维达洛芬,酮洛芬,中枢神经致敏 z-bo 2020-12-17 362

　　If the severe postoperative pain cannot be handled properly, the pain may be amplified and may cause long-term postoperative pain due to central nervous system sensitization. It is difficult to recover. The purpose of preventive analgesics is to reduce perioperative animal pain and reduce the use of analgesics. Because a single surgical incision is not the only trigger for central nervous system sensitization, prophylactic administration seems to be the main effective method to reduce postoperative pain. Other factors, such as perioperative pain, additional painful and noxious intraoperative input (such as retraction), and changes in the central nervous system of postoperative inflammatory process afferent input, correspondingly can enhance postoperative pain input. Emphasize that the use of preventive analgesics is to prevent changes in sensory processes during the pathophysiological process. The investigation of the effectiveness of preventive analgesics requires comparison of the results of receiving two ideal treatments (before and after surgery). The concept of "pre-analgesia" appeared in experimental studies of pre-analgesia in model animals. Pre-analgesia is an intervention for pain before or before the incision, which is more effective than the administration after the incision or after the operation. In the veterinary field, there are few comparisons between pre-analgesia and postoperative analgesia. In human clinical practice, the use of opioids for epidural pre-analgesia or local anesthetic-induced postoperative analgesia improvement, or the use of local anesthetics to improve the analgesic effect to pre-infiltrate the anesthesia, the first time Request for additional pain relief. It has been found in both humans and dogs; comparing preoperative administration with postoperative administration, non-steroidal anti-inflammatory drugs (NSAIDs) can also improve postoperative pain in some ways. NSAIDs inhibit the synthesis of prostaglandins in the periphery and the center. It can reduce the inflammatory response after tissue injury. In addition, the response to noxious stimuli is weakened.

　　Vidaprofen is a non-steroidal anti-inflammatory drug that can control pain and inflammation caused by clinical or experimental canine musculoskeletal diseases. Vidalorfen is a palatable gel preparation that can be quickly and effectively absorbed by dogs after oral administration. Oral administration and intravenous injection of the same dose have the same pharmacological half-life. However, the advantage of oral administration is that it has little stress to animals and can be easily fed to animals by humans after surgery. It is known that Vidaprofen can effectively inhibit cyclooxygenase-2 in dogs. The drug is safe. After 30-56 days of continuous administration, there will be minor intestinal irritation such as vomiting and diarrhea.

　　Although Vidalprofen has proven effective postoperative analgesia, no studies have investigated whether preoperative administration has a higher analgesic effect on postoperative pain control. Therefore, this is a prospective, randomized, blind study to investigate whether pre-administration of Vidaprofen in dogs undergoing maxillary and mandibular resection is more effective than postoperative Yaoyao for postoperative analgesia. Because there has been no report on the analgesic effect of virdaprofen before maxillary or mandibular resection, we designed a control group with ketoprofen, a non-steroidal anti-inflammatory drug, which can be used for dogs. Effective postoperative analgesia. Our hypothesis is that pre-administration of Vidaprofen can effectively reduce postoperative pain. The postoperative use of Vidaprofen or Ketoprofen is more effective for analgesia.

　　Result: According to the design, there is no obvious difference between the two sets of data. There was no significant difference in the duration of surgery (65±8 minutes PRE, 47±7 minutes in the pre-administration group, POST 50±4 minutes in the control group after the operation, and Control). Extubation time (4±1 min PRE, 3 ±1 min POST; 4±1 min Control) No mechanical ventilation device is needed in any group, and no clinical complications or side effects were found in any group during the recovery phase after anesthesia.

　　 In the two groups, adrenaline and cortisol increased significantly compared with the baseline values 30 minutes after extubation. (P<0.05; Figures 1 and 2) There were no significant differences in plasma norepinephrine and dopamine concentrations, pain and sedation scores within and between groups. There is no additional analgesic effect for dogs.

　　 At 2.5 hours in the PRE group, the highest scores of the Numerical Rating Scale (NRS) and Colorado Pain Scoring System (CPSS) were 3.9 and 1.3, respectively. It was 3.7 and 1.7 at 4.5h in the POST group, and 3.3 and 0.8 at 20h and 30min in the control group.

　　 There was no significant difference in heart rate in any group. In the postoperative (POST) and relative groups, the mean arterial pressure (MAP) was significantly lower than the baseline value (P<0.05) at the time of extubation and 30 minutes after extubation. 24h after extubation, compared with the baseline value, the MAP of the POST group and the control group increased (P<0.05) and decreased (P<0.05). In all groups, at the time of extubation and 30min, 2.5h, 4.5h, and 6h after extubation, the respiratory rate (fR) of all groups decreased significantly compared with the baseline value (P<0.05). In the control group, the respiratory rate decreased significantly after 20h and 24h after extubation. Compared with the PRE and POST groups, the control group also had a significant decrease at the corresponding time points (P<0.05). Compared with the baseline value, the rectal temperature will drop significantly when the tube is extubated, and the drop will continue to 4h (POST group) and 6h (PRE group and control group) (P<0.05). Heart rate, MAP, fR and rectal temperature are shown in Table 1.

　　Method Animal: The study was approved by the experimental animal ethics committee. Thirty dogs with oral tumors that require maxillary or mandibular resection are selected. The minimum sample size of the paired data is calculated by the power analysis method. Each group is required to have a 95% chance of finding a 2.5mm difference in pain index between different groups. And consider a standard deviation of 4mm. The PRE group has 5 female dogs and 5 male dogs, consisting of 4 crossbreed dogs, 3 poodles, 2 Cocker Spaniels and 1 Maltese dog. The POST group includes 6 male dogs and 4 female dogs, consisting of 4 poodles, 3 cocker spaniels, 2 hybrid dogs and 1 Airdale dog. The control group consisted of 6 males and 4 females, consisting of 4 poodles, 3 cocker spaniels, 2 hybrid dogs and 1 curly poodle. Animals are only used after clinical examination and other evaluations by radiography, ultrasonography, tomography, cytology or histopathology to determine that there are maxillary tumors used for research purposes. After a detailed health check, blood cell count, and blood biochemical analysis, it was determined that there were no clinical abnormalities in heart, lung, kidney, and liver function. The animal was scheduled to undergo maxillary resection in the morning. If the animal has contraindications to non-steroidal anti-inflammatory drugs (intestinal clinical symptoms, liver or kidney disease), it should be excluded from the study. With the customer's permission before conducting the test.

　　 Anesthesia and surgery: Animals were fasted 12h before anesthesia, and water was banned at 4h. Before anesthesia, all dogs received an intramuscular injection of acepromazine 0.05 mg.kg1 and a scalp needle was fixed in the left cephalic vein for intravenous administration or infusion after 10 minutes. All dogs received a slow intravenous injection of propofol to induce anesthesia, 5 mg.kg1 of oral tracheal intubation, and a dose of end-tidal isoflurane concentration of 1.6-1.8% and 100% oxygen through a semicircular system. The animal is maintained under anesthesia. A side-flow gas analyzer is connected between the inner gas tube and the Y tube to measure the end-tidal isoflurane concentration, end-tidal carbon dioxide concentration (ETCO2) and respiratory rate. Animals are allowed to breathe spontaneously, unless ETCO2 is not enough (35-45 mmHg), mechanical ventilation should be used. Heart rate, rhythm and NIBP are all collected by a multi-parameter monitor. The fluid flow rate during anesthesia is designed to be 10 mL.kg /1.hour1 A scalp needle is placed in the vein to collect blood samples.

　　 The operation is performed by the same senior surgeon, using the same surgical resection method and suture method. After the operation, the laryngeal reflex was recovered and the animal was extubated, and the animal was returned to the cage with a warm pad and recovered from it. The duration of the operation, the time to stop anesthetics, and the time of extubation were recorded. Provide drinking water to all dogs after awakening from anesthesia. Give the animals soft, liquid food during 5-12 post-surgery. Test design:

　　The animals randomly receive the following treatments

　　PRE group Vidalorfen was given 30 minutes before the operation (0.5 mg.kg1) and normal saline was given 10 minutes before the end of the operation.

　　 POST group, normal saline was given 30 minutes before the operation, and Vidaprofen was given 10 minutes before the end of the operation (0.5 mg.kg1).

　　 Control group: Normal saline was given 30 min before the operation, and ketoprofen (2 mg.kg1 IM) was given 10 min before the end of the operation

　　The reason for the administration of 10Min before the end of the operation is to ensure that the animal has enough time to absorb the drug to ensure that it can reach a certain concentration in the plasma when the operation is completed. Postoperative evaluation: Two types of scoring scales are used to evaluate postoperatively: a 10-category numerical rating scale (NRS 0 represents no pain and 10 represents severe pain) and Colorado Pain Score System (CPSS 0-4 0 represents no pain, 4 represents (Severe Pain) Pain was assessed by the same person who had no knowledge of this study. If the NRS score is ≥4 and the CPSS score is ≥2, additional analgesia with morphine (0.1 mg.kg1 IM) is required. Side effects The symptoms such as vomiting, diarrhea, and sedation are recorded during the 24h postoperative period. A sedation score scale from 0-3 is used to describe: 0-no sedation, no sensation or dyskinesia 1-moderate sedation, mild sensation or dyskinesia such as ataxia or orientation disorder; 2-moderate sedation, sternal recumbency and Slight third eyelid prolapse 3-severely sedated side lying and exacerbated third eyelid protrusion.

　　 Record before surgery (baseline value) Heart rate, MAP, respiration rate and body temperature are recorded after extubation and 0.5 (30 minutes), 2.5, 4.5, 6, 20 and 24 h. In addition, pain and sedation scores are also recorded separately. If there is a need to record the situation of the dog during the operation, and record the research data until 24h after the operation.