Keywords: Mean arterial pressure, Mortality, Norepinephrine therapy, Sepsis, Septic shock, Sepsis, Survival

Background & objective: It has been hypothesized that norepinephrine (NE) administration during the early phases of septic shock will improve survival and hemodynamic outcomes by rapidly restoring perfusion. This study compares the effects of early (< 2 hours) versus late (≥ 2 hours) NE administration in patients of septic shock on mortality and secondary outcomes.

Methodology: A prospective, double-blind, randomized controlled trial involving 200 adult patients with septic shock was conducted in the ICU of Faculty of Medicine, Ain Shams University, Cairo. The participants were assigned to either Group A, to receive early NE administration; or Group B, to receive NE ≥ 2 hours later in their treatment protocol. Key outcomes measured included mortality rate, hemodynamic parameters, serum lactate clearance, NE dosage, and length of hospital stay (LOS). Statistical analyses were conducted with chi-square and Mann-Whitney tests to determine significance of the results.

Results: Group A exhibited a significantly reduced 28-30 days mortality rate compared to Group B, with rates of 28% versus 46% (P = 0.008). The time required to reach the target mean arterial pressure (MAP) of ≥ 65 mmHg was significantly shorter for Group A; 1.0 ± 0.5 days vs. 1.5 ± 0.4 days in Group B (P < 0.01). Lactate clearance in Group A was markedly superior; 40.7% compared to 14.8% in Group B (P < 0.01). Patients in Group A required lower doses of NE, averaging 29.4 ± 9.7 mg versus 32.8 ± 10.0 mg in Group B (P < 0.01), and for a shorter duration of 2.6 ± 0.6 days compared to 2.9 ± 1.0 days (P = 0.038). However, LOS in Group A was slightly more than Group B, averaging 12.5 ± 8.5 days vs. 11.0 ± 6.0 days (P = 0.003). Serum lactate, creatinine, and C-reactive protein (CRP) levels were also higher in Group B, indicating a higher level of organ failure and systemic inflammation.

Conclusion: Early norepinephrine administration in septic shock patients results in improved hemodynamic and metabolic parameters as well as a notable decrease in death rates compared to delayed use of norepinephrine, highlighting the importance of prompt vasopressor use in sepsis treatment protocols.

Abbreviations: BMI: Body mass Index, CRP: C-reactive Protein, IVF: Intravenous Fluids, LOS: Length of Stay, MAP: Mean Arterial Pressure, NE: Norepinephrine, SOFA: Sequential Organ Failure Assessment, SSC: Surviving Sepsis Campaign.

Keywords: Mean arterial pressure; Mortality; Norepinephrine therapy; Sepsis; Septic shock, Sepsis; Survival

Citation: Elghareeb SH, Mohamed HY, Abd Elaleem AA, Mahmoud MS. Impact of early versus late administration of norepinephrine on the hemodynamic outcome and mortality in septic shock. Anaesth. pain intensive care 2025;29(4):283-91. DOI: 10.35975/apic.v29i4.2813

Received: January 18, 2025; Revised: May 08, 2025; Accepted: May 08, 2025