Effects And Mechanisms Of Different Doses Of Doxofylline On Pulmonary Protection Undergoing Esophagus Cancer Surgery

Objective:To compare with influences of doxofylline with different doses on curing inflammatory factors in perioperative period,oxidative stress,pulmonary ventilation function and postoperative lung complication for patients with radical surgery for esophageal carcinoma,discuss the lung protection effect and possible mechanism of doxofylline on curing patients with radical surgery for esophageal carcinoma,analyze the dose-effect relationship and provide clinical reference for rational utilization of doxofylline.Methods:80 patients who were treated with radical surgery for esophageal carcinoma in the middle and lower segment of the left chest under the general anesthesia were selected in this study,without limitation in gender,showing 45-70 years old,ASA I-II,BMI 20-30kg/m²,and FEV₁>50%.The double blind experiment was used to divide patients into four groups as the random number table:low-dose doxofylline group?doxofylline 1mg/kg,LD group?,middle-dose doxofylline group?doxofylline4mg/kg,MD group?,high-dose doxofylline group?doxofylline 8mg/kg,HD group?and control group?equivalent normal saline,C group?,including 20 patients in each group.After patients in four groups were induced by the conventional intravenous anesthesia,mechanical ventilation was conducted in the right double-lumen endotracheal intubation.The fiber bronchoscope was used for positioning.Before one-lung ventilation?OLV?,patients in each group were injected with 1mg/kg,4mg/kg,8mg/kg of doxofylline and equivalent normal saline as the above-mentioned doses within 30min.Before 10min?T0?of OLV,after 60min of OLV?T₁?,before two-lung ventilation?T₂?and before the end of operation?T₃?,the blood samples of radial artery were collected to detect serum TNF-?,IL-6,IL-10,MDA and SOD.The blood gas analysis was detected at each time point.Alveolar-arterial oxygen pressure difference P?A-a?O₂ and respiratory index?RI?were calculated.Ppeak,Pplat,Raw and Compl at T₀-T₃ time points were recorded.OLV time,blood loss,fluid infusion volumes,urine outputs,postoperative hyoxemia and lung inflammation were recorded during the operation.Results:1.There was no significant difference in the general condition of the four groups before operation?P>0.05?.No significant difference were observed in OLV time,blood loss,fluid infusion volumes and urine outputs during the operation?P>0.05?.)2.Comparison of the inflammatory factors and oxidative stress indexes at T₀-T₃ time points for patients in four groups1)Intra-class comparison:Compared with T₀ time point,the levels of plasma IL-6?TNF-??MDA and IL-10 were increased,while SOD was decreased at T₁-T₃ time points in four groups?P<0.05?.2)Comparison among groups:the levels of plasma IL-6,IL-10,TNF-?,MDA and SOD at T₀ time point for patients in four groups had no statistical difference?P>0.05?.the levels of plasma IL-6,IL-10,TNF-?,MDA and SOD at T₁-T₃ time points in C group and LD group had no statistical difference?P>0.05?.Compared with C group at T₁-T₃time points in MD group and HD group,the levels of plasma IL-6,TNF-?,MDA were decreased,while SOD and IL-10 were increased?P>0.05?.3.Comparison on PaO₂?pulmonary alveoli-arterial oxygen partial pressure and respiratory index for patients in four groups1)Intra-class comparison:Compared with T₀ time point,the levels of PaO₂ was decreased,while pulmonary alveoli-arterial oxygen partial pressure and respiratory index was increased at T₁-T₂ in four groups?P<0.05?.2)Comparison among groups:The lever of PaO₂?pulmonary alveoli-arterial oxygen partial pressure and respiratory index at T₀ time point for patients in four groups had no statistical difference?P>0.05?.By making a comparison between LD group and C group,PaO₂?pulmonary alveoli-arterial oxygen partial pressure and respiratory index at T₁-T₃time points had no statistical significance?P>0.05?.By comparing with C group at T₁-T₃time points in MD group and HD group,the levels of pulmonary alveoli-arterial oxygen partial pressure and respiratory index were decreased,while PaO₂ was increased?P<0.05?.4.Comparison on respiratory mechanics parameters at T₀-T₃ time points for patients in four groups1)Intra-class comparison:Compared with T₀ time point,Ppeak,Pplat,Raw were increased,while Compl was decreased at T₁-T₂ time points for patients in four groups?P<0.05?.2)Comparison among groups:Ppeak,Pplat,Raw and Compl at T₀ time point for patients in four groups had no statistical difference?P>0.05?.By making a comparison between LD group and C group,Ppeak,Pplat,Raw and Compl at T₁-T₃ time points had no statistical significance?P>0.05?.By comparing with C group at T₁-T₃ time points in MD group and HD group,Ppeak,Pplat,Raw were decreased,while Compl was increased?P<0.05?.5.Compared with C group,occurrence of postoperative hyoxemia and lung infection showed by radiography within 2 days were lower than MD group and HD group?P<0.05?.There was no statistical significance between LD group and C group?P>0.05?.Conclusions:Oxygenation of lung tissue were improved and postoperative pulmonary complications were reduced in patients underwent esophagus cancer surgery,duing to administration of doxofylline with dose of 4mg/kg and 8mg/kg after induction of anesthesia.The mechanism might be related to effect of doxofylline in expanding bronchus,improving ventilation,alleviating inflammation oxidative stress.