| Background and ObjectiveEsophageal cancer is one of the most common malignant tumors in our country, which involved middle-aged and old people mostly with high morbidity and mortality. They are often complicated by metabolic disorders, pre-operative malnutrition, and so on. Cardiac and pulmonary function compromise in these patients result in reduced tolerance for surgery and anesthesia. Currently lung isolation technique for radical esophagectomy is commonly used, so called one-lung ventilation anesthesia. One-lung ventilation is a special anesthesia method aiming to achieve isolation of both lungs, mainly used in thoracic surgery.During one-lung ventilation in radical esophagectomy, stimulation of anesthesia, surgery, position and double-lumen endobronchial tube together with the OLV induced intrapulmonary shunt and imbalance of ventilation perfusion, increased peak airway pressure and pulmonary ischemia-reperfusion injury and other physical derangement, can lead to acute lung injury (ALI), cause systemic inflammatory response syndrome (SIRS). A very small number of patients develop to the acute respiratory distress syndrome (ARDS), and even multiple organ dysfunction syndrome (MODS), a number of important organs caused by severe and irreversible damage, a serious threat to patient's lives.OLV lung injury and correlate inflammation is a complex pathological process, in which cytokines play a critical role. Pro-inflammatory cytokines (IL-1β,IL-2, IL-6, IL-8, INF-γ, TNF-αand granulocyte monocyte colony-stimulating factor)and suppressing inflammatory cytokines (IL-10) level and balance affect the intensity and progress of inflammatory response.At present, there are lots of clinical application of lung protection strategies. Administration of anticholinergic is one of them.Traditionaly hyoscyamine anticholinergic drugs play an important role in preventing inflammatory reaction and ischemia-reperfusion injury. However, as its non-selective for cholinergic receptors, their clinical use is often limited because of evident side effects. Penehyclidine hydrochloride is a new anti-cholinergic independently tritus by China. As penehyclidine hydrochloride with high M-cholinergic receptor subtype selectivity.It has long time effect and less side effects, greatly expands the scope of indications and application of anti-cholinergic drugs.However, Penehyclidine hydrochloride in lung protection research mainly focused on animal experiments. Animal experiments have shown that penehyclidine hydrochloride can inhibit the inflammatory response in the heart, lung, brain and other organs, thus play a role in organ protection. However, the clinical research is seldom and not be confirmed about that.The present study was designed to observe the changes of plasma concentration of IL-6 and IL-10 between intravenous after administration of penehyclidine hydrochloride in patients undergoing radical esophagectomy before and after OLV. Whether penehyclidine hydrochloride can inhibit pulmonary inflammatory response resulting in lung protection and the optimal dose was also explored, providing guidance for clinical practice.Materials and Methods80 patients undergoing radical esophagectomy with one-lung ventilation (ASAⅡ～Ⅲ) were studied.They were randomly divided into four groups:Penehyclidine group (group P1, group P2, group P3) and control group (group C), with 20 cases in each. None of the patients were given premedication. Followed by intravenous induction with midazolam 0.05mg/kg, fentanyl 4-5μg/kg, etomidate 0.3mg/kg, succinylcholine1.0～1.5mg/kg, double-lumen endobronchial tube was inserted successfully at first attempt and connected with anesthesia machine. Set tidal volume (VT) at 8～10ml/kg, respiratory frequency (f) 10～12 times/min, inspiratory/expiratory (I:E) 1:1.5～2.0, the oxygen flow rate 2～3L/min. Anesthesia was maintained in four groups with infusion of remifentanil 0.10～0.20ug/(kg·min), propofol 4～8mg/ (kg·h), intermittent intravenous injection of atracurium 0.15-0.2mg/kg.When OLV beginning, adjusting the respiratory parameters:Set tidal volume (VT) at 6～8ml/kg, respiratory rate 12～16 times/min, pulse oxygen saturation 95%～100%, partial pressure of carbon dioxide in endespiratory gas 35～45mmHg, the bispectral EEG analysis index (BIS) 40-55.5min before induction of anesthesia, P1 intravenous injection of penehyclidine O.Olmg/kg (diluted with saline to 5ml); P2 intravenous injection of penehyclidine 0.02mg/kg; P3 intravenous injection of penehyclidine 0.03mg/kg; C group was given the same volume of saline,respectively.5ml blood sample was taken at prior to induction 10min (TO), after intubation 10min (T1), one-lung 30 min (T2),90 min (T3) and re-lung ventilation 10 min (T4) 5 hours from the central venous, injected in the test tube to 4℃for 4000r/min centrifugal 15min recipe clear supernatant and -80℃ conservation, using polymerase chain reaction method (ELISA) plasma concentrations of IL-6 and IL-10. Perioperative hemodynamic changes and changes in respiratory parameters during OLV were recorded.Statistical analysis was performed with SPSS 13.0 software. All data were expressed as mean±SD.One-way analysis of variance was used to test the difference for general data. Analysis of variance for repeated measures was used to test the difference for repeated measurement data. Numeration data were analysed withχ2 test. A P-value less than 0.05 was considered significant.Results1. No significant differences were detected with regard to age, gender ratio, weight.2. No significant differences were detected with regard to operation time, one-lung ventilation time, infusion volume, bleeding volume, urine output, and postoperative complications.3. The SBP and DBP were lower in group P3 than that in group P1 and group C at five measuring point, and the difference were statistical significance (P<0.05)4. The levels of plasma cytokines.4.1 Interleukin-6:Compared within groups, at T2, the level of interleukin-6 gradually raised and the level to lower at T4. The difference is statistical significance (P<0.05)Compared between groups, the level of interleukin-6 were not statistically significant in group P1 and group C (P>0.05).The level of interleukin-6 were not statistically significant in group P2 and group P3 (P>0.05).The level of interleukin-6 were lower in group P2, group P3 after OLV(T2,T3 and T4) than that in group C and group P1 (P<0.05), and the difference were statistical significance.4.2 Interleukin-10:Compared within groups, the level of interleukin-10 were not statistically significant at T0, T1, T2, T4 time points in every groups (P>0.05). The difference of level of interleukin-10 were statistical significance at T3 and TO (P<0.05),and the level was lower at T0 than that at T3. The level difference of T3 and other time points were not statistically significant (P>0.05)Compared between groups, the level difference of interleukin-10 were not statistically significant (P>0.05)Conclusions1. One-lung ventilation can increase the plasma IL-6 and IL-10 concentration in radical esophagectomy.2. Intravenous Penehyclidine hydrochloride 0.02mg/kg can lower the plasma concentration of IL-6 and has no significant difference with group 0.03mg/kg. Intravenous Penehyclidine hydrochloride 0.01mg/kg had no obvious effect on plasma concentration of IL-6. It had no obvious effect on plasma concentration of IL-10 in this experiment. |
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