Residency · Residency · Internal Medicine

Anaphylaxis: Recognition, Epinephrine Use, and Disposition

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The pager blares. It's 3 AM, and the charge nurse sounds panicked. "We have a patient, post-penicillin, complaining of itching and difficulty breathing. BP is 80/40, O2 sats 88% on room air." Your mind races. This isn't a drill. This is anaphylaxis, a severe, potentially life-threatening systemic hypersensitivity reaction. You know one thing for sure: the clock is ticking, and rapid intervention is key. This patient needs epinephrine, and they need it now.

You rush to the bedside, adrenaline surging. The patient is mottled, diaphoretic, and struggling for breath, with urticarial rash spreading rapidly across their chest. You bark orders: "Large bore IVs! Get ready to push fluids! And most importantly, get me an Epinephrine auto-injector!" There's no time for detailed diagnostic criteria right now, just the clear presence of skin involvement, respiratory compromise, and hypotension after a clear allergen exposure. You administer the intramuscular epinephrine into the patient's mid-anterolateral thigh, the only true first-line treatment for this emergency.

As the patient stabilizes and the medical team gathers, you reflect on the crucial decisions made in those frantic minutes. You didn't delay treatment waiting for a full set of labs or for an antihistamine to kick in. You didn't dismiss the possibility of anaphylaxis because the rash wasn't the "classic" presentation. You remembered that epinephrine is the life-saving drug, and every minute counts. This patient will need continued monitoring, likely for an extended period to watch for biphasic reactions, and certainly will be discharged with an epinephrine auto-injector and a referral to allergy/immunology. But for now, the immediate crisis has passed, thanks to quick recognition and decisive action.

Introduction

Anaphylaxis is a severe, potentially life-threatening systemic hypersensitivity reaction that demands immediate recognition and treatment. Despite its clinical urgency, anaphylaxis remains underdiagnosed and undertreated, with epinephrine being significantly underutilized in both emergency and outpatient settings. Internal medicine residents must be proficient in the rapid identification and management of this condition.

Pathophysiology

• IgE-mediated degranulation of mast cells and basophils is the most common mechanism
• Release of histamine, tryptase, prostaglandins, and leukotrienes produces systemic vasodilation, increased vascular permeability, and bronchospasm
• Non-IgE-mediated anaphylaxis (anaphylactoid reactions) can occur via direct mast cell activation (e.g., radiocontrast, opioids)
• Biphasic reactions occur in 5-20% of cases, typically within 8-12 hours of the initial episode

Clinical Presentation and Diagnostic Criteria

NIAID/FAAN Criteria (Any ONE of Three)

• Criterion 1: Acute onset (minutes to hours) with skin/mucosal involvement PLUS respiratory compromise OR hypotension
• Criterion 2: Two or more of the following after exposure to a likely allergen: skin/mucosal involvement, respiratory compromise, hypotension, persistent GI symptoms
• Criterion 3: Hypotension after exposure to a known allergen for that patient

Organ System Involvement

• Skin/Mucosal (80-90%): urticaria, angioedema, flushing, pruritus
• Respiratory (70%): stridor, wheezing, dyspnea, hypoxia
• Cardiovascular (45%): hypotension, tachycardia, syncope, cardiac arrest
• Gastrointestinal (45%): nausea, vomiting, abdominal cramping, diarrhea

Common Triggers

• Foods: peanuts, tree nuts, shellfish, milk, eggs
• Medications: beta-lactam antibiotics, NSAIDs, neuromuscular blocking agents
• Hymenoptera stings: bees, wasps, hornets
• Idiopathic: no identifiable trigger in 20% of cases

Management

First-Line Treatment: Epinephrine

• Intramuscular epinephrine (1:1000 concentration, 0.01 mg/kg, max 0.5 mg) into the mid-anterolateral thigh
• Repeat every 5-15 minutes as needed
• There are NO absolute contraindications to epinephrine in anaphylaxis
• Delayed administration is associated with increased mortality and biphasic reactions
• IV epinephrine infusion (1-10 mcg/min) for refractory hypotension

Adjunctive Therapies

• IV fluid resuscitation: 1-2 L normal saline bolus for hypotension (up to 20 mL/kg in the first hour)
• Albuterol nebulization for bronchospasm not responsive to epinephrine
• H1-antihistamines (diphenhydramine 25-50 mg IV): symptom relief only; NOT a substitute for epinephrine
• H2-antihistamines (famotidine 20 mg IV): may reduce cutaneous symptoms
• Glucocorticoids (methylprednisolone 125 mg IV): theoretical benefit for biphasic reactions, but no strong evidence

Refractory Anaphylaxis

• Consider glucagon 1-5 mg IV for patients on beta-blockers
• Vasopressin for catecholamine-resistant shock
• Methylene blue has emerging evidence for vasoplegia in severe cases

Disposition and Follow-Up

Observation Period

• Minimum 4-6 hours observation after symptom resolution for uncomplicated cases
• Extended observation (12-24 hours) for severe presentations, prior biphasic reactions, or delayed epinephrine administration
• ICU admission for refractory symptoms, hemodynamic instability, or need for epinephrine infusion

Discharge Planning

• Prescribe epinephrine auto-injector (two devices) and provide training on proper use
• Develop a written anaphylaxis emergency action plan
• Refer to allergy/immunology for confirmatory testing and trigger identification
• Short course of oral corticosteroids (prednisone 40-60 mg daily for 3-5 days) is commonly prescribed but evidence is limited
• Educate on medical alert identification (bracelet or necklace)

Key Clinical Pearls

• Epinephrine is the ONLY first-line treatment for anaphylaxis; antihistamines and steroids are adjuncts, not substitutes
• Absence of skin findings does NOT exclude anaphylaxis; up to 10-20% of patients lack cutaneous manifestations
• Serum tryptase (drawn within 1-3 hours of symptom onset) supports the diagnosis but a normal level does not exclude it
• Always prescribe two epinephrine auto-injectors at discharge, as up to 35% of cases require a second dose

References

1. Shaker MS, Wallace DV, Golden DBK, et al. Anaphylaxis: A 2020 Practice Parameter Update, Systematic Review, and GRADE Analysis. J Allergy Clin Immunol. 2020;145(4):1082-1123.
2. Cardona V, Ansotegui IJ, Ebisawa M, et al. World Allergy Organization Anaphylaxis Guidance 2020. World Allergy Organ J. 2020;13(10):100472.
3. Lieberman P, Nicklas RA, Randolph C, et al. Anaphylaxis: A Practice Parameter Update 2015. Ann Allergy Asthma Immunol. 2015;115(5):341-384.
4. Campbell RL, Li JTC, Nicklas RA, et al. Emergency Department Diagnosis and Treatment of Anaphylaxis: A Practice Parameter. Ann Allergy Asthma Immunol. 2014;113(6):599-608.

For the intern

When your pager goes off at 3am for suspected anaphylaxis, immediately assess airway, breathing, and circulation. If the patient has any combination of respiratory distress (stridor, wheezing, hypoxia), hypotension, or skin findings after allergen exposure, give intramuscular epinephrine 0.3-0.5 mg into the mid-anterolateral thigh right now—do not wait for labs or perfect diagnostic certainty. Start large-bore IV access and fluid resuscitation if hypotensive. Call for help early if there's any airway concern. What can wait until morning: allergy referral, serum tryptase results (helpful but not required for diagnosis), and detailed trigger investigation. Your overnight job is recognition and epinephrine administration.

Common pitfalls

• Delaying epinephrine while reaching for antihistamines or steroids first. Diphenhydramine and methylprednisolone are adjuncts only—epinephrine is the life-saving intervention with no absolute contraindications, even in elderly patients with coronary disease.

• Dismissing anaphylaxis because skin findings are absent. Up to 20% of cases present without urticaria or flushing; hypotension plus gastrointestinal symptoms or isolated respiratory compromise after allergen exposure still qualifies.

• Assuming one dose of epinephrine is always sufficient. About one-third of patients need repeat dosing every 5-15 minutes; monitor closely and don't hesitate to re-dose if symptoms persist or recur.

• Discharging patients too early without epinephrine auto-injectors. Observe minimum 4-6 hours post-resolution, prescribe two EpiPens with hands-on training, and arrange allergy follow-up before discharge.

Make it stick

Imagine you're on call, and a patient develops sudden-onset angioedema, wheezing, and lightheadedness shortly after receiving a new antibiotic. Your first thought should be anaphylaxis. The immediate, life-saving intervention is intramuscular epinephrine – not waiting for a full diagnostic workup, not reaching for antihistamines first. Get that epinephrine in the patient’s mid-thigh, start fluids if they’re hypotensive, and then consider adjunctive therapies. Remember, the absence of skin findings doesn't rule it out, and delaying epinephrine significantly increases morbidity and mortality.

If you remember one thing

Epinephrine is the only first-line treatment for anaphylaxis, and there are no absolute contraindications to its use in this life-threatening scenario. Always prioritize administering intramuscular epinephrine rapidly, even before confirming the diagnosis with labs or consulting a specialist.

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