Ronna L. Campbell

Evaluation of National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network criteria for the diagnosis of anaphylaxis in emergency department patients

BACKGROUND Diagnostic criteria were proposed at the Second Symposium on the Definition and Management of Anaphylaxis convened by the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN). Validation is needed before these criteria can be widely adapted into clinical practice. OBJECTIVE Our aim was to retrospectively assess the diagnostic accuracy of the NIAID/FAAN criteria for the diagnosis of anaphylaxis in emergency department (ED) patients. METHODS A retrospective cohort study of ED patients presenting from April to October 2008 was conducted. Patients given a diagnosis of an allergic reaction or anaphylaxis and a subset of patients with related diagnoses were included. Electronic medical records were reviewed and data were abstracted to determine whether the NIAID/FAAN criteria were met. Records were also independently reviewed in a blinded fashion by 2 experienced attending allergists. Final diagnosis by allergists was considered the reference standard. RESULTS Of 214 patients, 86 (40.2%) met the NIAID/FAAN criteria for anaphylaxis. Allergists gave 61 (28.5%) patients diagnoses of anaphylaxis, 59 (96.7%) of whom satisfied the NIAID/FAAN criteria. The interrater agreement between allergists was substantial (κ = 0.77). The test characteristics of the NIAID/FAAN criteria were as follows: sensitivity, 96.7% (95% CI, 88.8% to 99.1%); specificity, 82.4% (95% CI, 75.5% to 87.6%); positive predictive value, 68.6% (95% CI, 58.2% to 77.4%); negative predictive value, 98.4% (95% CI, 94.5% to 99.6%); positive likelihood ratio, 5.48; and negative likelihood ratio, 0.04. CONCLUSIONS These results suggest that the NIAID/FAAN criteria are highly sensitive but less specific and are likely to be useful in the ED for the diagnosis of anaphylaxis.

Prescriptions for self-injectable epinephrine and follow-up referral in emergency department patients presenting with anaphylaxis

BACKGROUND Anaphylaxis guidelines recommend that patients with a history of anaphylactic reaction should carry self-injectable epinephrine and should be referred to an allergist. OBJECTIVE To evaluate how frequently patients dismissed from the emergency department after treatment for anaphylaxis received a prescription for self-injectable epinephrine or allergist referral. METHODS A retrospective medical record review identified patients with anaphylaxis in a community-based study from 1990 through 2000. Records of patients with Hospital Adaptation of the International Classification of Diseases, Second Edition or International Classification of Diseases, Ninth Revision codes representing anaphylaxis were reviewed, and a random sample of patients with associated diagnoses was also reviewed. Patients who met the criteria for diagnosis of anaphylaxis were included in the study. RESULTS Among 208 patients identified with anaphylaxis, 134 (64.4%) were seen in the emergency department and discharged home. On dismissal, 49 patients (36.6%; 95% confidence interval [CI], 28.4%-44.7%) were prescribed self-injectable epinephrine, and 42 patients (31.3%; 95% CI, 23.5%-39.2%) were referred to an allergist. Treatment with epinephrine in the emergency department (odds ratio, 3.6; 95% CI, 1.6-7.9; P = .001) and insect sting as the inciting allergen (odds ratio, 4.0; 95% CI, 1.6-10.5; P = .004) were significantly associated with receiving a prescription for self-injectable epinephrine. Patient age younger than 18 years was the only factor associated with referral to an allergist (P = .007). CONCLUSIONS Most patients dismissed after treatment for anaphylaxis did not receive a self-injectable epinephrine prescription or allergist referral. Emergency physicians may be missing an important opportunity to ensure prompt treatment of future anaphylactic reactions and specialized follow-up care.

Emergency department diagnosis and treatment of anaphylaxis: a practice parameter

Ronna L. Campbell, MD, PhD; James T.C. Li, MD, PhD; Richard A. Nicklas, MD; Annie T. Sadosty, MD Members of the Joint Task Force: David Bernstein, MD; Joann Blessing-Moore, MD; David Khan, MD; David Lang, MD; Richard Nicklas, MD; John Oppenheimer, MD; Jay Portnoy, MD; Christopher Randolph, MD; Diane Schuller, MD; Sheldon Spector, MD; Stephen Tilles, MD; Dana Wallace, MD Practice Parameter Workgroup: Ronna L. Campbell, MD, PhD; James T.C. Li, MD, PhD; Annie T. Sadosty, MD

Epinephrine in Anaphylaxis: Higher Risk of Cardiovascular Complications and Overdose After Administration of Intravenous Bolus Epinephrine Compared with Intramuscular Epinephrine

BACKGROUND Epinephrine is the drug of choice for the management of anaphylaxis, and fatal anaphylaxis is associated with delayed epinephrine administration. Data on adverse cardiovascular (CV) complications and epinephrine overdose are limited. OBJECTIVE To compare rates of CV adverse events and epinephrine overdoses associated with anaphylaxis management between various routes of epinephrine administration among patients with anaphylaxis in the emergency department. METHODS This was an observational cohort study from April 2008 to July 2012. Patients in the emergency department who met diagnostic criteria for anaphylaxis were included. We collected demographics; route of epinephrine administration; trigger; overdose; and adverse CV events, including arrhythmia, cardiac ischemia, stroke, angina, and hypertension. RESULTS The study cohort included 573 patients, of whom, 301 (57.6%) received at least 1 dose of epinephrine. A total of 362 doses of epinephrine were administered to 301 patients: 67.7% intramuscular (IM) autoinjector, 19.6% IM injection, 8.3% subcutaneous injection, 3.3% intravenous (IV) bolus, and 1.1% IV continuous infusion. There were 8 CV adverse events and 4 overdoses with 8 different patients. All the overdoses occurred when epinephrine was administered IV bolus. Adverse CV events were associated with 3 of 30 doses of IV bolus epinephrine compared with 4 of 316 doses of IM epinephrine (10% vs 1.3%; odds ratio 8.7 [95% CI, 1.8-40.7], P = .006). Similarly, overdose occurred with 4 of 30 doses of IV bolus epinephrine compared with 0 of 316 doses of IM epinephrine (13.3% vs 0%; odds ratio 61.3 [95% CI, 7.5 to infinity], P < .001). CONCLUSION The risk of overdose and adverse CV events is significantly higher with IV bolus epinephrine administration. Analysis of the data supports the safety of IM epinephrine and a need for extreme caution and further education about IV bolus epinephrine in anaphylaxis.

Antihypertensive medication use is associated with increased organ system involvement and hospitalization in emergency department patients with anaphylaxis

BACKGROUND Risk factors for increased anaphylaxis severity are poorly understood. Angiotensin-converting enzyme (ACE) inhibitors have been associated with severe anaphylactic reactions in patients with hymenoptera venom allergy. Studies evaluating the association between beta-blockers and severe anaphylaxis have been conflicting. OBJECTIVE To evaluate the association between antihypertensive medication use and increased anaphylaxis severity. METHODS We included emergency department anaphylaxis patients aged 18 years and older. Markers of severe anaphylaxis were defined as (1) syncope, hypotension, or hypoxia; (2) signs and symptoms involving 3 or more organ systems; and (3) hospitalization. Antihypertensive medications evaluated included beta-blockers, ACE inhibitors, calcium channel blockers, angiotensin receptor blockers, and diuretics. Simple and multiple logistic regression analyses were conducted to estimate the association between antihypertensive medication use and markers of increased anaphylaxis severity. RESULTS Among 302 patients with anaphylaxis, 55 (18%) had syncope, hypoxia, or hypotension, 57 (19%) required hospitalization, and 139 (46%) had 3 or more organ system involvement. After adjusting for age, gender, suspected trigger, and preexisting lung disease, beta-blocker, ACE-inhibitor, diuretic, or antihypertensive medication use in aggregate remained associated with both 3 or more organ system involvement and need for hospital admission. The adjusted associations between antihypertensive medication use in aggregate and 3 or more organ system involvement yielded an odds ratio of 2.8 (95% CI, 1.5-5.2; P=.0008) and with hospitalization an odds ratio of 4.0 (95% CI, 1.9-8.4; P=.0001). CONCLUSIONS In emergency department anaphylaxis patients, antihypertensive medication use is associated with increased organ system involvement and increased odds of hospital admission, independent of age, gender, suspected trigger, or preexisting lung disease.

Factors associated with repeated use of epinephrine for the treatment of anaphylaxis

BACKGROUND Studies looking at the use of repeated doses of epinephrine in patients experiencing anaphylaxis are limited. OBJECTIVE To determine which patients are most likely to receive repeated doses of epinephrine during anaphylaxis management. METHODS A population-based study with medical record review was conducted. All patients seen during the study period who met the criteria for the diagnosis of anaphylaxis were included. RESULTS The cohort included 208 patients (55.8% female). Anaphylaxis treatment included epinephrine in 104 patients (50.0%). Repeated doses were used in 27 patients (13.0%), 13 (48.1%) of them female. The median age of those who received repeated doses was 18.9 (interquartile range, 10-34) years vs 31.1 (interquartile range, 15-41) years for those who did not receive repeated doses (P = .06). The inciting agents were food (29.6%), insects (11.1%), medications (22.2%), others (7.4%), and unknown (29.6%). Patients who received repeated doses were more likely to have wheezing (P = .03), cyanosis (P = .001), hypotension and shock (P = .03), stridor and laryngeal edema (P = .007), nausea and emesis (P = .04), arrhythmias (P < .01), and cough (P = .04) and less likely to have urticaria (P = .049). They were more likely to be admitted to the hospital than patients who did not receive repeated doses (48.2% vs 15.6%; P < .001). There was no significant difference in the history of asthma between patients who received repeated doses and those who did not (P = .17). CONCLUSIONS Of the patients, 13.0% received repeated epinephrine doses. Patients were younger and were likely to present with wheezing, cyanosis, arrhythmias, hypotension and shock, stridor, laryngeal edema, cough, nausea, and emesis and less likely to have urticaria. A history of asthma did not predict use of repeated doses of epinephrine. Our results help identify high-risk patients who may benefit from carrying more than 1 dose of epinephrine.

A Consensus Parameter for the Evaluation and Management of Angioedema in the Emergency Department

Despite its relatively common occurrence and life-threatening potential, the management of angioedema in the emergency department (ED) is lacking in terms of a structured approach. It is paramount to distinguish the different etiologies of angioedema from one another and more specifically differentiate histaminergic-mediated angioedema from bradykinin-mediated angioedema, especially in lieu of the more novel treatments that have recently become available for bradykinin-mediated angioedema. With this background in mind, this consensus parameter for the evaluation and management of angioedema attempts to provide a working framework for emergency physicians (EPs) in approaching the patient with angioedema in terms of diagnosis and management in the ED. This consensus parameter was developed from a collaborative effort among a group of EPs and leading allergists with expertise in angioedema. After rigorous debate, review of the literature, and expert opinion, the following consensus guideline document was created. The document has been endorsed by the American College of Allergy, Asthma & Immunology (ACAAI) and the Society for Academic Emergency Medicine (SAEM).

Anaphylaxis in emergency department patients 50 or 65 years or older

BACKGROUND Anaphylaxis is a potentially life-threatening allergic reaction commonly managed in the emergency department (ED). Data describing patients 50 or 65 years or older with anaphylaxis are limited. OBJECTIVE To describe the presentation and management of patients with anaphylaxis who were 50 or 65 years or older and to compare these findings with those of younger patients. METHODS A consecutive cohort study of patients presenting to an ED with approximately 80,000 visits per year was conducted. Patients who met diagnostic criteria for anaphylaxis from April 2008 to June 2010 were included. Data were collected on suspected causes, signs and symptoms, management, ED disposition, and follow-up. RESULTS The study included 220 patients. Food was the most common suspected cause of anaphylaxis for patients younger than 50 (42.2%) or 65 years (38.5%) but was much less common in patients 50 (14.8%, P < .001) or 65 years or older (14.3%, P = .01). Cardiovascular symptoms were more likely to occur in older patients (≥50 years old, 55.6% vs 30.1%, P < .001; ≥65 years old, 64.3% vs 32.3%, P = .002). Patients 50 or 65 years or older were less likely to be dismissed home directly from the ED (≥50 years old, 35.2% vs 56.6%, P = .006; ≥65 years old, 32.1% vs 54.2%, P = .03) and were less likely to be prescribed self-injectable epinephrine (≥50 years old, 40.7% vs 63.3%, P = .004; ≥65 years old, 32.1% vs 61.5%, P = .003). CONCLUSIONS In ED patients presenting with anaphylaxis, age of 50 or 65 years or older is associated with a decreased likelihood of food-induced anaphylaxis, increased likelihood of experiencing cardiovascular symptoms, decreased dismissal to home directly from the ED, and decreased prescriptions for self-injectable epinephrine.

Outcomes of Allergy/Immunology Follow-Up After an Emergency Department Evaluation for Anaphylaxis

BACKGROUND Anaphylaxis guidelines currently recommend referring patients with anaphylaxis seen in the emergency department (ED) to an allergist for follow up. OBJECTIVE The objective of our study was to evaluate outcomes of allergy/immunology follow-up after an ED visit for anaphylaxis. METHODS A retrospective health records review was conducted from April 2008 to August 2012. Charts were reviewed independently by 2 allergists to determine outcomes. Descriptive statistics with corresponding 95% CIs were calculated. RESULTS Among 573 patients seen in the ED who met anaphylaxis diagnostic criteria, 217 (38%) had a documented allergy/immunology follow-up. After allergy/immunology evaluation, 16 patients (7% [95% CI, 5%-12%]) had anaphylaxis ruled out. Among those with an unknown ED trigger (n = 74), 24 (32% [95% CI, 23%-44%]) had a trigger identified; and, among those who had a specific suspected ED trigger (n = 143), 9 (6% [95% CI, 3%-12%]) had a trigger identified in a category other than the one suspected in the ED, and 28 (20% [95% CI, 14%-27%]) had an unknown trigger. Thus, there were a total of 77 patients (35% [95% CI, 29%-42%]) who had an alteration in the diagnosis of anaphylaxis or trigger after allergy/immunology evaluation. Four patients (2% [95% CI, 0.7%-4.6%]) were diagnosed with a mast cell activation disorder, and 13 patients (6% [95% CI, 4%-10%]) underwent immunotherapy or desensitization. CONCLUSION Overall, 35% of the patients with suspected anaphylaxis in the ED had an alteration in the diagnosis or suspected trigger after allergy/immunology evaluation. These results underscore the importance of allergy/immunology follow-up after an ED visit for anaphylaxis.

Apical ballooning syndrome after administration of intravenous epinephrine during an anaphylactic reaction.

To the Editor: First described in Japan, apical ballooning syndrome (ABS), or Takotsubo cardiomyopathy, is an acquired, reversible cardiomyopathy. Catecholamine-induced myocardial stunning is the leading hypothesis for its pathophysiology.1 Epinephrine is the treatment of choice for patients with anaphylaxis.2 Prompt intramuscular administration is recommended because adverse reactions are more likely with intravenous dosing.3 We describe a case of a woman who developed ABS after intravenous administration of epinephrine. A 41-year-old woman developed itching, hives, lip and tongue swelling, and shortness of breath after a bee sting. After self-administration of diphenhydramine, she presented to a local emergency department. Her vital signs were as follows: blood pressure, 116/93 mm Hg; pulse, 98 beats/min; respiratory rate, 24 breaths/min; oxygen saturation, 98%; and temperature, 36.7°C. She was given intravenous fluids and diphenhydramine. Oral edema appeared to be increasing. Records from the referring emergency department indicate that the physician ordered 0.5 mL of intravenous epinephrine (1:10,000), but nursing notes indicate that 0.5 mg (1:10,000) of epinephrine was administered intravenously. The patient became hypotensive. The physician ordered another 0.5-mL dose of intravenous epinephrine (1:10,000). Again, nursing records indicate that a 0.5-mg dose (1:10,000) of intravenous epinephrine was administered instead. The patient developed chest pain and wide complex tachycardia. Electrocardiography revealed ST-segment elevation in leads I and aVL and ST-segment depression in leads III and aVF, consistent with myocardial infarction. While still receiving nitroglycerin therapy, the patient was transferred to a tertiary center (Mayo Clinic). On arrival, she was treated with dexamethasone and antihistamines. She had a troponin T level of 0.49 ng/mL (reference ranges provided parenthetically) (≤0.01 ng/mL) and a creatine kinase-MB level of 11.4 ng/mL (≤6.2 ng/mL). Cardiac angiography revealed normal coronary arteries. Left ventriculography showed akinesis of posterolateral, lateral, anterolateral, diaphragmatic, and basal septal segments of the left ventricle (ejection fraction, 48%) (Figure). Follow-up echocardiography after 22 days showed less extensive wall motion abnormalities and an ejection fraction of 60%. FIGURE. Diastolic and systolic freeze frames from a left ventriculogram of the patient demonstrating basal contraction but akinesis of the anterolateral wall (arrows). Testing for IgE yellow jacket venom was positive (1.08 kU/L [<0.35 kU/L]). Catechol O-methyltransferase genotype testing showed that the patient was a heterozygote and an intermediate metabolizer. Skin tests showed positive reactions to wasp, yellow jacket, yellow hornet, and white-faced hornet venom. The clinical presentation of our patient met the Mayo Clinic ABS diagnostic criteria.1 To our knowledge, this case is the first to implicate intravenous epinephrine administration during anaphylaxis as a cause of ABS. Intravenous epinephrine is indicated in patients with severe hypotension or cardiac arrest unresponsive to intramuscular epinephrine and fluid resuscitation. A 0.2 μg/kg intravenous bolus is recommended for hypotension and a 0.1- to 0.5-mg dose for cardiovascular collapse.4 This patients hypotension appeared to occur after the first dose of epinephrine. The hypotension likely represented the initiation of adverse cardiac response to epinephrine. The temporal relationship between administration of epinephrine and onset of findings consistent with ABS supports the hypothesis of catecholamine-induced myocardial stunning as the mechanism for left ventricular dysfunction. The patients catechol O-methyltransferase genotype may have also increased her predisposition to ABS. Our case illustrates that administration of intravenous epinephrine, especially at high doses, may be a trigger for ABS and underscores the risk of inappropriate epinephrine dosing during anaphylaxis.5