Effects Of Dexmedetomidine On Pulmonary Function And Inflammatory Response During Perioperative Period In The Patients Undergoing Radical Esophagectomy

Background and ObjectiveEsophageal cancer is one of the most common digestive tract malignant tumor in our country, and the incidence is highest in henan province in our country.Patients with esophageal cancer often have many problems,such as,elderly, the preoperative malnutrition and metabolic disorders, more complications,more vital reduced organ function and so on. One-lung ventilation anesthesia in esophageal cancer, mechanical ventilation for a long time,and due to the position of special surgery can cause decline in lung function and inflammatory factors in patients with a large number of release, which can damage the lungs and heart and other important organs and affect surgical outcome.Today, single lung ventilation anesthetic techniques are used in radical resection of esophagus diffusely. Single lung ventilation is a especial type of anesthesia, main stipulated in the chest procedures. Its purpose is to achieve the isolation both of lungs and perfect the thoracotomy conditions meaningly. It also can offer a fine environment for the surgeon chest surgery.Now the single lung ventilation is widely applied in radical resection of esophagus.But the single lung ventilation also has its drawbacks. Malignant expansion of lung may bring about the increased pulmonary capillary pressure, which may result in the failure of blood gas barrier. The number of white blood cells and inflammatory mediators will recuite in the lung tissue,which may result in the lung injury.The blood perfusion of collapse lung was lessened gradually. Oxygen is in short supply will bring damage to the lung epithelial cells and pulmonary vascular endothelial cells, which can contribute to lung tissue inflammation of the cascade. Pulmonary ischemia/reperfusion injury,which can lead to the inflammation, was caused by the collapse lung followed by the re-expansion. The lost endothelial integrity and the falled lung compliance would make the pulmonary oedema formation become worse.Some serious patients may result in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which is fetal for them.Lung injury is a complex process,which was caused by the one-lung ventilation. The inflammatory cytokines plays an important role in this process. Inflammatory factor levels have a intimately relationship with the prediction of the postoperative complications and mortality. To discover an effective method can avoid the release of cytokines in the patients who underwent the radical esocophagectomy, which is meaningful for the rehabilitation of patients.TNF-a, as one of the most influential inflammatory mediators in the early inflammatory response, plays an significant part in the process of lung injury which induced by the single-lung ventilation. Many kinds of early inflammatory responses wrere also involved in the special process.The inflammatory cascade can be triggered by a mass of TNF-a,at the same time, a large number of inflammatory cytokines are released in this special process. Therefore, TNF-a is one of the most influential pro-inflammatory cytokines in the pathogenesis of ALI.SP-D is one of the specific pulmonary surfactant protein, its level can reflect the occurrence of SP-D lung epithelial cells and the cell permeability. Jujita etc with bleomycin copy of acute lung injury model found on the7th day of injection of bleomycin to28days, SP-D increases in plasma. PA-aO2and RI are reflect the index of pulmonary diffusion function, which can accurately reflect the degree of lung injury, its level and the degree of lung injury was positively associated. Cd is indicator of the elasticity of the lung tissue, lung surface active substance inactivation or missing, atelectasis, bronchospasm, secretion obstruction, pulmonary edema, etc all can affect the Cd. When esophageal thoracotomy lung injury, the perioperative period in patients with Cd monitoring value is also very has the reference value of clinical significance.Dexmedetomidine, as a highly selective α2adrenoceptor agonist,which acts as sympatholysis,sedation, anxiolysis, stable hemodynamic sympatholytic. Beyond that,, The inflammatory research of dexmedetomidine is principally centered in animal experiments. Some people found that the level of inflammatory cytokines in the animals receiving preconditioning dexmedetomidine1hour before the operation was meaningfully attenuated. They demonstrated that by down-regulating pro-inflammatory mediators sympatholytics would be a meanful adjunct sedative in patients with a high risk for developing sepsis.Some other people demonstrated that dexmedetomidine could decrease plama cytokines in the patients who underwent the hysterectomy.But, the clinical research is rarely among the patients who underwent the radical esophagectomy with ong-lung ventilation.This topic study was to observe the effects of dexmedetomidine on pulmonary function and inflammatory response during perioperative period in the patients who underwent the radical esophagectomy.We want to know whether dexmedetomidine can suppress inflammatory cytokines,so as to guide clinical practices.Materials and MethodsSixty ASA Ⅰ or Ⅱ patients aged51-69yr having a body weight index of18～25kg/m2scheduled for radical esophagectomy were randomly divided into3groups (20in each):control group (group C), low dose dexmedetomidine group (group D1) and high dose dexmedetomidine group (group D2). Same standard anesthesia protocol were used for induction and maintainence in all3groups. After induction, dexmedetomidine was infused at rate of0.3μg·kg-1·hr-1(group D1) and0.5μg·kg-1·hr-1(group D2) until30min before the end of operation. Group C received the equal volume of normal saline.Upon arrival at the operating room,patients were premedicated with intravenous penehyclidine0.01mg/kg.All the patients received an arterial catheter for continuous arterial blood pressure with1%lidocaine. Anesthesia was induced by midazolam0.05mg/kg, fentanyl4～5μg/kg, etomidate0.2～0.3mg/kg, Cis atracurium 0.1-0.15mg/kg. Anesthesia was maintained by continuous infusions of propofol at3～8mg/(kg·h) and remifentanil at0.10～0.20pμg/(kg·min). Cis atracurium was administered as0.05mg/kg intravenously to maintain muscular relaxation.The trachea and the left bronchus were intubated with a left double-lumen tube of Robertshaw. Correct DLT position was corroborated using fiber optic bronchoscopy. Then contact the DLT to Drager Fabius2000anesthesia machine to control breathing. Initial ventilation settings were adjusted to achieve a tidal volume of6～8ml/kg,a respiratory rate of15～18b.p.m.,an inspiratory:expiratory1:2.0, the oxygen flow rate2L/min. The correct position of the DLT was confirmed bronchoscopically again after positioning the patient in lateral position. When the one-lung ventilation was beginning, we shoud adjust the respiratory parameters:Set tidal volume (VT) for5～7ml/kg, respiratory rate for14～18times/min.During surgery, oxygen saturation (SpO2) was maintained95%～100%, end-tidle CO2gas tension (PETCO2) was maintained35-45mmHg,and the bispectral EEG analysis index (BIS) was maintained45～65.In three groups,Arterial blood samples were collected for blood gas analysis before induction of anesthesia (T0), before OLV (T1), at the end of OLV (T2), when the chest was closed (T3) and at24h after operation (T4). P(A-a)O2and respiratory index (RI) were calculated. Plasma TNF-a and SP-D were measured at To, T3and T4. Dynamic lung compliance(Cd) was calculated at T1～3. Artery blood was collected in the sterile plain tube.Samples were centrifuged at4000rpm for15min at4℃. Plasma was collected and stored frozen at-80℃until assaying. TNF-a and SP-D were measured in ELISA.We should observe and record perioperative hemodynamic and respiratory parameters changes.Statistical analysis was carried out by using the SPSS17.0for windows.All quantitative variables were expressed as mean±standard deviation. One-way analysis of variance was used to test the difference among groups. Repeated measurement analysis of variance was used to test the difference for continuous variables within groups,followed by LSD posttest.Qualitative variables were analysed withχ2test or Fisher’s exact probabities.P values<0.05where considered statically significant. Results1. There were no significant differences among the three groups in gender ratio, age, weight and BMI(P>0.05).2. No significant differences were noted with regard to duration of operation, one-lung ventilation time, infusion volume, urine output and blood loss(P>0.05).3. No significant differences were found in SBP,DBP,HR within groups and among the three groups in the five time points(P>0.05).4. The levels of Tumor necrosis factor-a and Surfactant Protein D HumanCompared within groups:Compared with To, plasma TNF-a and SP-D was increased critically at T3and T4, and the difference was statistical significance(P<0.05).Compared among groups:Plasma TNF-a and SP-D were not statistically significant among the three groups at To (P>0.05).Howere, Plasma TNF-aand SP-D in D2were lower than that of C at T3and T4,and the difference was significant(P<0.05). There was no difference between D1and D2at T3and T4(P>0.05).5. The comparisons of the three groups of patients with respiratory mechanics index of each time pointCompared within groups:Compared with T1, there were no difference in D1and D2at T2andT3(P>0.05).Compared with T1,the respiratory mechanics index was increased critically in C at T3, and the difference was statistical significance(P<0.05).Compared among groups:The respiratory mechanics index were not statistically significant among the three groups (P>0.05).6. The comparisons of three groups of patients with arterial blood gas analysis indicators at each time pointCompared within groups:Compared with To, the index of arterial blood gas analysis indicators were increased critically at T1、T2and T3, and the difference was statistical significance (P<0.05). Compared among groups:Compared with C, the index of arterial blood gas analysis indicators were not statistically significant in D1at T0、T1、T2and T3(P>0.05).Howere, the index of arterial blood gas analysis indicators in D2were higher than that of C at T2and T3,and the difference was significant(P<0.05). There was no difference between D1and D2at T0、T1、T2and T3(P>0.05).7. The number of the people who was injected with aphedrine was no significant difference among the the three groups(P>0.05).And so was the number of the people who was injected with atropine(P>0.05).Conclusions1. The plasma TNF-α and SP-D are increased in the patients undergoing radical esophagectomy with one-lung ventilation.2. Dexmedetomidine can prohibit inflammatory response of patients undergoing radical esophagectomy in dose-dependent.