In this episode, I’ll discuss the effect of phenylephrine push prior to continuous infusion norepinephrine in patients with septic shock.
Push dose vasopressors as a temporizing measure for profound hypotension in critically ill patients is frequently used in many institutions. However the extent of the data for this strategy comes from use in pregnant women experiencing hypotension from the effects of spinal anesthesia for C-section. This patient population and mechanism of hypotension is far removed from that of the critically ill septic shock population. While it is logical to want to fix hypotension promptly with a bolus of a vasopressor prior to continuous infusion, the effects of this practice in the critically ill is unknown.
To begin to examine this practice, researchers at the Cleveland Clinic Health System performed a retrospective, multi-centered, cohort study looking at the effect of phenylephrine push prior to continuous infusion norepinephrine in patients with septic shock. Patients receiving an initial phenylephrine push were propensity score-matched 1:2 to those not receiving an initial phenylephrine push. In all, 141 phenylephrine push patients were matched to 282 patients not receiving a phenylephrine push.
The primary outcome was the achievement of hemodynamic stability within 3 and 12 hours of norepinephrine initiation. This was defined as maintaining MAP ≥65 mm Hg for at least 6 hours without a need for an increase in continuous norepinephrine infusion vasoactive dosage.
The authors had 3 main findings:
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).
Because of the higher incidence of ICU mortality, the authors concluded:
Caution is warranted when clinicians are considering the use of phenylephrine pushes in patients with septic shock.
Although the propensity matching used attempts to remove confounders, a retrospective study of this sort still cannot prove causation. It is also unknown if the mortality difference is from using phenylephrine as the bolus vasopressor compared with norepinephrine or from the act of giving a bolus vasopressor itself.
It is still my preference for a pharmacist to be involved in the care of these hypotensive patients as they have a chance to predict the need for norepinephrine and have it at the bedside with the bag spiked, tubing primed, and infusion pump ready to go before the MD has a chance to think about using a bolus vs starting a drip.
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