine, reporting from the University of Chicago, regarding the distribution of iPads capable of running Epic via Citrix.

Sounds good, but it’s untrue.

What is true is that residents reported that they used the iPads for work.  The additionally thought that it saved them time, and thought it improved their efficiency on the wards.  This is to say, they liked using the iPad.

The part that isn’t true is where the authors claim an increase in “actual resident efficiency.”  By analyzing the hour of the day in which orders are placed, the authors attempt to extrapolate to a hypothetical reality in which this means iPads are helping their residents place orders more quickly on admitted patients, and to place additional orders while post-call, just before leaving the hospital.  There is, in fact, no specific data that using the iPad makes the residents more efficient, only data showing the hour of the day in which orders are placed has changed from one year to the next.  The iPad has, perhaps, changed their work habits – but without prospectively observing how these iPads are being used, it is impossible to conclude how or why.

But, at least they liked them!  And, considering how addictive Angry Birds is, I’m surprised their productivity isn’t decreased.

“Impact of Mobile Tablet Computers on Internal Medicine Resident Efficiency”

Ketamine + Propofol = Ketofol

Combining propofol, a beloved agent for procedural sedation for its rapid onset, quick recovery times, and titratable levels of sedation with ketamine, the world’s safest agent for unmonitored anesthesia, has been shown in case series to be as safe and effective as expected.

This small, randomized trial is a direct comparison between ketofol and propofol, with the primary outcome measure being the proportion of patients experiencing an adverse respiratory event using the standardized Quebec Criteria.  The authors are testing the hypothesis that use of ketofol will result in fewer adverse respiratory events, which they believe to be one of the weaknesses of propofol, and one of the strengths of ketamine.

With ~120 patients in each group, there is essentially no clinical or statistical difference between outcomes of the two groups.  Clinicians provided transient assisted ventilation for three ketofol patients and one propofol patient – which is not statistically different.  Secondary outcomes were similar, although a handful of ketofol patients experienced recovery agitation, some of which required treatment.

It seems odd to me that the authors would be testing the respiratory adverse events of ketofol – both ketamine and propofol are so profoundly safe, with already extremely low rates of assisted ventilation, and unplanned intubation rates of ~1 in 5,000 or more.  Ketofol has been similarly already shown to be extremely safe in terms of respiratory events, primarily in retrospective case series.  They’ve essentially set themselves up to test something that’s almost already conclusively expected to generate insignificant differences.  What is more interesting to clinicians now, when considering agents for sedation, is the secondary effects – hypotension, hypersalivation, vomiting, myoclonus, agitation – and how that affects procedural success and time to disposition.  Ketofol is a great combination – but its value seems to be in the mitigation of the non-airway adverse events.

“Ketamine-Propofol Combination (Ketofol) Versus Propofol Alone for Emergency Department Procedural Sedation and Analgesia:  A Randomized Double-Blind Trial”