Saturday, September 17, 2011

Ondansetron, Just Like Droperidol

Droperidol used to be one of the most widely used anti-nausea medications, particularly in the peri-operative period.  Now, none of my residents are familiar with it because it's rarely used since the FDA gave it a black box warning for its QT-prolonging effects.  We have largely and copiously replaced it with ondansetron, the supposedly safe alternative.

Now, the FDA is asking GlaxoSmithKline to go back and look at the safety profile for ondansetron...due to QT-prolonging effects: http://reut.rs/pDq6Yw  They are already changing the labels to reflect cardiovascular risk in the meantime.

It should be interesting to see the results.  It is fairly clear that ondansetron prolongs the QT interval probably nearly, but not quite, as much as droperidol.  The droperidol black box was based on cardiovascular events including only a mere 10 patients receiving doses in the therapeutic range of 0.625mg to 1.25mg, and those events had multiple confounding factors or drug co-administrations.  It would not surprise me if ample, if equally flimsy, evidence exists implicating ondansetron as well.

"Food and drug administration black box warning on the perioperative use of droperidol: a review of the cases."

"Droperidol and ondansetron-induced QT interval prolongation: a clinical drug interaction study."

"The effects of droperidol and ondansetron on dispersion of myocardial repolarization in children."

Friday, September 16, 2011

Putting Acetylcysteine To Rest

Essentially, another study to nail the coffin shut for using n-acetylcysteine to prevent contrast-induced acute kidney injury.

Over 1000 patients each in the acetylcysteine and placebo groups, this study showed exactly equal 12.7% chance of acute kidney injury resulting from contrast exposure during cardiac catheterization.  In addition, the 30-day mortality was nearly identical at 2.2% for acetylcysteine and 2.3% for placebo, and only 3 patients in each group required dialysis within 30 days.

Perplexingly enough, the only advantage acetylcysteine had was a lower incidence in adverse effects versus placebo, 2.2% vs. 1.3%.  They do not mention what formulation their placebo formulation was, but apparently it caused more nausea & vomiting.

The authors also do a mini meta-analysis to evaluate why previous studies showed a benefit, and they additionally find that studies that had appropriately blinded allocation showed identical outcomes while patients with inadequate blinding demonstrated an acetylcysteine advantage.

"Acetylcysteine for Prevention of Renal Outcomes in Patients Undergoing Coronary and Peripheral Vascular Angiography."

Wednesday, September 14, 2011

Rivaroxaban Can Be Reversed, But Not Dabigatran

We all hate coumadin - difficult to control levels and causes life-threatening bleeding, but at least we can measure its activity and reverse it in a straightforward manner.  However, coumadin's days are at an end with the approval of the new oral anticoagulants - and the two most extensively evaluated are dabigatran (direct thrombin inhibitor) and rivaroxaban (factor Xa inhibitor).

This is a randomized, placebo-controlled trial of the reversal of dabigatran and rivaroxaban using prothrombin complexe concentrates - which, most importantly, have been theorized to be the only used agent for dabigatran.  Their results - in groups of 12 healthy volunteers - is that PCCs have no effect on any of the laboratory clotting parameters for dabigatran, but fully reverse rivaroxaban.

So, while there are no studies as of yet describing the acute reversal of either of these agents in a clinical situation, this is definitely concerning that we still have no theoretical way to treat life-threatening bleeding with dabigatran.

"Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate."

Tuesday, September 13, 2011

Predicting Poor-Performing Residents

This is an entertaining look into the residency training experience in the United States, which is renowned for its brutality in certain specialities.  As far as sleep-deprivation goes, it ranks right up there with some of the lowest quality of life professional jobs.

This is, basically, the quality-of-life information from the Internal Medicine in-service training examination, as reported in JAMA.  The authors have linked it to in-training examination results for the, probably predictable, association of poor work/life balance and poor in-training scores.

Interesting tidbits I noticed:
 - 15.3% of residents stated that life was as good as it could be.
 - PGY-1 and PGY-2 residents had nearly equal poor quality-of-life and work/life balance - which improves significantly PGY-3.
 - Over 40% of residents have >$100,000 in debts - and that was associated with poorer quality-of-life scores.
 - Improvements in quality-of-life for PGY-3 was mirrored by a corresponding increase in depersonalization.

Not a healthy experience, by a longshot.  Pity those whose residencies are longer than the bare minimum of 3 years.

"Quality of Life, Burnout, Educational Debt, and Medical Knowledge Among Internal Medicine Residents."

Sunday, September 11, 2011

More Platelets In Massive Transfusion

Where are we going to get all these blood products?  The rapidly growing body of literature backing early transfusion of FFP and platelets in massive transfusion protocols continues to tilt towards the 1:1:1 ratio.

This is a retrospective review of whether platelet transfusion impacts survival in trauma.  They identify three categories of ratios of platelets to RBCs (>1:20, 1:2, and 1:1) and measure a variety of different outcomes.  Briefly, more platelets helped with survival to 24 hours, but more platelets also increased multi-organ failure.  In the end, the initial survival differences were great enough that they outweighed the additional multi-organ failure for a significant survival benefit (52% vs. 57% vs. 70%).

They exclude 25 patients who died within an hour in an effort to mitigate survival bias.  However, looking at the breakdown of survival times, it looks as though almost all the mortality benefit to increased platelet ratios was realized in the first 6 hours - and then the mortality numbers worsen in tandem after that.  The authors state they were unable to truly quantify retrospectively whether the patients survived because they received more platelets vs. whether patients surviving longer were able to receive more platelets, and note that prospective trials will need to be performed.

I would also note that a significant portion of their high ratio patients also received Factor VII, for whatever that's worth.

So, we continue to await high quality prospective trials that specifically address the impact of survival bias.

"Increased Platelet:RBC Ratios Are Associated With Improved Survival After Massive Transfusion."
http://journals.lww.com/jtrauma/Abstract/2011/08003/Increased_Platelet_RBC_Ratios_Are_Associated_With.2.aspx