Early Use of Norepinephrine Improves Survival in Septic Shock: Earlier than Early

The timing of initiation of Norepinephrine (NEP) in septic shock is controversial.

We evaluated the impact of early NEP simultaneously with fluids in those patients.

We randomized 101 patients admitted to the emergency department with septic shock to early NEP simultaneously with IV fluids (early group) or after failed fluids trial (late group). The primary outcome was the in-hospital survival while the secondary outcomes were the time to target mean arterial pressure (MAP) of 65 mmHg, lactate clearance and resuscitation volumes.

There was no significant difference between the two groups regarding the baseline characteristics. NEP infusion started after 25 (20-30) and 120 (120-180) min in the early and late groups (p = 0.000). MAP of 65 mmHg was achieved faster in the early group (2 [1-3.5] h vs. 3 [2-4.75] h, p = 0.003). Serum lactate was decreased by 37.8 (24-49%) and 22.2 (3.3-38%) in both groups respectively (p = 0.005). Patients with early NEP were resuscitated by significantly lower volume of fluids (25 [18.8-28.7] mL/kg vs. 32.5 [24.4-34.6] mL/kg) in the early and late groups (p = 0.000). The early group had survival rate of 71.9% compared to 45.5% in the late group (p = 0.007). NEP started after 30 (20-120 min) in survivors vs. 120 (30-165 min) in non-survivors (p = 0.013).

We concluded that early Norepinephrine in septic shock might cause earlier restoration of blood pressure, better lactate clearance and improve in-hospital survival.