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

Q: What are the key findings of this study?

Norepinephrine use was associated with a significantly higher risk of new-onset atrial fibrillation compared to phenylephrine in adult patients with septic shock (0.3% vs 0.01%, OR 3.05).

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Septic shock (n=276102). Intervention: Norepinephrine vs. Phenylephrine. Primary outcome: Incidence of new-onset atrial fibrillation (OR 3.05, 95% CI 2.55-3.65, p=<0.001).

Q: What does this research mean for the field?

In adult patients with septic shock, norepinephrine use is associated with a significantly higher risk of new-onset atrial fibrillation compared to phenylephrine (0.3% vs 0.01%, OR 3.05). Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To compare the incidence of new-onset atrial fibrillation within 72 hours of vasopressor initiation in adult septic shock patients treated with norepinephrine versus phenylephrine.

Laith Rhabneh; Ra’ed Ababneh; Ibrahim Dib; Qusai Alqudah; Abdel rahman Alwardat; Mohammed Aloqaily

doi:10.5339/qmj.2026.50

January 1, 2026Qatar medical journalOpen Access

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

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Key result

Norepinephrine is linked to ~3-fold higher odds of new-onset AF vs. phenylephrine in septic shock.

OR 3.05
95% CI 2.55-3.65
P<0.001
n=276,102

Figures

Why the study?

New-onset atrial fibrillation is a common complication in septic shock patients receiving vasopressors, and the influence of vasopressor choice on AF incidence is unclear.

Does norepinephrine increase the risk of new-onset atrial fibrillation and related adverse cardiac events compared to phenylephrine in adult patients with septic shock?

Key Points

To compare the incidence of new-onset atrial fibrillation within 72 hours of vasopressor initiation in adult septic shock patients treated with norepinephrine versus phenylephrine.
Retrospective observational cohort study using the TriNetX database analyzing adult septic shock patients without prior atrial fibrillation.
Applied 1:1 propensity score matching to balance baseline demographics, cardiovascular risk factors, and comorbidities, yielding 138,051 patients in each arm.
Evaluated outcomes within 72 hours of vasopressor initiation using Cox proportional hazards models and Kaplan–Meier survival analyses.
New-onset atrial fibrillation occurred in 0.3% (476 patients) of the norepinephrine group versus 0.01% (157 patients) of the phenylephrine group (OR 3.049; 95% CI: 2.545–3.652; p < 0.001; HR 3.055; 95% CI: 2.551–3.659; log-rank p < 0.001).
Norepinephrine use was associated with higher rates of electrical cardioversion (OR 3.721; 95% CI: 2.687–5.153; p < 0.001) and pharmacological cardioversion (OR 4.945; 95% CI: 4.667–5.240; p < 0.001).
Patients treated with norepinephrine had increased risks of other cardiac arrhythmias (OR 2.517; 95% CI: 2.425–2.613; p < 0.001) and composite embolic stroke (OR 2.376; 95% CI: 2.021–2.795; p < 0.001).

Study Design

Type

Cohort (n=276,102)

Multicenter

Yes

Structured PICO

Does norepinephrine increase the risk of new-onset atrial fibrillation and related adverse cardiac events compared to phenylephrine in adult patients with septic shock?

P

Population

276,102 propensity-matched adult patients with septic shock and no prior history of atrial fibrillation, evaluated for new-onset atrial fibrillation within 72 hours of vasopressor initiation.

E

Exposure

Norepinephrine initiated as the first-line vasopressor.

C

Comparator

Phenylephrine initiated as the first-line vasopressor.

O

Outcome

Incidence of new-onset atrial fibrillation within 72 hours of vasopressor initiation.safety

Main Result

Odds Ratio: 3.05 (95% CI 2.55–3.65)

Absolute Event Rate: 0.3% vs 0.01%

p-value: p=<0.001

In adult patients with septic shock, initiating vasopressor therapy with norepinephrine is associated with a significantly higher risk of new-onset atrial fibrillation and related adverse cardiovascular outcomes compared to phenylephrine.

Limitations

Reliance on an EHR database and ICD codes which are susceptible to coding errors.
Lack of precise data on timing, duration, dosage, and dose escalation of vasopressors.
Absence of illness severity scores such as SOFA or APACHE II introduces potential residual confounding.
Lack of data on anticoagulation use, AF duration, and other key stroke risk factors.
Reliance on ICD codes in the TriNetX EHR database, susceptible to coding errors and biases.
Lack of detailed medication information such as dosage, adherence, timing, and duration of vasopressor use.
Restricted generalizability as the population was limited to patients starting on solely norepinephrine or phenylephrine.
Potential residual confounding due to the absence of standardized illness severity scores (e.g., SOFA, APACHE II).
Unavailability of data on anticoagulation use, AF duration, and other stroke risk factors to properly adjust for embolic stroke risk.

Implication

Norepinephrine may confer higher new-onset AF risk than phenylephrine in septic shock; leaves open whether this association warrants practice change pending randomized trials.

Abstract

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.

Discussion

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Cite This Study

Rhabneh et al. (2026) conducted a cohort in Septic shock (n=276,102). Norepinephrine vs. Phenylephrine was evaluated on Incidence of new-onset atrial fibrillation (OR 3.05, 95% CI 2.55-3.65, p=<0.001). Norepinephrine use was associated with a significantly higher risk of new-onset atrial fibrillation compared to phenylephrine in adult patients with septic shock (0.3% vs 0.01%, OR 3.05).

synapsesocial.com/papers/6ad0fc963afa093ea9acfee3 https://doi.org/10.5339/qmj.2026.50

Topics

Atrial fibrillation

Persistent AF management

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

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Topics

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

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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