Effect of phenylephrine push prior to continuous infusion norepinephrine in patients with septic shock

Background Intravenous pushes of phenylephrine may be utilized 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 is unclear. Therefore, we sought to answer the question, in patients with septic shock, is administration of a phenylephrine push prior to norepinephrine initiation associated with a higher incidence of hemodynamic stability? Methods This retrospective, multi-centered, 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 ≥65 mm Hg for at least 6 hours without an increase in continuous infusion vasoactive agent dosage) within 3 and 12 hours 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% to 18%). Phenylephrine push receipt was independently associated with hemodynamic stability within 3 hours (adjusted OR 1.8, 95% CI 1.09-2.97) but not at 12 hours (adjusted OR 1.42, 95% CI 0.93-2.16). Phenylephrine push receipt was independently associated with higher ICU mortality (adjusted OR 1.88, 95% CI 1.1-3.21). Conclusion Phenylephrine pushes were associated with a higher incidence of early but not sustained hemodynamic stability, and were independently associated with higher ICU mortality. Caution is warranted when clinicians are considering the use of phenylephrine pushes in patients with septic shock.