Early initiation of norepinephrine in patients with septic shock: A propensity score-based analysis.

BACKGROUND: The use of vasopressors is vital in septic shock. However, the optimal timing of treatment remains unclear. Therefore, we aimed to explore the impact of early norepinephrine initiation on the survival of patients with septic shock. METHODS: We selected 4253 patients from the Medical Information Mart for Intensive Care IV database between 2008 and 2019. The primary outcome was 28-day mortality. Propensity score matching (PSM) was applied to minimize between-group imbalances, and a restricted mean survival time was used to quantify the beneficial impact of early norepinephrine treatment on survival. Sensitivity analyses were conducted to test the robustness of the study results in multiple cohorts. RESULTS: In the PSM cohort, 2862 patients were equally assigned to early (receiving norepinephrine within the first 3 h) and delayed (> 3 h) norepinephrine initiation groups. Patients in the early norepinephrine initiation group received significantly less fluid therapy (0 vs. 79 mL/kg), had lower 28-day mortality (30.0% vs. 37.8%), longer survival days (21.89 vs. 20.37 days), shorter duration of intensive care unit (4.9 vs. 7.2 days) and hospital stays (12.4 vs. 13.6 days), shorter duration of supportive norepinephrine and invasive mechanical ventilation, lower incidence of organ failure progression (64.4% vs. 79.2%) within 24 h after shock onset, and higher mean arterial pressure within 6 and 24 h after shock onset than patients in the delayed norepinephrine initiation group (p < 0.05). CONCLUSIONS: Norepinephrine initiation within the first 3 h, regardless of preload dependency, was associated with longer survival time and shorter duration of supportive norepinephrine and invasive mechanical ventilation and may delay or partially reverse rapid onset organ failure.

[An investigation of the protective effect of prostaglandin E1 liposome on acute lung injury in pig].

OBJECTIVE: To assess the protective effect of prostaglandin E1 liposome (lipo-PGE1) on acute lung injury (ALI) in a porcine model of ALI. METHODS: The ALI model was reproduced by lipopolysaccharide (LPS) intravenous instillation and high tidal volume ventilation. A total of 16 domestic pigs were randomized to receive lipo-PGE1 (n=8) or placebo (n=8). Parameters of haemodynamics and pulmonary gas exchange were monitored through pulmonary artery catheter and blood gas analysis at baseline and 2, 3, 4 and 5 hours after LPS instillation. The inflation quasi-static pressure-volume (P-V) curve was obtained by ventilator occlusion technique, and the P-V data sets were fit with sigmoidal equation in order to define and compare the respiratory mechanics in animals of two groups. Plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: There was a decrease in cardiac index (CI) and mean arterial pressure (MAP) in control group compared with those in the group who received lipo-PGE1. In the group receiving lipo-PGE1 the parameter of oxygenation, including partial pressure of oxygen in arterial blood (PaO(2)), oxygenation index (PaO(2)/FiO(2)), and alveolar-arterial oxygen difference (A-aDO(2)) were significantly improved (all P<0.05) and pulmonary shunt (Qs/Qt) associated with lung injury was also significantly reduced (P<0.05) compared with control group. The respiratory mechanics (including lower and upper inflection point) in the group given lipo-PGE1 were better than those of control group (all P<0.05). Plasma levels of TNF-alpha and IL-8 were found to rise in both groups, but the rise in TNF-alpha and IL-8 in the group in which lipo-PGE1 was given were lower with shorter period compared with control group(all P<0.05). CONCLUSION: Intravenous delivery of lipo-PGE1 significantly attenuate ALI caused by LPS instillation and high tidal ventilation, and it also shows beneficial effects on haemodynamics.