Combined Inhalation Of Isoflurane And Hyperoxia Was Beneficial To Sepsis

Sepsis is the systemic inflammatory response syndrome caused by infection, which is themain cause of death in surgical ICU. Today, there is one patient died of sepsis worldwideevery a few seconds. In the past decade, sepsis has been increased by an annual rate ofbetween8-13%. The pathogenesis of sepsis is multifaceted, and its main characteristicmanifestations are abnormal immuno-inflammatory response and coagulation dysfunction.Despite the advances in understanding the pathophysiology of sepsis, therapy for septicpatients remains largely goal-directed and supportive. Although there are some strategiesto be used in clinical researches, but48.7%of the mortality of sepsis still reminds us tolook for more effective treatment strategies. Oxygen, resource-rich, easy to use, iscurrently adjunct treatment widely used in clinical settings. Studies have proved that areasonable100%oxygen inhalation can effectively improve organ function, and reducemortality of septic animals. Isoflurane is the most recently available inhalational anestheticagent on the market today. Less than1%isoflurane (0.5minimum alveolar concentration (MAC) may be used in ICU patients for facilitating mechanical ventilation and sedation.Here, we observed that combined inhalation of0.5MAC isoflurane and hyperoxia wasbeneficial to sepsis.Materials and Methods1. Male ICR/Km mice (20-25g)/C57male mice (20-25g), were randomly divided into14groups: LPS+Air, LPS+40%Oxy, LPS+60%Oxy, LPS+80%Oxy, LPS+100%Oxy,LPS+0.5MAC ISO+Air, LPS+0.5MAC ISO+40%Oxy, LPS+0.5MAC ISO+60%Oxy,LPS+0.5MAC ISO+80%Oxy, LPS+0.5MAC ISO+100%Oxy, NS+Air, NS+100%Oxy,NS+0.5MAC ISO+Air, NS+0.5MAC ISO+100%Oxy. Sepsis was induced byintraperitoneal injection with50mg/kg lipopolysaccharide (LPS) in ICR/Km mice or30mg/kg in C57mice, the same volume of nomal saline (NS) was injected as the control. At1,6hours after intraperitoneal injection of LPS/NS, animal was given one hour ofinhalation therapy with air or oxygen or isoflurane or combined use of oxygen andisoflurane, respactively. The survival was consecutively recorded for7days after LPS/NSinjection.2. Male SD rats (250-300g), were randomly divided into six groups: Sham+Air,Sham+100%Oxy, Sham+0.5MAC ISO+60%Oxy; CLP+Air, CLP+100%Oxy,CLP+0.5MAC ISO+60%Oxy groups. The cecal ligation and puncture (CLP) inducedmodels of moderate and severe sepsis were made depending on the ligation proportion ofthe cecum from baseline to the end of the cecum (Moderate sepsis model,50%of cecumwas ligated; Severe sepsis model,75%of cecum was ligated). At1,6hours afterCLP/Sham procedures, inhalation therapy with air or100%oxygen or0.5MAC isofluranein60%oxygen for1hour, respectively. The survival was recorded for7days afterCLP/Sham. The tissue injury indexs (The tissue pathology of lung and liver; serumbiochemical parameters (ALT, AST, Cr, BUN, cTnI); arterial blood gas analysis; lungtissue protein leakage; lung tissue wet to dry weight ratio), the systemic inflammatorycytokines in serum and bacteria colonies in peritoneal lavage fluid were detected at24h after CLP/Sham.Result1. Combined inhalation of isoflurane and hyperoxia improved the survival rate ofanimals with LPS-induced sepsis. With LPS stimulation, the7-day survival rate ofICR/Km mice was10%(P <0.05vs. that of NS+Air group), the7-day survival rate ofC57mice was15%(P <0.05vs. that of NS+Air group), which was reversed by inhalationof0.5MAC isoflurane in60%-100%oxygen (P <0.05vs. that of LPS+Air group).2. Inhalation of100%oxygen or0.5MAC isoflurane in60%oxygen protected againstCLP-induced sepsis in SD rats. With the CLP challenge, the7-day survival rate wasreduced to40%and zero (P <0.05vs. that of Sham+Air group), which were reversed byinhalation of100%oxygen or0.5MAC isoflurane in60%oxygen (P <0.05). In animalswith CLP challenge, lung and liver tissue had significant pathology injury, abnormalserum biochemical indicators, inadequate tissue oxygenation, lung tissue protein leakage,abnormal ratio of wet to dry, abnormally changed inflammatory cytokines, as well asincreased bacteria colonies in peritoneal lavage fluid (P <0.05vs. that of Sham+Airgroup), which were reversed by inhalation of100%oxygen or0.5MAC isoflurane in60%oxygen (P <0.05vs. that of CLP+Air group).ConclusionInhalation of0.5MAC isoflurane in60%oxygen protected against sepsis.