开胸肺切除,术后急性期反应,术后应激 z-bo 2020-11-17 348

　　Background: Video-assisted thoracoscopic surgery (VATS) has been used as a diagnostic and treatment platform to perform various thoracic surgery operations. Including surgical lung biopsy, tumor staging, pneumothorax, pericardium and pericardial fenestration treatment. It is clinically recognized that VATS causes less pain and less stress than traditional thoracotomy. Recent reports have also confirmed the safety and benefits of VATS. Animal models are usually similar to human models as surgical procedures. Experimental pneumonectomy has been carried out on pigs. The short-term effect of thoracoscopic lobectomy for primary lung tumors has been reported in dogs. Several studies of the VATS procedure conducted on animals evaluated stress parameters and postoperative outcomes. In order to deeply explore the impact of minimally invasive surgical techniques on acute phase response, stress response, and postoperative pain, we designed a porcine clinical study to compare the feasibility and safety of VATS and thoracotomy methods.

　　Method: Animals: 14 Bama mini-pigs with an average weight of 22.57 ± 1.5 kg. The pigs are raised in a single cage, with constant temperature (about 20°C), light conditions (12 h light/dark cycle), and free eating and drinking. All animals undergo health assessment, physical examination and complete blood count before surgery. The animals were randomly divided into two groups: group I underwent thoracoscopic lung resection, and the second group underwent thoracotomy pneumonectomy.

　　Surgical preparation: Determine the baseline physiological parameters before surgery (T = 0), including blood routine, heart rate (HR), rectal temperature, serum C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6), cortisol concentration.

　　After 24 hours of fasting and 2 hours of water deprivation, all pigs were given the same general anesthesia and monitoring. Preoperatively, each pig was injected with atropine sulfate (0.04 mg/kg) and intramuscularly with cefazolin (20 mg/kg). General anesthesia was induced by intramuscular injection of xylazine (1 mg/kg) and ketamine hydrochloride (10 mg/kg), and the anesthesia was maintained by 1.5-3% isoflurane oxygen tube intubation. Keep breathing through mechanical ventilation and respiratory anesthesia machine (respiratory rate 12 breaths/minute, tidal volume 15-20 ml/kg, inhalation:expiration ratio = 1:2). All procedures use sterile instruments. The monitor monitors physiological parameters. The animal is placed in a supine position. The hair on the surgical site (from the clavicle to the last rib of the left chest and from the sternum to the spine) is shaved and prepared aseptically for surgery. Place a heating blanket between the animal and the operating table. In the same environment, all surgical operations are performed by the same trained veterinarian.

　　Video-assisted thoracoscopic surgery: Create two portals: an endoscopy portal (portal 1) and a surgical portal (portal 2). Portal 1 (1 cm in diameter) is created by a sleeve located inside a metal tube and located between the eighth and ninth ribs. Portal 2 (2-3 cm in diameter) is created by a scalpel and a high-frequency electrosurgical knife and is located between the fifth and sixth ribs. A 10/11 mm trocar cannula is inserted through the chest wall into portal 1. An endoscope (0°, diameter 10 mm, length 330 mm, Olympus) is connected to a video endoscope camera and light source (Olympus), and then enters the chest cavity through this sleeve. Use an electrocoagulation hemostatic knife to stop bleeding at the edge of the portal 2. Lung grasping forceps are used to lift the lung lobes and expose the hilum. Use hemostatic forceps and self-made tools to carefully separate the pulmonary artery, pulmonary vein and bronchi. Electrocautery is used to separate excess tissue. The pulmonary artery and pulmonary vein were clipped and transected, and the bronchus was double ligated after transected. Bronchial ligation requires additional penetrating sutures. All lung lobes are removed in the following order in the left thorax: middle lobe, upper lobe and lower adjacent lobe. Normal saline (approximately 200 ml, approximately 40°C) is used to check the bronchial ligation and the thoracic cavity with a syringe. The liquid is sucked by a vacuum cleaner.

　　Thoracic surgery: Use a scalpel and an electrocoagulation knife to create an 8-10 cm incision between the seventh and eighth ribs. Saw off the eighth rib to provide better operating space and views. Use a high-frequency electrosurgical knife for blood coagulation. Use wound dilators to expand the surgical field. The surgical procedure is the same as the thoracoscopy group.

　　Monitoring and post-operative care: All animals are raised and monitored in the same environment. The pig’s clinical manifestations, including mental status, exercise, appetite, appearance of feces, and wound healing (including existing bleeding and inflammation) were evaluated daily for 15 consecutive days. After anesthesia, the animal was placed in a warm room and transferred to a pig house 6 hours later. Free drinking water was allowed 6 hours after operation, and pig feed was given 18 hours after operation.

　　Give 5 mg fentanyl patch every 3 days for 6 consecutive days after the operation. Antibiotic prophylaxis, intramuscular injection of cefazolin sodium (50 mg/kg) twice a day for 2 consecutive days. Record the following parameters: HR, rectal temperature, operation time, incision size, postoperative complications, standing time. Hematology examinations including white blood cell (WBC), red blood cell count (EC), lymphocyte (LY), and granulocyte (Gran) count were performed before operation and 1, 2, 3, 5, 7, and 14 days after operation.

　　Blood samples were collected through the anterior vena cava (preoperative and postoperative 4 h, 1, 3, 5, 7 and 14 d), and centrifuged at 1000 g for 15 min. Analysis of biomarkers in serum stored at -80°C, and measured by a commercially available ELISA kit with specific monoclonal antibodies before and 4 hours after surgery, day 1, 3, 5, 7, and 14 days CRP, SAA, IL-6, Cortisol. 15 days after the operation, xylazine and ketamine hydrochloride induced anesthetization of the pigs, and then 300 mg lidocaine was injected intravenously to euthanize the pigs. Autopsy to check the chest cavity and postoperative compliance.

　　Result: All animals survived 14 days after the operation. Through thoracoscopy and thoracotomy, a total thoracic pneumonectomy was successfully performed, and all the left lobes of 14 animals were completely removed. The operation time of thoracoscopic surgery was significantly longer than that of thoracotomy (VATS160.6±16.2 VS thoracotomy 123.7±13.2, P＜0.05). There were no intraoperative and perioperative complications in the two groups of animals. No bleeding, no surgical instruments to cause iatrogenic trauma. The length of the skin incision was 4.5-5.5 cm in the VATS group and 8 -10 cm in the open chest group. No other abnormalities were found in both groups. All pigs were considered to have returned to normal activity levels 24 hours after surgery. The rectal temperature was measured before the operation (baseline), during the designated operation and at the time points after the operation. The rectal temperature decreased in all animals. Two pigs in the VATS group and four pigs in the open chest group were 1 and 2 days after the operation After experiencing high fever, he returned to baseline 5 days after surgery. The WBC counts of the two groups were significantly higher than that before operation on the first 1, 2, and 3 days after operation (P<0.05), and they returned to normal levels after operation. The red blood cell count did not change significantly after any group of operations. Both lymphocytes and granulocytes increased significantly on the first day after surgery. On the 5th day after the operation, the lymphocyte count returned to a normal level, and the granulocyte count returned to the normal level on the 7th day after the operation. The serum CRP levels of the two groups of animals were significantly higher at 4 h, 1st and 3rd day after surgery than before surgery. After 7 days, it gradually decreased to baseline. The CRP in the thoracoscopy group was significantly lower than that in the thoracotomy group on the first day after surgery. The serum SAA levels of the two groups increased significantly on the 1st and 3rd day after operation. After 7 days, it gradually decreased to baseline. SAA in the thoracotomy group is often higher than that in the VATS group, but the difference is not significant. There was no statistically significant difference between the two groups at any time point. The serum IL-6 levels of the two groups of animals were significantly higher than the preoperative level at 4 h, 1st and 3rd day after operation. After 5 days, it gradually decreased to baseline. The level of IL-6 in the thoracoscopy group was significantly lower than that in the thoracotomy group on the first postoperative day, and there was no significant difference between the groups. Serum cortisol levels in the two groups were significantly higher than that before surgery, and gradually decreased to baseline 5 days after surgery. Cortisol was significantly higher than the preoperative level at 4 hours and the first day after surgery. The cortisol level of the VATS group was significantly lower than that of the thoracotomy group at 4 hours and the first day after surgery. There was no significant difference in cortisol content between the two groups at other time points.

　　Conclusion: The use of minimally invasive surgery technology (VATS) reduces the acute phase reaction, surgical stress and postoperative pain in pigs. Thoracoscopic surgery is the best choice for pig breast surgery.