The Effect of Different Doses of Norepinephrine on Microcirculation in ICU Septic Patients: A Prospective Observational Study

Background Norepinephrine (NE) is the first-line vasopressor for septic shock, but high doses may exacerbate microcirculatory impairment and organ dysfunction. This study aimed to investigate the relationship between NE dose and microcirculation, as well as its impact on prognosis, in ICU septic patients. Methods A prospective observational study was conducted on adult septic patients admitted to the ICU of Zhongnan Hospital of Wuhan University between January and September 2025. Sublingual microcirculatory parameters (microvascular flow index (MFI), total vessel density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPV), heterogeneity index (HI)) were monitored using a handheld imaging system within 24 hours of admission and on Day 3. Clinical data were simultaneously collected. Multiple regression models were used to analyze associations between NE dose, microcirculation and clinical outcomes (28-day/90-day mortality), with preliminary exploration of their dose-response relationships. Result Of 144 screened adult septic patients, 66 were enrolled. NE dose was significantly correlated with multiple microcirculatory parameters: positive correlations were observed with Lac, mottling score, and HI (Lac: r  = 0.583, p  < 0.001; mottling score: r  = 0.364, p  = 0.003; HI: r  = 0.444, p  < 0.001); negative correlations with MFI and PPV (MFI: r = -0.492, p  < 0.001; PPV: r = -0.420, p  < 0.001). After adjusting for covariates including APACHE II scores, heart rate, and IL-6 levels, the generalized additive model (GAM) analysis revealed significant nonlinear relationships between NE dose and microcirculatory parameters (all p  < 0.05). When NE dose exceeds the threshold range of 0.71–0.80 \(\:\mu\:\)g/kg/min, microcirculation in septic patients deteriorates significantly. Multivariable Cox regression showed high NE dose (cut-off value = 0.80 \(\:\mu\:\)g/kg/min) was associated with increased mortality (HR = 1.14, 95% CI: 0.48 to 2.68, p  = 0.035). Conclusions This study demonstrates that excessive NE use is independently associated with worsening microcirculatory perfusion and increased mortality in ICU septic patients. When NE dose pumping over 0.71–0.80 \(\:\mu\:\)g/kg/min, microcirculatory dysfunction should be noted. This provides important evidence for the precise regulation of NE dose in sepsis management, emphasizing the significance of integrating microcirculation monitoring to avoid further deterioration and improve patient prognosis.