Efficacy of using early multimodal vasopressor therapy on survival after septic shock in patients receiving high-dose norepinephrine: a retrospective study based on the MIMIC database

Early multimodal vasopressor therapy was proposed recently to treat septic shock. However, the association between multimodal vasopressor therapy initiation timing and survival was not determined. This study aimed to investigate the association between early multimodal vasopressor therapy and survival in septic shock patients necessitating high dose norepinephrine. We conducted a retrospective single-center study of septic shock patients receiving norepinephrine as the first-line vasopressor at a maximum norepinephrine-equivalent dose >0.2 µg/kg/min. When the second vasopressor was initiated, patients were divided into three groups based on norepinephrine dosage. The primary outcome was 28-day mortality. Secondary endpoints included 90-day mortality, intensive care unit (ICU) and hospital mortality, and length of ICU and hospital stays. This study included 966 patients receiving a maximum norepinephrine-equivalent dose >0.2 µg/kg/min. Among them, 299 received an additional vasopressor when norepinephrine dose ≤0.2 µg/kg/min (early multimodal vasopressor therapy, EMMVT), 511 received an additional vasopressor when norepinephrine dose was between 0.2–0.5 µg/kg/min (later multimodal vasopressor therapy, LMMVT), and 156 received an additional vasopressor when norepinephrine dose ≥0.5 µg/kg/min (delayed multimodal vasopressor therapy, DMMVT). Age, admission type, sequential organ failure assessment (SOFA) score, metastatic cancer, liver diseases and obesity were associated with 28-day mortality. A significantly lower rate of 28-day, 90-day, ICU and hospital mortality was observed in the EMMVT group (p < 0.001 for all). In contrast to EMMVT, LMMVT (hazard ratio: 1.643, p < 0.001) and DMMVT (hazard ratio: 2.192, p < 0.001) were associated with an increased risk of 28-day mortality after adjusting for confounding factors. Multimodal vasopressor groups and SOFA did not interact statistically. Septic shock patients receiving norepinephrine as the first-line vasopressor and reaching a maximum norepinephrine-equivalent dose >0.2 µg/kg/min benefited from early multimodal vasopressor therapy with improved 28-day mortality, regardless of illness severity.

Septic shock; Norepinephrine; Early multimodal vasopressor therapy; Vasopressor

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