Different Concentrations Of Sufentanil Controlled By Target Con Trolled Infusion Influence MAC_BAR Of Sevoflurane Of Patients Undergoing Thoracic Surgery

Background: It has clinical significance that the interaction between opioids and volatile anesthetics, which can advise clinical trail more rational , make anesthesia more stable, and reduce cost and pollution. Sufentanil as a potent narcotic analgesic, with fast onset of action, safety and strong analgesic effect, is able to maintain better hemodynamic status. Operation of major thoracic surgery wounds stimulates strongly and is adjacent to the heart and great vessels, so patients need more analgesic. The use of sufentanil can reduce intraoperative complications and make the surgery more stable [1 Sevoflurane is a new drug with the characteristics of tasteless, less irritation and fast introduction and waking up. During operation, using sufentanil and sevoflurane can make up for the shortcomings that patients wake up slowly by using Sufentanil alone. It has been clearly demonstrated that opioid agents significantly reduce the minimal alveolar concentration (MAC) of inhaled anesthetics required to abolish consciousness ,intubate, and blunt the sympathetic response to skin incision, for examples, effect of fentanil on MAC of isoflurane, sevoflurane and desflurane and effect of remifentanil on MAC of enflurane and sevoflurane. However, there are no relative reports on Sufentanil on the MAC of sevoflurane. The text on blood concentration of sufentanil is very difficult, which requires testing with high sensitivity. Gas chromatography - mass spectrometry (GC-MS) is a perfect modern analytical technique. As the high separation performance of chromatography, it is combined with the characteristics of mass spectrometry to distinguish strongly and its high detection sensitivity. GC-MS has become the core analysis technique to study the pharmacokinetics and metabolism, as for its speed of quantitative measurement is fast and it has the ability for analysis of trace components which achieves the requirements of modern high-throughput and high precision.Objective:To study target-controlled infusion of sufentanil on the surgical response (MAC), and to explore the compatibility mode for two kinds of rational drug; to determinate the actual concentration of sufentanil in blood using GC-MC and to evaluate the accuracy and stability of TCI system.Methods:60 esophageal cancer patients, aged 35～65yr,with ASAⅠ～Ⅱgrade, body mass index (BMI)≤30%, no significant heart, lung, liver, kidney damage, no history of hypertension and no history of alcoholism and drug abuse, and free from inhalation anesthetics and Opiates. No opioids or analgesic are taken before one week of surgery. They are randomly divided into four groups (each with S0, S1, S2, S3 indicated), with each group 15 cases (n = 15). On arrival of the patient at the operating room, Atropine 0.5mg is administered intravenously. A radial artery cannula is inserted to monitor arterial pressure, and patients are monitored of heart rate, ECG, blood oxygen saturation and BIS too. For endotracheal intubation, Sufentanil is administered via TCI(plasma concentration of 0.3ng/mL), 2mg/kg propofol and 0.1mg/kg vecuronium are administered. After intubation, S0 group receive sevofluane alone and the end-tidal concentration is adjusted to reach the pre-concentration of 1.7% by gas concentration detector; S1, S2, S3 group respectively receive sufentanil (plasma concentration of 0.2ng / mL, 0.4ng/mL, 0.6ng/mL) plus sevoflurane (the pre-concentration of 0.8%, 0.7%, 0.5%) .Before skin incision, the end-tidal concentration of sevoflurane need maintain stable for at least 20min. End-tidal CO2 was controlled between 30 ~ 40mmHg. With the upper and lower cross-point method (sequential method), according to patient's heart rate or mean arterial pressure changes MACBAR of sevoflurane was calculated. The first patient in each group receive the pre-concentration of sevoflurane.If the HR or MAP of the first one in patients elevate greater than or equal to 15% of the basic value at skin incision, the end-tidal sevoflurane concentration of the next one increased of 10% to 15% ; if the HR or MAP of the first one elevated less than or equal to 15% of the basic value at skin incision, the end-tidal sevoflurane concentration of the next one decreased of 10% to 15%. A radial artery cannula is inserted and the 1mL arterial blood samples for sufentanil whole blood concentrations are taken 10min, 30min and 60min after infusion. For each blood sample,1mL arterial blood samples are collected into a vacutainer with sodium heparin ,and immediately placed in liquid nitrogen, and then frozened in freezer at-70℃.Blood samples are preserved within 5 days, the sufentanil whole blood concentrations are analyzed. They are extracted with acetoacetic acid and petroleum ether, and the measured value of sufentanil concentration is then compared with its predicted value by GC-MS. After observation,patients are immediately injected of midazolam 60~80ug/kg and received the sufentanil of original concentration plus sevoflurane which concentration is adjusted accordingly to surgical stimulation to maintain hemodynamic stability.Results:1 Age, sex composition ratio, body mass index (BMI), preoperative heart rate and mean arterial pressure among each group are no significant difference.2 Before induction of anesthesia, there is no significant difference among BIS values in each group (P> 0.05), there is significant difference between BIS values before anesthesia induction and at skin incision (P <0.05), at skin incision there is no difference between S0 and S1, but there is significant difference among BIS values in else groups (p < 0.05).There are no cases of intraoperative awareness.3 S0 group sevoflurane MACBAR is 2.63%±0.21%, S1 group is 1.25%±0.08%, S2 group is 0.96%±0.19%, S3 group is 0.56%±0.11%. The difference among each group is very significant, P <0.01.4 The indicators for the accuracy of TCI and systems, the forecast error (PE) is -11.8%, the median prediction error (MDPE) is -10.6%, the median absolute prediction error (MADPE) for the 22.5%, are within±30%, so the measured sufentanil concentrations is lower than the concentration of target-controlled infusion. Conclusions: Sufentanil reduces the sevoflurane MACBAR. Target-controlled infusion 0.2ng/mL sufentanil can reduce 53% of MACBAR, 0.4ng/mL can reduce 64%,and 0.6ng/mL can reduce 79%;TCI is able to maintain the measured sufentanil whole blood concentration accurately and stably during the administration of sufentanil.