Epinephrine in Overdose Management

Primary Indications

Epinephrine is the first-line vasopressor for life-threatening hypotension, bronchospasm, and anaphylactoid reactions in overdose patients, administered intramuscularly for anaphylaxis or intravenously for refractory shock and cardiac arrest. 1

Specific Overdose Scenarios

Anaphylactoid reactions (antihistamine, β-blocker, calcium-channel-blocker, or opioid-induced): Epinephrine is the mandatory first-line agent, never delayed for antihistamines or corticosteroids 1
β-blocker toxicity with hypotension: Epinephrine is more effective than dopamine for reversing hypotension 2
Refractory bronchospasm in any overdose: Epinephrine is indicated when standard bronchodilators fail 1

Intramuscular Dosing (First-Line for Anaphylaxis)

Adult Dosing

0.3–0.5 mg (0.3–0.5 mL of 1:1000 concentration) injected into the mid-anterolateral thigh at 90° 1, 3
Repeat every 5–15 minutes as needed for persistent hypotension, bronchospasm, or airway swelling 1, 3

Pediatric Dosing

0.01 mg/kg (maximum 0.3 mg initially) of 1:1000 concentration intramuscularly into the lateral thigh 1, 3
Repeat every 5–15 minutes if symptoms persist 1, 3

Critical Advantage

Intramuscular injection into the thigh provides rapid peak plasma concentrations and is preferred because it is easy, effective, and safe while the patient maintains perfusion 3

Intravenous Dosing (Reserved for Refractory Cases)

When to Use IV Epinephrine

IV epinephrine should only be administered during cardiac arrest or to profoundly hypotensive patients who have failed to respond to IV volume replacement (minimum 30 mL/kg crystalloid) and several injected doses of IM epinephrine. 1, 2

Adult IV Bolus Dosing (Refractory Anaphylaxis)

0.05–0.1 mg (50–100 mcg) slow IV push using 1:10,000 concentration (0.1 mg/mL) 1, 3
This represents 5–10% of the cardiac arrest dose 3
Repeat every 2–5 minutes as needed for persistent hypotension or bronchospasm 3
Critical warning: IV bolus epinephrine carries a 10% risk of cardiovascular complications (arrhythmias, cardiac ischemia, hypertension) versus 1.3% with IM administration 4

Pediatric IV Bolus Dosing

0.01 mg/kg (maximum 0.3 mg) of 1:10,000 solution administered slowly IV 1

Continuous IV Infusion (Refractory Shock)

Adult Infusion Preparation and Dosing

Standard preparation: Add 1 mg (1 mL of 1:1000) to 250 mL D5W to yield 4.0 mcg/mL 1, 5
Initial rate: 1–4 mcg/min (15–60 drops/min with microdrop apparatus) 1
Maximum rate: 10 mcg/min 1

Alternative Concentration for Titration

Add 1 mg (1 mL of 1:1000) to 100 mL saline to create 1:100,000 solution (10 mcg/mL) 1, 2
Initial rate: 30–100 mL/h (5–15 mcg/min) 1, 2
Titrate up or down based on clinical response or epinephrine toxicity 1

Pediatric Infusion Dosing

"Rule of 6" method: 0.6 × body weight (kg) = number of milligrams diluted to 100 mL saline; then 1 mL/h delivers 0.1 mcg/kg/min 1, 2
Standard range: 0.1–1.0 mcg/kg/min, starting at the lowest dose 2
Maximum: Up to 5 mcg/kg/min may be necessary in exceptional circumstances 2

Cardiac Arrest Dosing (Anaphylaxis Progressing to Arrest)

Immediate Protocol Change

If anaphylaxis causes cardiac arrest, immediately abandon the 0.3–0.5 mg IM protocol and switch to cardiac arrest dosing: 1 mg IV/IO epinephrine (1:10,000) every 3–5 minutes. 1, 3

Adult Cardiac Arrest

1 mg IV/IO (10 mL of 1:10,000) every 3–5 minutes during ongoing resuscitation 1, 3
Rapid progression to high dose: Common sequence is 1–3 mg slowly IV over 3 minutes, then 3–5 mg IV over 3 minutes, then 4–10 mg/min infusion 1

Pediatric Cardiac Arrest

Initial dose: 0.01 mg/kg (0.1 mL/kg of 1:10,000, maximum 1 mg) IV/IO every 3–5 minutes 1, 3
Higher subsequent doses: 0.1–0.2 mg/kg (0.1 mL/kg of 1:1000) may be considered for unresponsive asystole or pulseless electrical activity 1

Rationale for Dose Escalation

IM absorption is unpredictable during arrest due to absent peripheral perfusion 3
The 0.3–0.5 mg IM dose provides only 30–50% of the dose required for effective cardiac arrest therapy 3

Special Considerations for β-Blocker Overdose

Glucagon as Adjunct Therapy

When β-adrenergic blocking agents complicate treatment, add glucagon infusion alongside epinephrine. 1

Adult glucagon dose: 1–5 mg IV over 5 minutes, followed by infusion at 5–15 mg/min titrated to clinical response 1
Pediatric glucagon dose: 20–30 mcg/kg (maximum 1 mg) IV over 5 minutes, followed by infusion 1

Administration Route and Monitoring

Vascular Access

Central venous access is strongly preferred for IV epinephrine infusions to minimize extravasation risk and tissue necrosis 1, 2, 3
Peripheral IV or intraosseous may be used temporarily if central access is unavailable or delayed 2

Hemodynamic Monitoring

Monitor blood pressure and heart rate every 5–15 minutes during initial titration 2
Continuous hemodynamic monitoring is essential when IV epinephrine is used, though unavailability should not preclude administration if deemed essential after failure of several IM injections 1
Place arterial catheter as soon as practical for continuous blood pressure monitoring 2

Target Parameters

Mean arterial pressure ≥65 mmHg 2
Urine output >50 mL/h for at least 4 hours 2
Normalization of capillary refill and age-appropriate heart rate 2
Lactate clearance, mental status improvement 2

Critical Pitfalls and Error Prevention

Concentration Confusion (Most Common Fatal Error)

The 1:1000 concentration (1 mg/mL) used for IM anaphylaxis is ten times more concentrated than the 1:10,000 formulation (0.1 mg/mL) required for IV dosing; confusing the two causes severe iatrogenic cardiac complications. 3, 6

Survey finding: 6 of 7 hospitals lacked pre-filled IM syringes, amplifying error risk 6
Solution: Stock clearly labeled, color-coded pre-filled syringes—"ANAPHYLAXIS – INTRAMUSCULAR ONLY" for 1:1000 and "CARDIAC ARREST – IV/IO ONLY" for 1:10,000 3, 6
All overdoses in one study occurred with IV bolus administration; 13.3% of IV bolus doses caused overdose versus 0% with IM 4

Inadequate Volume Resuscitation

Never administer IV epinephrine without concurrent aggressive fluid resuscitation; vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure. 1, 2

Minimum crystalloid bolus: 30 mL/kg before or concurrent with epinephrine 2
Anaphylactic shock: Can result in loss of up to 37% of circulating blood volume 3
Repeat boluses: 500 mL–1 L rapid boluses as needed for persistent hypotension 5

Extravasation Management

If extravasation occurs, immediately infiltrate 5–10 mg phentolamine diluted in 10–15 mL saline intradermally at the site to prevent tissue necrosis. 1, 2, 3

Pediatric phentolamine dose: 0.1–0.2 mg/kg (maximum 10 mg) 2
Do not remove the IV catheter before administering phentolamine; it serves as a landmark for precise infiltration 2

Drug Incompatibility

Never mix epinephrine with sodium bicarbonate or other alkaline solutions in the IV line; epinephrine is inactivated in alkaline environments. 2, 3

Adjunctive Therapies (Second-Line Only)

Antihistamines

Diphenhydramine: 1–2 mg/kg or 25–50 mg parenterally 1
Ranitidine: 50 mg in adults, 12.5–50 mg (1 mg/kg) in children, diluted in D5W and injected IV over 5 minutes 1
Critical caveat: Antihistamines have much slower onset than epinephrine and should never be administered alone or delay epinephrine 1

Inhaled β-Agonists

Nebulized albuterol: 2.5–5 mg in 3 mL saline, repeated as necessary for bronchospasm resistant to adequate epinephrine 1

Corticosteroids

IV glucocorticosteroids: 1.0–2.0 mg/kg/day (equivalent dose) every 6 hours for severe or prolonged anaphylaxis 1
Rationale: Usually not helpful acutely but may prevent recurrent or protracted anaphylaxis 1

Alternative Vasopressors (Refractory Hypotension)

Dopamine: 400 mg in 500 mL D5W infused at 2–20 mcg/kg/min, titrated to maintain systolic BP >90 mmHg 1
Norepinephrine: 0.05–0.1 mcg/kg/min for persistent hypotension after 10 minutes despite epinephrine boluses and volume resuscitation 2

Observation and Follow-Up

Observation periods must be individualized; there are no reliable predictors of biphasic or protracted anaphylaxis based on initial presentation 1
Provide epinephrine autoinjector and proper self-administration instruction before discharge 1
Allergist-immunologist consultation is strongly recommended after acute anaphylaxis for diagnosis, prevention, and future treatment planning 1

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