Phenylephrine Plus Norepinephrine Inferior to Norepinephrine Alone in Septic Shock

Higher all-cause mortality were rates and longer durations of hospitalization were observed among patients with septic shock who received phenylephrine plus norepinephrine vs norepinephrine alone.

The combination of phenylephrine plus norepinephrine is inferior to norepinephrine alone for the treatment of septic shock. These study results were published in BMC Infectious Diseases.

Researchers conducted a single-center retrospective study among adult patients with septic shock. Outcomes were compared between patients who received an infusion phenylephrine plus norepinephrine vs norepinephrine alone. The primary outcomes were the rates of all-cause mortality during hospital and intensive care unit (ICU) admission. Between-group differences were assessed via multivariate logistic regression, propensity score matching, and doubly robust estimation.

The final analysis included 692 patients in the combination therapy group and 1055 in the monotherapy alone group, of whom the mean (SD) ages were 67.11 (15.26) and 67.45 (15.82), 43.8% and 46.9% were women, and 72.7% and 74.0% were White, respectively.

Patients in the combination vs monotherapy therapy groups had higher rates of congestive heart failure (43.6% vs 37.7%), cardiac arrhythmias (53.3% vs 36.4%), and liver disease (28.5% vs 20.5%). Rates of emergency department admissions (97.7% vs 94.4%) and hypertension (53.6% vs 51.6%) were higher among patients who received monotherapy.

The[se] results need to be confirmed in multicenter prospective randomized clinical trials.

After propensity score matching, all-cause in-hospital mortality rates were found to be higher among patients who received combination vs monotherapy (51.0% vs 38.7%; P <.001). Multivariate logistic regression also indicated a significant association between combination therapy and higher all-cause in-hospital mortality rates (odds ratio, 1.76; 95% CI, 1.36-2.28; P <.001).

Further analysis showed significantly longer durations of ICU admission (12.18 vs 9.25 days; P <.001), hospitalization (17.35 vs 15.19 days; P =0.019), and mechanical ventilation (160.26 vs 132.74 hours; P =.042) among combination vs monotherapy recipients.

No significant between-group differences in the rate of all-cause in-hospital mortality were observed in subgroup analyses.

Limitations of this study include the retrospective design, the single-center setting, and potential selection bias.

According to the researchers, “The[se] results need to be confirmed in multicenter prospective randomized clinical trials.”


He D, Hu H, Hong L, et al. Norepinephrine combined with phenylephrine versus norepinephrine in patients with septic shock: a retrospective cohort study. BMC Infect Dis. 2023;23(1):221. doi:10.1186/s12879-023-08142-x