Effects Of Inhalation, Intravenous Anesthesia And Continuous Positive Airway Pressure On Oxidative Stress During One-lung Ventilation

One-lung ventilation technique has been routinely applicatied to anesthesia and clinical treatment for many years. Recently, it was found that there was a significant increase of reactive oxygen species (ROS) production immediately after the resumption of two-lung ventilation (TLV) from one-lung ventilation (OLV). It has been well documaented that many postoperative complications such as myocardial dysfunction and lung infection might be associated with oxidative stress. However, the effects of anesthetics on oxidative stress during one-lung ventilation are still not clear. Volatile anesthetics such as isoflurane could reduce the release of ROS during ischemia and reperfusion injury. The antioxidant properties of propofol also has been confirmed by an assay of antioxidant potential. Continuous positive airway pressure (CPAP) can improve the systemic oxygenation and reduce the intrapulmonary shunt and incidence rate hypoxemia during OLV. Howere, it is unknown whether CPAP can decrease oxidative stress during OLV. Superoxide dismutase (SOD) is one of the most important free radical scavenging enzymes, and its activity reflects the body's ability to remove oxygen free radicals. Malondialdehyde (MDA) is the end product of lipid peroxidation. It can directly reflect the level of free radicals, and its content is an important symbol of tissue injury. Nitric oxide (NO) can play a dual biological effect in oxidative reactionthough the adjustment mechanism is unclear.In this study, hemodynamics, oxygenation, SOD, MDA and NO were measured to explore the effects of inhalation/intravenous anesthetics and CPAP with different pressures on oxidative stress during OLV.Part 1 Effects of inhalation or intravenous anesthesia on oxidative stress during one-lung ventilationMethods1. Forty-eight patients (ASAⅠ~Ⅱ,45~68 years of age) scheduled to undergo radical esophagus cancer resection, without significant cardiovascular, liver, kidney and other vital organs diseases. The patients did not receive chemotherapy or take vitamins. The lung function and other laboratory tests were generally normal. The patients were randomized into four groups (n=12): group propofol and OLV (Pro-OLV), group isoflurane and OLV (Iso-OLV), group propofol and TLV (Pro-TLV), group isoflurane and TLV (Iso-TLV).2. After radial artery and vein were cannulated and electrocardiography (ECG), pulse oxygen saturation (SpO2), end-tidal CO2 gas tension (PETCO2), mean arterial pressure (MAP) were monitored. Anesthesia was induced with midazolam (0.05mg/kg), propofol (1~2mg/kg), fentanyl (2μg/kg) and vecuronium (0.1mg/kg). After that, a left double-lumen endobronchial tube was placed in all patients. The position of the tube was adjusted by fiberoptic bronchoscope before and after patients turned to the lateral decubitus position. Ventilation was mechanically controlled by Drager anesthesia machine. It was performed with the following settings: tidal volume (VT)=8~10ml/kg, fraction of inspired O2 (FiO2)=1.0, respiratory rate (RR)=12~16per minute, finely adjusted to maintain PETCO2=35~45mmHg and I:E=1:2.3. In the propofol groups, propofol infusion was maintained at a rate of 4~8mg·kg-1·h-1 throughout the operation. In the isoflurane groups, isoflurane was inhaled continuously to maintain end-tidal concentration between 1.5% and 2.5%. Remifentanil infusion was maintained at a rate of 0.1~0.2μg·kg-1·min-1 in all groups. Incremental doses of vecuronium were given for sufficient muscle relaxation.4. Blood samples were drawn at designated time points, i.e. after induction of anesthesia with hemodynamic stabilization in the decubitus position and before OLV (T0) as a baseline reference, at 30min (T1), 90min (T2), 150 min (T3) after OLV and at the end of operation (T4) for measurement of SOD, MDA and NO. HR, SpO2, PETCO2 and MAP were recorded at the same time.Results1. SOD was significantly decreased and MDA, NO were significantly increased (P<0.01) during operation (from T1 to T4) as compared to baseline values (T0) in both OLV groups, but there were no significant difference in both TLV groups (P>0.05).2. SOD was significantly decreased and MDA, NO were significantly increased (P<0.01) from the time T1 to T4 in both OLV groups compared with that in both TLV groups.3. There were no significant difference between Pro groups and Iso groups on the same time points (P>0.05).Part 2 Effects of continuous positive airway pressure on oxidative stress during ong-lung ventilationMethods1. Forty-eight patients undergoing radical esophagus cancer resection were randomly divided into four groups (n=12): group TLV, group OLV, group 2cmH2O CPAP, group 5cmH2O CPAP.2. The conditions of patients, indicators for monitoring, anesthesia induction, the left double-lumen endobronchial tube and respiratory parameters were the same as part 1.3. 2cmH2O and 5cmH2O CPAP were administered to the non-ventilated lung during OLV in group 2cmH2O CPAP and group 5cmH2O CPAP, but the non-ventilated lung was kept open to the air during OLV in group OLV.4. Propofol infusion was maintained at a rate of 4~8mg·kg-1·h-1, and remifentanil infusion was maintained at a rate of 0.1~0.2μg·kg-1·min-1 during the operation. Incremental doses of vecuronium were given for sufficient muscle relaxation.5. Venous blood samples were drawn at designated time points, i.e. after induction of anesthesia with hemodynamic stabilization in the decubitus position and before OLV (T0) as a baseline reference, at 30min (T1), 90min (T2), 150min (T3) after OLV and at the end of operation (T4) for measurement of SOD, MDA and NO. Arterial blood gas analysis was performed and HR, SpO2, PETCO2 , MAP were recorded at the same time.Results1. Compared to group TLV, PaO2 was decreased from T1 to T4 in the OLV, 2cmH2O CPAP and 5cmH2O CPAP groups (P<0.05). In particular, the most significant reduction was the OLV group.2. PaO2 was increased from T1 to T4 in group 2cmH2O and 5cmH2O CPAP more than that in group OLV (P<0.05), but there were no significant difference between the two groups at the same time piont.3. Compared with group TLV, SOD was decreased and MDA, NO were significantly increased (P<0.05) during operation (from T1 to T4) in group OLV and in group 2cmH2O CPAP and group 5cmH2O CPAP (from T2 to T4). MDA and NO in group 2cmH2O and group 5cmH2O CPAP were significantly decreased (P<0.05) compared with group OLV from the time T1 to T4, but SOD was significantly increased at the time of T3 (P<0.05).4. MDA and NO in group 5cmH2O were increased significantly compared with group 2cmH2O at the time of T3 (P<0.05), but there was no significant difference for SOD (P>0.05).Part 3 Postoperative clinical investigation on patients undergoing one-lung ventilation with inhalation, intravenous anesthesia and the treatment of CPAPMethods1. The hospitalized information of the patients in our previous studies were collected between November 2008 and June 2009. We focused on reviewing the care and course records in the ICU and general wards after surgery, including general care, the special care items, the use of antibiotics and pleural drainage.2. Evaluation: All patients with postoperative complications were recorded such as arrhythmia, pulmonary infection, respiratory failure, etc. In addition, we also recorded the lowest oxygen saturation, the duration of ventilator support, frequency of suction, the time of atomization and the dose of ambroxol or doxofylline.ResultsThe incidence of postoperative arrhythmia and pulmonary infection was no significant difference in each group.Conclusions1. The degree of oxidative stress during one-lung ventilation was not relieved by anesthetic maintaining with propofol or isoflurane.2. CPAP could attenuate oxidative stress during one-lung ventilation. 2cmH2O CPAP was more suitable for clinical practice.3. Inhalation, intravenous anesthesia and the treatment of CPAP during one-lung ventilation are not lower the incidence of postoperative complications.