Comparison of Heart Rate After Phenylephrine vs Norepinephrine Initiation in Patients With Septic Shock and Atrial Fibrillation

BACKGROUND: Atrial fibrillation (AF) is a common complication of sepsis. It is unclear whether norepinephrine, an alpha- and beta-agonist, and phenylephrine, an alpha-agonist, are associated with different heart rates among patients with sepsis and AF. RESEARCH QUESTION: Among patients with sepsis and AF, what is the difference in heart rate after phenylephrine initiation vs norepinephrine initiation? STUDY DESIGN AND METHODS: With the use of an extensive database, we identified patients with sepsis and AF at the time of norepinephrine or phenylephrine initiation. We estimated the difference in heart rate between patients who received phenylephrine or norepinephrine 1 and 6 h after vasopressor initiation with the use of multivariable-adjusted linear regression, tested for effect modification by heart rate, and stratified by baseline heart rate 110 or < 110 beats/min. Secondary outcomes included conversion to sinus rhythm, bradycardia, vasopressor duration, ICU and hospital length of stay, and hospital death. Exploratory analyses were adjusted for practices that occurred after vasopressor initiation; sensitivity analyses used interrupted time series to estimate the difference in average heart rate between patients who received phenylephrine or norepinephrine. RESULTS: Among 1847 patients with sepsis and AF, 946 patients (51%) received norepinephrine, and 901 patients (49%) received phenylephrine. After multivariable adjustment, phenylephrine was associated with a lower heart rate at 1 h (-4 beats/min; 95% CI, -6 to -1; P < .001) and 6 h (-4 beats/min; 95% CI, -6 to -1; P = .004). Higher heart rate before vasopressor administration was associated with larger heart rate reduction in patients who received phenylephrine compared with norepinephrine. There were no differences in secondary outcomes. Results were similar in exploratory and sensitivity analyses. INTERPRETATION: In patients with sepsis and AF, the initiation of phenylephrine was associated with modestly lower heart rate compared with norepinephrine. Heart rate at vasopressor initiation appeared to be an important effect modifier. Whether modest reductions in heart rate are associated with clinical outcomes requires further study.