Una cuestión de presión…

La estadística de la insuficiencia cardíaca revela consistentemente que por lo menos el 50 % de estos pacientes presentan función sistólica normal (FeyVI >= 55 %) o casi normal (FeyVI entre 45 y 54 %). Entonces, evidentemente, no siempre alcanza con encontrar que la función sistólica está conservada para descartar insuficiencia cardíaca. Por lo general, … Sigue leyendo

‘Roid Rage – Right Route and Dose?

The Gist:  For many indications, such as croup, asthma, and anaphylaxis, oral steroids are equally as effective and work as quickly as intravenous steroids and the effective doses are likely lower than we frequently give.   Check out this free steroid converter to prevent preposterously high doses of methylprednisolone or dexamethasone.

The case: A 13 month old presents to the ED with a harsh, barky cough.  Parents report a few days of prodromal upper respiratory symptoms but the child has good oral intake and vital signs.  The child is playful, with a snotty nose and intermittent stridor.  Given the clinical diagnosis of croup, how much dexamethasone do you give?  These bits of Free Open Access Medical education (FOAM) served as the impetus behind the development of my steroid in croup practice: EM PEM podcast, HQMedEd videoEmergency Medicine Literature of Note post

Croup (laryngotracheobronchitis)- A single dose of steroids in croup is the mainstay of treatment in mild to moderate disease as they decrease return visits (RR 0.5, 95%CI 0.3-0.7) and hospital length of stay compared with placebo [1].  The number needed to treat (NNT) is 11 in the ED population (or 5 for improvement in a clinical score).  The historically touted dose of dexamethasone is 0.6mg/kg orally as this is the most studied dose; however, lower doses have demonstrated non-inferiority and have even made it into textbook recommendations [2,3]. The 0.6mg/kg dose of dexamethasone is equivalent to ~3.75mg/kg of prednisone - overkill for this disease process?
  • Dexamethasone 0.15mg/kg PO (can give IV solution orally)
A Cochrane Review demonstrates no significant difference in return visits between "high dose dexamethasone" (0.6mg/kg) and 0.15mg/kg with a risk ratio of 1.04 (95%CI 0.62-1.75) [1]. Hospitals, particularly in Australia where the bulk of the steroid in croup literature originates, have used 0.15mg/kg routinely for the past 18 years, and observational data demonstrates a decline in admissions [3,4].

Limitations - the studies are all pretty small and are not powered to detect small differences.  Are these small differences clinically significant?  Croup also tends to be a self-limiting disease so these studies may be far underpowered to capture rare complications.  Furthermore, many of the studies only look at mild to moderate croup so selection bias may demonstrate.  Yet Fifoot et al excluded this group (Westley score <2) and still found that 0.15mg/kg was as efficacious as larger doses.  The ToPDog study is pending in Australia to demonstrate the effective dose on a larger scale.

Asthma - Glucocorticoids, given within the first hour of presentation to the ED, may reduce need for hospitalization with a NNT of 8 to prevent one hospital admission and, in pediatrics, the length of stay [8].  The literature demonstrates that IV steroids have no superiority over the oral route and the American Thoracic Society recommends oral steroids [8,9].  In fact, Rosen's strongly emphasizes the preference of the oral route, unless the patient is vomiting, in extremis, or has gastrointestinal malabsorption [7].  Prednisone can be swallowed quickly between/during albuterol treatments.
  • Pediatrics: Prednisone 1-2 mg/kg PO
    • Dexamethasone phosphate 0.6 mg/kg PO 
  • Adults:  Prednisone 40-80 mg/day PO
    • Unable to take PO? Methylprednisolone is weight based, at 1mg/kg, not the standard 125 mg given routinely in the ED, which is equivalent to approximately 156 mg of prednisone.  
COPD - no effect on hospitalizaiton rate, but steroids decrease return visits [2]. 
  • Prednisone orally, No benefit to doses higher than 60 mg[2]. 
  • 5 days equivalent to longer courses [10].  
Anaphylaxis - The treatment for anaphylaxis is intramuscular epinephrine [2,7,11].  While glucocorticoids have become part of the standard treatment in anaphylaxis, it's crucial to remember that this therapy is classified as an "adjunct," and is not a treatment for acute anaphylaxis.  Steroids may play a role in resolving the cutaneous manifestations of urticaria and may prevent biphasic or refractory anaphylaxis; however, this is not a proven treatment modality and this intervention takes hours to work.  Furthermore, we historically do not give epinephrine readily enough in anaphylaxis and emphasis on second and third-line agents may detract from actually treating anaphylaxis.

The core emergency medicine texts, Rosen's and Tintinalli's, both recommend IV methylprednisolone in anaphylaxis, followed by a short burst of prednisone for 3-5 days but these recommendations do not come with supporting citations [2,7].  A Cochrane Review turned up no evidence on this therapeutic endeavor [12].  The pathophysiologic argument for IV steroids exists in the notion that patients may have impaired absorption secondary to shunting of blood away from the GI tract.  So, what's the answer?
  • Shock/sick patients - intravenous steroids such as hydrocortisone or methylprednisolone are likely the right answer.
  • The rest of the anaphylaxis patients that are able to swallow  - oral prednisone 40-60 mg/day for 3-5 days.   
Are there downsides to giving IV medications in anaphylaxis?  Medication errors abound in anaphylaxis and an IV may create an accidental error in route of administration (although this would be needed for resuscitation, should the patient be sick) [13].

1.  Russell KF, Liang Y, O’Gorman K, Johnson DW, Klassen TP. Glucocorticoids for croup. Cochrane database Syst. Rev. 2011;(1):CD001955.
2. Tintinalli's Emergency Medicine: A Comprehensive Study Guide.  7th ed, 2011.  p509, 515, 789-790, 805
3. Geelhoed GC, Macdonald WB SOPediatr  Oral dexamethasone in the treatment of croup: 0.15 mg/kg versus 0.3 mg/kg versus 0.6 mg/kg.  Pulmonol. 1995;20(6):362.
4.  Dobrovoljac M, Geelhoed GC. 27 Years of Croup: an Update Highlighting the Effectiveness of 0.15 Mg/Kg of Dexamethasone. Emerg. Med. Australas. 2009;21(4):309–14.
7.  Rosen's Emergency Medicine.  7th ed, 2009.  p 897.
8. Bh R, Spooner C, Ducharme F, Bretzlaff J, Bota G. Corticosteroids for preventing relapse following acute exacerbations of asthma ( Review ). 2008;(4).
9.   Schatz M, Kazzi A, et al.  Joint Task Force Report: Supplemental Recommendations for the Management and Follow-up of Asthma Exacerbations.  Proc Am Thorac Soc Vol 6. pp 353–356, 2009
10.  Leuppi JD, Schuetz P, Bingisser R, Bodmer M,et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial.  JAMA. 2013 Jun 5;309(21):2223-31. 
11.  Gaeta TJ, Clark S, Pelletier AJ, Camargo CA. National study of US emergency department visits for acute allergic reactions, 1993 to 2004.Ann Allergy Asthma Immunol. 2007 Apr;98(4):360-5.
12.  Kjl C, Fer S, Sheikh A. Glucocorticoids for the treatment of anaphylaxis ( Review ). 2012;(8).
13.  Benkelfat R, Gouin S, Larose G, Bailey B. Medication errors in the management of anaphylaxis in a pediatric emergency department. J Emerg Med. 2013 Sep;45(3):419-25. 

Dabigatran-related bleeding: a case series

Pradaxa32 out of 5 stars

Clinical Experience of Life-threatening Dabigatran-Related Bleeding at a Large, Tertiary Care, Academic Medical Center: a Case Series. Ross B et al. J Med Toxicol  2014 Jan 3 [Epub ahead of print]


The authors retrospectively reviewed patients on dabigatran (Pradaxa) admitted to UMass Memorial Medical Center (Worcester) for bleeding.

They identified 7 patients with intracranial hemorrhage (ICH) and 4 patients with gastrointestinal bleeding.  Although they present copious information regarding baseline characteristics, treatment modalities and outcomes, with a study population this small and non-standardized clinical management, the details represent essentially random noise.

The authors really don’t reach any useful conclusions from the data, and neither can I. Of note (or maybe not), 2 patients were treated with recombinant factor VIIa (rFVIIa) which, as the authors point out, “has not been prospectively studied in humans for the management of dabigatran-related bleeding.” Those 2 patients both had ICH and were the only ones who received rFVIIa. Of course, this association does not establish causation. However, since rFVIIa does not have an established benefit in these patients, but does increase the risk of thrombosis, I wish the authors had specifically discussed these cases. They state that “No patients in this observational case series suffered from any thrombotic event,” they do not explain the basis of this claim.

By the way, there were 3 deaths in this series, 2 in patients with ICH, 1 in a patient with GI bleeding.

Given the weakness of the data, the conclusion is somewhat lame: “Patients with severe dabigatran-related bleeding may benefit from a standardized approach to treatment.” Well, yes. They may benefit from any number of things. Unfortunately, the paper gives little insight into what this “standardized approach” might be.

Related posts:

Pearl: estimating renal function in patients on dabigatran (Pradaxa)

Massive bleeding associated with dabigatran

Case report: hemodialysis for dabigatran overdose

The many potential problems with using dabigatran

New York times on dabigatran

Case series: four patients with dabigatran-associated bleeding

Guidelines for reversing overdose of dabigatran (Pradaxa) and other new anticoagulants

Care Report: fatal GI bleed 6 days after one dose of dabigatran (Pradaxa)

Dabigatran: is laboratory monitoring really unnecessary?

Dabiagtran and the trauma patient

Dabigatran Toxicity: The Top 10 Questions

Review: the bleeding patient on dabigatran

Dabigatran and the elderly

Dabigatran etexilate: a new challenge for emergency physicians and toxicologists





Stop skin testing

This post came from a question received in our simulation lab a couple of weeks ago. Mainly, there was a simulated patient with latrodectus envenomation, and there was a fair amount of discussion about skin testing prior to administration on antivenom. Now, when I say discussion, what really happened was some faculty said skin testing was recommended by the package insert and all of their prior readings, whereas the residents were simply asking “why?” Then both groups practiced their google-fu and were able to come up with abstracts to support their viewpoints.

So, yet again, it seems there might be a generational gap between evidence and practice, so I figured I would try to answer their question here. And yet, when I went to search, there haven’t been a large amount of RCTs for skin testing, which isn’t shocking for the toxicology literature.

However, there have been a few decent case series that do not show a benefit to skin testing, as well as a few case series that demonstrate the safety profile of latrodectus antivenom. Putting these together, one could logically make the case against skin testing for latrodectus antivenom. However, there have now been two case reports of deaths from latrodectus antivenom use, one in a young woman with a history of asthma who received an undiluted push dose of antivenom, and more recently a man, also with asthma, who received a diluted dose of antivenom but died after experiencing anaphylaxis. The authors feel his death was likely from PE, but it still happened secondary to antivenom.

This article from Thailand was a retrospective review of snake bites who received antivenom. Over a little more than nine years, there were a total of 254 cases, 211 of which received skin testing. Ten of these patients had positive skin tests, and received different treatment. Desensitization was used in 5, and “close observation” was used in the other 5, but they still received undiluted antivenom. There were no reactions in any of the 10 patients with positive skin tests. Conversely, 7 patients with negative skin tests had reactions to the antivenom, and two who did not receive skin testing also had reactions. So the sensitivity of skin testing in their paper is 0%, and the specificity was 96.4%. Not terribly helpful for making decisions in management.

The good news for the practicing physician is that the weight of the current evidence has led the WHO to recommend against skin testing (at least for snake antivenom) as it leads to delays in treatment and does not help in decision making.

Skin and conjunctival “hypersensitivity” tests will reveal IgE mediated Type I hypersensitivity to horse or sheep proteins. However, since the majority of early (anaphylactic) or late (serum sickness type) antivenom reactions result from direct complement activation rather than from IgE mediated hypersensitivity, these tests are not predictive. Since they may delay treatment and can in themselves be sensitising, these tests should not be used [level of evidence T].

They do have the caveat that they only recommend antivenom treatment in patients who the benefits of said treatment outweigh the risks of allergic reactions.

My personal practice is to not perform skin testing. There is a very small number of patients who I feel need antivenom that I would withhold treatment based on a positive skin test. And since preventive treatment has not been proven effective, again it would only serve to delay definitive care. If I had a patient with a known severe allergy history, I would probably pretreat them (ore concurrently treat them), but I would also get epinephrine and advanced airway equipment to the bedside. The harms and costs of a single dose of steroids and antihistamines are exceedingly low, and you have less of a risk of some “expert” saying you were acting cavalier.

Low incidence of early reactions to horse-derived F(ab′)2 antivenom for snakebites in Thailand

Of note, skin testing doesn’t appear to work for drugs either, so maybe there’s no point in doing it for anything emergent. In this paper, the skin test for cephalosporins had a sensitivity of 0%, specificity of 97.5%, negative predictive value of 99.7%, and a positive predictive value of 0%. Nobody with positive skin tests reacted to the medication, and 4 people with negative tests did have immediate reactions.

Validation of the cephalosporin intradermal skin test for predicting immediate hypersensitivity: a prospective study with drug challenge.

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