What is the preferred vasopressor, epinephrine versus phenylephrine, for third-line pressure support in septic shock?

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Last updated: May 26, 2025View editorial policy

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From the FDA Drug Label

Epinephrine is a non-selective alpha- and beta-adrenergic agonist indicated to increase mean arterial blood pressure in adult patients with hypotension associated with septic shock. The suggested dosing infusion rate of intravenously administered epinephrine is 0.05 mcg/kg/min to 2 mcg/kg/min, and is titrated to achieve a desired mean arterial pressure (MAP).

There is no information in the provided drug labels that directly compares epinephrine to phenylephrine for third-line pressure support in septic shock. The FDA drug label does not answer the question.

From the Research

For third-line pressure support in septic shock, epinephrine is generally preferred over phenylephrine due to its ability to provide both alpha and beta adrenergic effects, improving cardiac output while maintaining vascular tone 1.

Key Considerations

  • Norepinephrine is typically the first-line agent, with vasopressin often added as a second agent 1.
  • If additional support is needed, epinephrine is generally preferred as the third-line agent over phenylephrine due to its inotropic effects and ability to improve cardiac output 1.
  • Phenylephrine is a pure alpha-1 agonist that increases blood pressure through vasoconstriction but lacks inotropic effects and may actually decrease cardiac output, which is particularly problematic in septic shock where maintaining tissue perfusion is crucial 2.

Monitoring and Titration

  • When adding epinephrine as a third agent, monitor closely for tachycardia, arrhythmias, and lactic acidosis 1.
  • The goal should be to maintain a mean arterial pressure of at least 65 mmHg while supporting organ perfusion, with vasopressors titrated to the minimum effective dose to limit adverse effects 1.

Recent Evidence

  • A recent study found that angiotensin-II was not associated with significantly improved clinical response at hour 24 compared with epinephrine as a third-line vasopressor in septic shock 3.
  • Another study found that phenylephrine pushes were associated with a higher incidence of early, but not sustained, hemodynamic stability and were associated independently with higher ICU mortality 2.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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