动物实验,心血管 z-bo 2020-09-11 372

　　Background: Ovariectomy in female dogs is a common surgical procedure in veterinary medicine. The ovaries of dogs are abundantly innervated by sensory, sympathetic and parasympathetic nerves, which are distributed along the ovarian artery and veins of the ovarian trunk. When performing an oocystectomy, stretching the ligaments and tightening the ovarian stem can cause particularly painful irritation. Injection of local anesthetics can significantly reduce the pain response of cats, horses and humans. In contrast, injecting lidocaine into dogs that had undergone ablation surgery did not reduce the amount of isoflurane required and the autonomous response to surgery. It may be necessary to consider other methods to reduce adverse reactions after ovarian stem surgery. Intraoperative pain detection relies on the observation of autonomic nerve changes, especially cardiovascular and respiratory system responses. Anesthesia and analgesia are inherently related, and autonomous parameters can be used as indicators of pain changes and pain balance and/or changes in depth of anesthesia. Midazolam acts as an agonist of GABAA receptors. Like other benzodiazepine agonists, it induces anticonvulsants, antidepressants, sedation/hypnosis, amnesia, and central muscle relaxation. The main purpose of this study was to determine the effect of midazolam on the cardiovascular response of ovarian surgery during selective hysterectomy. The second objective was to determine the effect of midazolam on the concentration of isoflurane required to maintain surgical anesthesia. The first hypothesis is that a single injection of midazolam at a dose of 0.25 mg/kg will not significantly affect the cardiovascular parameters of healthy dogs undergoing a third elective hysterectomy. Heart rate (HR) and mean arterial blood pressure (MAP). The second null hypothesis is that the use of midazolam does not have the preservation effect of intraoperative isoflurane. Methods: Animals: 39 female dogs were randomly assigned to midazolam (group M) and placebo group, and injected intravenously (IV) 5 minutes before the first ovarian surgery. Acepromazine (0.03 mg/kg) and petidin (3 mg/kg) were injected intramuscularly. Both groups of dogs were anesthetized. After intravenous injection of propofol, tracheal intubation was performed. All tracheal tubes are of appropriate size, and anesthesia is maintained by breathing anesthesia. During the whole process, all dogs can breathe naturally. When the partial pressure of carbon dioxide (PE'CO2) exhaled by the terminal exceeds 6.9 kPa or the inhalation time exceeds 5 minutes, intermittent positive pressure ventilation begins. During anesthesia, the animals were hydrated. At the beginning of anesthesia, the vaporizer was initially set to reach a final exhaled isoflurane concentration (FE'ISO) of 1.1%. The dog is continuously monitored by muscle relaxation (mandibular tension), eye position and eyelid reflex, and a multi-parameter monitor is manually evaluated. Then adjust the vaporizer settings according to the depth of anesthesia to maintain or change the isoflurane concentration at the end of the exhalation. If the dog becomes active or the eyelids respond during anesthesia, propofol should be injected intravenously. If the mean arterial blood pressure (MAP) or heart rate (HR) increases or decreases by 25% or more, adjust FE'ISO accordingly by 0.1%. If FE'ISO is higher than 1.6%, fentanyl (2μg/kg) is given intravenously for analgesia. From induction of anesthesia to the end of anesthesia, the monitoring parameters were recorded every 5 minutes. The monitored parameters include heart rate, electrocardiogram, respiratory rate, final partial pressure of carbon dioxide and final expiratory isoflurane concentration, hemoglobin oxygen saturation and arterial blood pressure. Measure non-invasive blood pressure in preparation for surgery. Slow morphine was injected intravenously into the operating room to provide intraoperative analgesia for all dogs. After identifying the first ovary and giving treatment (midazolam/placebo), the surgeon will stop all operations for 5 minutes to allow enough time to start midazolam treatment. Ovariectomy adopts three clamp method and double ligation method. Record the start and end time of midazolam administration and ovarian manipulation. The definition of ovarian surgery is the stretching and tearing of the suspensory ligament, the tightening and ligation of the ovarian rod, and the removal of the ovary. Slow pulse is defined as a heart rate of less than 80 beats/minute, tachycardia greater than 120 beats/minute, normal blood pressure of 70-120 mmHg and normal PE'CO2 of 4-7 kPa. .. The body temperature of a normal person is 37-39°C. The anesthesiologist may inject Atropin (20μg/kg) or glycopyrrolate (5μg/kg) intravenously into slowly pulsating animals as appropriate. Patients with inhalation and persistent hypercapnia (ie, 5 minutes) were mechanically ventilated, and meroxycam (5 mg/ml) analgesics were given after surgery. During recovery from anesthesia, the mask will provide oxygen. During and after the operation, the animal's body temperature is maintained by an external heating device. During the recovery period, animals are evaluated for vocalization and/or percussion, and for pain and irritability. Morphine (0.2 mg/kg) is given as an analgesic (CMP-SF score of 5/20 or 6/24 or higher) intravenously. A second dose of morphine (0.2 mg/kg) was given 3-4 hours after the first dose, and buprenorphine was given every 6-8 hours.

　　Results: The time of anesthesia, the time between administration time (midazolam/placebo) and the end of anesthesia, the amount of propofol required for induction of anesthesia did not differ between the two groups. There was no statistically significant difference in the rate of change of heart rate from baseline or the rate of change of MAP from baseline between the two groups. In different periods, the rate of change of heart rate and blood pressure showed statistically significant differences. In terms of heart rate, the rate of change in phase 5 is statistically significantly higher than in all other periods. Statistically, the blood pressure change rate in the first phase (baseline) and the second phase was significantly lower than the third, fourth and fifth phases. Statistically, cycle 1 is significantly shorter than cycle 2, and there is no statistical difference between cycles 3 and 4 and cycles 4 and 5. Statistically, period 3 was significantly longer than periods 1, 2 and 5. The difference between group P and group M was statistically significant, and group M had significant FE'ISO in the 3rd, 4th and 5th segments after midazolam administration Lower than P group. Four dogs needed pain relief during the operation, three in group P and one in group M. One dog in group M and one dog in group P needed additional emergency pain relief after surgery. In addition, the other dogs in the P group and the other three dogs in the M group needed emergency analgesia after surgery. There were no significant differences in emergency and analgesia requirements between the two groups during and after the operation. Five dogs in group M and seven dogs in group P required mechanical ventilation. There was no statistical difference in FR, PE'CO2 or artificial respiration between the two groups. Side effects during anesthesia include hypotension (group P: 13 animals, group M: 17 animals), hypertension (group P: 4 animals, group M: 2 animals) and slow pulse (group P: 2 animals) ). Dog; M group: 1 animal), tachycardia (P group: 5 animals; M group: 3 animals), apnea (P group: 2 animals; M group: 3 animals). Hypercarboemia (group P: 5 dogs; group M: 7 dogs) and hypothermia (group P: 3 dogs; group M: 5 dogs). There was no statistical difference in the incidence of complications between the M group and the P group. The use of dobutamine CRI, norepinephrine CRI or anticholinergic drugs was not statistically significant.

　　Conclusion: During ovarian hysterectomy, a single injection of midazolam before administration showed moderate isoflurane retention in dogs (14.3%). The results of this study do not support the use of midazolam to reduce cardiovascular responses in selective ovulation dogs.