Anaphylaxis Case File

Anaphylaxis Case File

Eugene C. Toy, MD, Barry C. Simon, MD, Terrence H. Liu, MD, MHP, Katrin Y. Takenaka, MD, Adam J. Rosh, MD, MS

Case 10

A 35-year-old woman is brought to the emergency department (ED) by ambulance after collapsing at home. She had been seen by her regular doctor earlier in the day and prescribed amoxillin for sinusitis. Paramedics report field vital signs remarkable for a blood pressure of 70/30 mm Hg, heart rate of 140 beats per minute, respiratory rate of 40 breaths per minute, and an oxygen saturation of 76%. Intravenous fluids and oxygen were administered during transport. Paramedics are assisting the patient’s breathing with bag-valve mask ventilation, but oxygen saturations remains low. On physical examination, the patient is obtunded with perioral cyanosis, tongue swelling, stidor, wheezing, and labored breathing. Her skin is cool and clammy with large urticarial lesions.

⯈ What are the next steps?

⯈ What treatments should be instituted?

ANSWER TO CASE 10:

Anaphylaxis

Summary: This patient is demonstrating signs and symptoms of anaphylaxis. Anaphylaxis is rapidly progressive severe allergic reaction which compromises a patient’s airway, breathing, and circulation. Patients may also exhibit flushing, hives, and swelling of mucous membranes. Successful treatment of anaphylaxis requires early recognition of the symptoms of anaphylaxis, support of the airway, and administration of epinephrine.

• • Next step: In the presence of symptoms meeting the diagnostic criteria for anaphylaxis, epinephrine should be administered immediately. The first dose should be administered intramuscularly. In the setting of a severe reaction like the one described above, moving quickly to intravenous infusion of epinephrine is recommended.
• • Further treatments: This patient requires rapid resuscitation and stabilization. Airway, breathing, and circulation (ABCs) should be managed appropriately and in that order, which will mean both procedural and pharmacological intervention. A definitive airway will need to be immediately established in the face of impending airway obstruction (see Case 1), and the patient’s cardiovascular compromise must be supported with epinephrine. Experts have referred to the ABCs of anaphylaxis as A E B C; the E is for epinephrine.

In addition to airway management and early administration of epinephrine, pharmacologic therapy is tailored to the other systemic manifestations of the anaphylactic response. These include volume resuscitation with crystalloid, nebulized beta agonists, nebulized racemic epinephrine, corticosteroids, antihistamines (including H2 blockers), and removal of any remaining antigen (ie, the bee stinger).

ANALYSIS

Objectives

1. Rapidly recognize the characteristic clinical features of anaphylaxis.
2. Understand the underlying pathophysiology of anaphylaxis.
3. Become familiar with the available treatment options; most importantly the correct administration of epinephrine.

Considerations

This patient is brought into the ED with swelling of the tongue and labored breathing. The perioral cyanosis, diffuse wheezing, stridor, and hypoxia all indicate impending respiratory failure. A delay of even a minute may be life-threatening. The most important intervention in addition to administration of epinephrine is securing an airway. This patient likely has edema of the pharynx and larynx making intubation technically difficult. Airway management in a patient like this often requires a cricothyroidotomy.

Intravenous access with administration of epinephrine is the most important pharmacologic intervention. Epinephrine should first be given intramuscularly; if that route fails, an intravenous drip should be initiated. Dosing of epinephrine will be covered below. Identification of the inciting agent is not essential for treatment of anaphylaxis, but is helpful in preventing further exposures and recurrence of symptoms.

Approach To:

Anaphylaxis

CLINICAL APPROACH

Epidemiology

Millions of people present to emergency departments every year complaining of allergic symptoms ranging from the minor rashes to multisystem anaphylaxis. Most of the time, it is difficult if not impossible to identify the trigger. Many reactions may occur in response to medical therapies such as antibiotics and radiologic contrast agents. Because the spectrum of allergic responses is so broad, anaphylaxis is likely underreported. As a result it is difficult to calculate a precise incidence of this disease. There are an estimated 30,000 ED visits every year for adverse food reactions. However, there are far more visits for more vague complaints and unknown exposures that may be difficult to identify as anaphylaxis. In the emergency department the goal is rapid diagnosis, symptomatic treatment, and prevention of further episodes.

Pathophysiology

True anaphylaxis is a type 1 hypersensitivity reaction occurring after a previous sensitizing exposure. In its purest form, this is an immune-mediated activation of basophils and mast cells with subsequent release of prostaglandins, leukotrienes, and histamine. From a clinical standpoint, an anaphylactoid reaction also includes release of these compounds but through non–immune-mediated pathways. The only clinical significance of this difference is that anaphylactoid reactions can occur without prior sensitization. Regardless of the underlying mechanism, their effects are similar, and early recognition will determine successful clinical management in these patients (see Table 10–1 for pitfalls).

When first exposed to a substance, binding antibodies trigger class switching and regulatory changes in gene expression, effectively priming the immune system for its next encounter with the offending agent. In certain cases, this leads to immunoglobulin (igE) binding mast cells and basophils. In the classically defined anaphylactic reaction, the antigen again encounters the immune system, binds to the IgE on the mast cells and basophils, and releases a flood of cytokines that set the clinical response in motion. In an anaphylactoid reaction, the antigen causes direct release

of cytokines by mast cells and basophils, without need for prior sensitization. In both cases, the end result is the same, and clinically indistinguishable.

The early stages of some anaphylactic reactions involve increased secretion by mucous membranes. In addition to watery eyes and rhinorrhea, increased bronchial secretions and increased smooth muscle tone cause wheezing and increase the work of breathing. Decreased vascular tone and increased capillary permeability lead to cardiovascular compromise and hypotension. Patients may lose over 30% of their blood volume to extravasation in the first ten minutes of their allergic reaction. Other cytokines, specifically histamine, can cause urticaria and angioedema. There are numerous cytokines involved in the immunologic cascade following exposure, but no one major substance is felt to be primarily responsible. Leukotriene C4, prostaglandin D2, histamine, and tryptase are known key components in the reaction. Elevated tryptase levels confirm the diagnosis.

Causes

Some of the most common causes of anaphylaxis are healthcare related, most notoriously allergies to penicillin and sulfa-containing medications. Some studies suggest as many as 1 in 500 exposures to penicillin will result in anaphylaxis. Radiographic intravenous contrast agents can also cause anaphylaxis. This reaction is not IgE mediated, and is more common in patients receiving the less-expensive hyperosmolar agents. Overall, there are an estimated 0.9 fatal reactions per 100,000 patients exposed to intravenous contrast. This number skyrockets to 60% in patients who have had a prior exposure and reaction.

Hymenoptera, or bee and wasp, stings are another cause of anaphylaxis. Anaphylaxis from stings results in an average of 50 deaths per year in the United States. Overall, the number of cases of arthropod anaphylaxis seen by physicians is small compared to the number of iatrogenic cases, but because exposures often occur miles from medical treatment, they can have serious outcomes.

Food sources round out the major causes of serious allergic reactions. Peanuts are easily the most common cause of serious allergies, but any food can be responsible. Other common food allergens include eggs and shellfish.

Diagnosis

The diagnosis of anaphylaxis is made clinically. The most commonly affected system is the skin, which manifests with angioedema, urticaria, erythema, and pruritus in at least 80% of patients with anaphylaxis. The cardiovascular system is also affected, primarily as a result of decrease vasomotor tone and capillary leakage.

This leads to hypotension and tachycardia. Respiratory compromise is common. Bronchospasm and bronchorrhea in the lower respiratory tract in combination with edema of the upper respiratory tract are the most feared and difficult to manage aspects of anaphylaxis. After administration of epinephrine, control of the airway the most important therapeutic intervention, as nearly all deaths caused by anaphylaxis are a result of airway compromise. Early and aggressive airway management— surgical if needed—is indicated in these patients. Gastrointestinal symptoms including nausea, cramping, and diarrhea may be seen, and are associated with particularly severe anaphylactic reactions.

Clinical Criteria for Diagnosis of Anaphylaxis

Clinical criteria were developed from a multidisciplinary symposium to best identify anaphylaxis early and accurately. Anaphylaxis is highly likely if any one of the following three diagnostic criteria exist.

1. Acute onset (minutes to hours) with reaction of the skin and/or mucosal tissue in addition to respiratory symptoms or hypotension. Skin symptoms include itching, redness, hives, generalized urticaria, and mucosal edema, Respiratory manifestations include laryngeal stridor, bronchospasm, bronchorrhea, and hypoxia. Hypotension results from extravasation of fluid from the vasculature and loss of vasomotor tone.
2. Two or more of the following occurring rapidly (minutes to hours) after exposure to a likely allergen: involvement of the skin-mucosal tissue, respiratory symptoms, hypotension, or gastrointestinal symptoms. Gastrointestinal symptoms include abdominal pain, cramping, and diarrhea.
3. Hypotension occurring rapidly (minutes to hours) after exposure to known allergen for that patient. Hypotension may present as faintness or altered mental status.

Treatment

Th e primary initial therapy for anaphylaxis is epinephrine (Table 10–2). Epinephrine will act as a pressor for hemodynamic support, a bronchodilator to relieve wheezing, as well as to counteract released mediators and prevent their further release. Epinephrine can be dosed intramuscularly or intravenously. Subcutaneous administration of epinephrine is no longer recommended as it has been proven less effective than intramuscular administration. Initial administration is intramuscular in the anterior thigh with the more concentrated 1:1000 dose at 0.3 to 0.5 mL every 5 minutes. If there is no response or if the patient is already demonstrating cardiovascular compromise, intravenous administration should be started immediately.

IV epinephrine dosing can be confusing and potentially dangerous by provoking cardiac dysrhythmias. In general, all ampules of epinephrine have 1 mg of medication (1 mL of 1:1000 = 1 mg of medication; 10 mL of 1:100,000 = 1 mg of medication). One method of administration is to place 1 mg (1 ampule) of epinephrine into 1 L of intravenous fluid (equivalent to 1 μg/mL) and infuse to 1 to 4 cc/min (1-4 μg/min). This allows for precise titration of dosing to desired effect, and

Reprinted, with permission, from Tintinalli JE, Kelen GD, Stapczynski JS, eds. Emergency Medicine. 6th ed. New York, NY: McGraw-Hill; 2004:250.

provides more rapid administration of epinephrine than intramuscular dosing. Caution should be exercised in the elderly and in those with known cardiovascular disease. Intravenous administration of epinephrine can cause hypertension, tachycardia, dysrhythmias, and myocardial ischemia.

Inhaled beta agonists are indicated for wheezing, and nebulized racemic epinephrine has been hypothesized to decrease laryngeal edema. Intravenous glucagon has been proposed for individuals on β-blockers in the event they are unresponsive to epinephrine. Glucagon may overcome hypotension by activating adenyl cyclase independent of the beta receptor.

Other adjuvants include systemic steroids, specifically methylprednisolone and prednisone. Steroids will not take action for at least 6 hours, but will blunt further immune responses. Steroids should be continued for days after the reaction and gradually tapered. H1 and H2 blockers should also be administered. Again, the goal of therapy is to mitigate the effects of as many cytokines as possible. Diphenhydramine and ranitidine are the most commonly employed agents. It should be remembered that these other medications, while safe and easy to administer, are not first-line agents, and will not counteract respiratory and cardiovascular compromise.

COMPREHENSION QUESTIONS

10.1 An 18-year-old woman is brought to the ED with suspected anaphylaxis. Which of the following most suggests anaphylaxis rather than a simple allergic reaction?

A. Itching

B. Watery eyes

C. Blood pressure of 80/40 mm Hg

D. Hives

E. Anxiety

10.2 A 6-year-old girl with a known peanut allergy is brought to the ED by ambulance after accidentally eating a cookie made with peanut butter at a school party. She is wheezing with hives. Which of the following should be the first intervention?

A. Endotracheal intubation

B. Normal saline 20 cc/kg IV

C. Examination of the skin

D. Epinephrine 0.15 mg intramuscular

E. Nebulized albuterol

10.3 Which of the following management options is the greatest determinant of patient outcome in anaphylaxis?

A. Timely administration of steroids

B. Administration of diphenhydramine

C. Early identification of the allergen

D. Early administration of epinephrine

E. Aggressive resuscitation with intravenous fluids

10.4 A 32-year-old man collapses in the emergency room after being brought in by paramedics. He was stung by a bee and known to be highly allergic. He appears cyanotic and had extreme stridor in the ambulance. Severe laryngeal edema is notable. Which of the following is the best treatment?

A. Nebulized albuterol, H1 and H2 antagonists, corticosteroids, and crystalloids

B. Subcutaneous epinephrine, H1 and H2 antagonists, and corticosteroids

C. Rapid sequence intubation, subcutaneous epinephrine, and corticosteroids

D. Intramuscular epinephrine, rapid sequence intubation, and corticosteroids

E. Intravenous epinephrine, rapid sequence intubation with preparation for a surgical airway, corticosteroids, nebulized albuterol, and H1 and H2 antagonists

ANSWERS

10.1 C. Hypotension indicates a systemic reaction and cardiovascular compromise, thereby classifying this allergic reaction as anaphylaxis. The other option may all be part of an anaphylactic response, but may also just be simple allergic reactions.

10.2 D. Intramuscular epinephrine should be administered immediately. If there is significant respiratory or airway compromise, then the patient should be controlled.

10.3 D. Again, early recognition of anaphylaxis and immediate dosing of epinephrine is most important.

10.4 E. This patient has severe anaphylaxis, and it would be appropriate to move straight to intravenous epinephrine. If intravenous dosing is not immediately available, then intramuscular epinephrine should be given. Attention should then be turned to managing the airway. Because of the significant laryngeal edema, endotracheal intubation will be nearly impossible; hence, cricothyroidotomy may be required. After securing the airway, steroids, beta agonists, H1 and H2 antagonists should be administered.

CLINICAL PEARLS

⯈ The airway should be secured early and often. It is much easier to extubate a patient without severe laryngeal edema than to intubate a patient with an occluded posterior oropharynx.

⯈ Epinephrine should be given at the first sign of cardiovascular compromise.

⯈ Look for causes of anaphylaxis after you have started your initial resuscitation.

⯈ Steroids, antihistamines, and beta agonists are all helpful pharmacologic adjuvants for managing the many symptoms of anaphylaxis.

References

Brau nwald E, Fauci AS, Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 15th ed. New York, NY: McGraw-Hill; 2001. 

Rowe BH, Carr S. Anaphylaxis and acute allergic reaction. In: Tintinalli JE, Kelen GD, Stapczynski JS, eds. Emergency Medicine. 6th ed., New York, NY: McGraw-Hill: 2004:108-124. 

Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: Summary report—Second National Institute of Allergy and Anaphylaxis Network Symposium. J Allergy Clin Immunol. 2006. 

Soar J, Pumphrey R, Cant A, et al. Emergency treatment of anaphylactic reaction: Guidelines for healthcare providers. Resuscitation. 2008;77:157-169.

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