Dose-related effects of norepinephrine on early-stage endotoxemic shock in a swine model  

作　　者：Hui Xiang Yuqian Zhao Siqing Ma Qi Li Kianoush B.Kashani Zhiyong Peng Jianguo Li Bo Hu 

机构地区：[1]Department of Critical Care Medicine,Zhongnan Hospital of Wuhan University,Wuhan 430071,Hubei,China [2]Clinical Research Center of Hubei Critical Care Medicine,Wuhan 430071,Hubei,China [3]Department of Critical Care Medicine,Qinghai Provincial People's Hospital,Xining 810007,Qinghai,China [4]Division of Pulmonary and Critical Care Medicine,Department of Medicine,Mayo Clinic,Rochester,MN,USA [5]Division of Nephrology and Hypertension,Department of Medicine,Mayo Clinic,Rochester,MN,USA

出　　处：《Journal of Intensive Medicine》2023年第4期335-344,共10页重症医学（英文）

基　　金：funded by the National Natural Science Foundation of China (Z.P.81560131);Subject Cultivation Project of Zhongnan Hospital of Wuhan University (Bo Hu,No.ZNXKPY2021002);Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University (Bo Hu,No.ZNJC202011);Qinghai Province Key R&D and Transformation Projects (S.M.2019-SF-132).

摘　　要：Background The benefits of early use of norepinephrine in endotoxemic shock remain unknown.We aimed to elucidate the effects of different doses of norepinephrine in early-stage endotoxemic shock using a clinically relevant large animal model.Methods Vasodilatory shock was induced by endotoxin bolus in 30 Bama suckling pigs.Treatment included fluid resuscitation and administration of different doses of norepinephrine,to induce return to baseline mean arterial pressure(MAP).Fluid management,hemodynamic,microcirculation,inflammation,and organ function variables were monitored.All animals were supported for 6 h after endotoxemic shock.Results Infused fluid volume decreased with increasing norepinephrine dose.Return to baseline MAP was achieved more frequently with doses of 0.8µg/kg/min and 1.6µg/kg/min(P<0.01).At the end of the shock resuscitation period,cardiac index was higher in pigs treated with 0.8µg/kg/min norepinephrine(P<0.01),while systemic vascular resistance was higher in those receiving 0.4µg/kg/min(P<0.01).Extravascular lung water level and degree of organ edema were higher in animals administered no or 0.2µg/kg/min norepinephrine(P<0.01),while the percentage of perfused small vessel density(PSVD)was higher in those receiving 0.8µg/kg/min(P<0.05)and serum lactate was higher in the groups administered no and 1.6µg/kg/min norepinephrine(P<0.01).Conclusions The impact of norepinephrine on the macro-and micro-circulation in early-stage endotoxemic shock is dose-dependent,with very low and very high doses resulting in detrimental effects.Only an appropriate norepinephrine dose was associated with improved tissue perfusion and organ function.

关 键 词：NOREPINEPHRINE Fluid resuscitation Endotoxemic shock MICROCIRCULATION Side stream dark-field PIGS 

分 类 号：R691[医药卫生—泌尿科学]