Early administration of norepinephrine in sepsis: Multicenter randomized clinical trial (EA-NE-S-TUN) study protocol

Area of Science:

• Critical Care Medicine
• Cardiovascular Physiology
• Sepsis Pathophysiology

Background:

• Hemodynamic restoration is crucial in sepsis management.
• Norepinephrine (NE) is a second-line agent after fluid expansion for persistent shock.
• Early NE initiation may optimize fluid management and shock control.

Purpose of the Study:

• To test if early low-dose NE improves shock control in adult septic patients within 6 hours.
• To compare early NE administration versus standard care in intensive care unit (ICU) settings.
• To evaluate the impact of early NE on hemodynamic parameters and organ function.

Main Methods:

• Randomized multicenter trial in ICU patients with sepsis and mean arterial pressure (MAP) < 65 mmHg.
• Two groups: early NE initiation versus standard care after fluid resuscitation.
• Primary outcome: shock control (MAP > 65 mmHg and diuresis > 0.5 ml/kg/h) within 6 hours.

Main Results:

• Study is ongoing; aims to enroll at least 100 patients per arm.
• Data collection includes lactates, cardiac ultrasound parameters (SV, CO, E/E'), P/F ratio, MAP, and diuresis.
• Secondary outcomes include lactate decrease, fluid volume, CO/E' variation, and 28-day mortality.

Conclusions:

• The study hypothesizes that early NE can enhance shock control and potentially reduce fluid administration in sepsis.
• Findings are expected to support early NE use to optimize fluid management in septic patients.
• This research may influence clinical guidelines for sepsis resuscitation.