Retiring Steroids for Hives

This is one of those perfectly unglamorous, yet infinitely practical sorts of topics we encounter in everyday Emergency Medicine. I must see a patient with urticaria, almost always without known underlying trigger or etiology, nearly every other shift. They are itching furiously, and, well – it’s an Emergency!

In true “don’t just stand there, do something!” fashion, I’ve done what I can to help. This typically means “something stronger”, something not over-the-counter, and is usually a dose of dexamethasone to augment antihistamine therapy.

This small trial of 100 patients randomized patients with uncomplicated urticaria to levocetirizine (a H1 receptor-blocker) plus 40 mg of prednisone for four days, or levocetirizine plus placebo. Patients were assessed at several subsequent time points for “itch score”, rash recurrence, and other adverse events – and the winner is: placebo! There was no obvious difference or trend favoring those patients receiving steroids.  There is, however, always the potential for Type II error with such a small sample, but when a positive outcome is difficult to demonstrate, the magnitude of effect is not likely to be large.

Interestingly, they screened 710 patients in order to enroll 100, with 412 not meeting inclusion criteria. These exclusions were mostly evenly distributed between the following criteria: angioedema or anaphylaxis, use of antihistamines or glucocorticoids prior to the ED visit, and rash of greater than 24 hours duration. These limitations do limit the generalizability of these findings, considering their study cohort was ultimately only about one-fifth of all comers. It is probably still reasonable to suggest from a Bayesian sense, at least, steroids should be assumed not to have value in somewhat wider a population than explicitly testing here, but this is not definitive.

“Levocetirizine and Prednisone Are Not Superior to Levocetirizine Alone for the Treatment of Acute Urticaria: A Randomized Double-Blind Clinical Trial”

Goodness Gracious We’re &*@ing Up Sinusitis

The American Academy of Allergy, Asthma, and Immunology has a lovely Choosing Wisely statement on sinusitis, featuring the following highlights:

  • Antibiotics usually do not help sinus problems.
  • Antibiotics cost money.
  • Antibiotics have risks.

So, how does one of the United States largest organized health systems fare for the treatment of such a simple, basic, commonplace condition?  A system, perhaps, that prides itself on internal quality initiatives and guideline adherence?  Well, based on this sample of 152,774 Primary Care, Urgent Care, and Emergency Department patients in Kaiser Southern California, they are: still awful.

  • ED patients received antibiotics 72.8% of the time.
  • UC patients received antibiotics 89.3% of the time.
  • PC patients received antibiotics 89.8% of the time.

And, not only that, antibiotic usage was all over the map, with large cohorts receiving prescriptions for less-appropriate options such as azithromycin and trimethoprim-sulfamethoxazole.

Why are we so terrible at this?

“Low-Value Care for Acute Sinusitis Encounters: Who’s Choosing Wisely?”

When Anaphylaxis Makes a Comeback

The frequency of biphasic anaphylaxis is a subject of some controversy, with most estimates derived from retrospective chart review.  The frequency may be as high as 20%, as low as 3%, or those may yet be gross overestimations based on partial symptom recurrence.

For these folks, the answer was: 14.7%.

This is yet another evaluation of Emergency Department visits for anaphylaxis, as collected by retrospective chart review.  Looking at one year’s worth of data collected at two pediatric hospitals in Canada, these authors identified 484 visits for anaphylaxis with adequate data for analysis.  Of these visits, 71 met their criteria for a biphasic reaction: a period of full symptom resolution lasting at least an hour, followed by recurrence of symptoms requiring additional pharmacologic intervention.  They subsequently reviewed features of the initial reaction to determine any potential predictors of biphasic manifestations.

Some of their features make sense, and some – none.  Independent predictors included delayed ED presentation, wide pulse pressure, multiple doses of epinephrine to treat the initial episode, and administration of beta-agonists in the initial episode.  Essentially, those patients with the most severe, multi-system involvement.  However, their strongest odds ratio for predicting return of symptoms was for patients simply aged 6-9 years of age – and the authors do not address the aberration in their discussion.

So, ultimately, this study doesn’t reliably alter our management.  Chances are, you’ve already been observing the mildest anaphylaxis for the shortest time, and the most severely ill for longer.  Thus, as seen in this cohort, most of these severely ill patients were still undergoing observation in the ED when the biphasic reaction occurred – 3 to 6.5 hours later.  All told, 18 patients were discharged from the ED and returned with biphasic symptoms – with a median time of 18.5 hours to return.  So, unfortunately, there’s no reasonably useful clinical endpoint to observation that would catch all revisits – and the best course of action is simply to ensure patients have epinephrine for home use at discharge, and inform them of the small likelihood of recurrence.

“Epidemiology and clinical predictors of biphasic reactions in children with anaphylaxis”

An Abbreviated IV Acetylcysteine Regime for Acute APAP Toxicity. Short, Sweet, and…. Safe?

A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at
Anyone who has perused the literature on APAP toxicity will notice the protocols we use to guide us in the diagnosis and treatment of acute APAP overdose are based primarily on ultra-conservative estimates of risk rather than true clinical data. As a result we are left with acetylcysteine (NAC) treatment regimes that, though effective are cumbersome and convoluted. The current IV NAC regime consists of 3 different weight-based doses over various time periods within the first 25 hours. This regime is costly and frequently causes vomiting and anaphylactoid reactions. In a move towards practicality, authors from the Royal Infirmary of Edinburgh (the birthplace of the Rumack-Matthew Nomogram) performed a RCT comparing this traditional dosing scheme to a far more rational one.

These authors propose the initial bolus dose of NAC to be infused over a longer period (2 hours vs 15 min) followed by a maintenance infusion delivered over 12 hours in contrast to the traditional 24. They theorized that these modifications would reduce the amount of adverse reactions, primarily due to the initial rate at which NAC is infused and at the same time, limit the duration of treatment required. In a 2X2 factorial design, the authors also examined the effects of ondansetron on the rates of adverse reactions in both the traditional and modified NAC regimes.

From September 2010 to December 2012, 222 patients underwent randomization at three different UK hospitals. The authors found that both the modified dosing regiment and ondansetron prophylaxis decreased the rate of vomiting and retching in patients undergoing treatment for acute APAP intoxication. More impressively the modified dose regime seemed to dramatically reduce the incidence of serious anaphylactoid reactions from a frighteningly high 31% to 5%.

As far as safety is concerned there was no difference between the traditional and modified dosing regimes in the number of patients with an elevation in AST levels or microRNA miR-122 harpega(a more sensitive marker of hepatic injury as per the authors’ claims). There was an interesting increase in both AST levels and microRNA miR-122 levels in those given ondansetron when compared to placebo. Though this did not translate into any long term hepatic injuries and it is unclear if this increase was just noise secondary to the small sample size, the authors warn against its prophylactic use before further studies are performed to assess its safety.

Given that the Rumack-Mathews Nomogram was designed to be highly sensitive at the cost of its specificity, and very few patients above treatment threshold go on to clinically relevant hepatic toxicity, it is hard to say how many of these patients actually benefited from treatment. In addition 30% of this population were under the 4 hr 200mg/L level and were only treated because of the recent changes in the UK guidelines to lower the treatment threshold to 100mg/L. Due to the poor specificity and small sample size, it is difficult to truly assess the safety of this refined protocol. Using surrogate endpoints thought to be more sensitive for hepatic injury like a 50% rise in AST  (in contrast to the more traditional measurement of AST > 1000 IU) and microRNA miR-122, may provide us with some idea of efficacy, but does not answer the more pressing question. Are the patients treated with this modified regime at a higher risk for clinically relevant hepatic injury? This would require a much larger study population.

“Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial”


Famoditine in Urticaria

Dredged up for Journal Club from The Year 2000 (that was the future, once).

You might scoff at this article because it enrolls a grand total of 25 participants with acute urticaria, ten of which receive diphenhydramine and fifteen receive famotidine.  You might be more impressed to know that this is pretty reflective of the evidence we have regarding H2-blockers in the treatment of urticaria.  Another study from 1993 compares diphenhydramine, famotidine, and cromolyn sodium – and only enrolls 20!

It is mildly amusing to see them report there is no significant difference between the groups when they don’t have the power to detect any.  Regardless, our H2 blockers provide some relief, it’s likely additive, and they’re inexpensive and safe.

The “definitive” study at present supporting our H1 + H2 blocker for acute urticaria or allergic reaction in the emergency department enrolls 91, and it shows diphenhydramine + cimetidine is superior to diphenhydramine alone.