Month: September 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.”

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.”

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.”

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

Impedance Threshold Devices Are Useless

So, supposedly, impedance threshold devices installed inline for ventilation during CPR potentially improve hemodynamics via negative intrathoracic pressure.  This is a prospective, randomized, multi-center, placebo-controlled sham study that really meets a very high standard for internal validity.  Over 4000 patients in the ITD group, the sham ITD group, and the not-enrolled comparison cohort.

Short summary:
 – Minimal differences between groups.
 – 27.8% sham vs. 27.1% active device ROSC in the ED.
 – 8.2% sham vs. 8.2% active device discharge from the hospital.
 – No apparent harms from the ITD device, but no benefits either.

The most important point from this article is that we have gotten sloppy in our rush to implement supposedly new and beneficial therapies in medicine.  Hypothermia, TPA for stroke, Factor VIIa, direct thrombin inhibitors, etc. and we should add impedance threshold devices to the list.  The AHA has had ITD as a class IIa recommendation to improve hemodynamics since 2005 – six years of useless therapy and costs based solely on a theoretical model without proof of improved outcomes.  Hammering this point home never gets old.

“A Trial of an Impedance Threshold Device in Out-of-Hospital Cardiac Arrest.”
www.ncbi.nlm.nih.gov/pubmed/21879897

More Mistakes In An Unfamiliar System

Probably tells us what we already know – and likely underestimates the problem.

These authors take a retrospective look at all the reported medication errors between 2000 and 2005, and then try to associate increased errors with the involvement of a temporary staff member.  The problem is, they don’t actually have staffing documents that report which employees are temporary – they rely on the population of a QA field listing “contributing factors”, under which temporary staff is an option.  So, you can dismiss this as a bit of garbage-in/garbage-out depending on how accurate the reporting is – but, I figure, if anything, people will forget to implicate temporary staffing more frequently than not.
More interesting – and potentially confounding re: temporary vs. permanent – are the perceived reported reasons behind the medication error.  Temporary staff were more likely to be reported to have knowledge deficits, performance deficits, and fail to follow appropriate procedures.  I might read into that data that it’s easier for an unfamiliar temp to appear knowledge-deficient, although that’s just my own imagination.
From a risk management standpoint, the solution seems to be: whatever the retention costs of your permanent staff members, they are almost assuredly lower than the costs associated with the errors inflicted upon patients by temps.
“Are Temporary Staff Associated with More Severe Emergency Department Medication Errors?”

Epinephrine Neither Wins Nor Fails

The crux of the problem – epinephrine continues to improve short-term ROSC with uncertain long-term outcome improvement.

This is a prospective out-of-hospital arrest study from Australia in which epinephrine or saline placebo was given to patients during resuscitation by EMS.  And, like many studies before it, it fails to show a meaningful difference between patients receiving epinephrine and patients receiving placebo.  Rather, their primary outcome of survival to hospital discharge had 1.9% with placebo and 4.0% with epinephrine – but this result was not statistically significant with a p-value of 0.15.

Of course, what the lack of statistical significance means in this case is that this difference could have occurred by chance 15 times out of 100 times they performed this study – which, while not meeting the gold standard of 5 out of 100, is still a reasonably interesting clinical trend.  Like all studies before it, the short-term endpoints met statistical significance, including ROSC of 8.4% for placebo and 23.5% for epinephrine.  There are a few confounding differences between groups: more placebo patients had witnessed arrest, although the number with bystander CPR was the same; more placebo patients were endotracheally intubated in the field, which usually confers a survival disadvantage; and more epinephrine patients were ultimately transported to the hospital from the field.

So, there’s two ways to look at it: 1) epinephrine works, and we just need to figure out how to salvage more of those ROSC or 2) epinephrine is flogging far too great a number of lost husks back to life that will go on to consume ICU resources and expire regardless.

But, if we’re not going to give epinephrine, how do we otherwise look busy during a code?  And, what happens downstream to our epinephrine ROSC that fail to leave the hospital or the ER, and can we prevent it?

I am still not sure what the right answer is – like many diseases, cardiac arrest patients are a heterogenous group in which there is almost certainly a subset of patients that benefits from epinephrine, but we don’t yet know who that might be.

“Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial.”
www.ncbi.nlm.nih.gov/pubmed/21745533

Thanks to @cliffreid of Resus M.E! for first noting this article.

Sternal IO is the Best IO

All our cardiac arrest patients roll in these days with an IO in place – and we are full proponents of rapid, successful access in the uncontrolled field environment.  But, how effective is it really in the CPR situation?

So, this is an animal study that tries to address the theoretical efficacy of intraosseous access versus central venous access.  They use injection of dye tracers into Yorkshire swine for a comparison between intraosseous sternal, intraosseous tibial, and external jugular central venous cannulation.

Unfortunately, this is a good news/bad news study.  The good news – peak concentrations were achieved only slightly more slowly in the arterial circulation following sternal intraosseus injection than the gold standard central venous injection.  And, the peak concentrations were nearly identical.  Bad news, the tibial IO was half the speed and half the arterial peak concentration of the sternal IO.

In theory, this is of relative importance depending on which medication you’re using – presumably the speed of administration matters in CPR and peak concentration may matter as well.  Of course, this is limited as 1) pigs and 2) efficacy vs. effectiveness, because they’re not measuring clinical outcomes.

But it’s interesting to worry about.  Too bad it’s hard to do chest compressions with your access point where your hands are supposed to go.  It would be interesting to compare this result to a humeral head IO.

“Pharmacokinetics of Intraosseous and Central Venous Drug Delivery During Cardiopulmonary Resuscitation.”
http://www.ncbi.nlm.nih.gov/pubmed/21871857

New Pediatrics UTI Guidelines

For children between 2 and 24 months of age, the relevant high points for EM:
 – Don’t use bag urines.  Catheterization or suprapubic aspiration is the only acceptable way to make a diagnosis.  However, if you’re stuck, and you have to use a bag, a completely normal bag urine is diagnostic.
 – Send a culture to definitively establish the diagnosis based on pyuria and/or bacteruria and the presence of at least 50,000 CFU/mL of a uropathogen.
 – Oral antibiotic recommendations listed include amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, and a range of oral cephalosporins for at least 7 days.  They do not have any evidence to compare 7, 10, and 14 day courses.  Nitrofurantoin is not appropriate.

Nothing terribly earthshaking – seems all pretty reasonable.

“Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis and Management of the Initial UTI in Febrile Infants and Children 2 to 24 Months.”
pediatrics.aappublications.org/content/early/2011/08/24/peds.2011-1330

When Does a Repeat Head CT Have Value?

Not practice-changing, but an interesting observational report regarding when these authors found value in performing a repeat head CT after minor head trauma.

Specifically, they looked at a subgroup of patients whose initial head CT was normal after blunt trauma, but received a repeat head CT an average of ~8 hours later for an abnormal neurologic examination.  These abnormal neurologic examinations were further stratified into three groups – a “persistently abnormal” exam, a “acute deterioration” in neurologic examination, and a catchall “unknown” group.  The first two groups had mean GCS of 12.4 and 14.5 – but the reason why the “unknown” group is what it is – their average GCS is 4.

They found that repeating the head CT in the 61 patients they had with persistently abnormal neurologic examinations did lead to some worsening of the initial findings – but did not change management in any cases.  However, 6 of the 21 patients who had an acute deterioration had a change in management, as well as 1 patient in the unknown group.

Small sample, but interesting, nonetheless.

“Utility of Repeat Head Computed Tomography in Patients With an Abnormal Neurologic Examination After Minimal Head Injury.”
www.ncbi.nlm.nih.gov/pubmed/21857258