Anaphylaxis

Anaphylaxis manifests as a severe, potentially fatal multiorgan system reaction ^[2]. Rapid recognition prevents delays in care. Clinical presentation often involves the spontaneous or triggered degranulation of mast cells ^[3]. The 2023 practice parameter update emphasizes revised diagnostic criteria focusing on multi-system involvement ^[1][5].

Clinical Presentation

Identify symptoms across multiple organ systems following exposure to a known or likely allergen:

• Cutaneous: Urticaria , angioedema , or generalized flushing.
• Respiratory: Dyspnea, wheezing, or stridor.
• Gastrointestinal: Severe crampy abdominal pain or recurrent vomiting.
• Cardiovascular: Hypotension , syncope, or signs of end-organ hypoperfusion.

In infants and toddlers, symptoms often differ from adults. Clinicians should monitor for sudden lethargy, inconsolable crying, or behavioral changes ^[1]. Patient age does not correlate with reaction severity ^[1]. Anaphylaxis rarely occurs during the very first exposure to a specific allergen ^[1].

Triage and Biphasic Monitoring

Biphasic anaphylaxis describes the recurrence of symptoms after the initial reaction resolves without further allergen exposure ^[2][6]D. Recurrence typically occurs within 1–48 hours of the initial onset ^[2]. Incidence rates range from 0.4% to 20% ^[6]D. Triage must prioritize observation for patients with severe initial symptoms or those requiring multiple doses of rescue therapy ^[4][6]D. The duration of monitoring depends on individual risk factors ^[2].

Immediate management of anaphylaxis requires a rapid, systematic approach to stabilize the patient. The first step is to call for emergency assistance and remove the inciting allergen whenever possible ^[8].

Airway and Breathing

Assess the airway for signs of angioedema or stridor . Administer high-flow oxygen to all patients with respiratory distress or hypotension ^[8]. Prepare for advanced airway management if upper airway obstruction progresses.

Circulation and Positioning

Patient positioning is critical to prevent "empty ventricle syndrome," a fatal collapse of venous return ^[8]. Place the patient in a supine position with the legs elevated ^[8].

• Do NOT allow the patient to stand or sit up suddenly.
• If the patient is vomiting, use the recovery position.
• In pregnancy, use the left lateral decubitus position to avoid aortocaval compression.

First-Line Pharmacotherapy

Epinephrine is the only first-line treatment for anaphylaxis ^[7][10]. It should be administered immediately upon recognition of a severe reaction ^[9][11]. While intramuscular (IM) injection is the standard, newer needle-free options like intranasal epinephrine 2.0 mg or sublingual epinephrine 12 mg are emerging as alternatives ^[7][9][11].

Epinephrine is the only first-line treatment for anaphylaxis ^[11]. Administer 0.01 mg/kg (maximum 0.5 mg) intramuscularly (IM) in the mid-outer thigh ^[15]. For pediatric patients weighing <15 kg, clinicians may prescribe 0.1 mg or 0.15 mg autoinjectors ^[15]. Prompt administration is vital, as delays increase the risk of fatality, particularly in high-risk groups like adolescents ^[13].

Alternative Delivery Systems

Needle-free options address injection reluctance ^[11]. Epinephrine nasal spray (ENS) at a 13.2 mg dose (two 6.6 mg sprays) provides a pharmacokinetic profile comparable to a 0.3 mg IM autoinjector ^[14]. Sublingual film (AQST-109) at a 12 mg dose is a device-free alternative currently in late-stage development ^[12][7].

Adjunctive Treatments

Adjuncts like H1-antihistamines (e.g., Cetirizine 10 mg), H2-antihistamines (e.g., Famotidine 20 mg), and corticosteroids (e.g., Prednisone 50 mg) should never delay epinephrine ^[11]. These agents treat cutaneous symptoms but do not prevent airway obstruction or vascular collapse ^[11].

Refractory Management

If symptoms persist after 5–15 minutes, repeat the IM dose ^[15]. For patients on beta-blockers who are unresponsive to epinephrine, administer Glucagon 1–5 mg IV over 5 minutes ^[15]. If symptoms resolve promptly and caregivers are comfortable with observation, emergency medical services (EMS) activation may not be required ^[15].

Patients presenting with anaphylaxis require clinical observation to monitor for biphasic reactions or symptom recurrence. Recurrence rates are estimated between 2.6% and 17.6% ^[18]. While standard protocols suggest an observation window of 4 to 8 hours, patients with severe initial presentations, such as cardiovascular collapse or those requiring multiple doses of epinephrine, may require prolonged monitoring ^[17][18].

Risk Factors for Recurrence

The most consistent risk factor for recurrent anaphylaxis is a personal history of food allergy ^[18]. Specific triggers, such as cow's milk, are associated with frequent recurrences in pediatric populations ^[16]. Comorbidities including asthma and atopic dermatitis further elevate the risk of biphasic events ^[18]. In cases of Hymenoptera venom-induced anaphylaxis (HVA), elevated basal serum tryptase (BST) levels serve as a marker for increased severity and potential recurrence ^[19].

Disposition and Discharge

Before discharge, clinicians must confirm the patient has a clear action plan and access to emergency medication. This includes prescriptions for epinephrine auto-injectors or the epinephrine nasal spray for patients aged ≥6 years ^[11]. Patients should be educated on the unpredictability of recurrences and the necessity of carrying rescue medication at all times ^[18].

Pregnancy

Anaphylaxis during pregnancy is rare, occurring in approximately 1.5 to 3.8 per 100,000 pregnancies ^[21]. The condition poses a dual risk of maternal mortality and fetal hypoxia ^[21]. A specific manifestation in this population is painful uterine contractions ^[22]. While systemic stabilization is the priority, research indicates that beta-2 agonists (e.g., Salbutamol 100-200 mcg via MDI) may be superior to epinephrine for specifically relieving these anaphylactic uterine contractions ^[22].

Pediatrics

Pediatric management is complicated by heterogeneous dosing algorithms and significant practice variation regarding observation periods ^[20][25]. Clinical decision models are increasingly used in the emergency department to identify children at high risk for biphasic reactions—the recurrence of symptoms after initial resolution—which informs the necessary duration of monitoring ^[25]. Weight-based dosing remains critical, as pediatric pharmacology varies significantly from adult standards ^[20].

Cardiovascular Comorbidities and Medications

Patients with underlying cardiovascular disease often take medications that alter the anaphylactic response. The use of beta-blockers and angiotensin-converting enzyme inhibitors (ACEIs) is associated with increased reaction severity ^[23]. These agents may also contribute to refractory anaphylaxis, making standard resuscitation efforts more challenging ^[23].

Long-term management focuses on preventing recurrence and ensuring community preparedness. Clinicians must provide a written emergency action plan and prescribe at least two epinephrine auto-injectors (EAI) for use in community settings ^[1][26]. Patient and caregiver education is critical; mobile-based programs significantly improve management knowledge and confidence in parents of school-aged children ^[28]. Schools and childcare centers should implement formal allergy training and consider stocking unassigned EAIs for emergency use ^[26].

Specialist Referral and Testing

Referral to an allergist is necessary for trigger identification via skin or in vitro testing. Measurement of basal serum tryptase (BST) helps identify underlying mast cell disorders , especially in patients with severe reactions to Hymenoptera stings ^[1][19]. A BST >11.4 ng/mL is a significant risk factor for severe Hymenoptera venom-induced anaphylaxis (HVA) ^[19].

Targeted Prophylaxis

For HVA, venom immunotherapy (VIT) is highly effective. Rush VIT protocols, such as a 3-session outpatient regimen, allow patients to reach maintenance dosing rapidly ^[29]. In cases of frequent idiopathic anaphylaxis (≥6 episodes/year), Omalizumab 300 mg SC every 2–4 weeks may reduce the frequency and severity of episodes ^[27].