Effects And Pharmacokinetics Of Diazepam Combined With Ketamine In Canine Intravenous Anesthesia

Ketamine, a derivative of cyclohexanone, structurally like the phencyclidine, is one anesthesia drug of short duration. This medicine with rapid induction, high security, strong analgesic effect, consciousness regaining quickly after the anesthesia, is the first choice drug in animal general anesthesia. But it has some side effects, such as twitch, muscle tension, apnea, excessive salivation and fever. Diazepam, another drug related with benzodiazepine, is widely used in animal surgery as a sedative and the medicine given before the general anesthesia. Its action is rather quick, plays its function 1-2 min after intravenous injection and sustains its effect for 1-2 h. Besides, its side effects are very few; breath suppression may appear only when high dosage is used and it may reduce the side effects produced by ketamine.The objectives of this study were to investigate the anaesthetic effects of ketamine combined with diazepan on changes of respiratory and cardiovesticular system in dogs and pharmacokinetics when ketamine, combined with diazepam, was administered to dogs by intravenous injection without other medicines given before the anesthesia. The dosage of ketamine was 7 mg/kg and that of diazepam was 0.7mg/kg. The results indicated that the combination of ketamine and diazepam was a suitable method for general anesthesia in dog and had the following advantages: good anesthetic effect, strong muscle relaxation and abirritation, less influence on physiological parameters and rapid metabolism in vivo. The study was divided into three major experiments:ExperimentⅠ: Influence of Ketamine and Diazepam Anaesthesia on the respiratory and cardiovesticular systemAfter giving the medicine, for every 5 min, the heart rate, breathing rate, blood oxygen saturation, body temperature and blood pressure (including systolic pressure, diastolic pressure and mean blood pressure) of the dogs were recorded. Meanwhile, the heart intensity and sound were guarded with the stethoscope. The experiment continues 60 min. The statistical data were analyzed with SPSS. The results revealed that the shift of the average heart rate and the average breath frequency was very evident in the first 10 min after intravenous anesthesia. Except that the body temperature continuously reduces, other physiological parameters had a gradual rising tendency until consciousness was regained, and the value of entire change was still in the range of canine tolerance.ExperimentⅡ: Effects of Ketamine combined with Diazepam on Canine Anesthesia6 dogs without giving medicines before anesthesia were induced with Ketamine (7 mg/kg) and diazepam (0.7 mg/kg) by intravenous injection. Each 5 min after injection, the effects of analgesia, sedation and muscle relaxation were observed, and scores given according to the standard reported by Liu Huanqi. The experiment continues 60 min. The results indicated that the anaesthetic effect appears approximately 35 s after the injection, and was sustained for about 28 min. Moreover, the anaesthesia was very deep and muscle relaxation was good.ExperimentⅢ: Pharmacokinetics of Ketamine combined with Diazepam in Canine Anesthesia;After giving the medicine, 2 mL blood from the latent vein was collected at 0 min, 5 min, 10 min, 20 min, 40 min and 60 min, respectively. Ketamine and diazepam in blood were determined with the high performance liquid chromatography (HPLC), to investigate the rule of metabolism of both, ketamine and diazepam, in vivo. The result indicated that the blood plasma medicine-time curve conforms to the two-room model, and after administration of the intravenous injection of ketamine, the main pharmacokinetic parameters measured as follows: half life T1/2 =7.05 min), the area under the curve (AUC): 4.58 ppm×min (or,μg/mL×min), the view distribution volume, V(c): 1.55 mg/kg, and body clean-out lead, CL(s): 0.15 mg/kg/min. After mainline of diazepam, its blood plasma medicine-time curve conforms to the one room model, and its main pharmacokinetic parameters measured were as follows: T1/2 = 45.84 min; the area under the curve (AUC): 66.98ppm x min (or,μg/mL×min)); the view distribution volume, V(c): 2.32 mg/kg; body clean-out lead CL(s): 0.10 mg/kg/min. Two kinds of medicines when used together, show quick metabolism, but the metabolism of ketaminewas quicker than that of diazepam.