Epinephrine use for anaphylaxis: Too seldom, too late (2017)

During the past 20 years, food allergy has dramatically increased, with a concomitant increased risk for anaphylaxis.[1]Sicherer S.H. Simons F.E.R. Self-injectable epinephrine for first-aid management of anaphylaxis.Pediatrics. 2007; 119: 638-646Crossref PubMed Scopus (137) Google Scholar Anaphylaxis is “a serious allergic reaction that is rapid in onset and may cause death.”[2]Song T.T. Worm M. Lieberman P. Anaphylaxis treatment: current barriers to adrenaline auto-injector use.Allergy. 2014; 69: 983-991Crossref PubMed Scopus (62) Google Scholar Foods are one of the common causes of anaphylaxis[3]Liberman D. Teach S. Management of anaphylaxis in children.Pediatr Emerg Care. 2008; 24: 861-866Crossref PubMed Scopus (33) Google Scholar over medications and insect stings, and food allergy has become a worldwide concern. Anaphylaxis is inadequately treated most of the time[4]Ben-Shoshan M. La Vieille S. Eisman H. et al.Anaphylaxis treated in a Canadian pediatric hospital: incidence, clinical characteristics, triggers, and management.J Allergy Clin Immunol. 2013; 132: 739-741.e733Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar because of inconsistent signs and symptoms; anaphylaxis can manifest differently in the same person, even when triggered by the same allergen. The first emergency medication indicated in anaphylaxis treatment is intramuscular epinephrine.[2]Song T.T. Worm M. Lieberman P. Anaphylaxis treatment: current barriers to adrenaline auto-injector use.Allergy. 2014; 69: 983-991Crossref PubMed Scopus (62) Google Scholar The most common cause of death from food allergies is delayed epinephrine administration.[5]Lieberman P. Biphasic anaphylactic reactions.Ann Allergy Asthma Immunol. 2005; 95: 217-226Abstract Full Text PDF PubMed Google Scholar This suggests the urgent need to educate health care providers on anaphylaxis diagnosis and appropriate epinephrine use. Guidelines need to highlight appropriate and timely therapy with a focus on epinephrine use as first-line treatment. There are no contradictions to the use of epinephrine for a life-threatening allergic reaction.[6]Simons F.E.R. Anaphylaxis: recent advances in assessment and treatment.J Allergy Clin Immunol. 2009; 124: 625-636Abstract Full Text Full Text PDF PubMed Scopus (190) Google Scholar Epinephrine is so crucial that administration is recommended even with the suspicion of a food allergic reaction occurring.[1]Sicherer S.H. Simons F.E.R. Self-injectable epinephrine for first-aid management of anaphylaxis.Pediatrics. 2007; 119: 638-646Crossref PubMed Scopus (137) Google Scholar Fatalities occur when epinephrine use is delayed or omitted altogether.[7]Pumphrey R. Lessons for management of anaphylaxis from a study of fatal reactions.Clin Exp Allergy. 2000; 30: 1144-1150Crossref PubMed Scopus (908) Google Scholar It is difficult to identify anaphylaxis when patients present to emergency departments (EDs) feeling better by the time they arrive. This happens when the body naturally secretes adrenalin owing to stress or when patients use antihistamines to treat cutaneous symptoms. Although antihistamines help cutaneous symptoms, they do not alleviate respiratory distress or shock.[8]Simons F.E.R. Ardusso L.R. Dimov V. et al.World Allergy Organization anaphylaxis guidelines: 2013 update of the evidence base.Int Arch Allergy Immunol. 2013; 162: 193-204Crossref PubMed Scopus (208) Google Scholar Another common and incorrect treatment occurs when health care providers far too often treat patients with diphenhydramine in the ED.[2]Song T.T. Worm M. Lieberman P. Anaphylaxis treatment: current barriers to adrenaline auto-injector use.Allergy. 2014; 69: 983-991Crossref PubMed Scopus (62) Google Scholar Cutaneous symptoms, including erythema, urticaria, pruritus, and angioedema, are common and typically treated with antihistamines. It is important to continue to closely monitor these patients to ensure that other anaphylactic symptoms do not manifest. The delayed or partial administration of epinephrine owing to improper technique increases the risk for a second reaction.[5]Lieberman P. Biphasic anaphylactic reactions.Ann Allergy Asthma Immunol. 2005; 95: 217-226Abstract Full Text PDF PubMed Google Scholar Patients with anaphylactic reactions are often discharged from EDs without a prescription for an epinephrine auto-injector (EAI), education, or referral to a specialist.[9]Clark S. Bock S.A. Gaeta T.J. Brenner B.E. Cydulka R.K. Camargo C.A. Multicenter study of emergency department visits for food allergies.J Allergy Clin Immunol. 2004; 113: 347-352Abstract Full Text Full Text PDF PubMed Scopus (228) Google Scholar Health care providers, who are the first line of contact with patients, need to educate patients on the importance of an EAI and demonstrate proper technique using a training device.[1]Sicherer S.H. Simons F.E.R. Self-injectable epinephrine for first-aid management of anaphylaxis.Pediatrics. 2007; 119: 638-646Crossref PubMed Scopus (137) Google Scholar This needs to be followed up by the patient's personal care team to remind and enforce the carrying of an EAI at all times. Anaphylaxis mismanagement can be fatal. Multiple worldwide studies have illustrated inconsistent management of anaphylaxis despite recommendations provided in guidelines.[2]Song T.T. Worm M. Lieberman P. Anaphylaxis treatment: current barriers to adrenaline auto-injector use.Allergy. 2014; 69: 983-991Crossref PubMed Scopus (62) Google Scholar A study of the UK registry reported that nearly 40% of all anaphylactic deaths did not receive any epinephrine.[10]Storey P. Fitzharris P. Adrenaline in anaphylaxis: overtreatment in theory, undertreatment in reality.Postgrad Med J. 2015; 91: 1-2Crossref PubMed Scopus (8) Google Scholar Song et al[2]Song T.T. Worm M. Lieberman P. Anaphylaxis treatment: current barriers to adrenaline auto-injector use.Allergy. 2014; 69: 983-991Crossref PubMed Scopus (62) Google Scholar reported similar results from a 2-month US study of 34 hospitals where 2,333 ED visits for anaphylaxis occurred with only 19% of patients receiving epinephrine. Another study reviewing 2,114 patients from Germany, Austria, and Switzerland who presented with severe anaphylaxis discovered that fewer than 14% were treated with epinephrine.[2]Song T.T. Worm M. Lieberman P. Anaphylaxis treatment: current barriers to adrenaline auto-injector use.Allergy. 2014; 69: 983-991Crossref PubMed Scopus (62) Google Scholar Clark et al[9]Clark S. Bock S.A. Gaeta T.J. Brenner B.E. Cydulka R.K. Camargo C.A. Multicenter study of emergency department visits for food allergies.J Allergy Clin Immunol. 2004; 113: 347-352Abstract Full Text Full Text PDF PubMed Scopus (228) Google Scholar summarized emergency visits for 678 anaphylactic reactions and identified 50% as severe. Of these cases, 90% received antihistamines, 50% received systemic steroids, and only 16% received epinephrine. Further investigation at discharge showed only 40% mentioned allergen avoidance, 16% prescribed epinephrine, 12% referred to an allergist, and only 2% of patients received all 3 interventions.[9]Clark S. Bock S.A. Gaeta T.J. Brenner B.E. Cydulka R.K. Camargo C.A. Multicenter study of emergency department visits for food allergies.J Allergy Clin Immunol. 2004; 113: 347-352Abstract Full Text Full Text PDF PubMed Scopus (228) Google Scholar A study of Canadian children from 2004 through 2009 with physician-confirmed peanut allergy showed that severe reactions were treated with epinephrine only 21% of the time.[11]Nguyen-Luu N.U. Ben-Shoshan M. Alizadehfar R. et al.Inadvertent exposures in children with peanut allergy.Pediatr Allergy Immunol. 2012; 23: 134-140Crossref Scopus (74) Google Scholar Sicherer and Simons[1]Sicherer S.H. Simons F.E.R. Self-injectable epinephrine for first-aid management of anaphylaxis.Pediatrics. 2007; 119: 638-646Crossref PubMed Scopus (137) Google Scholar identified 13 children who experienced anaphylaxis to food, and 6 episodes were fatal owing to delayed epinephrine administration. The 7 children who survived were given epinephrine within the first 5 minutes of the reaction. This study emphasizes the importance of prompt epinephrine administration. A study in Australia that explored fatal anaphylaxis to foods categorized a delay in epinephrine as any period longer than 20 minutes.[12]Mullins R.J. Wainstein B. Barnes E. et al.Increases in anaphylaxis fatalities in Australia from 1997 to 2013.Clin Exp Allergy. 2016; 46: 1099-1110Crossref PubMed Scopus (177) Google Scholar The available evidence shows that anaphylactic reactions are often treated with antihistamines, bronchodilators, and prednisone,[11]Nguyen-Luu N.U. Ben-Shoshan M. Alizadehfar R. et al.Inadvertent exposures in children with peanut allergy.Pediatr Allergy Immunol. 2012; 23: 134-140Crossref Scopus (74) Google Scholar but using them as first-line treatments, thus delaying timely epinephrine administration, in cases of suspected anaphylaxis is inappropriate. Paramedics are first responders with emergency medical services. Discussions with emergency pharmacist T. Furst in a Canadian pediatric hospital in 2013 showed that, at times, paramedics administer epinephrine in the arm rather than the leg. Although administration can be subcutaneous or intramuscular in the deltoid or vastus lateralis, the vastus lateralis has the fastest absorption rate.[2]Song T.T. Worm M. Lieberman P. Anaphylaxis treatment: current barriers to adrenaline auto-injector use.Allergy. 2014; 69: 983-991Crossref PubMed Scopus (62) Google Scholar Patient morbidity and health care costs are being affected by the variable use of epinephrine by health care providers.[13]White S. Spruce L. Perioperative nursing leaders implement clinical practice guidelines using the Iowa Model of Evidence-Based Practice.AORN J. 2015; 102: 50-59Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar Health care providers, spanning from ED physicians, nurses, and paramedics to family physicians, pediatricians, allergy educators, and school nurses, need to be properly educated regarding guidelines. A unified voice is crucial to ensure that patients with food allergies receive proper care. The World Allergy Organization surveyed allergy and immunology specialists from 44 countries and found 36% used guidelines developed within the country of practice, 34% adopted guidelines from other countries, and 30% did not have any anaphylaxis guidelines.[14]Simons F.E.R. World Allergy Organization survey on global availability of essentials for the assessment and management of anaphylaxis by allergy-immunology specialists in health care settings.Ann Allergy Asthma Immunol. 2010; 104: 405-412Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar Without any guidelines, health care providers do not have a structured reference to follow. “The importance of having a management protocol cannot be over-emphasized because retention of memorized facts and algorithms can be poor in a crisis and there is little or no time to look up information.”[8]Simons F.E.R. Ardusso L.R. Dimov V. et al.World Allergy Organization anaphylaxis guidelines: 2013 update of the evidence base.Int Arch Allergy Immunol. 2013; 162: 193-204Crossref PubMed Scopus (208) Google Scholar There are several barriers to anaphylaxis treatment. Lack of knowledge of obvious signs, symptoms, and management of anaphylaxis are part of the issue, in addition to a lack of understanding of the evidence associated with it. One study found that a delay in epinephrine treatment for children resulted from a lack of ability to recognize anaphylactic symptoms and was compounded by not following emergency guidelines.[15]Sicherer S.H. Furlong T.J. DeSimone J. et al.The US Peanut and Tree Nut Allergy Registry: characteristics of reactions in schools and day care.J Pediatr. 2001; 138: 560-565Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar One case study described an anaphylactic reaction that resulted in a fatality when the physician misdiagnosed the patient as having an anxiety attack.[7]Pumphrey R. Lessons for management of anaphylaxis from a study of fatal reactions.Clin Exp Allergy. 2000; 30: 1144-1150Crossref PubMed Scopus (908) Google Scholar Because this type of severe allergic reaction occurs in only approximately 2% of the population,[16]Gold M.S. Sainsbury R. First aid anaphylaxis management in children who were prescribed an epinephrine autoinjector device (EpiPen).J Allergy Clin Immunol. 2000; 106: 171-176Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar the knowledge deficit can be attributed to the lack of firsthand experience of the health care provider. The European Academy of Allergy and Clinical Immunology has publically announced that all individuals diagnosed with a food allergy must carry an EAI.[2]Song T.T. Worm M. Lieberman P. Anaphylaxis treatment: current barriers to adrenaline auto-injector use.Allergy. 2014; 69: 983-991Crossref PubMed Scopus (62) Google Scholar Song et al[2]Song T.T. Worm M. Lieberman P. Anaphylaxis treatment: current barriers to adrenaline auto-injector use.Allergy. 2014; 69: 983-991Crossref PubMed Scopus (62) Google Scholar described many challenges associated with carrying an EAI, such as the lack of availability in some countries, prohibitive costs to obtaining an EAI, not carrying the device, and improper use.[2]Song T.T. Worm M. Lieberman P. Anaphylaxis treatment: current barriers to adrenaline auto-injector use.Allergy. 2014; 69: 983-991Crossref PubMed Scopus (62) Google Scholar In urban settings, patients tend to rely on emergency medical services rather than self-treatment.[17]Money A.G. Barnett J. Kuljis J. et al.Patient perceptions of epinephrine auto-injectors: exploring barriers to use.Scand J Caring Sci. 2013; 27: 335-344Crossref PubMed Scopus (26) Google Scholar Although there can be several reasons for or barriers to using epinephrine on oneself when experiencing anaphylaxis, a health care provider using antihistamines for anaphylaxis rather than epinephrine in an emergency setting unintentionally demonstrates that epinephrine is not necessary to treat anaphylaxis. This creates a false sense of “appropriate management” in patients' minds. For the proper message to be translated to the public, it must be practiced by those who preach it. For instance, it is not uncommon for parents to be aware of the need for epinephrine, yet during their child's anaphylactic reaction, they fail to administer the auto-injector, possibly because of fear of using a needle[4]Ben-Shoshan M. La Vieille S. Eisman H. et al.Anaphylaxis treated in a Canadian pediatric hospital: incidence, clinical characteristics, triggers, and management.J Allergy Clin Immunol. 2013; 132: 739-741.e733Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar and physically hurting their child. Instead, they take a risk by driving their child to the ED rather than calling an ambulance, and the child is not treated with epinephrine. The child survives, reinforcing the idea that the treatment provided by the health care providers was correct, their actions were appropriate, and epinephrine was not required. Because most cases of inappropriately treated anaphylaxis do not end in fatalities, this scenario is continually repeated, reinforcing inadequate treatment and increasing the risk of morbidity and fatality. The benefit for patients to carry and use an auto-injector is lost on them when they see health care providers in an emergency situation not using epinephrine promptly. Recently, more emphasis has been placed on knowledge translation. Although there are discussions about the benefits of adapting guidelines to fit a specific organization, anaphylaxis treatments are specific and not dependent on special equipment or personnel. Strategies can include interactive educational sessions directed toward health care providers and initiation of specific care maps. Because passive learning is inadequate, it is important to apply new knowledge at the time of decision making.[18]Harrison M.B. Légaré F. Graham I.D. et al.Adapting clinical practice guidelines to local context and assessing barriers to their use.CMAJ. 2010; 182: E78-E84Crossref PubMed Scopus (223) Google Scholar After an anaphylactic admission, discussions or case scenarios can be presented at staff meetings to highlight appropriate guideline use and generate discussions that allow ongoing education for health care providers at the organization. One study in the United States implemented an electronic guideline on a local network, including an order set for anaphylaxis management, and assessed whether diagnosis and management changed after implementation. After implementation of guidelines, there were more anaphylaxis diagnoses, possibly because of the education, more hospital epinephrine administration, and a decrease of hospital admission.[19]Desai S.H. Jeong K. Kattan J.D. et al.Anaphylaxis management before and after implementation of guidelines in the pediatric emergency department.J Allergy Clin Immunol Pract. 2015; 3: 604-606.e602Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar This reinforces the idea that implementation strategies work if they fit within the organizational structure. Visual aids, such as posters or a care map, can be a helpful reminder. Visualizing a schematic diagram can provide a stepwise, structured approach to managing a possibly confusing situation. This timely implementation not only will be conducive to reinforce practice but also can be a learning opportunity for health care providers to recognize the multiple facets of anaphylaxis. Feedback can be instrumental when implementing change; therefore, review and discussion of case management might help to teach and reinforce staff. Management of food allergy requires specific knowledge about allergen avoidance, reading food labels, recognizing symptoms of a reaction, and using an EAI.[20]Carlisle S.K. Vargas P.A. Noone S. et al.Food allergy education for school nurses: A needs assessment survey by the consortium of food allergy research.J Sch Nurs. 2010; 26: 360-364Crossref PubMed Scopus (24) Google Scholar There is a need for more non-allergist health care providers to be educated on the topic of food allergies to meet the medical needs of their patients so that they are prepared and confident in their ability to manage a reaction.[20]Carlisle S.K. Vargas P.A. Noone S. et al.Food allergy education for school nurses: A needs assessment survey by the consortium of food allergy research.J Sch Nurs. 2010; 26: 360-364Crossref PubMed Scopus (24) Google Scholar Experts in allergy and clinical immunology around the world unanimously agree that prompt administration of epinephrine is the first line of anaphylaxis treatment.[2]Song T.T. Worm M. Lieberman P. Anaphylaxis treatment: current barriers to adrenaline auto-injector use.Allergy. 2014; 69: 983-991Crossref PubMed Scopus (62) Google Scholar Guidelines from the American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology recommend prompt epinephrine administration at the first indication of anaphylaxis and even go as far as to suggest administering the medication when in doubt.[2]Song T.T. Worm M. Lieberman P. Anaphylaxis treatment: current barriers to adrenaline auto-injector use.Allergy. 2014; 69: 983-991Crossref PubMed Scopus (62) Google Scholar Currently, there are only 2 preset doses of EAIs available in North America. For any individual weighing more than 25 kg, the recommended intramuscular epinephrine dose is 0.3 mg. A patient weighing 10 to 25 kg should receive 0.15 mg of epinephrine. For children weighing less than 10 kg, epinephrine dosing becomes more complex. With a recommended dose of 0.01 mg/kg, there is potential for overdosing when using prefilled EAIs.[1]Sicherer S.H. Simons F.E.R. Self-injectable epinephrine for first-aid management of anaphylaxis.Pediatrics. 2007; 119: 638-646Crossref PubMed Scopus (137) Google Scholar However, given the option of epinephrine ampules and a syringe, until lower-dose EAIs are available, the 0.15-mg EAIs are preferable. Morbidity and mortality from anaphylaxis are associated with delay or lack of epinephrine use. This risk can be minimized by recognizing the variable signs and symptoms of anaphylaxis and treating promptly with intramuscular epinephrine. Reviewing guidelines and implementing strategies that enforce epinephrine as the first line of treatment could be helpful. It is imperative that hospitals, clinics, and other health care organizations emphasize appropriate use of epinephrine for best patient outcome, consistency of care, and health promotion within the community. Health care providers, spanning from ED physicians, nurses, and paramedics to family physicians, pediatricians, allergy educators, and school nurses, need to be properly educated regarding guidelines. Strategies should focus on improving education of health care providers who deal with anaphylactic reactions.