Key result
Adding early esmolol to norepinephrine is linked to ~67% lower 28-day mortality in septic shock.
Why the study?
Sepsis and septic shock cause high ICU mortality despite standard care with norepinephrine, leaving unclear whether early combination therapy with norepinephrine and esmolol improves hemodynamics and 28-day survival.
Does early combination therapy with norepinephrine and esmolol improve hemodynamic stability and reduce 28-day mortality in patients with septic shock?
Cohort (n=252)
No
Does early combination therapy with norepinephrine and esmolol improve hemodynamic stability and reduce 28-day mortality in patients with septic shock?
Absolute Event Rate: 7.81% vs 23.39%
p-value: p=<0.001
Early addition of esmolol to norepinephrine in patients with septic shock significantly improved hemodynamic stability, tissue perfusion, and 28-day survival without increasing adverse events.
Should not alter septic shock practice; leaves open esmolol benefit pending randomized trials.
Sepsis and septic shock are leading causes of intensive care unit (ICU) mortality, with persistent high mortality despite standard care including norepinephrine. This study aimed to investigate whether early combination therapy with norepinephrine and esmolol improves hemodynamics and 28-day survival in septic shock patients. This retrospective cohort study enrolled patients with septic shock between June 2020 and June 2023. Patients were divided into a norepinephrine only (NEO) group and a norepinephrine plus esmolol (NEC) group. Hemodynamic parameters were monitored at baseline, 24 h, and 48 h. Oxygenation/tissue perfusion markers and disease severity scores were assessed at baseline and 48 h. Clinical outcomes included 28-day mortality, ICU, and hospital length of stay. A total of 252 patients were analyzed (NEO = 124, NEC = 128). Compared to the NEO group, the NEC group showed significantly lower heart rate (93.42 vs. 96.15 at 48 h, p = 0.002) and systemic vascular resistance index (163.31 vs. 180.95 at 48 h, p < 0.001), and higher cardiac index (3.66 vs. 3.34 at 48 h, p < 0.001). The NEC group also had higher post-treatment ScvO₂ (79.08% vs. 75.82%, p = 0.001) and lower lactate (1.68 vs. 1.93, p < 0.001). SOFA and APACHE II scores improved more in the NEC group (p < 0.001). The 28-day mortality was significantly lower in the NEC group (7.81% vs. 23.39%, p < 0.001). Early combined use of norepinephrine and esmolol was associated with improved hemodynamic stability, enhanced tissue perfusion, accelerated organ function recovery, and reduced 28-day mortality in patients with septic shock. Not applicable
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Cai et al. (2026) conducted a cohort in Septic shock (n=252). Norepinephrine combined with esmolol vs. Norepinephrine monotherapy was evaluated on 28-day mortality (p=<0.001). Early combined use of norepinephrine and esmolol reduced 28-day mortality to 7.81% compared to 23.39% with norepinephrine alone in patients with septic shock.
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