Effects Of Mild Hypothermia(33±0.5℃)-based Rats Model On Propofol Metabolism

Objective At present,the incidence of hypothermia in general anesthesia is still high,and intraoperative hypothermia has a significant impact on drug metabolism and prognosis of patients.Propofol is a commonly used first-line drug in clinic,and its metabolic changes in hypothermia are worthy of attention.In this study,the drug metabolism of propofol in rat model of mild hypothermia was investigated.Methodological research methods and steps:1)Preparation and grouping of rat model of mild hypothermia(33±0.5 ℃):Twenty-four healthy male rats weighing 250-350 g were randomly divided into two groups(n=12).They were divided into control group(N group)and mild hypothermia group(H group),and improved according to Katz’s rat model.Rats were induced with 1% propofol 9 mg/kg and then intubated through orotracheal tube.After intubation,rats were anesthetized with 1% propofol 30 mg/kg-1.h-1 oxygen mechanical ventilation.Left femoral vein puncture and catheterization were performed,and blood samples were taken in time.In group H,anesthesia tracheal intubation and left femoral vein puncture were performed and ice debris was lowered.Within 3 minutes,the temperature of rectum and temporalis muscle was lowered to(33±0.5 ℃)and maintained for 3 hours.Group N only underwent anesthesia tracheal intubation and left femoral vein puncture and intubation,and maintained ventilator treatment for 3 hours,without cooling treatment,and routine heat preservation measures.2)Blood samples were taken from rats in each group at a set time point for examination.3)Determination of propofol concentration by high performance liquid chromatography(HPLC).The chromatographic column is Kromasil C18(5 micron,4.6 mm *250mm,column number: KR-002545);column pressure: 90-100 kg.cm-1;column temperature: 40 C,mobile phase: acetonitrile-water(70:30);flow rate: 1 ml.min-1;fluorescence excitation wavelength: 276 nm;emission wavelength 310 nm;internal standard: thymol;quantitative method: peak area method.The determination of endogenous substances in plasma by high performance liquid chromatography showed no interference.The internal standard thymol was completely separated from propofol.The retention time of internal standard thymol was about 7.1 min and that of propofol was about 11.1 min.Result 1)Compared with the control group,the blood loss in the mild hypothermia group increased slightly(3.05 + 0.55 ml vs 1.05 + 0.35 ml).2)The plasma concentration of propofol in mild hypothermia group increased significantly from 10 minutes after the beginning of propofol pump to 150 minutes after the stopping of propofol pump compared with the control group.3)In mild hypothermia group,Cmax(ug/ml),t1/2(min),AUC0-t [mg/(L.min)],AUC0-∞[mg /(L·min)],MRT0-t(min),MRT0-∞(min)and other parameters were significantly increased compared with the control group.4)After propofol infusion,MAP decreased in both groups,but the mild hypothermia group was more significant than the control group.Conclusion In the rat model under mild hypothermia,propofol t1/2 prolongs and MRT prolongs significantly in vivo.Under the same conditions,propofol blood concentration increases significantly and metabolism slows down.It is suggested that propofol dosage should be appropriately reduced in clinical anesthesia for patients with intraoperative hypothermia,so as to avoid adverse consequences such as circulatory depression and delayed awakening caused by slow drug metabolism.