Sepsis With Atrial Fibrillation: Effect of Phenylephrine vs Norepinephrine on Heart Rate

Atrial Fibrillation
Atrial Fibrillation
In patients with sepsis and atrial fibrillation, how does treatment with phenylephrine vs norepinephrine affect heart rate?

In patients with sepsis and atrial fibrillation (AFib or AF), treatment with phenylephrine is associated with a moderately lower heart rate than sepsis or AFib treatment with norepinephrine. Moreover, patients with a higher heart rate when initiating phenylephrine experience greater heart rate declines than patients receiving norepinephrine, according to findings of a recent analysis published in Chest.

The Surviving Sepsis Guidelines recommend using norepinephrine as the primary treatment for septic shock, but the drug can cause unwanted changes in heart rate. Moreover, AF is common among patients with sepsis. Researchers from the Boston University School of Medicine therefore sought to compare how phenylephrine vs norepinephrine affect heart rate in patients with sepsis and AF. “There is limited literature examining the use of phenylephrine in septic shock, and even fewer studies specifically examining the effect of phenylephrine on heart rate compared to norepinephrine during AF,” the authors observed.

Investigators performed a systematic search of the Medical Information Mart in Intensive Care (MIMIC)-IV database for patients with sepsis and AF who were given norepinephrine or phenylephrine. Multivariable-adjusted linear regression was used to assess the differences in heart rate between the 2 patient groups 1 and 6 hours after vasopressor commencement. The researchers then stratified patients by baseline heart rate (≥110 or <110) and analyzed the treatment effect of norepinephrine and phenylephrine by heart rate.

The primary outcomes for the study were heart rates at 1 hour and 6 hours. Secondary outcomes during the 6-hour follow-up were conversion into sinus rhythm and heart rate less than 60 bpm. Other secondary outcomes included vasopressor duration, length of stay in the intensive care unit, length of stay in hospital, and hospital mortality.

Of the 1847 patients with sepsis and AF identified in the search, 946 (51%) were given norepinephrine and 901 (49%) received phenylephrine. The review demonstrated that phenylephrine use correlated with a lower heart rate at 1 hour (-4 bpm; 95% CI, -6 to -1; P <.001) and 6 hours (-4 bpm; 95% CI, -6 to -1; P =.004).

The data also showed that the higher the heart rate before vasopressor administration, the greater the decline in the heart rate of patients receiving phenylephrine compared with those getting norepinephrine. “Baseline heart rate appeared to be an important effect modifier,” the authors noted. No differences in secondary outcomes were observed. Exploratory and sensitivity analyses confirmed the results.

Strengths of the study included the large data sample size that enabling adjustment for  multiple clinical variables as well as primary results using linear regression strong enough to stand up to sensitivity analyses. Limitations included the study’s retrospective design, in-hospital outcomes confined to a single medical center, and a shortcoming of the MIMIC IV database, which omitted data on chronic comorbidities and medications taken at home.

The authors said their study complemented other studies showing lower heart rates using catecholamine-sparing strategies. “Our finding that  phenylephrine — a catecholamine with primarily a-1 and a-2 activity — is also associated with reduced heart rates in patients with septic shock, provides evidence that avoidance of b-1 stimulation may mediate heart rate differences,” they affirmed.


Law AC, Bosch NA, Peterson D, Walkey AJ. Comparison of heart rate after phenylephrine versus norepinephrine initiation in patients with septic shock and atrial fibrillation. Chest. Published online May 5, 2022. doi:10.1016/j.chest.2022.04.147