Emergency medicine updates: Anaphylaxis

IntroductionAnaphylaxis is a potentially deadly condition that requires emergent therapy. While frequently treated in the emergency department (ED), recent evidence updates may improve the diagnosis and management of this condition.ObjectiveThis paper evaluates key evidence-based updates concerning the diagnosis and management of anaphylaxis for the emergency clinician.DiscussionThe presentation of anaphylaxis can vary. Current diagnostic criteria can be helpful when evaluating patients for anaphylaxis, though multiple criteria exist. While the most common causes of anaphylaxis include medications, insect venom, and foods, recent literature has identified an IgE antibody response to mammalian galactose alpha-1,3-galactose, known as alpha-gal anaphylaxis. Epinephrine is the first-line therapy and is given in doses of 0.01 mg/kg (up to 0.5 mg in adults) intramuscularly (IM) in the anterolateral thigh. Intravenous (IV) epinephrine administration is recommended in patients refractory to IM epinephrine and IV fluids, or those with cardiovascular collapse. Antihistamines and glucocorticoids should not delay administration of epinephrine and do not demonstrate a significant reduction in risk of biphasic reactions. Biphasic reactions may affect 1–7% of patients with anaphylaxis. Risk factors for biphasic reaction include severe initial presentation and repeated doses of epinephrine. Disposition of patients with anaphylaxis requires consideration of several factors.ConclusionsEmergency clinicians must be aware of current updates in the evaluation and management of this disease.     

The Use of Epinephrine for Out-of-Hospital Treatment of Anaphylaxis: Resource Document for the National Association of EMS Physicians Position Statement

Abstract

Anaphylaxis is a potentially life-threatening condition that requires both prompt recognition and treatment with epinephrine. All levels of emergency medical services (EMS) providers, with appropriate physician oversight, should be able to carry and properly administer epinephrine safely when caring for patients with anaphylaxis. EMS systems and EMS medical directors should develop a mechanism to review the charts of patients who received epinephrine and were not in cardiac arrest. This will help to ensure the safe and appropriate use of epinephrine in order to provide continued quality improvement. Despite the safety of epinephrine, EMS systems that carry epinephrine autoinjectors should establish protocols to deal with patients or emergency responders who have an unintentional injection of epinephrine into the hand or digit. Continued research is needed to better define the role that EMS plays in the management of anaphylaxis. This paper serves as a resource document to the National Association of EMS Physician position on the use of epinephrine for the out-of-hospital treatment of anaphylaxis.     

Anaphylaxis Knowledge Among Paramedics: Results of a National Survey

Abstract

Background. Very little is known about prehospital providers’ knowledge regarding anaphylaxis care. Objectives. The purpose of this study was to evaluate how well nationally registered paramedics in the United States recognize classic and atypical presentations of anaphylaxis. We also assessed knowledge regarding treatment with epinephrine, including dosing, route of administration, and perceived contraindications to epinephrine use. Methods. This was a blinded, cross-sectional online survey of a random sample of paramedics registered by the National Registry of Emergency Medical Technicians that was distributed via e-mail. The survey contained two main sections: demographic data/self-assessment of confidence with anaphylaxis care and a cognitive assessment. Results. A total of 3,537 paramedics completed the survey, for a 36.6% response rate. Among the respondents, 98.9% correctly recognized a case of classic anaphylaxis, whereas only 2.9% correctly identified the atypical presentation. Regarding treatment, 46.2% identified epinephrine as the initial drug of choice; 38.9% chose the intramuscular (IM) route of administration, and 60.5% identified the deltoid as the preferred location (11.6% thigh). Of the respondents, 98.0% were confident they could recognize anaphylaxis; 97.1% were confident they could manage anaphylaxis; 39.5% carry epinephrine autoinjectors (EAIs) on response vehicles; 95.4% were confident they could use an EAI; and 36.2% stated that there were contraindications to epinephrine administration in anaphylactic shock. Conclusions. Whereas a large percentage of the paramedics recognized classic anaphylaxis, a very small percentage recognized atypical anaphylaxis. Less than half chose epinephrine as the initial drug of choice, and most respondents were unable to identify the correct route/location of administration. This survey identifies a number of areas for improved education.     

Safety of epinephrine for anaphylaxis in the emergency setting

BACKGROUND:

While epinephrine is the recommended first-line therapy for the reversal of anaphylaxis symptoms, inappropriate use persists because of misunderstandings about proper dosing and administration or misconceptions about its safety. The objective of this review was to evaluate the safety of epinephrine for patients with anaphylaxis, including other emergent conditions, treated in emergency care settings.

METHODS:

A MEDLINE search using PubMed was conducted to identify articles that discuss the dosing, administration, and safety of epinephrine in the emergency setting for anaphylaxis and other conditions.

RESULTS:

Epinephrine is safe for anaphylaxis when given at the correct dose by intramuscular injection. The majority of dosing errors and cardiovascular adverse reactions occur when epinephrine is given intravenously or incorrectly dosed.

CONCLUSION:

Epinephrine by intramuscular injection is a safe therapy for anaphylaxis but training may still be necessary in emergency care settings to minimize drug dosing and administration errors and to allay concerns about its safety.KEY WORDS: Allergy, Anaphylaxis, Epinephrine, Safety, Cardiovascular side effects     

Anaphylaxis

Background

Anaphylaxis is the quintessential critical illness in emergency medicine. Symptoms are rapid in onset and death can occur within minutes. Approximately 1500 patients die annually in the United States from this deadly disorder. It is imperative, therefore, that emergency care providers be able to diagnose and appropriately treat patients with anaphylaxis. Any delays in recognition or initiation of therapy can result in unnecessary increases in patient morbidity and mortality.

Discussion

Recent literature, including updated international anaphylaxis guidelines, has improved our understanding and management of this critical illness. Anaphylaxis is a multisystem disorder that can manifest signs and symptoms related to the cutaneous, respiratory, cardiovascular, and gastrointestinal systems. Epinephrine remains the drug of choice and should initially be administered intramuscularly, into the anterolateral thigh, as soon as the diagnosis is suspected. For patients unresponsive to repeated intramuscular injections, a continuous infusion of epinephrine should be started. Antihistamines and corticosteroids are second-line medications and should never be given in lieu of, or prior to, epinephrine. Aggressive fluid resuscitation should also be used to treat the intravascular volume depletion characteristic of anaphylaxis. Patient observation and disposition should be individualized, as there is no well-defined period of observation after resolution of signs and symptoms.

Conclusions

For patients with anaphylaxis, rapid and appropriate administration of epinephrine is critical for survival. Additional therapy, such as supplemental oxygen, intravenous fluids, antihistamines, and corticosteroids should not delay the administration of epinephrine.     

The Use of Epinephrine for Out-Of-Hospital Treatment of Anaphylaxis

Abstract

The National Association of EMS Physicians (NAEMSP) believes that all levels of emergency medical services (EMS) providers should be allowed to carry and administer epinephrine for the treatment of anaphylaxis. This document is the official position of the NAEMSP.     

Appropriate use of epinephrine in anaphylaxis

We are submitting a case-based presentation illustrating medical errors in the use of epinephrine for the treatment of anaphylaxis. Readers will learn from mistakes made by other emergency caregivers in treating anaphylaxis. The article will specifically review the recommended use of epinephrine in the management of anaphylaxis. Four patients are presented who were seen in consultation by our outpatient allergy service. In all 4 cases, the history was suggestive of an episode of anaphylaxis in which emergency care providers mismanaged treatment. In 2 cases, the patients required ICU care after improperly receiving intravenous epinephrine. In the remaining 2 cases, epinephrine use was either omitted or significantly delayed in its administration. Our presentation includes a review of consensus statements regarding the treatment of anaphylaxis with particular regard to the use of epinephrine. We hope that this information will help prevent similar errors from harming other patients.     

Effects of long‐term whole‐body cold exposures on plasma concentrations of ACTH,beta‐endorphin,cortisol, catecholamines and cytokines in healthy females

Objective. Cold therapy is used to relieve pain and inflammatory symptoms. The present study was designed to determine the influence of long‐term regular exposure to acute cold temperature. Two types of exposure were studied: winter swimming in ice‐cold water and whole‐body cryotherapy. The outcome was investigated on humoral factors that may account for pain alleviation related to the exposures. Material and methods. During the course of 12 weeks, 3 times a week, a group of healthy females (n = 10) was exposed to winter swimming (water 0–2°C) for 20?s and another group (n = 10) to whole‐body cryotherapy (air ?110°C) for 2?min in a special chamber. Blood specimens were drawn in weeks 1, 2, 4, 8 and 12, on a day when no cold exposure occurred (control specimens) and on a day of cold exposures (cold specimens) before the exposures (0?min), and thereafter at 5 and 35?min. Results. Plasma ACTH and cortisol in weeks 4–12 on time‐points 35?min were significantly lower than in week 1, probably due to habituation, suggesting that neither winter swimming nor whole‐body cryotherapy stimulated the pituitary‐adrenal cortex axis. Plasma epinephrine was unchanged during both experiments, but norepinephrine showed significant 2‐fold to 3‐fold increases each time for 12 weeks after both cold exposures. Plasma IL‐1‐beta, IL‐6 or TNFα did not show any changes after cold exposure. Conclusions. The main finding was the sustained cold‐induced stimulation of norepinephrine, which was remarkably similar between exposures. The frequent increase in norepinephrine might have a role in pain alleviation in whole‐body cryotherapy and winter swimming.     

Customizing Anaphylaxis Guidelines for Emergency Medicine

Background

Most episodes of anaphylaxis are managed in emergency medical settings, where the cardinal signs and symptoms often differ from those observed in the allergy clinic. Data suggest that low recognition of anaphylaxis in the emergency setting may relate to inaccurate coding and lack of a standard, practical definition.

Objective

Develop a simple, consistent definition of anaphylaxis for emergency medicine providers, supported by clinically relevant consensus statements.

Discussion

Definitions of anaphylaxis and criteria for diagnosis from current anaphylaxis guidelines were reviewed with regard to their utilization in emergency medical settings. The agreed-upon working definition is: Anaphylaxis is a serious reaction causing a combination of characteristic findings, and which is rapid in onset and may cause death. It is usually due to an allergic reaction but can be non-allergic. The definition is supported by Consensus Statements, each with referenced discussion. For a positive outcome, quick diagnosis and treatment of anaphylaxis are critical. However, even in the emergency setting, the patient may not present with life-threatening symptoms. Because mild initial symptoms can quickly progress to a severe, even fatal, reaction, the first-line treatment for any anaphylaxis episode—regardless of severity—is intramuscular injection of epinephrine into the anterolateral thigh; delaying its administration increases the potential for morbidity and mortality. When a reaction appears as “possible anaphylaxis,” it is generally better to err on the side of caution and administer epinephrine.

Conclusion

We believe that this working definition and the supporting Consensus Statements are a first step to better management of anaphylaxis in the emergency medical setting.     

Syringe Administration of Epinephrine by Emergency Medical Technicians for Anaphylaxis

Objective: In recent years, the costs of epinephrine autoinjectors (EAIs) in the United States have risen substantially. King County Emergency Medical Services implemented the “Check and Inject” program to replace EAIs by teaching emergency medical technicians (EMTs) to manually aspirate epinephrine from a single-use 1 mg/mL epinephrine vial using a needle and syringe followed by prehospital intramuscular administration of the correct adult or pediatric dose of epinephrine for anaphylaxis or serious allergic reaction. Treatment was guided by an EMT protocol that required a trigger and symptoms. We sought to determine if the “Check and Inject” program was safely implemented by EMTs treating presumed prehospital anaphylaxis or serious allergic reaction. Methods: We conducted a prospective investigation of all cases treated as part of the “Check and Inject” program from July 2014 through December 2016 in suburban King County, Washington, and January 2016 through December 2016 within the city of Seattle. All cases were prospectively collected using a custom quality improvement data form completed by the first responding EMTs. Two physicians completed a structured review of each EMS medical record to determine if the EMTs followed the Check and Inject protocol and determine if epinephrine was clinically-indicated based on physician review. Results: Of the 411 cases eligible for analysis, EMTs followed the protocol appropriately in 367 (89.3%) cases. In the remaining 44 (10.7%) cases, the EMS incident report form failed to document either a clear inciting allergic trigger or an appropriate symptom from the protocol list. Physician review determined that epinephrine was clinically indicated in 36 of the 44 cases. Among the remaining 8 cases (1.9%) that did not meet protocol criteria and were not clinically-indicated based on physician review, none had a documented adverse reaction to the epinephrine. Conclusion: We observed that EMTs successfully implemented the manual “Check and Inject” program for severe allergic reactions and anaphylaxis in a manner that typically agreed with physician review and without any overt identified safety issues.     

Assessment of ED triage of anaphylaxis patients based on the Emergency Severity Index

ObjectivesTo describe the emergency department (ED) triage of anaphylaxis patients based on the Emergency Severity Index (ESI), assess the association between ESI triage level and ED epinephrine administration, and determine characteristics associated with lower acuity triage ESI assignment (levels 3 and 4).MethodsWe conducted a cohort study of adult and pediatric anaphylaxis patients between September 2010 and September 2018 at an academic ED. Patient characteristics and management were compared between Emergency Severity Index (ESI) triage level 1 or 2 versus levels 3 or 4 using logistic regression analysis. We adhered to STROBE reporting guidelines.ResultsA total of 1090 patient visits were included. There were 26 (2%), 515 (47%), 489 (45%), and 60 (6%) visits that were assigned an ESI triage level of 1, 2, 3, and 4, respectively. Epinephrine was administered in the ED to 53% of patients triaged ESI level 1 or 2 and to 40% of patients triaged ESI level 3 or 4. Patients who were assigned a lower acuity ESI level of 3 or 4 had a longer median time from ED arrival to epinephrine administration compared to those with a higher acuity ESI level of 1 or 2 (28 min compared to 13 min, p < .001). A lower acuity ESI level was more likely to be assigned to visits with a chief concern of hives, rash, or pruritus (OR 2.33 [95% CI, 1.20–4.53]) and less likely to be assigned to visits among adults (OR, 0.43 [0.31–0.60]), patients who received epinephrine from emergency medical services (OR 0.56 [0.38–0.82]), presented with posterior pharyngeal or uvular angioedema (OR, 0.56 [0.38–0.82]), hypoxemia (OR, 0.34 [0.18–0.64]), or increased heart (OR 0.83 [0.73–0.95]) or respiratory (OR 0.70 [0.60–0.82]) rates.ConclusionPatients triaged to lower acuity ESI levels experienced delays in ED epinephrine administration. Adult and pediatric patients with skin-related chief concerns were more likely to be to be assigned lower acuity ESI levels. Further studies are needed to identify interventions that will improve ED anaphylaxis triage.     

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 59 187 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.     

D IAGNOSIS AND T RIAGE BY EMS P ROFESSIONALS

Abstract

Background. Systematic evaluation of the performances of prehospital providers during actual pediatric anaphylaxis cases has never been reported. Epinephrine medication errors in pediatric resuscitation are common, but the root causes of these errors are not fully understood. Objective. The primary objective of this study was to identify underlying causes of prehospital medication errors that were observed during a simulated pediatric anaphylaxis reaction. Methods. Two- and 4-person emergency medical services crews from eight geographically diverse agencies participated in a 20-minute simulation of a 5-year old child with progressive respiratory distress and hypotension from an anaphylactic reaction. Crews used their own equipment and drugs. A checklist-based scoring protocol was developed to help identify errors. A trained facilitator conducted a structured debriefing, supplemented by playback of video recordings, immediately after the simulated event to elicit underlying causes of errors. Errors were analyzed with mixed quantitative and qualitative methods. Results. One hundred forty-two subjects participated in 62 simulation sessions. Ninety-five percent of crews (59/62) gave epinephrine, but 27 of those crews (46%) delivered the correct dose of epinephrine in an appropriate concentration and route. Twelve crews (20%) gave a dose that was ≥5 times the correct dose; 8 crews (14%) bolused epinephrine intravenously. Among the 55 crews who gave diphenhydramine, 4 delivered the protocol-based dose. Three crews provided an intravenous steroid, and 1 used the protocol-based dose. Underlying causes of errors were categorized into eight themes: faulty reasoning, weight estimation errors, faulty recall of medication dosages, problematic references, calculation errors, dose estimation, communication errors, and medication delivery errors. Conclusion. Simulation, followed by a structured debriefing, identified multiple, underlying causes of medication errors in the prehospital management of pediatric anaphylactic reactions. Sequential and synergistic errors were observed with epinephrine delivery.     

A potential association between myocardial ischemia and epinephrine for anaphylaxis

A previously healthy 60-year-old man presented to our emergency department with anaphylactic shock. We initiated fluid resuscitation with Ringer's lactate solution; injected 0.3 mg epinephrine intramuscularly; and administered d-chlorpheniramine maleate 5 mg, famotidine 20 mg, and methylprednisolone 80 mg intravenously. His symptoms resolved within 10 min. Thirty minutes after the epinephrine injection, he complained of sudden chest discomfort. Physical examination provided no evidence of anaphylaxis. The 12-lead electrocardiogram (ECG) showed ST-segment depression on leads II, III, aVF, and V3-6. Transthoracic echocardiography revealed normal ventricular contraction. After administration of 0.3 mg of sublingual nitroglycerin, his chest pain resolved immediately and his ECG normalized. A coronary angiogram showed normal coronary artery perfusion. The next day, his high-sensitivity troponin I was slightly elevated. We suspected that he had myocardial ischemia caused by coronary artery spasm. The symptoms of biphasic reaction of anaphylaxis are inconsistent, and using epinephrine for myocardial ischemia following anaphylaxis may aggravate the condition. Nonetheless, epinephrine is the drug of choice for treating anaphylaxis with critical airway, respiratory, and circulatory compromise. Thus, physicians should not hesitate to use epinephrine for patients who present with life-threatening conditions due to suspected anaphylaxis. Physicians should observe patients closely following epinephrine administration, and if they develop some symptoms, should carefully examine the patients because the treatments of anaphylaxis and myocardial ischemia differs. Physicians should be alert to the risk of myocardial ischemia after treatment of anaphylaxis, especially following epinephrine administration.     

Biphasic anaphylaxis: A review of the literature and implications for emergency management

Background

The biphasic reaction is a feared complication of anaphylaxis management in the emergency department (ED). The traditional recommended ED observation time is 4–6?h after complete resolution of symptoms for every anaphylaxis patient. However, there has been great controversy regarding whether this standard of care is evidence-based.

Improving Prehospital Protocol Adherence Using Bundled Educational Interventions

Background: Seizures and anaphylaxis are life-threatening conditions that require immediate treatment in the prehospital setting. There is variation in treatment of pediatric prehospital patients for both anaphylaxis and seizures. This educational study was done to improve compliance with pediatric prehospital protocols, educate prehospital providers and decrease variation in care. Objective: To improve the quality of care for children with seizures and anaphylaxis in the prehospital setting using a bundled, multifaceted educational intervention. Methods: Evidence-based pediatric prehospital guidelines for seizures and anaphylaxis were used to create a curriculum for the paramedics in the EMS system. The curriculum included in-person training, videos, distribution of decision support tools, and a targeted social media campaign to reinforce the evidence-based guidelines. Prehospital charts were reviewed for pediatric patients with a chief complaint of anaphylaxis or seizures who were transported by paramedics to one of ten hospitals, including three children's hospitals, for 8 months prior to the intervention and eight months following the intervention. The primary outcome for seizures was whether midazolam was given via the preferred intranasal (IN) or intramuscular (IM) routes. The primary outcome for anaphylaxis was whether IM epinephrine was given. Results: A total of 1,402 pediatric patients were transported for seizures by paramedics to during the study period. A total of 88 patients were actively seizing pre-intervention and 93 post-intervention. Of the actively seizing patients, 52 were given midazolam pre-intervention and 62 were given midazolam post-intervention. Pre-intervention, 29% (15/52) of the seizing patients received midazolam via the preferred IM or IN routes, compared to 74% (46/62) of the seizing patients post-intervention. A total of 45 patients with anaphylaxis were transported by paramedics, 30 pre-intervention and 15 post-intervention. Paramedics administered epinephrine to 17% (5/30) patients pre-intervention and 67% (10/15) patients post-intervention. Conclusion: The use of a bundled, multifaceted educational intervention including in-person training, decision support tools, and social media improved adherence to updated evidence-based pediatric prehospital protocols.