A second dose of epinephrine for anaphylaxis: How often needed and how to carry
2006; Elsevier BV; Volume: 117; Issue: 2 Linguagem: Inglês
10.1016/j.jaci.2005.11.015
ISSN1097-6825
Autores Tópico(s)Contact Dermatitis and Allergies
ResumoTo the Editor: Epinephrine is the treatment of choice for anaphylaxis. A new epinephrine autoinjector containing 2 doses of epinephrine has recently been marketed (Twinject; Verus Pharmaceuticals, San Diego, Calif). A currently more widely used device is marketed in both 1-packs and 2-packs (EpiPen; DEY, LP, Napa, Calif). This raises the question of how often more than 1 dose of epinephrine is required to treat an anaphylactic reaction. A study published in 1999 reviewed the authors' experience with 105 anaphylactic reactions in the clinic severe enough to require at least 1 dose of epinephrine.1Korenblat P. Lundie M.J. Dankner R.E. Day J.H. A retrospective study of epinephrine administration for anaphylaxis: how many doses are needed?.Allergy Asthma Proc. 1999; 20: 383-386Crossref PubMed Scopus (91) Google Scholar Sixty-one were to aeroallergen injections, 14 were to Hymenoptera injections, and 30 were to intentional Hymenoptera stings as part of a study. In 38 cases (36%; 95% CI, 28% to 46%), more than 1 dose of epinephrine was administered. A 2005 study of patients with food-induced anaphylaxis in the community found that in 4 of 22 cases (1 of 10 children and 3 of 12 adults; 18%; 95% CI, 7% to 39%) in which epinephrine was administered, a second dose was also given.2Uguz A. Lack G. Pumphrey R. Ewan P. Warner J. Dick J. et al.Allergic reactions in the community: a questionnaire survey of members of the anaphylaxis campaign.Clin Exp Allergy. 2005; 35: 746-750Crossref PubMed Scopus (141) Google Scholar We reviewed our experience with systemic reactions to allergen immunotherapy injections in regard to the number of epinephrine doses administered. During a 5-year period (calendar years 2000-2004), there were 9592 visits to the Allergy Clinic for allergy injections. The vast majority were aeroallergen injections, with a small percentage of Hymenoptera injections. The majority of patients received 2 injections per visit (average number of injections per visit, 1.82). During 64 of these 9592 injection visits (0.67%; 95% CI, 0.51% to 0.85%), the patients had a systemic reaction severe enough to require the administration of at least 1 dose of epinephrine. The number of doses of epinephrine used to treat these 64 reactions was 1 in 54 cases (84%), 2 in 8 cases (13%), and 3 in 2 cases (3%). Thus, in 10 of the 64 cases (16%; 95% CI, 9% to 27%), more than 1 dose of epinephrine was used. In comparing the 10 patients who required more than 1 dose of epinephrine with the 54 patients requiring only 1 dose of epinephrine, there was no difference in mean age (29 vs 27 years; P = .64), sex (40% male vs 35% male; P = 1.0), or type of extract injected (% receiving venom immunotherapy, 0% vs 7%; P = 1.0). Of note, recent studies have indicated that the intramuscular administration of epinephrine delivers blood levels higher and sooner than subcutaneous administration.3Simons F.E. Roberts J.R. Gu X. Simons K.J. Epinephrine absorption in children with a history of anaphylaxis.J Allergy Clin Immunol. 1998; 101: 33-37Abstract Full Text Full Text PDF PubMed Scopus (337) Google Scholar, 4Simons F.E. Gu X. Simons K.J. Epinephrine absorption in adults: intramuscular versus subcutaneous injection.J Allergy Clin Immunol. 2001; 108: 871-873Abstract Full Text Full Text PDF PubMed Scopus (370) Google Scholar It is possible that with intramuscular administration of a first dose, a second dose may be required less often, but this is not clear from the available data. In the study of 105 reactions to allergy injections and intentional stings in the clinic cited,1Korenblat P. Lundie M.J. Dankner R.E. Day J.H. A retrospective study of epinephrine administration for anaphylaxis: how many doses are needed?.Allergy Asthma Proc. 1999; 20: 383-386Crossref PubMed Scopus (91) Google Scholar where 36% went on to require a second dose, all of the epinephrine doses were administered subcutaneously. In the study of 22 reactions to foods in the community cited,2Uguz A. Lack G. Pumphrey R. Ewan P. Warner J. Dick J. et al.Allergic reactions in the community: a questionnaire survey of members of the anaphylaxis campaign.Clin Exp Allergy. 2005; 35: 746-750Crossref PubMed Scopus (141) Google Scholar where 18% went on to require a second dose, the route of administration of epinephrine is not stated but is presumed to be intramuscular. There is extremely limited published experience on treatment of anaphylaxis outside medical settings. The difference in the need for a second dose in these 2 studies may reflect a difference in how the drug is used in the clinic versus the community, rather than a difference in response to subcutaneous versus intramuscular use. During the period of the present study (2000-2004), epinephrine was administered subcutaneously exclusively until 2002, and only occasionally intramuscularly in subsequent years. The choice may have been driven in part by the perceived severity of the reaction, with intramuscular use for more severe reactions. In only 5 of the 64 cases was the first dose given intramuscularly. One of these 5 went on to require additional doses. This is not different than the 9 of 59 who received the first dose subcutaneously and went on to require additional doses (P = 1.0). In the 2 patients requiring 3 doses of epinephrine, 1 received the first dose subcutaneously and the next 2 intramuscularly, and the other received all 3 intramuscularly. Of note, although intramuscular administration is now recommended, subcutaneous administration was effective treatment for the vast majority of cases. Both available autoinjectors deliver the drug intramuscularly. Even given the paucity of current data, it would seem that in cases of anaphylaxis severe enough to require a dose of epinephrine, it is not uncommon (16% to 36% of cases) to require a second dose. It would thus seem prudent to consider having patients, particularly those at greatest risk for a severe reaction, carry a second dose, either as 2 single injectors or 1 double injector. A common reason for prescribing 2 separate epinephrine units is to be able to keep them in separate locations. However, if a decision is made that a patient should have 2 doses available at all times, then the choice would be either to prescribe 2 EpiPens or 1 Twinject per location. A number of factors could go into this choice of devices, including cost, ease of carrying (bulkiness and weight of the devices), and ease of use. Each of the 2 currently available devices would seem to have advantages and disadvantages regarding these parameters (Table I, Fig 1).Table IHaving 2 doses of self-injectable epinephrine available by carrying 2 EpiPens or 1 Twinject (all apply to both 0.15-mg and 0.3-mg doses)Carrying 2 EpiPens as a 2-PakCarrying 1 TwinjectNumber of doses per device12Average wholesale cost$104.00$70.00Weight130 g (4.6 oz) (60 g [2.1 oz] each plus joining clip)45 g (1.6 oz)Dimensions Length16 cm (6.2 in)16 cm (6.2 in) Width5.5 cm (2.2 in)2.0 cm (0.8 in) Circumference15 cm (5.9 in)7.0 cm (2.8 in)Both doses by autoinjectionYesNo (second dose requires disassembly and use of needle and syringe)Needle left exposed after autoinjectionYesYes, and this needle is used for second doseSecond dose can be saved and used on another occasion if not used for current episodeYesNoTrainer device includedYes, unless devices prescribed individually ($54.00 each)No, unless prescribed as a 2-Pack (2 devices, each with 2 doses [$116.00]) Open table in a new tab
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