Early combination of terlipressin and norepinephrine in the treatment of patients with septic shock

• Early low-dose terlipressin reduced norepinephrine dependence in septic shock. • Low-dose terlipressin increased vasopressor-free days within the first 7-days. • Earlier terlipressin improved hemodynamic stabilization and lactate clearance. • Low-dose terlipressin promoted faster renal, hepatic, and platelet recovery. • Early low-dose terlipressin was associated with fewer ischemic adverse events. This study set out to determine whether early use of Terlipressin (TP) as an adjunct to Norepinephrine (NE) could improve clinical outcomes in patients with septic shock. In this prospective, randomized trial, 104 patients with septic shock were assigned to three groups receiving TP at different NE thresholds: Low-dose (L, ≥ 0.25 μg/kg/min), Mid-dose (M, ≥ 0.5 μg/kg/min), and High-dose (H, ≥ 0.75 μg/kg/min). Primary outcomes included 28-day mortality and vasopressor-free days. Secondary outcomes encompassed hemodynamic parameters, organ function recovery, inflammatory markers, and adverse events. No significant difference was observed in 28-day mortality among groups (L: 42.86 %, M: 47.06 %, H: 51.43 %; p = 0.328). However, the L group exhibited significantly more vasopressor-free days (defined as days alive and free of all vasopressor support for ≥ 24 consecutive hours within the first 7-days after randomization; median 4.2, IQR 2.1–5.3) than the M (3.1-days) and H groups (2.3-days; p < 0.01). Key secondary outcomes showed superior hemodynamic stabilization in the L group, with shorter time to target MAP (4.2 vs. 5.6–6.5 h, p < 0.05) and accelerated lactate clearance ( p < 0.01). Organ function recovery was significantly enhanced in the L group, demonstrated by reduced CRRT duration (3.5 vs. 6.8–7.5 days, p < 0.001), improved renal and hepatic function, higher platelet counts (215 vs. 130–165 × 10⁹/L, p < 0.001), and more rapid inflammatory resolution (Procalcitonin and CRP reduction, all p < 0.05). Adverse events were significantly lower in the L group ( p < 0.001). Early low-dose TP adjunctive therapy reduces NE dependence, enhances hemodynamic stability, promotes multi-organ function recovery, and improves safety profile in septic shock, without significantly affecting 28-day mortality. These findings support its role as a beneficial adjunct vasopressor when initiated at lower NE doses.