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- Epinephrine -
7/25/01 re: Myocardial infarct after epinephrine treatment Coincidentally your article Subcut epi in the elderly (Academy News-Oct 2001) arrived shortly after I saw a patient with an interesting and unhappy history. This patient is only in his 30's and had a clear-cut anaphylactic reaction to a hymenoptera sting. He went to the ER. Besides the other signs of anaphylaxis, he had hypotension. Ostensibly only 45 seconds after sub-cut Epi was administered he developed crushing chest pain and EKG showed signs of acute MI. He remained in the hosp for a week. Cardiology convinced he developed coronary spasm from the epi. No history of cardiovascular disease. When I saw this patient, I thought that it was most unusual and your article confirmed my thoughts. Seems to me a good case to write up. Some of the details need to be confirmed and I am in the process of doing such. I thought that you might be interested in this info and any thoughts you might have about where to submit this case report would be appreciated. Based on my review of the literature, your case does sound very unusual if the patient had no predisposing anatomic or metabolic abnormality. Was a coronary arteriogram performed to look for an underlying anatomic abnormality? Have a lipid profile and studies for hypercoagulable state been done? I have enclosed below the abstract of a case report similar to that described by you except that the patient had a number of predisposing risk factors. I would appreciate hearing from you if further investigation detected risk factors for coronary artery disease in your patient.
Ann Allergy 1993 May; 70(5): 396-8
Myocardial infarction induced by coronary vasospasm after self-administration of epinephrine.
Saff R, Nahhas A, Fink JN.
Department of Medicine, Medical College of Wisconsin, Milwaukee.
"A case of a 30-year-old man who developed a myocardial infarction after self-administering an Epi-Pen for an episode of idiopathic anaphylaxis is reported. The patient had numerous risk factors for coronary artery disease, and it was suspected that epinephrine-induced coronary spasm caused the infarct. The Epi-Pen Junior may be indicated in such adults with numerous risk factors for coronary artery disease who are at risk for recurrent anaphylaxis."7/25/01 re: Epi-pen dosage in children Why is there a difference in the following Academy publications: 1) Journal of Allergy & Clinical Immunology August 1998 Volume 102 No 2 - AAAAI position statement says to use Epi-pen JR (0.15mg) from 10-20 kg. 2) April/May Academy news (page 17) says that the AAAAI position statement urges us to use the Epi-pen JR (0.15mg) from 10-15 kg (not 10-20 kg as noted in reference #1). I know that there is little science to this, but why is there the discrepancy between the two ACADEMY publications on the same topic? I was not involved in the formulation of either of the recommendation statements you mentioned so cannot personally tell you the discussion on which these statements were based. I do believe that there were no typos involved but rather a reflection of the varied opinions about the appropriate Epi-Pen dose to use in children of various sizes. This "flexibility" in Epi-Pen dosing is reflected in the dosing instructions written by the Epi-Pen manufacturer for the PDR (55th Edition, year 2001): "A dosage of 0.01 mg/kg body weight is recommended. Epi-Pen Jr., which provides a dose of 0.15 mg, may be more appropriate for patients weighing less than 30 kg. However, the prescribing physician has the option of prescribing more or less than these amounts, based on careful assessment of each individual patient and recognizing the life-threatening nature of the reactions for which this drug is being prescribed."
I believe that the recommendations you mentioned were based on a consensus of the participating allergists. However, because the recommendations made in the 1998 Position Statement were directly tested by an expert such as Dr. Simons, I would go along with her recommendation to you that the use of Epi-Pen, Jr for children up to 20 kg weight is reasonable. Recall also her comment that the dose-dependent desired effects couldn’t be divorced from the dose-dependent adverse effects of epinephrine.
7/10/01 re: What is current epinephrine dosing in children? After reading Dr. Estelle Simon's very interesting work on the dose of epinephrine to be used in anaphylaxis, I again looked up the "official" guidelines from the AAAAI, and seem to have two different recommendations which are as follows: 1) In the April/May 1997 Academy News (page 17), a "Position Statement: Anaphylaxis in schools & other childcare settings)" states that the EpiPen Jr should be used for children weighing 10-15 kg (or 22 to 33 lbs). The EpiPen 0.3mg should be used for those weighing greater than 15 kg (or 33 lbs).
2) In the Journal of Allergy & Clinical Immunology August 1998 Vol 102 No 2, the Position Statement of the AAAAI entitled "Anaphylaxis in schools and other child-care settings" states in its appendix II that Epipen Jr is used for children weighing 10 to 20 kg (22-45 lbs), and that EpiPen 0.3 mg is used for those weighing greater than 20 kg (45 lbs).
Thus the Academy News says EpiPen 0.3 should be used for kids over 15 kg, while the JACI version of this position statement says 0.3 mg EpiPen should be used for those weighing greater than 20 kg.
Can you explain the discrepancy? And which is the actual AAAAI recommendation?
I consulted Dr. Estelle Simons concerning your question and learned that she had recently responded to a direct question from you about this matter. I enclose a copy of that response which was forwarded to me from her office, below: "The AAAAI Position Statement (J Allergy Clin Immunol 1998;102:173-6) states that the EpiPenTM Jr 0.15 mg should be used for children weighing 10 to 20 kg and that the EpiPenTM 0.3 mg should be used for children weighing more than 20 kg. These recommendations differ from those found in other sources, including the EpiPenTM Jr and EpiPenTM package inserts. They are, however, the recommendations we tested in our pilot study (Epinephrine Injection (EpiPenTM Jr vs EpiPenTM) in Young Children at Risk for Anaphylaxis, J Allergy Clin Immunol 2001;107;S58), in which we found that the beneficial pharmacologic effects of epinephrine could not be divorced from the adverse pharmacologic effects. Based on this data, the AAAAI 1998 recommendations are reasonable."
5/16/01 re: Principles of ER treatment of anaphylaxis What are the current recommendations for the ER treatment of anaphylaxis? The approach to treating anaphylaxis is a complex subject that involves evaluation of the severity of the reaction, the organ systems involved, the age of the patient, co-morbid conditions and other treatment agents taken by the patient. Space limitations do not allow me to give a detailed description of all these facets. For background material, I suggest that you review the Practice Parameters created by the Joint Task Force in Allergy and Immunology. This is also published in the J. of Allergy Clin. Immunology 1998;101:S469-71. Another good source of information is a review chapter on anaphylaxis written by Michael Blaiss (Current Practice of Medicine, 1998).
Some points not commonly discussed and worth mentioning:
1) Epinephrine is still the key therapeutic agent. However, it has to be given promptly in adequate doses. Studies have shown that a characteristic common in fatal and near-fatal anaphylactic episodes was the delay in epinephrine administration until there was a catastrophic event (e.g. cardiac arrest). How much to give depends on the patient's body size with some debates among authors (see Korenblat et al. Allergy and Asthma Proceedings 1999;20:383-6). Studies by Simons et al have shown that epinephrine is absorbed more rapidly (very important) from intramuscular than from the customary subcutaneous administration, particularly if the patient is hypotensive ((JACI 1998;101:33-7). Unfortunately, the inhalation route for epinephrine is not practical because of the large number of inhalations required to get adequate systemic dosing (Pediatrics 2000;106:1040-4). Inhaled epinephrine may help if there is upper airway edema but is not a substitute for expert installation/maintenance of an artificial airway if needed.
2) H1 antihistamines generally work too late to help in the critical early minutes of anaphylaxis, but may help decrease later or recurrent symptoms (see below). H2 antihistamines should theoretically help if there is major vasodilatation with hypotension although it is difficult to find definitive evidence of their efficacy in the literature.
3) However, administration of adequate amounts of fluid is very important if there is hypotension. This may be more effective than epinephrine in reversing hypotension. Sometimes very large amounts of fluid (possibly containing colloid) are needed because of the large amount of fluid leaking from the vascular compartment into the extracellular space
4) A very important aspect of ER treatment is the recognition that anaphylactic manifestations often recur hours after what appears to be initial therapeutic reversal of the acute reaction. Therefore, monitoring the patient closely for a period of up to 8 hours after apparently initial control is a prudent step, particularly if the reaction was severe and/or the patient has underlying major disease, particularly cardiac disease.
