The Effect Of Different Doses Of Fluid Resuscitation On Septic Shock In Rats

Objective:Sepsis is a systemic inflammatory response syndrome(SIRS) mediated byinfection factors, and is a hot and difficult issue researched in the critical medical field.The sepsis is insidious onset, rapid progression and have a high mortality rate.Although the diagnosis and treatment of sepsis is promoting in recent years, it is stillthe primary factor in the death of critically ill patients. In order to better grasp themechanism of inflammation response in vivo, the development process, and the basicpathophysiological changes of the sepsis, and put forward the better target therapeuticstrategies, the sepsis and septic shock animal model emerged. Classic cecal ligationand puncture preparation in rats with sepsis model due to poor stability and can notfully meet the needs of animal experiment, through the improvement of the model ismore simple, and have a good repeatability, so as to establish a more stable model,and obtain the reliable data. Early fluid resuscitation is one of the key measures oftreatment of septic shock, about the dose and time of fluid resuscitation, theguidelines only emphasizes the dose of early fluid resuscitation at least30ml/kg,did not explicitly limit the dose of early fluid resuscitation, when get sepsis,the tissue and cell permeability increased, increase the fluid volume have a potentialrisk of tissue edema, fluid accumulation and cardiopulmonary load increase. Thisstudy improved the sepsis model, and application of the modified model for fluidresuscitation with different dose, to explore the improved model and different dose offluid infusion effect on the resuscitation of rats with septic shock and evaluate thesafety.Methods:(1) The improve of cecal ligation and puncture model of sepsis in rats: theexperimental rats were divided into sham-operated group (Sham group), classic cecalligation puncture group (CLP-0group) and improved group (CLP-1group). Collect each groups relevant data after modeling in6h,12h,24h, invasive monitoring of ratheart (HR) and mean arterial blood pressure (MABP), and monitoring of serum tumornecrosis factor-α (TNF-α), interleukin-6(IL-6) and interleukin-10(IL-10) levels;determining the pH, PCO2, Lac in blood gas of the shock rats, and observing thechanges of the organizational structure of lung, liver, kidney and heart, record the timeof death in rats.(2) The effect of different doses of fluid resuscitation on septic shockin rats: divided the improved model rats into3hours experimental group,6hoursexperimental group and the control group. when the rats shock, divided the twoexperimental groups each for three subgroups according to the30ml/kg,45ml/kg,60ml/kg infusion rates. Each experimental group were measured TNF-α, IL-6andIL-10levels after rehydration; observing the changes of the tissue structure of lung,liver, kidney and heart after rehydration; record the time of death in rats.Results:(1) Improved CLP model group in48h mortality was significantly higher thanthe classic model group.(2) Improved CLP model compared with the classic model in heart rate,bloodpressure and shock blood gas analysis did not show significant difference(P＞0.05),compared with the sham group with significant difference(P<0.05).(3) Improved CLP model compared with the sham group in lung, liver, kidneyand heart tissue structure changes sham group, and compared with classic model withno significant difference.(4) Septic shock treated with different doses of fluid resuscitation, comparedwith the control group could reduce early mortality (3d), for long-term mortality (7d)without significantly reduced.(5) There were no significant difference(p>0.05) in each group of TNF-α，IL-6and IL-10when septic shock treated with a dose of fluid resuscitation.(6) Compared the changes of tissue structure of lung, liver, kidney and heart indifferent doses of fluid resuscitation groups, there were no significant difference.Conclusion:(1) Establish the rat model of septic shock by cecal ligation and puncture, after fluid resuscitation can reduce early mortality in rats with septicshock rate, but can not reduce the mortality rate of long-term in rats with septic shock.(2) Given the30ml/kg dose of fluid resuscitation to the rats with septic shock canachieve early recovery target.(3) For septic shock rats to quickly reached early recovery target, the doseof early fluid resuscitation can be adjusted in30ml/kg and60ml/kg, safeand reliable, no obvious pathological tissue swelling,no fluid accumulation andpathologic changes in heart, lung and liver.