What is the maximum number of epinephrine (adrenaline) doses that can be administered to a patient, particularly in cases of anaphylaxis or cardiac arrest?

Maximum Epinephrine Dosing

There is no absolute maximum number of epinephrine doses—you should continue administering epinephrine every 3-5 minutes during cardiac arrest until return of spontaneous circulation (ROSC) is achieved, and every 5-15 minutes for anaphylaxis until symptoms resolve. 1, 2, 3

Cardiac Arrest Dosing Protocol

Continue epinephrine 1 mg IV/IO every 3-5 minutes throughout the entire resuscitation effort without a predetermined stopping point. 2, 3 The American Heart Association guidelines establish a repeating cycle rather than a dose ceiling:

• Administer the first dose within 5 minutes of starting chest compressions for optimal outcomes 3
• Repeat 1 mg IV/IO every 3-5 minutes until ROSC is achieved 2, 3
• Use 1:10,000 concentration (0.1 mg/mL) for IV/IO administration 1, 2
• Give each dose as a rapid bolus followed by at least 5 mL normal saline flush 3

For pediatric cardiac arrest, use 0.01 mg/kg (0.1 mL/kg of 1:10,000 solution) IV/IO every 3-5 minutes, with a maximum single dose of 1 mg. 1, 3 In refractory pediatric arrest, higher doses of 0.1-0.2 mg/kg may be considered, though this is not standard practice 1.

Important Caveat on High-Dose Epinephrine

High-dose epinephrine (0.1-0.2 mg/kg) does not improve survival to discharge or neurological outcomes compared to standard 1 mg dosing, and may actually worsen post-arrest outcomes despite potentially increasing ROSC rates 2. Stick with standard 1 mg dosing every 3-5 minutes rather than escalating doses.

Anaphylaxis Dosing Protocol

Repeat intramuscular epinephrine every 5-15 minutes as needed until anaphylaxis symptoms resolve—there is no maximum number of doses. 1, 2, 4

• Adults and children ≥30 kg: 0.3-0.5 mg IM (1:1000 concentration) into the anterolateral thigh 1, 2, 4
• Children <30 kg: 0.01 mg/kg IM (1:1000 concentration), maximum 0.3 mg per dose 1, 2, 4
• Administer through clothing if necessary into the vastus lateralis muscle 1, 4
• The FDA label specifies repeating every 5-10 minutes, while American Heart Association guidelines allow 5-15 minute intervals 1, 2, 4

Transitioning to IV Epinephrine in Severe Anaphylaxis

For anaphylactic shock refractory to IM dosing, IV epinephrine is reasonable but requires dramatically lower doses than cardiac arrest protocols: 2

• Bolus dose: 0.05-0.1 mg (50-100 mcg) using 1:10,000 concentration 1, 2
• Infusion rate: 5-15 mcg/min (0.05-0.1 mcg/kg/min) 2
• Close hemodynamic monitoring is mandatory due to rapid cardiovascular changes 1, 2

Critical Safety Considerations

Preventing Dosing Errors

The most dangerous error is administering cardiac arrest doses (1 mg IV) to anaphylaxis patients, which can cause severe cardiotoxicity including transient systolic dysfunction, ventricular arrhythmias, and even death. 5 To prevent this:

• Stock clearly labeled, pre-filled IM epinephrine syringes (1:1000) that are easily distinguished from IV formulations (1:10,000) 1, 5
• Never give the 1 mg cardiac arrest dose IV push for anaphylaxis—this is 10-20 times higher than the appropriate IV dose 1, 2, 5

Cardiotoxicity Risk

Approximately 5% of adult ED patients receiving IM epinephrine for anaphylaxis experience some degree of cardiotoxicity, including ischemic ECG changes (2.4%), elevated troponin (1.8%), or arrhythmias (1.8%) 6. Risk factors include:

• Advanced age 6
• Multiple comorbidities 6
• Multiple doses of epinephrine or epinephrine infusions 6

Despite this risk, the presence of cardiovascular disease should not deter epinephrine use in anaphylaxis, as the benefits far outweigh the risks. 4

Site-Specific Warnings

• Never inject into buttocks, digits, hands, or feet due to risk of tissue necrosis from vasoconstriction 4
• Do not administer repeated injections at the same site 4
• If IV extravasation occurs, infiltrate the site with phentolamine to prevent tissue necrosis 1

Special Populations

Patients on Beta-Blockers

Patients on beta-blockers may have refractory hypotension despite epinephrine and may require glucagon 1-5 mg IV over 5 minutes followed by infusion (5-15 mcg/min) 2.

Post-ROSC Management

After achieving ROSC, immediately transition from bolus dosing to a continuous epinephrine infusion starting at 0.05-0.1 mcg/kg/min, titrated to maintain MAP ≥65 mmHg 3. Never continue bolus dosing after ROSC, as this can cause dangerous blood pressure spikes 3.