Effect of Phenylephrine Push Before Continuous Infusion Norepinephrine in Patients With Septic Shock

Chest. 2021 May;159(5):1875-1883. doi: 10.1016/j.chest.2020.11.051. Epub 2020 Dec 13.


Background: IV pushes of phenylephrine may be used for patients with septic shock with the intent of rapidly achieving mean arterial pressure (MAP) goals. However, the clinical effectiveness and safety of this approach are unclear.

Research question: In patients with septic shock, is administration of a phenylephrine push before norepinephrine initiation associated with a higher incidence of hemodynamic stability?

Methods: This retrospective, multicenter cohort study included adult patients with septic shock initiated on norepinephrine. Propensity scores for initial phenylephrine push receipt were generated, and patients receiving an initial phenylephrine push were propensity score-matched 1:2 to those not receiving an initial phenylephrine push. The primary outcome was achievement of hemodynamic stability (defined as maintaining MAP of ≥ 65 mm Hg for at least 6 h without an increase in continuous infusion vasoactive agent dosage) within 3 and 12 h of norepinephrine initiation.

Results: Of 1,317 included patients, 181 received an initial phenylephrine push; 141 phenylephrine push patients were matched to 282 patients not receiving a phenylephrine push. More patients who received a phenylephrine push achieved hemodynamic stability at hour 3 than those who did not receive a phenylephrine push (28.4% vs 18.8%; risk difference, 10%; 95% CI, 0.9%-18%). Phenylephrine push receipt was associated independently with hemodynamic stability within 3 h (adjusted OR, 1.8; 95% CI, 1.09-2.97), but not at 12 h (adjusted OR, 1.42; 95% CI, 0.93-2.16). Phenylephrine push receipt was associated independently with higher ICU mortality (adjusted OR, 1.88; 95% CI, 1.1-3.21).

Interpretation: Phenylephrine pushes were associated with a higher incidence of early, but not sustained, hemodynamic stability and were associated independently with higher ICU mortality. Caution is warranted when clinicians are considering the use of phenylephrine pushes in patients with septic shock.

Keywords: hemodynamics; sepsis; septic shock; vasopressor.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Administration, Intravenous
  • Cardiotonic Agents / administration & dosage*
  • Female
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Norepinephrine / administration & dosage*
  • Organ Dysfunction Scores
  • Phenylephrine / administration & dosage*
  • Propensity Score
  • Retrospective Studies
  • Shock, Septic / drug therapy*


  • Cardiotonic Agents
  • Phenylephrine
  • Norepinephrine