Anaphylaxis Management

Pathophysiology (Brief)

Diagnosis - Clinical Criteria

1. Acute onset of illness with skin/mucosal involvement (hives, flushing, swollen lips/tongue) PLUS either respiratory compromise OR reduced BP/end-organ symptoms
2. Two or more of the following occurring rapidly after exposure to a likely allergen: skin/mucosal symptoms, respiratory compromise, reduced BP, or persistent GI symptoms
3. Reduced BP after exposure to a known allergen

Common Triggers

Clinical Manifestations

Note: Cardiovascular collapse can occur without skin features, particularly with insect sting anaphylaxis or perioperative reactions.

Management Algorithm

Step-by-Step Treatment

1. Immediate Actions (Simultaneous)

• Remove / stop the trigger (discontinue IV infusion, remove insect stinger)
• Call for help; activate emergency response if in community setting
• Positioning: supine with legs elevated (hypotension); left lateral decubitus (pregnancy); allow sitting up if respiratory distress or vomiting - do not stand the patient up suddenly
• Supplemental oxygen (high-flow, 100%)
• IV/IO access - large-bore peripheral line
• Continuous monitoring - cardiac, pulse oximetry

2. Epinephrine - First-Line, No Contraindications

Epinephrine is the sole first-line drug. There are no absolute contraindications. Antihistamines and corticosteroids are adjuncts only and must never precede or replace epinephrine.

• Adults: 0.3-0.5 mg (0.3-0.5 mL of 1:1000 / 1 mg/mL solution) IM in the lateral thigh (vastus lateralis)
• Children: 0.01 mg/kg of 1:1000 solution IM in the lateral thigh (max 0.5 mg)
• Can be repeated every 5-10 minutes - up to 30% of patients require more than one dose
• IM into the vastus lateralis achieves peak plasma concentration in ~8 minutes vs. ~34 minutes subcutaneously - subcutaneous route is no longer recommended

• Prepare: 1 mg in 1000 mL NS or D5W → concentration 1 mcg/mL
• Adults: start at 1 mcg/min, titrate up to maximum 10 mcg/min
• Children: 0.1 mcg/kg/min, up to 1.5 mcg/kg/min
• Requires cardiac monitoring; use central line if possible (extravasation causes tissue necrosis)

• α1: vasoconstriction, reduces mucosal edema
• β1: positive inotropy and chronotropy
• β2: bronchodilation, stabilizes mast cells/basophils and reduces further mediator release

3. IV Fluids (Circulatory Collapse)

• Large volumes may be required - up to 1-2 L bolus initially in adults; repeat as needed
• Crystalloids (normal saline or Ringer's lactate) are first choice
• Massive fluid shifts can rapidly reduce intravascular volume due to increased capillary permeability

4. Airway Management

• Maintain airway patency - early intubation if laryngeal edema is developing
• If laryngeal edema does not respond rapidly to epinephrine: cricothyrotomy or tracheotomy
• Nebulized albuterol for persistent bronchospasm:
  • Adults/children: 2.5 mg in 3 mL NS, repeat as needed or continuous
  • Add ipratropium: adults 0.5 mg; children 0.25 mg in 3 mL NS

5. Adjunct Medications (Secondary - After Epinephrine)

Corticosteroids have no significant immediate effect and do not reliably prevent biphasic reactions, but are commonly given. They should never delay epinephrine. - Washington Manual

Antihistamines relieve skin symptoms and may shorten reaction duration but have no effect on cardiovascular or respiratory components.

6. Refractory Anaphylaxis / Vasopressor Support

Special Situations

Beta-Blocker Use

ACE Inhibitor Use

Radiocontrast Media Premedication

• Prednisone 50 mg oral at 13 h, 7 h, and 1 h before
• Diphenhydramine 50 mg oral 1 h before
• Consider ephedrine 25 mg oral 1 h before
• Consider H2 antagonist (famotidine 20 mg) 3 h before

Pregnancy

Biphasic Reactions

• Occur in up to 20% of anaphylaxis cases - symptoms recur without re-exposure to the trigger
• Most occur within 8 hours, but can be delayed up to 72 hours
• Risk factors: hypotension, wide pulse pressure, unknown trigger, >1 epinephrine dose, prior anaphylaxis, delayed epinephrine administration
• Corticosteroids have not been shown to reliably prevent biphasic reactions

Disposition

Discharge Instructions

1. Epinephrine auto-injector (EpiPen) - 2 devices prescribed; demonstrate use
2. Individualized anaphylaxis action plan in writing
3. Allergen avoidance counseling
4. Medical ID (bracelet/wallet card) for known trigger
5. Allergist/immunologist referral - for trigger workup, venom immunotherapy eligibility, and long-term management

Key Points Summary

• Epinephrine IM (lateral thigh) is always first-line - give it early, give it without hesitation
• Studies show only ~30% of prehospital patients and 50-70% of ED patients with anaphylaxis actually receive epinephrine - this is a significant care gap
• Antihistamines and steroids are adjuncts and must not delay or replace epinephrine
• Beta-blocker patients may need glucagon for refractory bronchospasm/hypotension
• Observe for biphasic reactions; discharge planning must include auto-injector prescription and follow-up

• ROSEN's Emergency Medicine: Concepts and Clinical Practice, Chapter 106
• Goldman-Cecil Medicine, Chapter 233 (Schwartz & Castells)
• Washington Manual of Medical Therapeutics, Chapter on Allergy/Immunology
• Textbook of Family Medicine 9e, Chapter 19

Anaphylaxis: Diagnosis and Management

1. Definition

2. Diagnosis

Anaphylaxis is primarily a CLINICAL diagnosis

NIAID/FAAN + WAO Diagnostic Criteria (Box 106.5, Rosen's)

• Respiratory compromise (dyspnea, wheeze, stridor, hypoxemia)
• Reduced BP or end-organ symptoms (hypotonia, syncope, incontinence)

• Skin/mucosal involvement (hives, flushing, swollen lips/tongue)
• Respiratory compromise (dyspnea, wheeze, stridor, hypoxemia)
• Reduced BP or associated symptoms (syncope, collapse)
• Persistent GI symptoms (cramping, vomiting)

• Adults: systolic BP <90 mmHg or >30% drop from baseline
• Infants/children: age-specific low systolic BP

Key point: Criterion 2 catches anaphylaxis without skin features - this occurs in cardiovascular collapse from insect stings or perioperative reactions and is frequently missed.

Clinical Manifestations by System

Note: In infants and children, hypotension is uncommon; skin and respiratory features predominate.

Diagnostic Testing (Supportive, Not Acute)

"The absence of an elevated tryptase level does not exclude anaphylaxis." - Washington Manual

Differential Diagnosis (Harrison's 22E, Table 364-1)

3. Management

Management Algorithm

STEP 1 - Immediate Simultaneous Actions

• Remove/stop the trigger (stop IV infusion, remove insect stinger, tourniquet proximal to sting site)
• Call for help
• Position the patient:
  • Hypotension → supine, legs elevated
  • Respiratory distress/vomiting → allow comfortable position, elevate legs if possible
  • Pregnancy → left lateral decubitus (prevents vena cava compression)
  • Never stand patient up suddenly - can cause fatal cardiovascular collapse
• Supplemental high-flow oxygen (100%)
• Large-bore IV access (16-18 gauge preferred)
• Monitoring: continuous cardiac, BP, pulse oximetry

STEP 2 - Epinephrine (FIRST-LINE - No Contraindications)

Epinephrine is the sole first-line drug. Delay is associated with hypoxic encephalopathy and death. There are NO absolute contraindications in anaphylaxis.

• Repeat every 5-10 minutes - up to 30% need more than one dose
• IM into the thigh reaches peak plasma level in ~8 minutes vs ~34 minutes subcutaneously
• Subcutaneous and inhaled routes are no longer recommended
• Auto-injectors (EpiPen 0.3 mg; EpiPen Jr 0.15 mg) are acceptable alternatives

• Prepare: 1 mg in 1000 mL NS or D5W → 1 mcg/mL concentration
• Adults: start 1 mcg/min, titrate to max 10 mcg/min
• Children: 0.1 mcg/kg/min, titrate to max 1.5 mcg/kg/min
• Requires cardiac monitoring; use central line if possible (extravasation → tissue necrosis)

STEP 3 - IV Fluids

• Start rapid isotonic crystalloid (normal saline):
  • Adults: 1000 mL IV in the first 5 min; several liters may be needed
  • Children: 20-30 mL/kg in increments
• Massive fluid shifts occur from capillary leak - aggressive resuscitation may be required

STEP 4 - Airway Management

• Ensure patent airway at all times
• Early endotracheal intubation if laryngeal edema is developing - do not wait for full obstruction
• If laryngeal edema does not respond rapidly to epinephrine: cricothyrotomy or tracheotomy
• Nebulized bronchodilators for bronchospasm:
  • Albuterol: 2.5 mg in 3 mL NS (adults and children), repeat or continuous
  • Ipratropium: 0.5 mg (adults) / 0.25 mg (children) in 3 mL NS

STEP 5 - Second-Line Adjuncts (AFTER Epinephrine - Never Before)

Corticosteroids have no significant immediate effect and reliable evidence showing they prevent biphasic reactions is lacking. They must never precede or delay epinephrine.

STEP 6 - Refractory Cases / Special Situations

• Epinephrine may have blunted effect
• Glucagon 1-5 mg IV bolus (adults) / 20-30 mcg/kg max 1 mg (children) over 5 min, then 5-15 mcg/min infusion
• Glucagon acts via cAMP pathway, bypassing beta-receptors
• Pre-treat with antiemetic - nausea/vomiting are common side effects

4. Biphasic Reactions

• Occur in up to 20% of patients - recurrence of anaphylaxis without re-exposure
• Most within 8 hours, rarely up to 72 hours
• Corticosteroids have not been shown to reliably prevent biphasic reactions

• Hypotension at presentation
• Wide pulse pressure
• Unknown trigger

• 1 dose of epinephrine required

• Prior history of anaphylaxis
• Delayed epinephrine administration
• Cutaneous signs and symptoms

5. Disposition

6. Discharge - Mandatory Steps

1. Two epinephrine auto-injectors prescribed - demonstrate how to use them
2. Written individualized anaphylaxis action plan
3. Allergen avoidance education
4. Medical ID (bracelet or wallet card) listing known trigger
5. Allergist/immunologist referral - for allergen confirmation (skin/IgE testing), venom immunotherapy eligibility, and long-term desensitization options

Summary - Key Priorities

• ROSEN's Emergency Medicine, Chapter 106 (Box 106.5, 106.7)
• Harrison's Principles of Internal Medicine 22E (2025), Chapter 364
• Goldman-Cecil Medicine, Chapter 233
• Washington Manual of Medical Therapeutics, Allergy/Immunology chapter

Sinus Bradycardia: Evaluation and Management

1. Definition and ECG Criteria

• Normal P-wave morphology (upright in I, II; inverted in aVR)
• Fixed P-P interval = R-R interval (each P followed by a QRS)
• PR interval normal (0.12-0.20 s)
• Rate < 60 bpm

Rates of 45-50 bpm at rest can be physiologically normal in athletes and during sleep. A rate < 40 bpm is more specific for significant sinus node dysfunction (SND).

2. Causes

Physiologic (Normal) Causes

• Well-conditioned athletes (high vagal tone)
• Sleep, rest
• Young adults with elevated resting vagal tone

Medical Conditions

Drugs Causing Sinus Bradycardia (Goldman-Cecil / Harrison's)

Note: Beta-blocker eye drops for glaucoma are a frequently overlooked cause of systemic bradycardia.

3. Spectrum of Sinus Node Dysfunction (SND)

4. Clinical Features and Symptoms

• Fatigue, exercise intolerance (most common, often underappreciated)
• Dizziness, presyncope, syncope (particularly in tachy-brady or severe pauses)
• Palpitations (in tachy-brady syndrome - the tachyarrhythmia phase)
• Worsening heart failure (chronotropic incompetence reducing cardiac output)
• Cognitive impairment (in elderly)

Asymptomatic sinus bradycardia has not been associated with adverse outcomes and does not typically warrant treatment.

5. Evaluation

Step-by-Step Approach (2018 ACC/AHA/HRS Guideline)

Step 1 - History and Physical Exam

• Full medication review (drugs most common reversible cause)
• Symptoms: onset, duration, correlation with activity/rest, syncope
• Exertional symptoms (suggest chronotropic incompetence)
• Associated conditions: thyroid disease, sleep apnea, Lyme exposure, recent MI

Step 2 - 12-Lead ECG

• Confirm sinus bradycardia
• Assess for AV block (often coexists with SND)
• Look for inferior MI pattern (RCA/SA nodal artery ischemia)
• PR interval prolongation, bundle branch block

Step 3 - Laboratory Tests

Step 4 - Echocardiography (Class IIa)

• Evaluate for structural heart disease (cardiomyopathy, valvular disease, wall motion abnormalities)
• Assess LV/RV function
• Look for infiltrative disease (amyloid, sarcoid)

Step 5 - Ambulatory ECG Monitoring (Class I for symptomatic patients)

Step 6 - Exercise Stress Testing (Class IIa)

• Used to assess chronotropic incompetence
• Failure to reach 80% of age-predicted maximum HR = chronotropic incompetence
• Also useful for exertion-related symptoms

Step 7 - Advanced Imaging (Class IIa)

• Cardiac MRI (sarcoidosis, amyloid, myocarditis)
• Cardiac CT (ACHD, structural)

Step 8 - Electrophysiology Study (EPS) (Class IIb - limited role)

• Not recommended as a primary diagnostic tool for SND
• May be useful when EPS is already indicated for AV block or syncope
• Can measure sinus node recovery time (SNRT) and sinoatrial conduction time

6. Management

Acute / Emergency Management

Atropine is ineffective in post-cardiac transplant patients because the transplanted heart is denervated.

Chronic Management

Step 1 - Remove/Treat Reversible Causes

• Stop or reduce offending drugs (beta-blockers, CCBs, digoxin, amiodarone)
• Treat hypothyroidism, sleep apnea, Lyme disease, ischemia
• Correct electrolytes
• If drug is medically necessary, consider pacemaker to allow continued use

Step 2 - Asymptomatic Sinus Bradycardia

• Observe - no treatment required
• Permanent pacing is Class III (Harm) for asymptomatic sinus bradycardia

Step 3 - Symptomatic SND with Confirmed Symptom-Rhythm Correlation

Atrial-based pacing is preferred over single-chamber ventricular pacing - reduces incidence of AF, pacemaker syndrome, and heart failure.

Pharmacologic Options (Limited Role)

• Oral theophylline (methylxanthine): Class IIb - may increase HR and improve symptoms; used as trial when symptom-rhythm correlation is uncertain, or as bridge/alternative when patient declines PPM
• Terbutaline (beta-agonist): Occasionally used as temporary bridge when PPM must be delayed (e.g., active infection)

7. Special Situations

8. Summary Approach

Sinus Bradycardia Found
        ↓
Symptomatic? (fatigue, dizziness, syncope, exercise intolerance)
     ↙              ↘
   NO               YES
Observe       Review medications → Stop offending drug if possible
              Check TSH, electrolytes, ECG for MI
              Echo (if structural disease suspected)
              Ambulatory monitor for symptom-rhythm correlation
                    ↓
              Symptoms correlate with bradycardia?
                 ↙              ↘
               YES            UNCERTAIN
          Permanent          Oral theophylline
          Pacemaker          trial → If responds → PPM
          (Class I)          If not → Observe

• ROSEN's Emergency Medicine, Chapter 65
• Harrison's Principles of Internal Medicine 22E (2025), Chapter 251 (Figure 251-3)
• Goldman-Cecil Medicine, Chapter 51 (Table 51-3)
• Fuster and Hurst's The Heart 15E, Chapter 38 (Figures 38-6, 38-7 - ACC/AHA/HRS 2018 algorithms)
• Harrison's 22E, Chapter 251 - Medical Conditions and Medications Associated with SND