Anaphylaxis & Acute Angioedema
Critical emergency management of severe allergic and histaminergic emergencies: diagnostic criteria for anaphylaxis, first-line intramuscular epinephrine protocols, refractory anaphylaxis infusions, glucagon in beta-blocker patients, and bradykinin-mediated angioedema therapies.
Resuscitation Quick Ribbon (First 2 Minutes)
Bottom-Line Clinical Pearl
Epinephrine is the ONLY first-line medication that stops the progression of anaphylaxis and reduces mortality. Antihistamines and corticosteroids are second-line adjuvants that do NOT treat airway edema or shock. Administer Epinephrine 0.3–0.5 mg (1:1,000) Intramuscularly into the anterolateral mid-thigh immediately. Never hesitate or wait for wheezing/hypotension. In patients on beta-blockers refractory to epinephrine, administer Glucagon (1–5 mg IV). For ACE-inhibitor angioedema, recognize that it is bradykinin-mediated—epinephrine and steroids are ineffective; evaluate airway early.
Anaphylaxis is a severe, life-threatening generalized or systemic hypersensitivity reaction characterized by rapid onset of life-threatening airway, breathing, or circulatory problems. The diagnosis is clinical—do not wait for laboratory tests (e.g., serum tryptase):
| Diagnostic Presentation | Clinical Criteria Components | Common Triggers & Diagnostic Caveats |
|---|---|---|
| Criterion 1: Acute Skin/Mucosal Involvement + EITHER Respiratory OR Hypotensive Compromise | Acute onset (minutes to several hours) of skin/mucosal tissue involvement (generalized hives, pruritus, flushing, swollen lips/tongue/uvula) PLUS AT LEAST ONE OF: A) Respiratory compromise (dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia); B) Reduced BP or associated symptoms of end-organ dysfunction (hypotonia, syncope, incontinence). | Most common presentation (> 80%). Skin signs can be absent in up to 10–20% of fatal anaphylaxis. |
| Criterion 2: Two or More Rapid Symptoms Post-Likely Allergen Exposure | Two or more of the following occurring rapidly after exposure to a LIKELY allergen for that patient: 1) Skin/mucosal tissue; 2) Respiratory compromise; 3) Reduced BP or end-organ dysfunction; 4) Persistent gastrointestinal symptoms (cramping abdominal pain, vomiting). | Food allergens (peanuts, tree nuts, shellfish), medications (penicillins, NSAIDs), insect stings (Hymenoptera). |
| Criterion 3: Hypotension Post-Known Allergen Exposure | Reduced blood pressure after exposure to a KNOWN allergen for that patient: Infants/children: low SBP (age-specific) or > 30% drop in SBP; Adults: SBP < 90 mmHg or > 30% drop from baseline. | Occurs rapidly following IV medication administration or insect envenomation. |
Intramuscular Epinephrine is the sole first-line therapy in anaphylaxis. It stimulates alpha-1 receptors (reverses peripheral vasodilation and mucosal edema), beta-1 receptors (increases inotropy and heart rate), and beta-2 receptors (causes bronchodilation and inhibits mast cell/basophil degranulation):
| Patient Population | Dose & Concentration | Route & Anatomical Site | Frequency & Safety Protocol |
|---|---|---|---|
| Adults (>= 30 kg) | 0.3 mg to 0.5 mg (0.3–0.5 mL of 1:1,000 / 1 mg/mL solution) | INTRAMUSCULAR into anterolateral mid-thigh (vastus lateralis) | Repeat every 5 to 15 minutes as needed for persistent or worsening symptoms. |
| Pediatrics (< 30 kg) | 0.01 mg/kg (0.01 mL/kg of 1:1,000 solution); max single dose 0.3 mg (Autoinjector: 0.15 mg for 15–30 kg) | INTRAMUSCULAR into anterolateral mid-thigh | Do NOT inject into deltoid or buttocks (vastus lateralis achieves 5x faster peak plasma levels). |
| Refractory Anaphylaxis (>= 2 IM doses) | Continuous IV Infusion: 2 to 10 mcg/min (titrate q2–5min to MAP >= 65 and airway stability) | Intravenous via dedicated infusion pump or push-dose bridge (10 mcg IV q2–3min) | Indicated when shock or severe airway obstruction persists despite multiple IM doses. |
| Beta-Blocker Refractory Anaphylaxis | Glucagon 1 to 5 mg IV push over 5 minutes; follow with 5–15 mcg/min continuous infusion | Intravenous bolus + infusion | Bypasses beta-adrenergic receptors to stimulate adenylate cyclase directly. Pre-treat with antiemetic (causes nausea). |
Angioedema is non-pitting edema of the deep dermis and subcutaneous tissues, often involving the lips, tongue, uvula, and larynx. Determining the underlying mediator is vital because bradykinin-mediated angioedema does NOT respond to epinephrine, antihistamines, or steroids:
| Type of Angioedema | Pathophysiologic Mediator | Clinical Features & Triggers | Targeted Medical Therapy |
|---|---|---|---|
| Histaminergic Angioedema | Histamine released from mast cells / basophils | Urticaria (hives) and severe pruritus present; rapid onset < 1 hour post-exposure to food, drug, or sting. | IM Epinephrine + H1 blocker (Diphenhydramine 50 mg IV) + H2 blocker (Famotidine 20 mg IV) + Corticosteroid (Methylprednisolone 125 mg IV). |
| ACE-Inhibitor Induced Angioedema | Bradykinin accumulation (ACE normally breaks down bradykinin) | NO hives; NO pruritus; prominent massive tongue, lip, and laryngeal edema. Occurs in 0.5% of patients on Lisinopril/Enalapril (can occur after years of uneventful therapy!). | Discontinue ACE inhibitor permanently. Epinephrine/steroids ineffective. Early fiberoptic nasopharyngoscopy to assess airway; prepare for awake fiberoptic intubation or surgical cricothyroidotomy. |
| Hereditary Angioedema (HAE) | Bradykinin accumulation due to C1-esterase inhibitor deficiency (Type 1) or dysfunction (Type 2) | Recurrent episodes of painless non-pruritic swelling, severe recurrent abdominal cramping pain (intestinal wall edema); positive family history. | 1) C1-esterase inhibitor concentrate (Berinert 20 U/kg IV); 2) Icatibant (Firazyr 30 mg SubQ, bradykinin B2 receptor antagonist); 3) Ecallantide (Kalbitor 30 mg SubQ, plasma kallikrein inhibitor); 4) Fresh Frozen Plasma (FFP 2–4 units) if targeted agents unavailable. |
The Angioedema Airway Alert: In severe angioedema with tongue or laryngeal involvement, mucosal swelling progresses relentlessly over hours. Do NOT wait for stridor or respiratory distress to secure the airway. Stridor indicates > 80% laryngeal occlusion and makes intubation nearly impossible. Perform immediate fiberoptic nasopharyngeal laryngoscopy; if laryngeal or epiglottic edema is present, perform awake fiberoptic intubation in the OR or trauma bay with surgical cricothyroidotomy equipment open at the bedside.
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