What are the neurological effects of excessive epinephrine (adrenaline) administration during cardiac arrest?

Neurological Effects of Excessive Epinephrine During Cardiac Arrest

Excessive epinephrine administration during cardiac arrest can cause cerebral microvascular insufficiency, potentially leading to unfavorable neurological outcomes despite improved return of spontaneous circulation (ROSC). 1

Mechanism of Action and Standard Dosing

• Epinephrine is administered during cardiac arrest primarily for its α-adrenergic (vasoconstrictor) properties, which increase coronary perfusion pressure (CPP) and cerebral perfusion pressure during CPR 2
• The American Heart Association recommends administering 1 mg of IV/IO epinephrine every 3-5 minutes during adult cardiac arrest (Class IIb, Level of Evidence B-R) 2
• There is no officially defined maximum cumulative dose or number of doses in the current guidelines 3

Neurological Effects of Excessive Epinephrine

• High doses of epinephrine can lead to:

  • Cerebral microvascular insufficiency, compromising brain tissue perfusion despite increased systemic blood pressure 1
  • Extreme elevation of arterial pressure, potentially resulting in cerebrovascular hemorrhage, particularly in elderly patients 4
  • Metabolic acidosis due to elevated blood lactic acid levels, which can impair neurological function 4

• Recent research suggests that cumulative epinephrine doses above 3 mg during cardiac arrest may be associated with unfavorable neurological outcomes, particularly in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR) 1

High-Dose vs. Standard-Dose Epinephrine

• High-dose epinephrine (0.1 to 0.2 mg/kg) is not recommended for routine use in cardiac arrest 2

• While high-dose epinephrine may increase ROSC rates, studies have consistently shown no improvement in:

  • Survival to hospital discharge 2, 5
  • Neurological outcomes 2, 5
  • Long-term survival 2, 5

• The adverse effects of higher doses in the post-arrest period may negate any potential advantages during the arrest 2

• Some studies suggest that high-dose epinephrine may actually worsen neurological outcomes in certain patient populations 5

Timing and Neurological Impact

• Earlier administration of epinephrine (within 5 minutes of CPR initiation) is associated with improved ROSC and survival rates compared to delayed administration 2, 6
• However, the impact on neurological outcomes remains controversial:
  • The PARAMEDIC 2 trial showed an increase in short-term survival with unfavorable neurological outcomes with epinephrine use 2
  • Epinephrine may improve survival but not necessarily provide patients with meaningful neurological recovery 7

Special Considerations and Exceptions

• High-dose epinephrine may be considered in exceptional circumstances such as:
  • β-blocker overdose 2, 6
  • Calcium channel blocker overdose 2, 6
  • When titrated to real-time physiologically monitored parameters 2

Common Pitfalls and Caveats

• Using high-dose epinephrine routinely without specific indications can lead to worse neurological outcomes 3, 5

• Excessive epinephrine administration can cause:

  • Potentially fatal cardiac arrhythmias, including ventricular tachycardia and fibrillation 4
  • Myocardial ischemia and infarction, particularly in patients with underlying heart disease 4
  • Pulmonary edema due to peripheral vasoconstriction combined with cardiac stimulation 4
  • Renal insufficiency and failure 4

• The β-adrenergic effects of epinephrine may increase myocardial work and reduce subendocardial perfusion, potentially worsening post-resuscitation myocardial function 2