Friday, July 6, 2012

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

Wednesday, July 4, 2012

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

Monday, July 2, 2012

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