The Role Of Reducing Pulmonary Vascular Resistance In The Treatment And Fluid Therapy Of Sepsis Shock

In Existing medical setting,Mortality from sepsis and septic shock remains high.Fluid overload in septic intensive care unit patients is common and strongly associated with poor outcome.there is an urgent need for finding new therapeutic regimens and fluid strategy.Objectives: To explore if decreasing pulmonary vascular resistance by Treprostinil in sepsis shock would improve hemodynamics,short‐term survival and fluid therapy.Methods: The animals were randomly assigned into two parts(4different groups,n=6): the first part consisted of Group 1(LPS control group)and Group 2(Treprostinil treatment group),and the fluid of this part was to maintain adequate physiological needs.The second part consisted of Group 3(Fluid therapy group)and Group 4(Treprostinil and Fluid combined treatment group),and the animals of this part received a SVdirected fluid therapy except for maintenance fluids.Treprostinil intravenous infusion was 80 ng/kg/min.The primary outcomes were cardiac output and short‐term survival。Measurements and main results: Primary outcomes were cardiac performance and short‐term survival.Secondary outcomes were mean urine volume,fluid balance volume,and dose of norepinephrine administrated.during the LPS infusion,all animals established a sharp increase in pulmonary artery pressure and pulmonary vascular resistance,accompanying a significant decrease in stroke volume and ejection fraction of the right heart.Compared with the control group,the treprostinil treatment group showed significantly reduced pulmonary vascular resistance(T4.5-T9.5,p<0.05,Wilcoxon’s rank-sum test)and increased cardiac output(T5-T9,p<0.05,Wilcoxon’s rank-sum test),right ventricular stroke volume(T6-T7.5,p<0.05,Wilcoxon’s rank-sum test),right ventricular ejection fraction(T6.5-T8,p<0.05,Wilcoxon’s rank-sum test),and short term survival(median survival time: 9 h vs.10 h;Log rank test,p<0.05),and mean urine volume(1.6 ml/kg/h vs.3.8 ml/kg/h,p<0.05,ttest).Compared with the fluid resuscitation group,the treprostinil treatment plus fluid resuscitation group had significantly reduced pulmonary vascular resistance(T6.5-T10,p<0.05,Wilcoxon’s rank-sum test),increased cardiac output(T7-T10,p<0.05,Wilcoxon’s rank-sum test)right ventricular stroke volume(T8-T10,p<0.05,Wilcoxon’s rank-sum test),right ventricular ejection fraction(T6.5-T10,p<0.05)and decreased fluid balance volume(10.88 ml/kg/h vs.7.19 ml/kg/h,p<0.05,t-test),but no statistically significant difference in norepinephrine consumption.Conclusions: Our study shows that the high-resistance pulmonary circulation in sepsis becomes a "barrier" that impedes the blood flow from the right side to the left side of the heart.The "barrier" effect is likely one of the most important contributors to lower cardiac output in sepsis.Weakening the "barrier" can increase the fluid responsiveness in septic shock and more efficiently convert intravenous infusion into cardiac output,thereby improving the circulation and outcomes in sepsis.