Comparison Of Pharmacokinetics Of Dexmedetomidine At Different Doses By Nasal Administration In Pediatric General Anesthesia

Objective:This study was to evaluate theeffects of intranasal different doses of dexmedetomidine for premedication on preoperative anxiety andemergence delirium after anesthesia in children.To compare the phamacokinefics of intranasal different doses of dexmedetomidine during general anesthesia in children,and the dexmedetomidine plasma concentrations were measured with ultra-performance liquid chromatography-tandem mass spectrometry?UPLC-MS/MS?.Methods:In this study,36 children undergoing surgery were randomly assigned into groups NDDG1,NDDG2 and NDDG3.Dexmedetomidine was administered as intranasal of 1.0,1.5 or 2.0?g/kg respectively.Levelof sedation were measured at 5,1 0,20 and 30min after intranasl administration.Parental separation scores,Ramsay sedation scores and PACU agitation scores were recorded.Side effects were observed in perioperative period.Venous blood samples were drawn at 0,5,10,15,20,25,30,45,60,90,120 and 150 min after stop of intranasal,and the dexmedetomidine plasma concentrations were measured with ultra performance liquid chromatography-tandem mass spectrometry?UPLC-MS/MS?.The pharmacokinetic parameters were calculated using software WinNonlin5.2.1.Result:1.The Ramsay sedation scores was significantly higher in group NDDG2than in group NDDG1?P<0.05?.There were no significant differences in the Ramsay sedation scores between group NDDG2 and group NDDG3?P>0.05?.2.The parental separation scores was significantly lower in group NDDG1 than in the other 2 groups?P<0.05?.3.The PACU agitation scores was significantly higher in group NDDG1 than in the other 2 groups?P<0.05?.4.The pharmacokinetic parameters were as follows:Group NDDG1:t_1/2??min?10.16±2.41t_1/2??min?111.85±32.19Tmax?min?38.67±3.96Cmax?ng/ml?0.37±0.018AUC?0-t??ng/ml·min^-1?42.35±4.25AUC?0-???ng/ml·min^-1?76.83±14.14Vd?L/kg?2.10±0.25CL/F?L/min·kg^-1?0.013±0.0023Group NDDG2:t_1/2??min?8.63±1.97t_1/2??min?103.11±25.96Tmax?min?33.69±3.66Cmax?ng/ml?0.54±0.024AUC?0-t??ng/ml·min^-1?58.98±7.59AUC?0-???ng/ml·min^-1?100.71±16.41Vd?L/kg?2.22±0.24CL/F?L/min·kg^-1?0.015±0.0024Group NDDG3:t_1/2??min?6.91±1.73t_1/2??min?120.64±33.64Tmax?min?30.24±4.04Cmax?ng/ml?0.61±0.031AUC?0-t??ng/ml·min^-1?68.43±9.46AUC?0-???ng/ml·min^-1?127.32±25.11Vd?L/kg?2.73±0.28CL/F?L/min·kg^-1?0.016±0.0031There is difference in the pharmacokineties of dexmedetomidine during general anesthesia between different doses.Dexmedetomidine 1.5?g/kg is the dose of choice for anesthesia induction in the study.Conclusion:1.Preoperative intranasal adminstration of dexmedetomidine in children conferreds satisfactory sedation.2.These results suggest that intranasal administration of l.5?g/kg dexmedetomidine is more clinical eriective with few side effects.