Effect of timing of norepinephrine administration on prognosis of patients with septic shock: A prospective cohort study

Abstract

Background

Sepsis and septic shock are major healthcare problems worldwide, associated with substantial mortality. Early administration of norepinephrine in septic shock patients has been associated with an increased survival rate, but the timing from septic shock to norepinephrine initiation is controversial. This study examined the associations between the timing of initial norepinephrine administration and clinical outcomes in adult patients with septic shock.

Methods

This prospective cohort study was conducted from September 2021 to June 2022 in an intensive care unit (ICU) of a tertiary general hospital. All enrolled patients were divided into early and late norepinephrine groups according to whether the time from the onset of septic shock to the first application of norepinephrine was >1 h. The primary outcome was 28-day mortality. Secondary outcomes included ICU length of stay (LOS), hospital LOS, time to achieve a mean arterial pressure (MAP) ≥65 mmHg, 24-hour infusion volume, 6-hour Lac clearance, mechanical ventilation days, and continuous renal replacement therapy (CRRT )ratio. Multivariable logistic regression analysis was used to evaluate the independent risk factors for 28-day mortality.

Results

This study enrolled 120 patients, including 42 patients (35.0%) and 78 patients (65.0%) in the early and late norepinephrine groups, respectively. The 28-day mortality was lower in the early group than in the late group (28.6% vs. 47.4%, P=0.045). The median time to achieve MAP ≥65 mmHg was shorter in the early group than in the late group (1.0 h vs. 1.5 h, P=0.010). The median 24-hour intravenous fluids volume in the early group was lower than that in the late group (40.7% vs. 14.9%, P=0.030). The median 6-hour lactate (Lac) clearance rate in the early group was higher than that in the late group (40.7% vs. 14.9%, P=0.009). There were no significant differences between early and late groups by ICU LOS (P=0.748), hospital LOS (P=0.369), mechanical ventilation time (P=0.128), and CRRT ratio (P=0.637). The independent risk factors for 28-day mortality included being male (odds ratio [OR]=3.288, 95% confidence interval [CI]: 1.236 to 8.745, P = 0.017), time to norepinephrine initiation >1 h (OR=4.564, 95% CI: 1.382 to 15.079, P = 0.013), and time to achieve MAP ≥65 mmHg (OR=1.800, 95% CI: 1.171 to 2.767, P = 0.007).

Conclusions

Norepinephrine initiation ≤1 h is associated with lower 28-day mortality in patients with septic shock. Early norepinephrine administration is also associated with a shorter time to achieve MAP ≥65 mmHg, lower 24-hour intravenous fluids volume, and higher 6-hour Lac clearance rate. Being male, time to achieve MAP ≥65 mmHg, and norepinephrine initiation >1 h are independent risk factors for 28-day mortality.

Trial registration Chinese Clinical Trial Registry Identifier: ChiCTR2100044071.