Incidence of new-onset atrial fibrillation following phenylephrine vs. norepinephrine use in septic shock patients: A retrospective cohort study.

BACKGROUND: Septic shock is a severe form of sepsis characterized by circulatory failure and organ dysfunction, often requiring vasopressor support to maintain adequate mean arterial pressure. Norepinephrine is the recommended first-line vasopressor, but new-onset atrial fibrillation (AF) is a common complication in septic shock patients receiving vasopressors, potentially influenced by vasopressor choice. This study compares the incidence of new-onset AF and related cardiac outcomes in septic shock patients treated with norepinephrine versus phenylephrine. OBJECTIVE: To compare the incidence of new-onset AF within 72 hours of vasopressor initiation in adult septic shock patients treated with norepinephrine versus phenylephrine. METHODS: A retrospective observational cohort study was conducted using the TriNetX database, including adult septic shock patients without prior AF who received either norepinephrine or phenylephrine. Propensity score matching balanced baseline characteristics across cohorts. The primary outcome was incidence of new-onset AF; secondary outcomes included cardioversion events, rate control medication use, other arrhythmias, and embolic stroke incidence. Outcomes were analyzed using Cox proportional hazards models and Kaplan-Meier survival curves. RESULTS: After matching, 138,051 patients were included in each group. New-onset AF occurred in 0.3% of norepinephrine-treated patients versus 0.01% in the phenylephrine group (OR 3.05; 95% CI: 2.55-3.65; p < 0.001). Norepinephrine use was also associated with significantly increased rates of electrical and pharmacological cardioversion, rate control medication utilization, other arrhythmias, and embolic stroke (all p < 0.001). Kaplan-Meier analysis confirmed higher AF incidence in the norepinephrine group (log-rank p < 0.001). CONCLUSION: In septic shock patients, norepinephrine is associated with a significantly higher risk of new-onset AF and related adverse cardiac events compared to phenylephrine. These findings suggest vasopressor choice may influence arrhythmia risk and highlight the need for prospective studies to guide optimal vasopressor selection and management strategies in this population.