Veena Manivannan

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.

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.

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.

Effect of anticoagulant and antiplatelet therapy in patients with spontaneous intra-cerebral hemorrhage: Does medication use predict worse outcome?

OBJECTIVES To assess the impact of anticoagulants and antiplatelet agents on the severity and outcome of spontaneous non-traumatic intra-cerebral hemorrhage (ICH). To evaluate associations between reversal of anticoagulation and mortality/morbidity in these patients. METHODS Data was collected on a consecutive cohort of adults presenting with ICH to an academic Emergency Department over a 3-year period starting January 2006. RESULTS The final cohort of 245 patients consisted of 125 females (51.1%). The median age of the cohort was 73 years [inter-quartile (IQR) range of 59-82 years]. Antiplatelet (AP) use was seen in 32.6%, 18.4% were using anticoagulant (AC) and 8.9% patients were on both drugs (AC+AP). Patients on AC had significantly higher INR (median 2.3) and aPTT (median 31 s) when compared to patients not on AP/AC (median INR 1.0, median aPTT 24s; p<0.001). Similarly patients on AC+AP also had higher INR (median 1.9) and aPTT (median 30s) when compared to those not on AC/AP (p<0.001). Hemorrhage volumes were significantly higher for patients on AC alone (median 64.7 cm(3)) when compared to those not on either AC/AP (median 27.2 cm(3); p=0.05). The same was not found for patients using AP (median volume 20.5 cm(3); p=0.813), or both AC+AP (median volume 27.7 cm(3); p=0.619). Patients on AC were 1.43 times higher at risk to have intra-ventricular extension of hemorrhage (IVE) as compared to patients not on AC/AP (95% CI 1.04-1.98; p=0.035). There was no relationship between the use of AC/AP/AC+AP and functional outcome of patients. Patients on AC were 1.74 times more likely to die within 7 days (95% CI 1.0-3.03; p=0.05). No relationship was found between use of AP or AC+AP use and mortality. Of the 82 patients with INR>1.0, 52 patients were given reversal (minimum INR 1.4, median 2.3). Therapy was heterogeneous, with fresh frozen plasma (FFP) being the most commonly used agent (86.5% patients, median dose 4U). Vitamin K, activated factor VIIa and platelets were the other agents used. Post reversal, INR normalized within 24h (median 1.2, IQR 1.1-1.3). There was no association between reversal and volume of hemorrhage, IVE, early mortality (death<7 days) or functional outcome. CONCLUSIONS Anticoagulated patients were at 1.7 times higher risk of early mortality after ICH. Reversal of INR to normal did not influence mortality or functional outcome.

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

A multifaceted intervention for patients with anaphylaxis increases epinephrine use in adult emergency department.

BACKGROUND Studies have documented inconsistent emergency anaphylaxis care and low compliance with published guidelines. OBJECTIVE To evaluate anaphylaxis management before and after implementation of an emergency department (ED) anaphylaxis order set and introduction of epinephrine autoinjectors, and to measure the effect on anaphylaxis guideline adherence. METHODS A cohort study was conducted from April 29, 2008, to August 9, 2012. Adult patients in the ED who were diagnosed with anaphylaxis were included. ED management, disposition, self-injectable epinephrine prescriptions, allergy follow-up, and incidence of biphasic reactions were evaluated. RESULTS The study included 202 patients. The median age of the patients was 45.3 years (interquartile range, 31.3-56.4 years); 139 (69%) were women. Patients who presented after order set implementation were more likely to be treated with epinephrine (51% vs 33%; odds ratio [OR] 2.05 [95% CI, 1.04-4.04]) and admitted to the ED observation unit (65% vs 44%; OR 2.38 [95% CI, 1.23-4.60]), and less likely to be dismissed home directly from ED (16% vs 29%, OR 0.47 [95% CI, 0.22-1.00]). Eleven patients (5%) had a biphasic reaction. Of these, 5 (46%) had the biphasic reaction in the ED observation unit; 1 patient was admitted to the intensive care unit. Six patients (55%) had reactions within 6 hours of initial symptom resolution, of whom 2 were admitted to the intensive care unit. CONCLUSIONS Significantly higher proportions of patients with anaphylaxis received epinephrine and were admitted to the ED observation unit after introduction of epinephrine autoinjectors and order set implementation. Slightly more than half of the biphasic reactions occurred within the recommended observation time of 4 to 6 hours. Analysis of these data suggests that the multifaceted approach to changing anaphylaxis management described here improved guideline adherence.

An Assessment of the Incremental Value of the ABCD2 Score in the Emergency Department Evaluation of Transient Ischemic Attack

STUDY OBJECTIVE We study the incremental value of the ABCD2 score in predicting short-term risk of ischemic stroke after thorough emergency department (ED) evaluation of transient ischemic attack. METHODS This was a prospective observational study of consecutive patients presenting to the ED with a transient ischemic attack. Patients underwent a full ED evaluation, including central nervous system and carotid artery imaging, after which ABCD2 scores and risk category were assigned. We evaluated correlations between risk categories and occurrence of subsequent ischemic stroke at 7 and 90 days. RESULTS The cohort consisted of 637 patients (47% women; mean age 73 years; SD 13 years). There were 15 strokes within 90 days after the index transient ischemic attack. At 7 days, the rate of stroke according to ABCD2 category in our cohort was 1.1% in the low-risk group, 0.3% in the intermediate-risk group, and 2.7% in the high-risk group. At 90 days, the rate of stroke in our ED cohort was 2.1% in the low-risk group, 2.1% in the intermediate-risk group, and 3.6% in the high-risk group. There was no relationship between ABCD2 score at presentation and subsequent stroke after transient ischemic attack at 7 or 90 days. CONCLUSION The ABCD2 score did not add incremental value beyond an ED evaluation that includes central nervous system and carotid artery imaging in the ability to risk-stratify patients with transient ischemic attack in our cohort. Practice approaches that include brain and carotid artery imaging do not benefit by the incremental addition of the ABCD2 score. In this population of transient ischemic attack patients, selected by emergency physicians for a rapid ED-based outpatient protocol that included early carotid imaging and treatment when appropriate, the rate of stroke was independent of ABCD2 stratification.

Epinephrine use and outcomes in anaphylaxis patients transported by emergency medical services

BACKGROUND Anaphylaxis is a potentially life-threatening allergic reaction that may require emergency medical system (EMS) transport. Fatal anaphylaxis is associated with delayed epinephrine administration. Patient outcome data to assess appropriateness of EMS epinephrine administration are sparse. OBJECTIVES The objectives of this study are to (1) determine the frequency of epinephrine administration in EMS-transported patients with allergic complaints, (2) identify predictors of epinephrine administration, and (3) determine frequency of emergency department (ED) epinephrine administration after EMS transport. METHODS A cohort study was conducted from over 5 years. A total of 59187 EMS transports of an Advanced Life Support (ALS) ambulance service were studied. RESULTS One hundred and three patient transports for allergic complaints were analyzed. Fifteen patients received EMS epinephrine, and epinephrine was recommended for 2 additional patients who refused, for a total of 17 (17%) patients for whom epinephrine was administered or recommended. Emergency medical system epinephrine administration or recommendation was associated with venom as a trigger (29% vs 8%; odds ratio [OR], 4.70; 95% confidence interval [CI], 1.28-17.22; P = .013), respiratory symptoms (88% vs 52%; OR, 6.83; 95% CI, 1.47-31.71; P = .006), and fulfillment of anaphylaxis diagnostic criteria (82% vs 49%; OR, 3.50; 95% CI, 0.94-13.2; P = .0498). Four (4%) patients received epinephrine after ED arrival. CONCLUSION Low rates of epinephrine administration were observed. The association of EMS administration of epinephrine with respiratory symptoms, fulfillment of anaphylaxis diagnostic criteria, and low rate of additional epinephrine administration in the ED suggest that ALS EMS administered epinephrine based on symptom severity. Additional studies of EMS anaphylaxis management including ED management and outcomes are needed.