Put Hydroxyethyl Starch Away

The use of colloid solutions as volume expanders is tempting – massive crystalloid resuscitation suffers from third-spacing, limiting the practical intravascular volume provided.  Colloid resuscitation, in theory, uses the oncotic pressure of the solute to favor intravascular expansion.  One of the alternatives that I’d seen use, but was unaware it was widely used, are hydroxyethyl starches.  Earlier studies, at least, the ones I was familiar with, linked the high-molecular weight HES to renal failure.

This trial, from Denmark, evaluated a low-molecular weight HES (Tetraspan) with Ringer’s acetate resuscitation in an intensive care setting, enrolling patients diagnosed with sepsis in need of fluid resuscitation.  The trial was randomized and blinded, with the resuscitation fluids being hung in identical black bags.  Each enrolled patient could receive up to 33 mL per kg ideal body weight of the trial fluid, and additional fluid was unmasked Ringer’s acetate.

With 800 well-matched patients between groups, 51% of the HES group was dead at 90 days, compared with 43% in the Ringer’s acetate group (RR 1.17, CI 1.01 to 1.36).  Renal replacement therapy was needed in 22% of the HES group, compared with 16% of Ringer’s acetate group – and was a predictor of death.

Investigators did not see any particular fluid volume advantage to the HES solution, and the toxic effects of the hydroxyethyl starch molecules, unfortunately, were associated with greater morbidity and mortality.

Seems like another great-sounding idea that needs to be rapidly curtailed until a better safety profile and outcome benefit can be demonstrated.

“Hydroxyethyl Starch 130/0.4 versus Ringer’s Acetate in Severe Sepsis”
http://www.nejm.org/doi/full/10.1056/NEJMoa1204242

Could Ordering Reprints Help You Get Published?

Medical journals, to a certain extent, require independent sustainable business models.  The full-time editorial staff, the administrative personnel, and the printing costs must be defrayed by elements such as advertising, subscription fees, or other largess.  One of these sources of largess – particularly for journals with high impact factors – is the ordering of reprints.  After gifts, the major promotional material circulated by pharmaceutical companies among physicians is reprints of publications.

This recent study in the BMJ queried the most prominent medical journals regarding their reprints, hoping to gauge the scope of the reprint requests, as well as the financial windfall these might represent.  JAMA, NEJM, and Annals of Internal Medicine all declined to provide data, so these authors were left with the Lancet and the BMJ family of journals.  Of the most-frequently reprinted articles in these journals, they were far more likely to be industry-sponsored, and represented significant sources of income for the journals – up to a $2.4 million USD order from the Lancet.

There are significant limitations to this study, but, clearly, the revenue stream from reprints may be substantial enough that it may further influence and bias the publication of medical literature.

“High reprint orders in medical journals and pharmaceutical industry funding: case-control study”
http://www.bmj.com/content/344/bmj.e4212

Warfarin and tPA Mix – If They’re Subtherapeutic

These authors almost have a conclusion I can’t quibble with – but, rather than “Among patients with ischemic stroke, the use of intravenous tPA among warfarin-treated patients (INR ≥1.7) was not associated with increased sICH risk compared with non-warfarin-treated patients” I would add the caveat to say “after multiple adjustments”.

This is a retrospective registry review published in JAMA, comparing the rate of sICH in warfarin-treated patients with non-warfarin-treated patients who received tPA for ischemic stroke.  And, 5.7% of warfarin patients developed sICH vs. 4.6% in the non-warfarin group.  However, after adjustments for multiple variables – the warfarin group tended to be older, had more previous strokes, and had higher NIHSS – the OR was 1.01.  Not terribly surprising there wasn’t much difference, considering the mean INR in the warfarin cohort was only 1.2.  Their confidence intervals start getting very wide above 1.6, but there’s suggestion of a clear association with increasing sICH as the INR increases.

There are plenty of reasons not to give tPA, but subtherapeutic warfarin use probably should not exclude patients from consideration.

“Risks of Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Receiving Warfarin and Treated With Intravenous Tissue Plasminogen Activator”
http://jama.jamanetwork.com/article.aspx?articleid=1199153

Xigris Isn’t Dead – Just Hibernating

Activated Protein C, also known as Xigris, which has had an infamous and circuitous career of sorts, is back.

After a short life of use in severe sepsis, the continued investigations into its efficacy have finally been unable to establish its benefit.  Although many expensive therapies without conclusive benefit are still in use in medicine, we’ll score this one (belatedly) for the good guys.

This early animal research, published as a letter in Nature Medicine, reports on interventions targeting the aPC pathway to prevent lethal radiation injury to hematopoietic cells.  They say that starting infusions of aPC within 24 hours of lethal radiation exposure mitigated radiation mortality in mice.  Probably quite a long way off for real-world usage, but any potential treatment is better than none.

“Pharmacological targeting of the thrombomodulin–activated protein C pathway mitigates radiation toxicity”

http://www.ncbi.nlm.nih.gov/pubmed/22729286

Failings of Modern Medicine

A brilliant piece that eloquently states many of the ideas espoused on this blog, focusing on pulmonary embolism as the poster child for over-testing, over-diagnosis, and lack of sound evidence underlying treatment.

These authors, in the Archives of Internal Medicine, accurately describe the chimeric nature of pulmonary embolism – historically described as a dreaded disease, diagnosed clinically from the manifestations of pulmonary infarction, to the modern manifestation of filling defects noted on CTA during an episode of pleuritic chest pain.  They discuss the handful of patients who benefited from the first heparinization for treatment, and argue the disease for which anticoagulation is the treatment is not the disease we are diagnosing today.

This article covers so many excellent points, and ties the clinical problems so tightly into the underlying principles, that it’s almost the sort of must-read article to which medical students should be exposed – in order to bring about that frightening moment of maturity in medicine in which you realize the emperor is distinctly lacking in clothes.

Lovely work!

“The Diagnosis and Treatment – of Pulmonary Embolism: A Metaphor for Medicine in the Evidence-Based Medicine Era”
www.ncbi.nlm.nih.gov/pubmed/22473672

Impaled in a Rowing Accident

This article I dredged up from the archives is mostly of sentimental value – although, I could claim it’s related to Olympic sport-related trauma with the upcoming Games.


This is from the series “Case records of the Massachusetts General Hospital”, which run the gamut all the way out to some of the most esoteric diagnoses possible.  This particular article describes the management and outcomes of a man impaled by a rowing shell while on the Charles River.  Eight-person rowing shells are ~17 meters in length, have a crewed weight of nearly 1,000 kg, and travel fast enough that a water skier may be towed behind.  There is a small rubber bumper affixed to the, otherwise sharp, wooden or carbon-fiber bow that is meant to reduce the potential for injury in event of a collision.  In this incident, the momentum of a head-on impact dislodged the bow ball and resulted in the unfortunate impalement incident described.  A fascinating little read.


Rowing collisions are uncommon, injuries are rare, and this is probably nearly unique.


“Case records of the Massachusetts General Hospital. Case 10-2007. A 55-year-old manimpaled in a rowing accident.”
www.ncbi.nlm.nih.gov/pubmed/17392306

Nephropathy Was As Common as PE after CTPA

It’s Jeff Kline Week at EMLitOfNote, with the second Carolinas paper this week – and, as a Patient Safety and Quality Fellow, I just can’t help but cite articles that deal with the consequences of otherwise well-meaning practice.

This small study followed 174 patients undergoing CTPA demonstrated a yield of 7% for PE.  On the other hand, this same cohort demonstrated a yield of 14% for contrast-induced nephropathy – as defined by an increase in serum Cr of 0.5 mg/dL or >25%.  Three of the 24 patients with CIN progressed to severe renal failure, two of whom died.  The proportion of CIN and renal failure were similar to the outcomes observed in the additional 459 patients they followed for CT imaging on other contrast protocols.

So, the rate of CIN is not insignificant – particularly compared to the rate of diagnosis of PE at this institution.  It seems to be suggested by this study, although not shown, that the relative risk of death conferred by receiving contrast and developing CIN might even exceed the number of adverse events that might have occurred from PE if left undiagnosed or untreated.

“Prospective Study of the Incidence of Contrast-induced Nephropathy Among Patients Evaluated for Pulmonary Embolism by Contrast-enhanced Computed Tomography”
http://www.ncbi.nlm.nih.gov/pubmed/22687176

Chest Pain – Here, Your Problem Now

In the United States, a quarter of our medical malpractice payments result from missed myocardial infarctions.  Therefore, in states with sub-optimal liability environments, emergency physicians are stuck in a quagmire of conflicted interests and fear of litigation if a discharged patient has an MI.

Therefore, a common strategy is to make low-risk chest pain Someone Else’s Problem.  And, this article from Archives of Internal Medicine shows the internist evaluating the patient simply makes the same surrender to defensive medicine.  In this retrospective cohort, 2,107 admitted patients underwent 1,474 stress tests during their two-year study period.  Of those 1,474, 12.5% were abnormal.  Of those 184 patients, only 11.6% underwent cardiac catheterization, and a grand total of 9 patients received a revascularization.

So, the authors suggest two salient points:
 – 2,107 admissions to yield 9 (supposedly) beneficial interventions – how crazy is that?
 – What about the 88.4% of patients with abnormal stress tests that didn’t undergo an invasive test within 30 days – why are we using an evaluation strategy we don’t act on?

The authors think we might be able improve upon this practice pattern.

“Outcomes of Patients Admitted for Observation of Chest Pain”
www.ncbi.nlm.nih.gov/pubmed/22566486

National Quality Measure for Pulmonary Embolism

The overuse of CTA in the Emergency Department and the over-diagnosis of pulmonary emboli of non-physiologic significance has been demonstrated as a significant societal harm.  In response to this, the National Quality Forum has been looking at developing a quality measure aimed at reducing CTA use in the Emergency Department.

The NQF estimated 7 to 25% of CTAs in the ED might be unnecessary.  From Jeff Kline’s shop at Carolinas, they prospectively gathered data on all their potential pulmonary emboli and attempted to determine which scans were “inappropriate.”  For their purposes, a scan was “inappropriate” if it was a low-risk patient with a negative D-dimer assay, or it was a low-risk patient without D-dimer testing.  11% were D-dimer negative and 22% were low-risk without D-dimer testing performed, which sums to 32% potentially avoidable imaging.

Of the 1,205 “potentially avoidable” scans, there were 58 positives.  The clinical significance of these potential misses is uncertain.  Whether this represents an acceptable miss rate for a quality measure in a liability prone environment is another matter entirely.

“Evaluation of Pulmonary Embolism in the Emergency Department and Consistency With a National Quality Measure”
www.ncbi.nlm.nih.gov/pubmed/22664742

How to Be Popular at the Beach

The summer is a great time for swimming – and, luckily, there’s an evidence-based systematic review of treatment of jellyfish stings available from Annals of Emergency Medicine.  Unfortunately, it’s only the relatively benign and inconvenient species from North America, rather than the life-threatening species found more commonly in the southern hemisphere.

Literally, everything has been tried on jellyfish stings in an attempted in treatment, from vinegar, to ammonia, to ethanol, to meat tenderizer, to magnesium chloride, and the list goes on.  Essentially, the attempted treatments fall into two camps – wash off the nematocysts without inducing discharge, or simply to treat the pain and tissue damage from the venom itself.

The American Red Cross First Aid consensus suggests the use of vinegar – which, according to this review, induces nematocyst discharge in everything but some Physalia species.  The real answer is…no single agent reliably inactivates nematocysts from every organism.  The authors recommend simply using readily available saltwater to wash the affected area.  For post-envenomation pain, topical anesthetics such as lidocaine and hot water were found to be most reliably effective.  Given the limited availability of anesthetics to laypersons, the best treatment is likely to be hot water submersion to help inactivate the toxins.

“Evidence-Based Treatment of Jellyfish Stings in North America and Hawaii”
www.ncbi.nlm.nih.gov/pubmed/22677532