伦敦帝国大学右美托咪定课件

1、1Clinical Applications of Dexmedetomidine:From bench to bedside Dr. Daqing Ma MD, PhDAnaesthetics, Pain Medicine & Intensive Care Department of Surgery & CancerImperial College LondonMagill Anaesthesia departmentChelsea and Westminster HospitalAnnual meeting of Chinese Society of Anesthesiology -Sep

2、t 24 , 2010 Beijing 新晨卫星会Outline Introduction Laboratory bench work Bedside: clinical applications (sedation; pain relief; anaesthesia) ConclusionsAlpha-2 adrenoceptor agonist History Old drug for veterinary anaesthesia since 1967. Central alpha-2 receptor being established at 1981. Xylazine + Ketam

3、ine for rodents Cattle Anxiolysis AnalgesiaSedation Anaesthetic sparingCytoprotection Clonidine2:1 = 200:110 min9-12 hrs20%1.7-2.5 L/kgLiver 50%Kidney 30%Faeces 20%Dexmedetomidine2:1 = 1600:15 min2 hrs94%200L?ClClNNHNHNNHCCH3HCH3H3CAlpha-2 adrenoceptor agonist-Pharmacokinetics Selectivityt1/2 t1/2 B

4、inding to albuminVolume distributionMetabolisedAlpha-2 adrenoceptor agonist-Pharmacodynamics Ca+Ca+Ca+Decrease in influx of Ca+Decrease in actionpotential due tohyperpolarization2A2ARGoGkK+K+K+Alpha-2 adrenoceptor agonist-Pharmacodynamics Hypotension Bradycardia Imidazoline receptor agonist DexTwo s

5、ubtypes of imidazoline receptor I1 and I2I1 receptors: restricted distribution in the ventrolateral medulaI2 receptors: Brain, kidney and pancreas, function not clearDexmedetomidine: SedationDexmedetomidine vs sedation or sleep The sleep switch: hypothalamic control of sleep and wakefulness(Saper et

6、 al, 2001)Dexmedetomidine vs sedation or sleep DEX induced a qualitatively similar pattern of c-Fos (a neuronal activation marker) expression in rats as seen during normal NREM sleep: i.e. A decrease in the LC and TMN An increase in the VLPO. (Nelson et al, Anesthesiology 2003) Dexmedetomidine vs Cy

7、toprotection(Qiao et al. Critical Care 2009) Dexmedetomidine vs Cytoprotection(Qiao et al. Critical Care 2009) Outcomes in MV patients sedated with DexmedetomidineDose used: Dex 1.5 g/kg/hr 120 hrs. Outcomes in MV patients sedated with DexmedetomidineSepsis vs no SepsisEfficacy outcomes in patients

8、treated with Dex vs Midazolam Dose used: Dex 0.2-1.4 g/kg/hr until extubation or 30 days. Long term sedation with Dex a case report Boy suffered liver cirrhosis Had liver transplantation at the age of 9 monthsLong-term MVSedated with midazolam (1.7 mg/kg/hr) and Fentanyl (3.5g/kg/hr)- inadequate. On

9、 postopertive day 29, Dex was added (1.4 g/kg/hr). Supplement with midazolam or ketamineWas extubated 10 weeks after operationConclusion: Dex was used for 2 weeks with no signs of withdrawal effects. Dex can be used for sedation for an infant who reuired MV for a prolonged period of time. Dexmedetom

10、idine: AnalgesiaDexmedetomidine vs AnalgesiaSaline Dex 1gDex 3.5gDex 7g(Guo et al. Anesthesiology 1996) Dexmedetomidinemorphine PCADexmedetomidine: Anaesthesia (deep)Dexmedetomidine vs Evoked Potential Recording pain signalDexmedetomidine vs Scoliosis Surgery (Anschel et al. J Clin Neurophysiol 2008

11、) Sevoflurane + Nitrous oxide in Oxygen +Fentanyl (3 g/kg loading dose and then 1 g/kg/hr)+Propofol (200 g/kg/min) +Dex (0.5 g/kg over 20 min loading and then dose-0.5 g/kg /hr) Induction Anaesthetic regimens Maintenance +Propofol (reducing dose to maintain BIS 35 to 45) +Dex (0.5 g/kg over 20 min l

12、oading dose-0.5 g/kg /hr) +Controlled hypotension (Esmolol or SNP) 1.Fentanyl (3 g/kg loading dose)+Propofol (3-5 mg/kg) +Dex (0.5 g/kg over 20 min loading) Induction Maintenance 2.Fentanyl (1 g/kg/hr)+Propofol (200 g/kg/min) +Dex (0.5 g/kg /hr) If needed, 0.2mg/kg rocuronium was used for muscle rel

13、axation. Dexmedetomidine for functional neurosurgery Functional Neurosurgery Neurosurgical procedurces + Monitoring brain Function Brain tumor, epilepsy, dystonia EEG or Electrocorticography (ECocG) for cortical brain mappingWithout sedation-venous air embolism and even deathSedated with Dex 0.3 -0.

14、6 g/kg/hr No interfere EEG mapping Satisfactory sedation Stable hemodynamics(A&A 2006;103: 1224; Curr Opin Anaesthesiol 208;21:537; J C Anaesthesai 2009;21:213) Dexmedetomidine: Anaesthesia (light)Dexmedetomidine vs Respiration Isobologram(Ma et al., Acta Anaesthesiol Scand 1998)(Knowles et al., BJA

15、 1994)Dexmedetomidine vs Respiration Systemic clearance (ml/min/kg) Pharmacokinetic Interaction Between Fentanyl and Midazolam Elimination time (min)Placebo group Fentanyl group Fentanyl group P = 0.002P = 0.04(Hase I, et al., BJA 1997)Placebo group (Bailey PL, et al., Anesthesiology 1990)Midazolam

16、(M) and Fentanyl (F) on RespirationDexmedetomidine: use in nonintubated patients requiring sedation Dex has sedative and analgesic effect, short acting, quick onset, less respiratory depressionIt becomes an ideal sedative agent for monitored anesthesia care (MAC)Fiberoptic scopy; Dental procedures;

17、ophthalmology; head and neck procedures; Neurosurgery; cardiac catheterization; MRI or CTDosage: loading dose - 0.5 to 5 g/kg Infusion dose- 0.2 to 10 g/kg/hr (EJA 2010;27:648; Therapeutics and Clinical Risk Management 2010;6:111)Conclusions Dex has sedative and analgesic effect, short acting, quick onset, less respiratory depression, but can cause hypotension and bradycardia. It becomes an ideal sedative agent for sedation and monitored anesthesia care (MAC). Man