Effects Of Dexmedetomidine On The Concentration Of Tnf-αand Il-6in The Patients Undergoing Radical Esophagectomy With One-lung Ventilation

Background and ObjectiveIn our country esophageal neoplasm is one of the most common malignant tumors. Most of the patients with esophageal neoplasm are middle-aged or old people. The number of the male patients is more than that of the female.Its death rate is also high.Esophageal cancer surgery is still the most suitable procedure at present.Nowadays,one-lung ventilation anesthesia technique is widely used during radical esophagectomy.One-lung ventilation is a special type of anesthesia, mainly mandated in thoracic procedures. Its purpose is to achieve isolation of both lungs and improve the thoracotomy conditions significantly. It can offer a favorable environment for the surgeon carry out chest surgery.At present,one-lung ventilation is widely used in radical esophagectomy.Howerer,one-lung ventilation has its disadvantages.Hyperinflation of the dependent lung may lead to increased pulmonary capillary pressure,which may contribute to the failure of the blood-gas-barrier. That a number of leukocyte and inflammatory mediators will recruite in the lung tissue can induce pulmonary injury. As the time goes on, The blood perfusion of collapse lung was decreased.The inadequate oxygen supply will bring damage to the pulmonary vascular endothelial cells and lung epithelial cells, which can contribute to the inflammatory cascade in the lung tissue.The collapse lung followed by re-expansion will bring pulmonary ischaemia/reperfusion injury which can result in inflammatory response. Pulmonary surfactant is secreted decreasingly. The poor lung compliance and lost endothelial integrity may exacerbate pulmonary oedema formation.Some patients may develop acute lung injury (ALI), and even acute respiratory distress syndrome (ARDS) which highly affect patient’s lives.Lung injury induced by one-lung ventilation is a complex procedure in which inflammatory cytokines play a vital role.Levels of inflammatory cytokines are closely related to the prediction of postoperative complication and mortality. It is significant for us to find a way to inhibit the release of cytokines in the patients undergoing radical esocophagectomy with one-lung ventilation,which is conducive to the rehabilitation of patients.TNF-a is one of the most influential inflammatory mediators in the early inflammatory response, and plays an significant role in the process of lung injury induced by one-lung ventilation. It is also involved in a variety of early inflammatory responses.High levels of TNF-a can trigger inflammatory cascade, in which a large number of inflammatory cytokines are released. In all, TNF-a is one of the most important pro-inflammatory cytokines in the pathogenesis of ALI.IL-6is secreted by activated macrophages, endothelial cells, fibroblasts and smooth muscle cells. In the process of acute inflammatory response, IL-6promote Leukocyte proliferation and activation. The level of IL-6in plasma was associated with postoperative the severity of stimulus.It has highly specificity and sensitivity, and plays an irreplaceable role in inflammation induced by one-lung ventilation.Dexmedetomidine is a highly selective a2adrenoceptor agonist. It acts as sedation,sympatholysis,anxiolysis,sympatholytic,stable hemodynamic.What is more, It has limited effects on respiratory function.However, dexmedetomidine in inflammatory research is mainly centered in animal experiments. Some people demonstrated that the level of inflammatory cytokines in the animals receiving preconditioning dexmedetomidine1hour before the operation was significantly attenuated. They found that by down-regulating pro-inflammatory mediators sympatholytics may be a useful adjunct sedative in patients with a high risk for developing sepsis.Mang Ligang found that dexmedetomidine could reduce plama cytokines in the patients undergoing hysterectomy.However, the clinical research is seldom among the patients undergoing radical esophagectomy with ong-lung ventilation.This topic study was to observe the changes of plasma concentration of TNF-αand IL-6in patients undergoing radical esophagectomy with one-lung ventilation. We want to know whether dexmedetomidine can suppress inflammatory cytokines,so as to guide clinical practices.Materials and MethodsSixty patients undergoing open radical esophagectomy (ASA Ⅱ)were enrolled in this study. They were randomly divided into three groups: preprocessing guoup group D1, continuous infusions group D2and control group (group C), of20patients each. The patients of D1were injected with dexmedetomidine intravenously at0.6μg/kg20min before induction of anesthesia; The patients of D2were injected with dexmedetomidine intravenously at0.3μg/(kg·h) after induction of anesthesia and it didn’t stop until30min before the end of the surgery; The patients of C were the control group.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 atracurium0.1～0.15mg/kg, induction of anesthesia. Anesthesia was maintained by continuous infusions of propofol at3～8mg/(kg·h) and remifentanil at0.10～0.20μg/(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 of8-9ml/kg,a respiratory rate of10～12b.p.m.,an inspiratory:expiratory1:2, 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 maintained30～40mmHg, and the bispectral EEG analysis index (BIS) was maintained45～65.In three groups,Blood samples were taken5ml at5time points20min before anesthesia induction (To),10min after tracheal intubation (T1),30min after one-lung ventilation(T2),90min after one-lung ventilation (T3) and10min after resuming two-lung ventilation(T4) from the radial artery. 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 IL-6were measured in ELISA.We should observe and record perioperative hemodynamic and respiratory parameters changes.Statistical analysis was carried out using SPSS17.0for windows.All quantitative variables were expressed as mean±standard deviation. One-way analysis of variance was used to test the difference between 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 plasma cytokines4.1Tumor necrosis factor-aCompared within groups: Compared with To, there were no difference in the three groups at T1andT2(P>0.05). Compared with To, plasma TNF-a was increased critically at T3and T4, and the difference was statistical significance(P<0.05).Compared among groups:Plasma TNF-a were not statistically significant among the three groups at To,T1and T2(P>0.05).Howere, Plasma TNF-a in D1and 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).4.2Interleukin-6:Compared within groups:Compared with To,there was no difference at T1,T2and T3in the three groups(P>0.05). Plasma IL-6was higher at T4than that of To,and there was significant difference(P<0.05).Compared among groups:Plasma IL-6were not statistically significant among the three groups at To,T1,T2and T3(P>0.05). Plasma IL-6at T4was lower in GroupD1and Group D2than that of Group C(P<0.05). There was no difference between D1and D2at T4(P>0.05).5. The number of the people who was injected with aphedrine was no significant difference among the the three groups(P>0.05). The number of the people who was injected with atropine was no significant difference among the the three groups(P>0.05).Conclusions1. The plasma TNF-a and IL-6are increased in the patients undergoing radical esophagectomy with one-lung ventilation. 2. A single bolus dose of0.6μg/kg dexmedetomidine before induction of anesthesia could inhibit the production of plasma TNF-a and IL-6in the patients undergoing radical esophagectomy with one-lung ventilation. So does the continuous infusion dose of0.3μg/(kg·h) dexmedetomidine after induction of anesthesia.