比较BIS和OAA/S评分对不同剂量右美托咪定镇静深度监测的准确性
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摘要
背景和目的：右美托咪定是一种新型、强效、高选择性的α2-肾上腺受体激动剂,是咪唑类衍生物,具有较强的镇静、抗焦虑、无呼吸抑制、稳定血流动力学等作用。脑内α2-肾上腺受体最密集的区域是负责调解觉醒和睡眠的脑干蓝斑。右美托咪定的镇静作用主要是因为它与脑内蓝斑核内的α2-肾上腺受体结合,能引发并维持自然非动眼睡眠。右美托咪定作用于脑内蓝斑核内的α2-肾上腺受体,产生镇静、镇痛、抑制交感活动的同时,能有效的保持患者术中唤醒状态。同时也有研究表明,右美托咪定在发挥良好镇静效果的同时,也对脑神经细胞有一定的保护作用。BIS是将脑电图(electmencepha-logram,EEG)的功率和频率经快速傅立叶转换及双频技术处理后得到的一个数字,用0—100表示,数值越大,患者越趋于清醒。BIS能反映大脑皮质的功能状况,已被认为是评估患者意识状态的敏感、准确的客观指标。OAA/S评分是临床镇静评分中非常有代表性的一种主观评价方法,它主要是通过对患者进行声音指令和触觉干扰指令来判断患者的镇静深度。本实验目的就在于比较BIS与OAA/S评分对不同剂量右美托咪定镇静深度监测的准确性。方法：择期腰硬联合麻醉行下肢手术60例患者,性别不限,年龄18-60岁,ASA分级Ⅰ-Ⅱ级,随机分为D1.0组(右美托咪定1.0ug/kg)、D0.75组(右美托咪定075ug/kg)和D0.5组(右美托咪定0.5ug/kg),每组20例。所有患者心肺肝肾功能正常,无精神神经系统疾病史,无水电解质紊乱及酸碱失衡,术前没有使用精神镇静药物。手术时间均长于2小时。BIS电极贴在左侧颞额部,BIS结果显示良好。选择L3-4椎间隙行腰硬联合麻醉,麻醉效果满意。摆好手术体位后开始静脉输注不同初始剂量盐酸右美托咪定(4ug/ml),D1.0组1Omin输注1.0ug/kg,D0.75组10min输注0.75ug/kg,D0.5组10min输注0.5ug/kg,三组均按0.5ug/kg/h维持剂量输注,到手术结束前30min停药。输注盐酸右美托咪定前记录BIS和OAA/S评分为基础值,初始量输注结束后每5min记录一次BIS(?)0AA/s评分
结果：1.三组患者一般资料组间比较差异无统计学意义;2.OAA/S评分为5、4、3、2、1时,患者BIS值分别为94(97-88)、80(86-73)、71(76～58)、55(59-48)、44(49～36)：3.三组病人BIS与OAA/S评分具有较好相关性;4.OAA/S评分≤2时,患者最佳BIS值为55。
结论：BIS能较为准确地监测右美托咪定的镇静深度,但其比OAA/S评分法没有优势。
Objective The dexmedetomidine set a new, potent, highly selective alpha2-adrenergic receptor agonist, imidazole derivatives. Both a strong sedative, anxiolytic, respiratory depression, stable hemodynamics role.Brain alpha2-adrenergic receptor receptor most intensive area is responsible for the mediation of arousal and sleep brainstem locus coeruleus. The sedative effect of dexmedetomidine given mainly because it is combined with the alpha2-adrenergic receptor within the brain locus coeruleus, can lead to maintaining the natural non-REM sleep.Dexmedetomidine role of alpha2-adrenergic receptor in the brain locus coeruleus, produce sedation, analgesia, while inhibition of sympathetic activity, which can effectively keep the patients in the wake state. Studies have shown that dexmedetomidine set at the same time play a good sedative effect, a protective effect on brain cells.BIS (electmencepha-logram, EEG), EEG power and frequency by fast Fourier transform and dual-band technology processing a number with0-100, the greater the value, the patients tend to be more awake. BIS can reflect the functional status of the brain cortex is considered to be sensitive, accurate assessment of the patients state of consciousness objective indicators.OAA/S score is very representative clinical sedation score a subjective evaluation method, it is primarily to determine the patient's depth of sedation in patients with voice commands and tactile interference instruction.Our Purpose of the experiment is to compare the accuracy of the application of BIS and OAA/S score in monitoring sedation depth with different doses of dexmedetomidine.
Methods60patients undergoing combined spinal-epidural anesthesia for lower limb operation(ASA grade Ⅰ-Ⅱ grade) were randomly divided into group D1.0, group D0.75and group DO.5(n=20). Male or female. Operation times were longer than2hours,. Combined spinal-epidural anesthesia were performed at L3-4, and anaesthesia effects were satisfactory. Different initial doses of dexmedetomidine (4ug/ml) were infused after the patients were well positioned. Group D1.0:1.0ug/kg dexmedetomidine was infused for10min, Group DO.75:0.75ug/kg dexmedetomidine was infused for10min, Group DO.5:0.5ug/kg dexmedetomidine was infused for10min, All of the groups were followed by continuous infusion(0.5ug/kg/h) until30min before the end of the operation. BIS and OAA/S scores were recorded before the infusion of dexmedetomidine for the basic value, and every5min after the initial infusion of dexmedetomidine.
Results:1There was no significant difference between the general information of the three group of patients;2when the OAA/S scores were94(97～88)、80(86～73)、71(76～58)、55(59～48)、44(49～36);3There was a good correlation between BIS and the OAA/S scores of the three groups of patients;4When the OAA/S scores≤2,the optimal BIS value of dexmedetomidine group patients was55.
Conclusion BIS can accurately monitor the sedation depth of dexmedetomidine, but it shows no advantages over the OAA/S scores.
结果：1.三组患者一般资料组间比较差异无统计学意义;2.OAA/S评分为5、4、3、2、1时,患者BIS值分别为94(97-88)、80(86-73)、71(76～58)、55(59-48)、44(49～36)：3.三组病人BIS与OAA/S评分具有较好相关性;4.OAA/S评分≤2时,患者最佳BIS值为55。
结论：BIS能较为准确地监测右美托咪定的镇静深度,但其比OAA/S评分法没有优势。
Objective The dexmedetomidine set a new, potent, highly selective alpha2-adrenergic receptor agonist, imidazole derivatives. Both a strong sedative, anxiolytic, respiratory depression, stable hemodynamics role.Brain alpha2-adrenergic receptor receptor most intensive area is responsible for the mediation of arousal and sleep brainstem locus coeruleus. The sedative effect of dexmedetomidine given mainly because it is combined with the alpha2-adrenergic receptor within the brain locus coeruleus, can lead to maintaining the natural non-REM sleep.Dexmedetomidine role of alpha2-adrenergic receptor in the brain locus coeruleus, produce sedation, analgesia, while inhibition of sympathetic activity, which can effectively keep the patients in the wake state. Studies have shown that dexmedetomidine set at the same time play a good sedative effect, a protective effect on brain cells.BIS (electmencepha-logram, EEG), EEG power and frequency by fast Fourier transform and dual-band technology processing a number with0-100, the greater the value, the patients tend to be more awake. BIS can reflect the functional status of the brain cortex is considered to be sensitive, accurate assessment of the patients state of consciousness objective indicators.OAA/S score is very representative clinical sedation score a subjective evaluation method, it is primarily to determine the patient's depth of sedation in patients with voice commands and tactile interference instruction.Our Purpose of the experiment is to compare the accuracy of the application of BIS and OAA/S score in monitoring sedation depth with different doses of dexmedetomidine.
Methods60patients undergoing combined spinal-epidural anesthesia for lower limb operation(ASA grade Ⅰ-Ⅱ grade) were randomly divided into group D1.0, group D0.75and group DO.5(n=20). Male or female. Operation times were longer than2hours,. Combined spinal-epidural anesthesia were performed at L3-4, and anaesthesia effects were satisfactory. Different initial doses of dexmedetomidine (4ug/ml) were infused after the patients were well positioned. Group D1.0:1.0ug/kg dexmedetomidine was infused for10min, Group DO.75:0.75ug/kg dexmedetomidine was infused for10min, Group DO.5:0.5ug/kg dexmedetomidine was infused for10min, All of the groups were followed by continuous infusion(0.5ug/kg/h) until30min before the end of the operation. BIS and OAA/S scores were recorded before the infusion of dexmedetomidine for the basic value, and every5min after the initial infusion of dexmedetomidine.
Results:1There was no significant difference between the general information of the three group of patients;2when the OAA/S scores were94(97～88)、80(86～73)、71(76～58)、55(59～48)、44(49～36);3There was a good correlation between BIS and the OAA/S scores of the three groups of patients;4When the OAA/S scores≤2,the optimal BIS value of dexmedetomidine group patients was55.
Conclusion BIS can accurately monitor the sedation depth of dexmedetomidine, but it shows no advantages over the OAA/S scores.
引文
[1]中华医学会重症医学分会.中国重症加强治疗病房患者镇痛和镇静治疗指导意见[J].中华外科杂志,2004,641(7)：115-8.
[2]Kasuya Y, Govinda R, Rauch S, et al.The correlation between bispectral index and observational sedation scale in volunteers sedated with dexmedetomidine and propofol[J]. Anesth Analg,2009,109 (6):1811-1815.
[3]Lin WHD, Thorp AS, Graham SG, et al. Incidence of awareness and recall during general anesthesia. Anaesthesia,1991,437-439.
[4]Price RJ, Urquhart C, Wallace CJ. Depth of anaesthesia by bispectral index monitoring for inter-hospital transfer.Anaesth Intensive Care,2007,35(1): 145-146.
[5]Ibramm AL, Taraday JK Kharach ED. Bispectral index monitoring during sedation with sevoflurane, midazolam and propofol. Anesthesiology,2001,95(5):1151 1159.
[6]Liu J, Singh H, White PF. Electroencephalogram bispectral analysis predicts of the depth of midazolam-induced sedation. Anesthesiology,1996,84(1):64-69.
[7]Ronan KP, Gallagher TJ, George B, et al. Comparison of propofol and midazolam for sedation in intensive care patients[J]. Crit Care Med,1995,23(2):286-293.
[8]P VSackey, P JRadell, F Granath, C RMartling. Bispectral index as a predictor of sedation depth during isoflurane or midazolam sedation in ICU patient. Anaesthesia and Intensive Care,2007,35:348-356.
[9]Klein K.J, Woerd A et al. Auditory information proeessing during adequate. propofol anesthesia monitored by electroencephalogram bispectral index[J]. Anesth Analg,2001,92:1210-1214.
[10]Degoute CS, Macabeo C, Dubreuil C, et al. EEG bispectral index and hypnotic component of anaesthesia induced by sevoflurane:comparison between children and adults. Br J Anaesth,2001,86(2):209-212.
[11]Kurehara K, Takashashi M, Horiuchi T, et al. Propofol concentration during maintenance of and emergence from propofol/epidural anesthesia:comparison between younger and elderly patient. Masui,2001,50(5):501-506.
[12]Shapko BA. Bispectal index:better information for sedation in the intensive care una. Crit Care Med,1999,27:1663-1664.
[13]Sleigh, et al. Sleep and the bispectral index. Anesth Analg 1999,88:659-661.
[14]Glass PS, et al. Bispeetral analysis measures sedation and memory effects of propofol, midazol, isoflurane, and alfentanil in healthy volunteers. Anesthesiology 1997,86:836-847.
[15]Iselin-Chaves IA, et al. Changes in the auditory evoked potentials and the bispeclral index following propofol or pmpofol and alfentanfl. Anesthesiology 2000, 92(5):1300-1309.
[16]Katoh T, et al. Electroencephalographic derivatives as a tool for predicting the depth of sedation and anesthesia induced by sevoflurane. Anesthesiology,1998, 88(3):642-650.
[17]Sakai T, et al. The effect of kemmine on clinical endpoints of hypnosis and EEG variables during propofol infusion. Acta Anaesthesiol Scand,1999,43(2):212-216.
[18]Friedbcrg BL. The effect of a dissociative dose of ketamine on the bispectral index (BIS) during propofol hypnosis. J Clin Anesth,1999, 11(1):4-7.
[19]Merat S, Levecque JP, Le Gulluche Y, et al. BIS monitoring may allow the detection of severe cerebral ischemia. Can J Anaesth,2001,48(11):1055-1060.
[20]Chemik DA, Gillings D, Laine H, et al. Validity and reliability of the observer's assessment of alertness/sedation scale:study with intravenous midazolam. J Clin Psychopharmacol,1994,10:244-251.
[21]Arcangeli A, D Alo C, Gaspari R. Dexmedetomidine use in general anaesthesia [J]. Curr Drug Targets,2009,10(8):687-695.
[22]Coull J T, Jones M, Egan T, et al. Attentional effects of no-radrenaline vary with arousal level:selective activation of thalamic pulvinar in humans[J]. Neuro Image, 2004,22(1):315-322.
[23]Sanders RD, Sun P. Patel S, et al. Dexmedetomidine provides cortical neuroprotection:impact on anaesthetic-induced neuroapoptosis in the rat developing brain [J]. Acta Anaesthesiol Scand,2010,54(6):710-716.
[1]. Siobal MS, Kallet RH, Kivett VA,et al. Use of dexmedetomidine to facilitate extubation in surgical intensive-care-unit patients who failed previous weaning attempts following prolonged mechanical ventilation:a pilot study. Respir Care,2006; 51(5):492-6.
[2]. Venn RM, Bradshaw CJ, Spencer R, et al. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia,1999; 54(12):1136-42.
[3]. Jones JG, Taylor PM. Receptor-specific reversible sedation:dangers of vascular effects. Anesthesiology,1999;90(5):1489-90.
[4]. Urban MK, Wukovits B, Flynn E. Dexmedetomidine versus propofol for sedation of ventilated spinal patients. Anesthesiology,2004;101(3A):A158.
[5]. Schaffrath E, Kuhlen R, Tonner PH. Analgesia and sedation in intensive care medicine. Anaesthesist,2004;53(11):1111-30.
[6].Ickeringill M, Shehabi Y, Adamson H, et al. Dexmedetomidine infusion without loading dose in surgical patients requiring mechanical ventilation haemodynamic effects and efficacy. Anaesth Intensive Care,2004;32(6):741-5.
[7]. Dutta S, Karol M D, Cohen T, et al. Effect of dexmedetomidine on propofol requirements in healthy subjects.J Pharm Sci,2001;90(2):172-81.
[8]. Ramsay M A, Luterman DL. Dexmedetomidine as a total intravenous anesthetic agent. Anesthesiology,2004;101(3):787-90.
[9]. Seybold J L, Ramamurthi R J, Hammer G B, et al. The use of Dexmedetomidine during laryngoscopy, bronchoscopy, and tracheal extubation following tracheal reconstruction. Pediatric Anesthesia,2007; 17(12):1212-4.
[10]. Taittonen M T, Kirvella O A, Aantaa R, et al. Effect of clonidine and dexmedetomidine premedication on perioperative oxygen consumption and haemodynamic state. Br J Anaesth,1997;78(4):400-6.
[11]. Abdalla N, Soliman A H. The effects of dexmedetomidine premedication on cortisol and interleukin-6 in patients undergoing major abdominal surgery. EG J Anaesth,2003;19(1):283-90.
[12]. Scheinin B, Lindgren L, Randell T, et al. Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation and reduces the need for thiopentone and preoperative fentanyl.Br J Anaesth,1992;68; 126-131.
[13]. Sturaitis M, Kroin J, Swamidoss CS,et al. Effect of intraoprative dexmedetomidine infusion on hemodynamic stability during brain tumor resection. Anesthesiology,2002;97(3A):A310.
[14]. Doufas AG, Lin CM, Suleman MI, et al. Dexmedetomidine and meperidine additively reduce the shivering threshold in humans. Stroke,2003;34(5):1218-23.
[15]. Bicer C, Esmaoglu A, Akin A,et al. Dexmedetomidine and meperidine prevent postanaesthetic shivering. Eur J Anaesth,2006;23(2):149-53.
[16]. Talke P, Tayefeh F, Sessler DI, et al. Dexmedetomidine does not alter the sweating threshold, but comparably and linearly decreases the vasoconstriction and shivering thresholds. Anesthesiology,1997;87(4):835-41.
[17]. Shukry M, Clyde MC, Kalarick al PL, et al. Does dexmedetomidine prevent emergence delirium in children after sevoflurane based general an esthesia? Paediatr Anaesth,2005,15:1098-1104.
[18]. Maldonado JR, Wysong A, vander Starre PJ,et al. Dexmedet omidine and the reduction of postoperative delirium aftercardiacs urgery. Psychosomatics,2009,50: 206-217.
[19].Tariq M, Cerny V, Elfaki I, et al. Effects of subchronic versus acute in utero exposure to dexmedetomidine on foetal developments in rats.Basic Clin Pharmacol Toxicol,2008,103:180-185
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[25].Mattingly J E,D'Alessio J,Ramanathan J,Effects of obstetric and anesthetics on the neonate:a review.Paediatr Drugs,2003,5:615-627.
[2]Kasuya Y, Govinda R, Rauch S, et al.The correlation between bispectral index and observational sedation scale in volunteers sedated with dexmedetomidine and propofol[J]. Anesth Analg,2009,109 (6):1811-1815.
[3]Lin WHD, Thorp AS, Graham SG, et al. Incidence of awareness and recall during general anesthesia. Anaesthesia,1991,437-439.
[4]Price RJ, Urquhart C, Wallace CJ. Depth of anaesthesia by bispectral index monitoring for inter-hospital transfer.Anaesth Intensive Care,2007,35(1): 145-146.
[5]Ibramm AL, Taraday JK Kharach ED. Bispectral index monitoring during sedation with sevoflurane, midazolam and propofol. Anesthesiology,2001,95(5):1151 1159.
[6]Liu J, Singh H, White PF. Electroencephalogram bispectral analysis predicts of the depth of midazolam-induced sedation. Anesthesiology,1996,84(1):64-69.
[7]Ronan KP, Gallagher TJ, George B, et al. Comparison of propofol and midazolam for sedation in intensive care patients[J]. Crit Care Med,1995,23(2):286-293.
[8]P VSackey, P JRadell, F Granath, C RMartling. Bispectral index as a predictor of sedation depth during isoflurane or midazolam sedation in ICU patient. Anaesthesia and Intensive Care,2007,35:348-356.
[9]Klein K.J, Woerd A et al. Auditory information proeessing during adequate. propofol anesthesia monitored by electroencephalogram bispectral index[J]. Anesth Analg,2001,92:1210-1214.
[10]Degoute CS, Macabeo C, Dubreuil C, et al. EEG bispectral index and hypnotic component of anaesthesia induced by sevoflurane:comparison between children and adults. Br J Anaesth,2001,86(2):209-212.
[11]Kurehara K, Takashashi M, Horiuchi T, et al. Propofol concentration during maintenance of and emergence from propofol/epidural anesthesia:comparison between younger and elderly patient. Masui,2001,50(5):501-506.
[12]Shapko BA. Bispectal index:better information for sedation in the intensive care una. Crit Care Med,1999,27:1663-1664.
[13]Sleigh, et al. Sleep and the bispectral index. Anesth Analg 1999,88:659-661.
[14]Glass PS, et al. Bispeetral analysis measures sedation and memory effects of propofol, midazol, isoflurane, and alfentanil in healthy volunteers. Anesthesiology 1997,86:836-847.
[15]Iselin-Chaves IA, et al. Changes in the auditory evoked potentials and the bispeclral index following propofol or pmpofol and alfentanfl. Anesthesiology 2000, 92(5):1300-1309.
[16]Katoh T, et al. Electroencephalographic derivatives as a tool for predicting the depth of sedation and anesthesia induced by sevoflurane. Anesthesiology,1998, 88(3):642-650.
[17]Sakai T, et al. The effect of kemmine on clinical endpoints of hypnosis and EEG variables during propofol infusion. Acta Anaesthesiol Scand,1999,43(2):212-216.
[18]Friedbcrg BL. The effect of a dissociative dose of ketamine on the bispectral index (BIS) during propofol hypnosis. J Clin Anesth,1999, 11(1):4-7.
[19]Merat S, Levecque JP, Le Gulluche Y, et al. BIS monitoring may allow the detection of severe cerebral ischemia. Can J Anaesth,2001,48(11):1055-1060.
[20]Chemik DA, Gillings D, Laine H, et al. Validity and reliability of the observer's assessment of alertness/sedation scale:study with intravenous midazolam. J Clin Psychopharmacol,1994,10:244-251.
[21]Arcangeli A, D Alo C, Gaspari R. Dexmedetomidine use in general anaesthesia [J]. Curr Drug Targets,2009,10(8):687-695.
[22]Coull J T, Jones M, Egan T, et al. Attentional effects of no-radrenaline vary with arousal level:selective activation of thalamic pulvinar in humans[J]. Neuro Image, 2004,22(1):315-322.
[23]Sanders RD, Sun P. Patel S, et al. Dexmedetomidine provides cortical neuroprotection:impact on anaesthetic-induced neuroapoptosis in the rat developing brain [J]. Acta Anaesthesiol Scand,2010,54(6):710-716.
[1]. Siobal MS, Kallet RH, Kivett VA,et al. Use of dexmedetomidine to facilitate extubation in surgical intensive-care-unit patients who failed previous weaning attempts following prolonged mechanical ventilation:a pilot study. Respir Care,2006; 51(5):492-6.
[2]. Venn RM, Bradshaw CJ, Spencer R, et al. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia,1999; 54(12):1136-42.
[3]. Jones JG, Taylor PM. Receptor-specific reversible sedation:dangers of vascular effects. Anesthesiology,1999;90(5):1489-90.
[4]. Urban MK, Wukovits B, Flynn E. Dexmedetomidine versus propofol for sedation of ventilated spinal patients. Anesthesiology,2004;101(3A):A158.
[5]. Schaffrath E, Kuhlen R, Tonner PH. Analgesia and sedation in intensive care medicine. Anaesthesist,2004;53(11):1111-30.
[6].Ickeringill M, Shehabi Y, Adamson H, et al. Dexmedetomidine infusion without loading dose in surgical patients requiring mechanical ventilation haemodynamic effects and efficacy. Anaesth Intensive Care,2004;32(6):741-5.
[7]. Dutta S, Karol M D, Cohen T, et al. Effect of dexmedetomidine on propofol requirements in healthy subjects.J Pharm Sci,2001;90(2):172-81.
[8]. Ramsay M A, Luterman DL. Dexmedetomidine as a total intravenous anesthetic agent. Anesthesiology,2004;101(3):787-90.
[9]. Seybold J L, Ramamurthi R J, Hammer G B, et al. The use of Dexmedetomidine during laryngoscopy, bronchoscopy, and tracheal extubation following tracheal reconstruction. Pediatric Anesthesia,2007; 17(12):1212-4.
[10]. Taittonen M T, Kirvella O A, Aantaa R, et al. Effect of clonidine and dexmedetomidine premedication on perioperative oxygen consumption and haemodynamic state. Br J Anaesth,1997;78(4):400-6.
[11]. Abdalla N, Soliman A H. The effects of dexmedetomidine premedication on cortisol and interleukin-6 in patients undergoing major abdominal surgery. EG J Anaesth,2003;19(1):283-90.
[12]. Scheinin B, Lindgren L, Randell T, et al. Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation and reduces the need for thiopentone and preoperative fentanyl.Br J Anaesth,1992;68; 126-131.
[13]. Sturaitis M, Kroin J, Swamidoss CS,et al. Effect of intraoprative dexmedetomidine infusion on hemodynamic stability during brain tumor resection. Anesthesiology,2002;97(3A):A310.
[14]. Doufas AG, Lin CM, Suleman MI, et al. Dexmedetomidine and meperidine additively reduce the shivering threshold in humans. Stroke,2003;34(5):1218-23.
[15]. Bicer C, Esmaoglu A, Akin A,et al. Dexmedetomidine and meperidine prevent postanaesthetic shivering. Eur J Anaesth,2006;23(2):149-53.
[16]. Talke P, Tayefeh F, Sessler DI, et al. Dexmedetomidine does not alter the sweating threshold, but comparably and linearly decreases the vasoconstriction and shivering thresholds. Anesthesiology,1997;87(4):835-41.
[17]. Shukry M, Clyde MC, Kalarick al PL, et al. Does dexmedetomidine prevent emergence delirium in children after sevoflurane based general an esthesia? Paediatr Anaesth,2005,15:1098-1104.
[18]. Maldonado JR, Wysong A, vander Starre PJ,et al. Dexmedet omidine and the reduction of postoperative delirium aftercardiacs urgery. Psychosomatics,2009,50: 206-217.
[19].Tariq M, Cerny V, Elfaki I, et al. Effects of subchronic versus acute in utero exposure to dexmedetomidine on foetal developments in rats.Basic Clin Pharmacol Toxicol,2008,103:180-185
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