Why is the recommendation for epinephrine injection in the lateral thigh as opposed to the anterior thigh muscles?


The recommendation for injecting epinephrine in the lateral thigh is to facilitate most rapidly achieving epinephrine in the peripheral blood to combat anaphylaxis. The greater vascularity of muscle makes IM injection preferable to SQ injection. The subcutaneous body fat tends to be thinner allowing IM access most readily at this location. Previously the recommendations were to use subcutaneous injections to minimize the risk of inadvertent intravenous injection. This minimal risk is more than compensated by the greater benefit in treating an immediate, potentially life-threatening condition. The median time to cardiac or respiratory arrest in fatal food allergy reactions was 30 minutes, for insect anaphylaxis was 15 minutes and for in hospital medicine reactions was 5 minutes (Humphrey; Greenberger). Thus, time for treatment is critical.

The data for this recommendation is founded primarily on information from Dr. Estelle Simons and colleagues.

I have enclosed a question from the archives of Ask The Expert that also provides another reference.

Humphrey RS. Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy. 2000;30:1144e1150 (III).

Greenberger P, Rotskoff BD, Lifschvitz B. Fatal anaphylaxis: post-mortem findings and associated comorbid diseases. Ann Allergy Asthma Immunol. 2007;98:252e257 (III).

Simons FE, Roberts JR, Gu X, Simons KJ. Epinephrine absorption in children with a history of anaphylaxis. J Allergy Clin Immunol. 1998;101:33e37 (Ib).

Simons FE, Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular subcutaneous injection. J Allergy Clin Immunol. 2001;108:871e876 (Ib).

Quote from Practice Parameter: The Diagnosis and Management of Anaphylaxis
“Administer epinephrine. Aqueous epinephrine 1:1000 dilution (1 mg/ml), 0.2-0.5 ml (0.01 mg/kg in children, max 0.3 mg dosage) intramuscularly in the lateral aspect of the thigh or subcutaneously every 5 min, as necessary, to control symptoms and increase blood pressure. If the clinician deems it appropriate, the 5-minute interval between injections can be liberalized to permit more frequent injections. Intramuscular epinephrine injections into the thigh have been reported to provide more rapid absorption and higher plasma epinephrine levels in both children and adults than intramuscular or subcutaneous injections administered in the arm. However, similar studies comparing intramuscular injections to subcutaneous injections in the thigh have not been done. These studies were not performed in patients experiencing anaphylaxis. The generalizability of these findings to the clinical setting of anaphylaxis has not been established. There are no studies that support the use of epinephrine in the treatment of anaphylaxis when delivered by a non-parenteral route. However, alternative routes of administration have been anecdotally successful. These include, for example, inhaled epinephrine in the presence of laryngeal edema or sublingual administration if an intravenous route cannot be obtained. Endotracheally administered dosages have also been proposed for use when intravenous access is not available in intubated patients experiencing cardiac arrest.”

Appropriate route of administration for epinephrine to treat an anaphylactic reaction
Q: I have Dr.'s orders to give Epinephrine sub cu in case of allergic reaction. What is the best injection site? I have read there are several different thoughts on this. Can you give me the most current information regarding this question?

A: The preferred route for the administration of epinephrine is intramuscular in the right lateral thigh as is discussed in the reference noted below. This is because the rate of absorption (time to maximum concentration in the serum) is far quicker than when the drug is given subcutaneously. Just as important, however, is the location since the absorption from the deltoid in the arm is far less speedy than when the drug is given in the right lateral thigh due to the rich vasculature of the thigh muscle.

Curr Opin Allergy Clin Immunol. 2003 Aug;3(4):313-8.
Use of epinephrine in the treatment of anaphylaxis.
Lieberman P.
Author information
Division of Allergy and Immunology, Department of Medicine, University of Tennessee, Memphis, Cordova, Tennessee 38018, USA.
Purpose of Review: This paper is intended to review recent literature that impacts the use of epinephrine in the therapy of anaphylaxis.
Recent Findings: The most important recent finding regarding the administration of epinephrine is that the intramuscular route of administration is the route of choice for the treatment of anaphylaxis, and the lateral aspect of the thigh is the site of choice. In addition, recent research emphasizes the fact that epinephrine is grossly underused in the management of anaphylaxis, which accentuates the need for further education of both physician and patient in this regard.
Summary: Several major themes have emerged from this review of the recent literature. The finding that the intramuscular route of administration for epinephrine is superior has now been recognized by the guidelines, and because the site of choice has been found to be the lateral aspect of the thigh, the needle used for injection must be long enough to penetrate the vastus lateralis muscle. The reasons for the underutilization of epinephrine in the treatment of anaphylaxis are also discussed. Other important findings include the fact that outdated EpiPens can usually be administered safely, and alternative routes of administration, which may be more acceptable to patients, may be on the horizon as a result of preliminary studies assessing the administration of sublingual epinephrine by wafer. Finally, it is now understood that epinephrine prescription data may be one of our best tools to study the epidemiology and incidence of anaphylactic episodes.

Phil Lieberman, M.D.

I hope this information is of help to you and your patients.

All my best.
Dennis K. Ledford, MD, FAAAAI

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