October 2011 – Page 2 – Emergency Medicine Literature of Note

Stroke After-Care Is Far More Important

Somewhere in the rush to but up billboards and focus the medical establishment on experimental revascularization interventions for acute stroke (e.g., time is brain), we’ve overlooked what truly matters – follow-up care after the ischemic event. This is a lovely study that reminds us of what we probably knew once, but have forgotten – that even in the absence of acute therapy, simple protocols to prevent fever, prevent hyperglycemia, and prevent aspiration pneumonia lead to profound differences in the number of patients with zero or minimal disability after stroke.

This is a prospective interventional study in which acute stroke units in New South Wales Australia were randomized to either no protocolized intervention, or an intervention with nursing protocols named above. At the end of the three-year intervention period, 42% of the control group had mRS 0 or 1 at 90 days, and 58% of the intervention group had mRS 0 or 1 at 90 days. There were small differences in the type of stroke, education level, and prior ability to work that probably favored the intervention group, but the differences at baseline were far smaller than the magnitude of the treatment effect. In short, a basic nursing protocol intervention improved outcomes more than any other intervention for acute stroke.

“Implementation of evidence-based treatment protocols to manage fever, hyperglycemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomised controlled trial.”
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61485-2/fulltext

Yes, Let MONA Fade Away

These authors make a brief argument regarding the inappropriateness of the commonly taught acronym of “MONA” for the initial treatment of acute coronary syndrome. It is probably the case that well-read Emergency Physicians have since moved on, but it bears repeating.

– Morphine, which has been associated with worsened outcomes in CRUSADE, but the results are confounded by other factors. Narcotics are still probably reasonable for nitrate-resistant pain.
– Oxygen, in which hyperoxia is associated with coronary vasoconstriction, exacerbates reperfusion injury and infarct size. It is currently recommended that oxygen only be used for patients who are hypoxic.
– Nitrates, suitable for the relief of anginal symptoms in selected patients.
– Aspirin, the only element of MONA proven to be strongly beneficial.

And, presumably, future trials will involve the use of newer anti-platelet and other agents in the inital treatment of ACS.

The market is ripe for a replacement acronym!

“Initial treatment of acute coronary syndromes. Is there a future for MONA acronym after the 2010 guidelines?”
http://www.ncbi.nlm.nih.gov/pubmed/21982924

High-Sensitivity Troponin For Better Or Worse

The premise of this article seems fine – as we all learned in medical school, the ~~LDH~~ ~~CK-MB~~ Troponin is now our most sensitive and specific assay for myocardial injury, but, we were also taught that it takes a certain amount of time for the assay to turn positive. Thus, the inpatient rule-out with multiple sets of cardiac enzymes. These investigators looked a new assay, with a lower detection limit, and hope to prove that it has 100% sensitivity with a single measurement, obviating the need for additional enzymatic testing.

There were two phases – a cohort observational portion and a clinical deployment portion. The observational phase was intended to verify prior data suggesting 99% sensitivity for the assay and, of their 703 patients, 195 had initial hs-cTnT levels of <3ng/L – and none had acute MI in their 6 month follow-up period (97.8 to 100% sensitivity). In their clinical deployment phase, they collected 915 patients who received two sets of the hs-cTnT assay, and found that only one patient had a subsequent hs-cTnT rise after an initially undetectable hs-cTnT, giving a sensitivity of 99.8% (99.1-100).

So, they say, there is no longer any realistic need to get multiple sets of cardiac enzymes in a patient if the first level is undetectable. This is probably true, but whether it reduces inpatient stays and follow-up invasive cardiac testing is another matter. My guess is that widespread availability of this assay would lead to clinicians ordering troponins on patients they wouldn’t have previously ordered them on, and – perhaps you know how this story will probably play out – a story in which use of the d-Dimer assay would decrease chest imaging for pulmonary embolism, but didn’t. Too many clinicians are applying it incorrectly and using its weak positive likelihood ratio to light up patients unnecessarily, and I expect this to lead to more patients being kept for testing, not fewer, as the authors propose.

“Rapid Exclusion of Acute Myocardial Infarction in Patients With Undetectable Troponin Using a High-Sensitivity Assay”
www.ncbi.nlm.nih.gov/pubmed/21920261

Popular Dehydration Scales Fare Poorly In 3rd-World Use

I like the author’s use of the word “popular” to describe pediatric clinical dehydration scales. In case you’re not part of the “in crowd”, today’s “popular” dehydration scales include the World Health Organization scale, the Gorelick scale, and the Clinical Dehydration Scale.

This article is a prospective application of each of the three scales by a healthcare provider upon admission to one of three hospitals in Rwanda. Children were weighed on admission and then on discharge, and the gain in weight was used as the gold standard for comparison to each standardized dehydration scale.

So, bad news: each of these dehydration scoring scales is too complicated to hold in working memory, and you’d have to have it posted on a wall.

But, good news: in the words of the authors, “The WHO scale, Gorelick scale, and CDS did not have an area on the ROC curve statistically different from the reference line.”

Which means, you get to save your wall space because the dehydration scales gave false negatives or false positives as frequently as they gave true negatives and true positives. More research is necessary to derive more accurate clinical assessment of children presenting with possible dehydration.

“Comparing the accuracy of the 3 popular clinical dehydration scales in children with diarrhea.”

www.ncbi.nlm.nih.gov/pubmed/21902838

600mg Is Probably Your Best Clopidogrel Loading Dose

Most STEMI is the result of an acute thrombotic event, so, more thrombotic inhibition is better, right? Italy, Hungary, Serbia and Belgium band together for ARMYDA-6 to test a randomized, prospective 600mg vs. 300mg clopidogrel loading dose prior to PCI in STEMI.

They didn’t look at mortality and only followed 30-day outcomes – probably because they didn’t have statistical power from only 201 patients to detect a difference – but their surrogate markers of infarct size, successful PCI, LVEF and 30-day “major cardiovascular events” all favored clopidogrel. Unfortunately, almost every nonsignificant difference between the two clinical groups favored the 600mg group – younger, less diabetes, fewer prior MIs, higher LVEF at baseline, faster loading and cath lab times, less multivessel disease, more TIMI flow >1 pre-PCI.

That being said, it’s consistent with the prior ARMYDA-1 and CURRENT-OASIS studies, and even if this isn’t a fabulous study, it’s another but of evidence to consider.

“Outcome Comparison of 600- and 300-mg Loading Doses of Clopidogrel in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segement Elevation Myocardial Infarction”

content.onlinejacc.org/cgi/content/full/58/15/1592

Not Long, But Short QT

Another rare channelopathy that I was not previously aware of, but that carries the same risks of sudden death as long-QT syndromes.

This is a longitudinal observational study of the European Short QT Registry – which has a grand total of 53 patients – who were followed for, on average, 5 years. The diagnosis of short QT does not have a generally accepted definition, but typically means a QTc less than 340 or 360, and the other literature shows a high association with sudden death and QTc less than 340. In their registry 23% had a HERG gain-of-function mutation identified, and there is also an autosomal dominant inheritance pattern identified.

Based on their follow-up for events, or for cardiac events recorded by implantable defibrillators, there was a 4.9% incidence of syncope, defibrillator shocks, or nonsustained polymorphic ventricular tachycardia. Prophylactic treatment involves either the implantable defibrillator or daily hydroquinidine therapy to prolong QT.

Something new to look for on EKGs that you’ll probably never see, but will seem really smart if you do.

“Long-term follow-up of patients with short QT syndrome”
www.ncbi.nlm.nih.gov/pubmed/21798421

Lack of IV Access, Harbinger of Death

Interesting observational study of 56,332 patients picked up in an EMS system in King County, looking at IV access and outcomes.

For reasons they don’t look into in this study, they find that IV access is an independent predictor of decreased in-hospital mortality. Not for the less-acute patients, but for patients of high-acuity, lack of IV access shows a pretty significant trend towards poor outcomes. They don’t look at fluid therapy, medication therapy, etc. as confounding variables – so we don’t know what it is specifically about IV access that confers a survival advantage.

They do a brief breakdown of the systolic blood pressure and the percentage of patients receiving IV access, and, as expected, more IVs are attempted at the extremes. This leads me to believe there are patients who were high acuity, required IV access, but had failed IV access attempts – but there’s no data on that either.

This is a study that could end up telling us something, or nothing. Interesting, nonetheless.

“Intravenous Access During Out-of-Hospital Emergency Care of Noninjured Patients: A Population-Based Outcome Study”
http://www.ncbi.nlm.nih.gov/pubmed/21872970

C-Collars Cannot Stabilize Unstable Injuries

This is another cautionary anatomic study that demonstrates cervical collars are not adequate immobilization devices – except in patients who already do not need them.

This is a cadaveric spinal immobilization study in which C5/C6 instability was induced, and the Ambu extrication collar, the Aspen collar, and no collar were evaluated for range of bending and rotation during a bed transfer simulation.

The results are pretty straightforward. Before the instability was induced, patients had minimal neck movement, whether immobilized or not. After instability was induced, the patients all had significant bending and rotation – nearly the same for the patients in the collars as in no collar at all.

This is consistent with the small amount of prior work done in actual unstable spines; most of the cervical collar data is in healthy volunteers. The limitations of a cervical collar should be recognized, and patients should have their cervical spine evaluated and cleared or intervened on immediately.

“Cervical collars are insufficient for immobilizing an unstable cervical spine injury.”
www.ncbi.nlm.nih.gov/pubmed/21397431

Linezolid Is Superior To Vancomycin For Pneumonia

This is consistent with prior studies and not particularly earthshaking, but if you needed more literature to support switching antibiotics in the case of treatment failure, this would be another one.

This is in pigs, and it’s an animal model of MRSA ventilator-associated pneumonia. Four groups – controls, twice-daily vancomycin, continuous vancomycin infusion, and linezolid. Treatment was initiated after 12 hours of bacterial inoculation in ventilated pigs. At the end of their 96 hour treatment period, 75% of controls, 11% of each vancomycin group, and 0% of linezolid pigs were BAL positive for MRSA by culture. Likewise, pathologic sections also showed decrease inflammation and damage in the linezolid group.

Short story, linezolid is better – but not quite better enough that we can’t still start with vancomycin and keep it in reserve.

N-acetylcysteine Overdose With Anaphylactoid Reaction and Myocardial Infarction

This is another toxicology case that illustrates a point I make (probably too often) to my residents – that every action we take has a risk of harm, whether known or unanticipated. I’m probably the only attending who cancels their IM ketorolac orders and changes them to PO ibuprofen. Why? Because of cases like this.

This is an entirely appropriate therapy – N-acetylcysteine given for hydrocodone-acetaminophen overdose – gone wrong because of a mixing error resulting in 10-fold overdose (126,000mg loading dose!). Anaphylactoid reactions are known side effects in N-acetylcysteine, and, unfortunately, this patient’s reaction was more severe than most, suffering an inferior MI with a peak troponin of 658ng/mL. He expired 17 hour after the N-acetylcysteine overdose.

I’ve seen epinephrine given IV instead of SQ more than once (one time resulting in an MI), many medications are tissue toxic if they extravasate, you can get sterile abscess formation from intramuscular injections, etc. The fewer interventions and the less invasive the interventions, the less risk at which we place our patients.

“Fatal myocardial infarction associated with intravenous N-acetylcysteine error”