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Brook Eide MD, MS FACEP Objectives Prevalence of allergies Pathophysiology of allergic reactions Recognition of reactions Common allergens When is a reaction anaphylaxis Appropriate treatment of allergies and anaphylaxis Anaphylaxis – The Numbers The lifetime prevalence of anaphylaxis is 2% The median time between the onset of symptoms and respiratory or cardiac arrest was 5 minutes in iatrogenic anaphylaxis, 15 minutes in stinging insect venom-induced anaphylaxis, and 30 minutes in food induced anaphylaxis Foods are the most common cause in children Medications and insect stings are more common in adults Anaphylaxis Acute, potentially fatal, multi-organ system reaction caused by the release of chemical mediators from mast cells and basophils Classic form involves prior sensitization to an allergen with later re-exposure, producing symptoms via an immunologic mechanism Laboratory Studies Anaphylaxis is a clinical diagnosis and treatment cannot await laboratory confirmation Tryptase: Needs to be obtained within 3 hours of symptom onset More likely to be elevated with anaphylaxis from stinging insect venom or medication A normal tryptase does not rule out a diagnosis of anaphylaxis Lab Studies Plasma Histamine: Peak within 5 to 15 minutes and decline to baseline within 60 minutes More likely to increase than the tryptase Helpful in hospitalized patients when blood samples can be collected immediately By the time community based patients make it to the ED levels have usually returned to baseline Diagnosis Primarily a clinical diagnosis Patients are commonly restless and anxious Multiple organ systems involved Laboratory studies are not usually required and rarely helpful Signs and Symptoms Anaphylaxis may present with various combinations of approximately 40 potential symptoms and signs Most commonly affects the cutaneous, respiratory, cardiovascular, and gastrointestinal systems Skin or mucous membranes are involved in around 80% ***Skin symptoms are absent or unrecognized in 20% of all episodes*** Signs and Symptoms Majority of adults have urticaria, erythema, pruritus, or angioedema Children (poorly understood reasons) present more commonly with respiratory symptoms followed by cutaneous Some of the most severe cases present in the absence of skin findings Dermatologic: Flushing, Urticaria, Angioedema, Cutaneous or Conjunctival Injection, Pruritus, Warmth, Swelling Respiratory: Nasal Congestion, Choryza, Rhinorrhea, Sneezing, Throat Tightness, Wheezing, Shortness of Breath, Cough, Hoarseness, Dyspnea Cardiovascular: Dizziness, Weakness, Syncope, Chest Pain, Palpitations Gastrointestinal: Dysphagia, Nausea, Vomiting, Diarrhea, Bloating, Cramps Neurologic: Headache, Dizziness, Blurred Vision, Seizure Other: Metallic Taste, Sense of Impending Doom Time Course of anaphylaxis Usual course is rapid onset, evolution, and resolution of symptoms within seconds to hours Anaphylaxis is UNPREDICTABLE It may be mild and resolve spontaneously due to endogenous production of compensatory mediators It may be severe and progress within minutes to respiratory or cardiovascular compromise and death At the onset of an anaphylactic episode it is not possible to predict how severe it will become, how rapidly it will progress, and whether it will resolve promptly and completely or become biphasic or protracted The factors that determine the course of anaphylaxis in an individual patient are not fully understood Anaphylactic Disease Course The time course of an anaphylactic reaction: A uniphasic reaction occurs immediately after exposure and resolves with or without treatment within the first minutes to hours, and then does not recur during that anaphylactic episode. A biphasic reaction includes a recurrence of symptoms that develops after apparent resolution of the initial reaction. Biphasic reactions have been reported to occur in 1% to 20% of anaphylaxis episodes and typically occur about 8 hours after the first reaction, although recurrences have been reported up to 72 hours later A protracted reaction is any anaphylaxis episode that lasts for hours or days following the initial reaction New diagnostic criteria for anaphylaxis were published in 2006 to help health care professionals both recognize the spectrum of signs and symptoms that constitute anaphylaxis and establish a more systematic approach to its diagnosis and management 12 Reduced BP after exposure to a known allergen for that patient (minutes to several hours). Reduced BP is defined: In adults, as a systolic BP of less than 90 mm Hg or greater than 30% decrease from that person's baseline In infants and children, as a low systolic BP (age-specific) or greater than 30% decrease in systolic BP. Low systolic BP is defined as: Less than 70 mm Hg for ages 1 month to 1 year Less than (70 mm Hg plus twice the age) for ages 1 to 10 years Less than 90 mm Hg for ages 11 to 17 years Note: In infants and young children, hypotension may be a late manifestation of hypovolemic shock. Tachycardia, in the absence of hypotension, also may indicate shock. 259 Anaphylactic Disease Course The time course of an anaphylactic reaction may be uniphasic, biphasic, or protracted A uniphasic reaction occurs immediately after exposure and resolves with or without treatment within the first minutes to hours, and then does not recur during that anaphylactic episode A biphasic reaction includes a recurrence of symptoms that develops after apparent resolution of the initial reaction. Biphasic reactions have been reported to occur in 1% to 20% of anaphylaxis episodes and typically occur about 8 hours after the first reaction, although recurrences have been reported up to 72 hours later A protracted reaction is any anaphylaxis episode that lasts for hours or days following the initial reaction Food Allergy 15 million Americans with food allergies A food allergy can begin at any age Affects 1 in 13 children in the United States Roughly 2 in every classroom Economic cost of children’s food allergies is nearly $25 billion per year. In the U.S., food allergy is the leading cause of anaphylaxis outside the hospital setting. Food Allergy Food allergies among children increased approximately 50% between 1997 and 2011 The number of people who have a food allergy is growing, but there is no clear answer as to why More than 17 million Europeans have a food allergy, and hospital admissions for severe reactions in children have risen seven-fold over the past decade, according to the European Academy of Allergy and Clinical Immunology (EAACI) Food Allergy Every 3 minutes, a food allergy reaction sends someone to the emergency department – that is more than 200,000 emergency department visits per year. The U.S. Centers for Disease Control reported that food allergies result in more than 300,000 ambulatorycare visits a year among children under the age of 18. Food allergy is the leading cause of anaphylaxis outside the hospital setting. Food Allergy Eight foods account for 90% of all reactions: milk, eggs, peanuts, tree nuts, soy, wheat, fish and shellfish. Even trace amounts of a food allergen can cause a reaction Studies show the number of children living with peanut allergy appears to have tripled between 1997 and 2008 Food Allergies The foods most associated with food allergy in children are: Milk Eggs Peanuts Children may outgrow their allergic reactions to milk and to eggs. Peanut and tree nut allergies are likely to persist. The most common food allergens in adults are: Fruit and vegetable pollen (oral allergy syndrome) Peanuts and tree nuts Fish and shellfish Food Allergies Symptoms caused by a food allergy can range from mild to life-threatening The severity of each reaction is unpredictable People who have previously experienced only mild symptoms may suddenly experience a life-threatening reaction This is why allergists do not like to classify someone as “mildly” or “severely” food allergic - there is just no way to tell what may happen with the next reaction Food Allergies Anyone with a food allergy should always have his or her auto-injector close at hand Be sure to have two doses available, as the severe reaction can recur in about 20% of individuals There are no data to help predict who may need a second dose of epinephrine, so this recommendation applies to all patients with a food allergy If you are uncertain whether a reaction warrants epinephrine, use it right away; the benefits of epinephrine far outweigh the risk that a dose may not have been necessary Food Allergies Fatalities associated with food-induced anaphylaxis are most commonly associated with peanut or tree nut ingestion Such fatalities are associated with delayed use or lack of proper epinephrine dosing The highest risk groups for fatal anaphylaxis associated with food ingestion are: Adolescents and young adults Individuals with known FA and with a prior history of anaphylaxis Individuals with asthma, especially those with poor control (although fatal reactions may occur even in individuals with mild asthma) Exercise-Induced Anaphylaxis Exercise-induced anaphylaxis in adults is triggered by foods in about one third of patients It has a natural history marked by frequent recurrence of the episodes 37% of the patients reported a food trigger, most commonly crustacean shellfish (16%), alcohol (11%), tomatoes (8%), cheese (8%), and celery (7%) All patients met criteria for exercise-induced anaphylaxis (anaphylactic symptoms, urticaria, or angioedema with symptoms consistent with upper respiratory obstruction) or had cardiovascular collapse during exercise 75% of the patients were female The average number of episodes per year at the time of initial presentation was 14.5, but this frequency decreased to 8.3 at the time of the survey Exercise-Induced Anaphylaxis The most frequently occurring symptoms were pruritus (92%), urticaria (86%), angioedema (72%), flushing (70%), and shortness of breath (51%) About 50% of the patients reported seasonal rhinitis or dust allergies, 19% also reported having asthma, and 10% had eczema Most cases of exercise-induced anaphylaxis are associated with food, the food can be ingested without symptoms in the absence of exercise Exercise-Induced Anaphylaxis Cessation of physical activity usually results in immediate improvement of symptoms Exercise-induced anaphylaxis attacks are not consistently elicited by the same type and intensity of physical activity in a given patient Co-factors such as foods, alcohol, temperature, drugs (ie. aspirin and other nonsteroidal anti-inflammatory drugs), humidity, seasonal changes, and hormonal changes are important in the precipitation of attacks Exercise-Induced Anaphylaxis A distinct subset of exercise-induced anaphylaxis is food-dependent exercise-induced anaphylaxis (FDEIA), in which anaphylaxis develops only if physical activity occurs within a few hours after eating a specific food Neither food intake nor physical activity by itself produces anaphylaxis The foods most commonly implicated in fooddependent exercise-induced anaphylaxis are wheat, shellfish, tomatoes, peanuts, and corn Medication Approximately 10% of all US patients report having had an allergic reaction to a penicillin-class antibiotic in the past However, less than 1% of the population has an immunoglobulin E (IgE)–mediated reaction to penicillin, indicating a true drug allergy They may have had side effects or a symptom of the underlying illness that was interpreted as an allergy, such as a viral exanthema or rash in a child on amoxicillin Medication Furthermore, even patients with true penicillin allergies may lose the allergy over time About 80% of patients with an IgE-mediated penicillin allergy lose their sensitivity by 10 years after their reaction 1 in 5000 exposures to penicillin or cephalosporin causes anaphylaxis` Drug Allergies Onset of hives within a few hours of taking a new medication is easily recognized Many clinical presentations are complex or take place in the setting of illness and/or polypharmacotherapy ie. ICU patient taking multiple medications Drug Allergies Risk factors for the development of drug allergy include female sex, prior history of drug allergic reaction, recurrent drug exposure, genetic factors, and certain disease states Reactions to ampicillin occur more commonly in patients with atypical or abnormal lymphocytes (EBV, leukemia) Patients with AIDS have a very high rate of dermatologic reactions Generalized herpes virus also has high rate of skin reactions Non allergic Rash A common problem is exanthematous skin reactions in small children treated with antibiotics, usually penicillins These mostly mild and transient skin reactions appear to be due to a combined effect of the drug use and various viral infections causing immune stimulation The vast majority of children will tolerate penicillins if given them again later Insect Hymenoptera stings account for more deaths in the United States than any other envenomation Most deaths result from immunologic mechanisms, some are from direct toxicity Ants sting 9.3 million people each year Other Hymenoptera species account for more than 1 million stings annually Anaphylaxis secondary to Hymenoptera envenomation affects roughly 3% of the general population Hymenoptera Reactions Hymenoptera stings of all types are more common in males than in females, probably because of more frequent exposure Most deaths were in older (>50 years) and younger (< 10 years) males Individuals with large local reactions have a 5-10% risk of subsequent development of a severe systemic reaction if re-stung Hymenoptera Reactions Rapid onset of symptoms is the rule; 50% of deaths occur within 30 minutes of the sting, and 75% occur within 4 hours Fatal allergic reactions can occur as the first generalized reaction Far more common, however, is a fatal reaction following a previous, milder generalized reaction The shorter the interval since the last sting, the more likely it is that a severe reaction will take place Hymenoptera Reactions Venom load may be sufficient to cause fatal injury without the added effects of the endogenous system This may result from as few as 30 vespid stings or 200 honeybee stings Since the compounds are similar in anaphylactic and toxic reactions, pathology and treatment also are similar Hymenoptera Reactions People who have been stung should remove the bee stinger as quickly as possible Removal method is not as important as rapidity because the stinging apparatus actively injects venom into the wound for 1 minute after the sting, even if the bee has been killed or knocked away from the site Hymenoptera Reactions Most endangered patients die within 30 minutes of a sting Increased vascular permeability in anaphylaxis may result in transfer of 50% of the intravascular fluid into the extravascular space within 10 minutes Check airway and ventilatory status Treatment should include an initial intravenous (IV) bolus of 10-20 mL/kg isotonic crystalloids in addition to diphenhydramine and epinephrine Observe for sufficient duration to ensure symptoms do not rebound after initial treatment Rebound phenomena may occur up to 12 hours after sting IV Contrast Immediate Hypersensitivity Reaction Symptoms develop within one hour of adminstration and many begin within 5 minutes Signs and symptoms are similar to those of anaphylaxis Flushing, Pruritis, Urticaria, Angioedema, Bronchospasm, Wheezing, Laryngeal Edema, Stridor, Hypotension, Shock, Loss of Consciousness IV Contrast Test dosing is not recommended Severe and fatal reactions to usual doses of Contrast Medium have occurred in patients who tolerated test doses of the agent Fatalities have resulted from the test doses themselves, even to amounts as small as 1-2 mL Premedication Administer 13 hours prior: Prednisone – Orally 13 hours prior, 7 hours prior, and 1 hour prior at 50 mg per dose Children are on the same time scale at a dose of 0.5 to 0.7 mg/kg per dose Diphenhydramine – Oral or parenteral 1 hour before at a 50 mg dose in adults and 1.25mg/kg in children up to 50 mg IV Contrast Pretreatment reduces the rate of breakthrough reactions from 17-60% down to 9% Premedication was effective regardless of the severity of the initial reaction It is very likely that the most severe reactors were not entered into this protocol This was done with hyperosmolal contrast agents which are associated with a higher rate of reaction IV Contrast To avoid further reactions, the patient should never receive same agent that caused the initial reaction If the reaction was to high osmolal contrast material, use either nonionic low osmolal contrast or an isoosmolal agent in combination with premedications If the reaction was to low osmolal contrast, use an isoosmolal agent in combination with premedications Low osmolal agents cause significantly fewer reactions compared to high osmolal contrast, and non-ionic low osmolal agents are recommended for any patient with a previous anaphylactic reaction IV Contrast Factors associated with recurrent reaction despite premedication include: prior severe allergic reaction to any substance, one or more drug allergies, chronic oral glucocorticoid use, allergy to four or more allergens IV Contrast The incidence of any adverse reaction to ICM is about 15%. Most of these reactions are mild and require no treatment The overall risk of any adverse reaction was 12.66% with ionic ICM and 3.13% with nonionic ICM The risk of death was 1 death in 100,000 patients with either type of agent IV Contrast The reason that low-osmolality ICM have not completely replaced the older high-osmolality ICM is the higher cost of the low-osmolality agents Professional organizations have formulated guidelines regarding the selective use of low-osmolality ICM for certain high-risk patients However, with the selective use of nonionic ICM, severe adverse contrast reactions are 3 times as likely in low-risk patients who receive conventional ionic agents (0.09%) than in high-risk patients who receive nonionic agents (0.03%) Thus, the single most important risk factor for an adverse reaction is the type of contrast agent that is chosen for injection IV Contrast Idiosyncratic reactions may occur in people with a previous reaction to ionic or nonionic ICM, asthma, and/or food or medication allergies Previous reactions to ionic or nonionic ICM increase the relative risk of a repeat reaction 3.3- to 6.9-fold compared with the risk in the general population Approximately 60% of patients who had hives after ICM administration in the past have hives with a repeat exposure Similarly, facial edema has a recurrence rate in 68% of patients; difficulty breathing, 59%; and bronchospasm, 38%. IV Contrast People with asthma have 1.2-2.5 times the risk of such reactions than the general population In addition, when the reactions occur, they are more likely to be severe Severe reactions are 5-9 times more common in people with asthma than in others Patients with allergies, including hay fever, are 1.5-3 times more likely to have an adverse reaction to ICM than other people However, no consistent data warrant the use of any unique precautions in patients who have seafood or shellfish allergies IV Contrast No intervention completely eliminates the risk of a breakthrough immediate hypersensitivity reaction In an uncontrolled study, patients with previous hypersensitivity reactions to conventional contrast medium, pretreatment with prednisone and diphenhydramine combined with the use of a nonionic low osmolar agent, reduced the rate of reactions to 0.7% Management Anaphylaxis is a medical emergency that requires immediate recognition and intervention Management depends on the severity of initial reaction Purely local reactions do not require much intervention Severe or refractory anaphylaxis will require admission and a longer treatment and observation ManagementNonpharmacotherapy Supportive care Airway management High-flow oxygen Cardiac monitoring and pulse oximetry IV access Fluid resuscitation with isotonic crystalloid solution Supine position with legs elevated Management- Pharmacotherapy Adrenergic agonists (epinephrine) Antihistamines H2 receptor antagonists Bronchodilators Corticosteroids Positive inotropic agents Vasopressors Initial Management Elimination of additional allergen exposure IM injection of epinephrine These actions should be quickly followed by these additional steps Placement of the patient in a recumbent position (if tolerated), with the lower extremities elevated Provision of supplemental oxygen Administration of intravenous (IV) fluid (volume resuscitation) Life Saving Epi Administer epinephrine as soon as possible once anaphylaxis is recognized, and transport the patient to the nearest emergency facility Delayed administration of epinephrine has been implicated in contributing to fatalities. In a study of 13 fatal or near-fatal food-induced anaphylactic reactions in children, 6 of the 7 children who survived received epinephrine within 30 minutes of ingesting the food, whereas only 2 of the 6 children who died received epinephrine within the first hour Epinephrine, therefore, should be available at all times to patients at risk A recent study in schools also highlights the fact that children with FA often do not have ready access to epinephrine at school, thus placing them at increased risk Life Saving Epi Experts in the field agree that epinephrine is the only first- line treatment for anaphylaxis. There is no substitute for epinephrine, thus all other treatments are adjunctive. In the treatment of anaphylaxis, H1 and H2 antihistamines and corticosteroids are commonly used, but little or no data exist demonstrating their functional role or effectiveness. The use of antihistamines is the most common reason reported for not using epinephrine and may place a patient at significantly increased risk for progression toward a life-threatening reaction. Life Saving Epi In August 2015, the recommendation for epinephrine… Do not hesitate to use epinephrine for possible anaphylaxis, even in the absence of proof that patients' symptoms are the result of an allergic reaction Epinephrine in appropriate doses is safe, and there are no absolute contraindications for its use in treating anaphylaxis, according to a consensus statement prepared by an expert panel of emergency physicians and allergists Life Saving Epi Delay in administration of epinephrine may lead to more severe and treatment resistant anaphylaxis It is not necessary for the [National Institute of Allergy and Infectious Disease and the Food Allergy and Anaphylaxis Network] criteria to be met to administer epinephrine Antihistamines and glucocorticoids do not work fast enough to be an appropriate first-line treatment for a severe reaction, but they may be administered after epinephrine at the discretion of the treating physicians Life Saving Epi There are no absolute contraindications to epinephrine use in anaphylaxis However, there are subgroups of patients who might theoretically be at higher risk for adverse effects during epinephrine therapy Because the risk of death or serious disability from anaphylaxis itself usually outweighs other concerns, existing evidence clearly favors the benefit of epinephrine administration in most situations Sept 2014 Study Results Epinephrine is the first-line treatment for anaphylaxis, but at the ED, steroids were the most common medication given (69%), followed by antihistamines (66%), epinephrine (42%) and Albuterol (28%) ED intake procedures for allergic emergencies show quick processing, with the majority of patients (69%) seen immediately or within five minutes of arriving at the ED However, discharge procedures demonstrate that the majority of patients are not receiving critical information needed for effective ongoing management of severe allergies Sept 2014 Study Results While 64% of respondents received advice to continue steroids/antihistamines upon discharge from the ED, only 36% were given a prescription for epinephrine, and less than a quarter of respondents (24% and 18%, respectively), were given information about food allergies or a referral to an allergist When looking at only those patients who experienced firsttime reactions, the numbers improved, but only slightly: 41% were given a prescription for epinephrine, 31% were given information about food allergies and 32% were given a referral to an allergist Epi Administration IV epinephrine (1:10,000 solution) is recommended for patients who do not respond to an initial (or repeated) IM injection of epinephrine and fluid resuscitation and may not be adequately perfusing muscle tissue Endotracheal or intra-osseous epinephrine can be delivered if IV access cannot be obtained immediately The efficacy of this delivery method is based on a single study of a small number of patients experiencing cardiac arrest Life Saving Epi Epinephrine is the drug of choice for anaphylaxis and should be administered as first-line therapy The pharmacologic actions of this agent address the pathophysiologic changes that occur in anaphylaxis better than any other single drug Failure to administer epinephrine early in the course of treatment has been repeatedly implicated in anaphylaxis fatalities Despite this fact, physicians often fail to prescribe epinephrine In addition, the timing of emergency responses can determine when epinephrine is injected Life Saving Epi The therapeutic actions of epinephrine, which encompass a broad range of effects germane to the mechanisms of anaphylaxis, include the following: Increased vasoconstriction, increased peripheral vascular resistance, and decreased mucosal edema via α1-adrenergic agonist receptor effects Increased inotropy and increased chronotropy via β1adrenergic receptor agonist effects Bronchodilation and decreased release of mediators of inflammation from mast cells and basophils via β2adrenergic receptor agonist effects Life Saving Epi In therapeutic doses and by any route, epinephrine frequently causes mild transient adverse effects in individuals of all ages These include anxiety, fear, restlessness, headache, dizziness, palpitations, pallor, and tremor Rarely, epinephrine may lead to ventricular arrhythmias, angina, myocardial infarction, pulmonary edema, sudden sharp increase in BP, and intracranial hemorrhage These severe adverse effects are more likely to occur when epinephrine is given in overdose by any route for example, after an intravenous bolus injection or intravenous injection of a 1:1,000 epinephrine solution instead of a 1:10,000 epinephrine solution. Life Saving Epi Epinephrine has an onset of action within minutes but is rapidly metabolized Therefore, the effect is often short-lived and repeated doses may be necessary If a patient responds poorly to the initial dose or has ongoing or progressive symptoms despite initial dosing, repeated dosing may be required after 5 to 15 minutes Reports of patients receiving epinephrine for food-induced or nonfood-induced anaphylaxis note that as high as 10% to 20% of individuals who receive epinephrine will require more than 1 dose before recovery of symptoms In many of the cases, the subsequent doses of epinephrine were given more than 15 minutes after the first dose (some more than 1 hour), despite recommendations to repeat dosing as frequently as every 5 to 15 minutes The optimal dosing interval for repeated dosing has not been studied prospectively Epinephrine can be delivered through a variety of routes, including IM, IV, and endotracheal or intraosseous IM epinephrine is recommended over subcutaneous injection because it provides a more rapid increase in plasma and tissue concentrations of epinephrine The IM dose should be given in the anterolateral thigh in the vastus lateralis muscle The needle used should be of adequate length to reach the muscle beneath the subcutaneous adipose tissue over the vastus lateralis muscle IM injection into the thigh may be impossible in overweight or obese individuals, especially women who have thicker subcutaneous fat tissue In the circumstance of inadequate IM dosing, subcutaneous dosing will provide some benefit but will be less effective than IM dosing When an epinephrine auto-injector is used, children weighing less than 25 kg should receive the 0.15 mg dose Children over 25 kg through adults should receive the 0.3 mg dose autoinjector When a 1:1,000 epinephrine solution is used, patients should receive a dose of 0.01 mg/kg with a maximum dose of 0.5 mg Life Saving Epi Some level of decision making regarding the risk-to-benefit ratio may be warranted, and especially for patients: Who have cardiovascular disease and are reluctant to receive epinephrine due to fear of adverse cardiac effects These patients should be made aware that myocardial ischemia and dysrhythmias can occur in untreated anaphylaxis Receiving monoamine oxidase inhibitors (which block epinephrine metabolism) or tricyclic antidepressants (which prolong epinephrine duration of action) Receiving stimulant medications (for example, amphetamines or methylphenidate used in the treatment of attention-deficithyperactivity disorder) or abusing cocaine With certain pre-existing conditions, such as recent intracranial surgery, aortic aneurysm, uncontrolled hyperthyroidism, or hypertension Meds affection Epi Certain medications also may affect symptom severity and treatment response in patients with food-induced anaphylaxis, for example: β-adrenergic antagonists may decrease the response to epinephrine therapy in patients undergoing anaphylaxis Angiotensin-converting enzyme inhibitors and, to a lesser extent, angiotensin II receptor blockers may interfere with endogenous compensatory mechanisms, resulting in more severe or prolonged symptoms α-adrenergic blockers may decrease the effects of endogenous or exogenous epinephrine at α-adrenergic receptors, rendering patients less responsive to epinephrine Adjuvant Medications Glucagon Treatment of anaphylaxis may be complicated by concomitant use of β-adrenergic receptor antagonists When administered orally, parenterally, or topically (for example, eye drops), these antagonists may decrease the effects of endogenous or exogenous epinephrine at β-adrenergic receptors and render patients less responsive to epinephrine This class of drugs may cause patients to be resistant to treatment with epinephrine, and they can develop refractory hypotension and bradycardia Glucagon should be administered in this setting because it has inotropic and chronotropic effects that are not mediated through β-receptors A single dose of 1-5 mg in adults (in children, 20-30 μg/kg, to a maximum of 1 mg) administered intravenously over 5 minutes is recommended, which may be repeated or followed by an infusion of 5-15 μg/minute Rapid administration of glucagon can induce vomiting Adjuvant Medications H1 antihistamines. In contrast to epinephrine, very limited scientific evidence supports the use of H1antihistamines in the emergency treatment of anaphylaxis H1 antihistamines are useful only for relieving itching and urticaria They do not relieve stridor, shortness of breath, wheezing, GI symptoms, or shock Therefore, they should be considered adjunctive therapy and should not be substituted for epinephrine Adjuvant Medications For oral and IV dosing, first-generation H1 antihistamines such as diphenhydramine 25-50 mg are used Sedation and cognitive and psychomotor impairment are recognized side effects of the first-generation H1 antihistamines, and these may contribute to decreased awareness of anaphylaxis symptoms Alternative oral dosing with a less-sedating, secondgeneration H1 antihistamine (such as cetirizine 10 mg) may be used because it has a relatively rapid onset of action compared with other second-generation H1 antihistamines and is available in generic formulations Adjuvant Medications Bronchodilator medications For the treatment of bronchospasm not responsive to IM epinephrine, inhaled bronchodilators such as albuterol should be used as needed and should be considered to be adjunctive therapy to the administration of epinephrine Albuterol does not relieve airway edema (for example, laryngeal edema) and should not be substituted for IM epinephrine dosing in the treatment of anaphylaxis In most emergency care settings, nebulized therapy may be more practical than metered-dose inhalers (MDIs) (with spacers) for patients with respiratory distress, but MDIs also can be helpful when the respiratory distress is mild or when nebulized therapy is not available Moreover, the effectiveness of albuterol delivery via nebulizer vs MDI (with spacer) remains uncertain for patients with severe respiratory distress Therefore, albuterol administration via nebulizer (if available) is recommended in this setting Adjuvant Medications H2 antihistamines Minimal evidence supports the use of H2 antihistamines in the emergency treatment of anaphylaxis Some health care professionals use these medications concurrently with H1 antihistamines for relief of symptoms; however, rigorous studies in anaphylaxis that support this idea are lacking Adjuvant Medications Corticosteroids Very little information is available to support or refute the use of corticosteroids for the treatment of acute anaphylaxis However, their empiric use is prevalent and supported by many health care professionals Corticosteroids are not helpful in the treatment of acute anaphylaxis due to their slow onset of action (4 to 6 hours) These agents often are given because of their anti-inflammatory properties that benefit allergic and inflammatory disease and also because they may help prevent biphasic or protracted reactions, which occur in up to 20% of individuals Treatment should be stopped within 2 to 3 days, since all biphasic reactions reported to date have occurred within 3 days Adjuvant Medications Vasopressors Patients who have persistent hypotension despite the administration of epinephrine and IV fluids should receive vasopressor medications titrated to the desired effect of restoring BP Ideally, continuous non-invasive monitoring of blood pressure and heart rate should be performed Due to the narrow risk-to-benefit ratio of these medications, patients requiring vasopressors should be transferred to a hospital setting for acute care No compelling evidence exists to support one vasopressor over another in this clinical scenario Adjuvant Medications Atropine Consider intravenously administered atropine for patients with bradycardia Supplemental oxygen therapy Oxygen should be administered initially to all patients experiencing anaphylaxis, especially those with evidence of hypoxia or respiratory distress Supplemental oxygen helps not only with optimization of oxygen delivery and organ perfusion, but also with bronchodilation Adjuvant Medications IV fluids Many patients with anaphylaxis require IV fluids Massive fluid shifts can occur rapidly in anaphylaxis due to increased vascular permeability, with transfer of up to 35% of the intravascular volume into the extravascular space within minutes Any patient who does not respond promptly and completely to injected epinephrine should be assumed to have intravascular volume depletion causing persistent hypotension despite maximum vasoconstriction These patients should receive large-volume fluid resuscitation, with normal saline being the preferred treatment Large-volume fluid resuscitation should be initiated immediately in patients who present with orthostasis, hypotension, or incomplete response to IM epinephrine. Supportive Measures Patient positioning The patient should be placed in a recumbent position (when tolerated) with the lower extremities elevated to maximize perfusion of vital organs This also helps prevent empty ventricle syndrome, in which severe hypotension leads to inadequate cardiac filling and electrical cardiac activity without a pulse Individuals with respiratory distress or vomiting may not tolerate a recumbent position Treatment Course Review Dosing with IM epinephrine followed by transfer to an emergency facility for observation and possible further treatment Observation for 4 to 6 hours or longer based on severity of the reaction Education for patient and family on: Allergen avoidance Early recognition of signs and symptoms of anaphylaxis Anaphylaxis emergency action plan implementation Appropriate IM epinephrine administration Medical identification jewelry or an anaphylaxis wallet card Treatment Course Review Epinephrine auto-injector prescription and training provided at the time of discharge Continuation of adjunctive treatment after patient discharge: H1 antihistamine: diphenhydramine every 6 hours for 2-3 days; alternative dosing with a non-sedating second generation antihistamine H2 antihistamine: ranitidine twice daily for 2-3 days Corticosteroid: prednisone daily for 2-3 days Follow-up appointment with primary health care professional (after the food-induced anaphylactic reaction), with consideration for additional follow-up with a clinical specialist such as an allergist/immunologist Take Home points Allergic Reactions are common and becoming more common 1 in 50 people will have an anaphylactic reaction in there life Take Food and insect sting reactions seriously Inappropriate antibiotics have individual consequences You don’t have to have a rash to have anaphylaxis Take Home Epi…. Epi…. Epi Epinephrine is the ONLY first line treatment for anaphylaxis There is no real contraindication to giving epi Think about glucagon if now responding to epi Add oxygen to you steroid antihistamine regiment DC with an epi pen