1. 1 Dr. G.K.KUMAR MD.,DA. Asst.Professor Madras Medical college Chennai

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3. 3 WOULD YOU LIKE TO SEDATE YOUR PATIENT ? WOULD YOU EXPECT PATIENT SAFETY? “ SAFE ANESTHESIOLOGIST”

4. 4 SAFE ANESTHESIOLOGIST ‘SAFEST DRUG’

5. 5 SAFEST DRUG?

6. 6 Dexmeditomidine -Clinician ’s journey

7. 7 JOURNEY WITH DEXMEDETOMIDINE ALPHA2 AGONISTS CLONODINE TO DEXMEDETOMIDINE KEY POINTS

8. 8 The initiation for the use of α 2 agonists in anesthesia resulted from observations made who were receiving clonidine therapy. α 2 Agonists

9. 9 Sedation Anxiolysis Hypnosis Analgesia Sympatholysis α 2 Agonists -Effects

10. 10 α 2 Agonists α 2 Receptors

11. 11 α 2 Receptors Alpha2-adrenoceptors are located in CNS & PNS Vascular smooth muscle Other organs-Liver,Platelets,Kidney,Pancreas

12. 12 α 2 Receptors Location CNS & PNS Pre & Postsynaptic Action Produce inhibitory functions

13. 13 Action of Dexmedetomidine SEDATION, SYMPATHOLYSIS ANALGESIA CNS SC PNS

14. 14 JOURNEY WITH DEXMEDETOMIDINE

15. Dexmedetomidine 15 Dextro (s) isomer of medetomidine Introduced 1999 Approved for short term sedation by FDA –USA

16. Dexmedetomidine 16 An intravenous anesthetic agent Selective α2 receptor agonist. (  2 :  1 1620:1) Provides -Sedation -Anxiolysis -Analgesia.

17. Dexmedetomidine 17 No respiratory depression. Mild antihypertensive effects Decrease the need for other analgesic medications such as opioids

18. 18 Mechanism of Action of Dexmedetomidine NE release decreased Binding on alpha2 receptor Inhibit Firing rate & Substance P release SEDATION, SYMPATHOLYSIS ANALGESIA

19. 19 ? Pharmacological profile Rapid redistribution: 6 min Elimination half-life: 2 h Protein binding: 94% Metabolism: biotransformation in liver to inactive metabolites + excreted in urine No accumulation after infusions 12-24 h Pharmacokinetics similar in young adults + elderly

20. 20 Difference from other sedatives Patients sedated, but, arousable, alert, and to respond without uncomfortable They may quickly return to sedation again

21. 21 Hemodynamic effects of Dexmedetomidine Reduces sympathetic activity- reduction in HR & BP No rebound effects

22. 22 Respiratory effects of Dexmedetomidine NO RESPIRATORY DEPRESSION A Comparison of the Sedative, Hemodynamic, and Respiratory Effects of Dexmedetomidine and Propofol in Children Undergoing Magnetic Resonance Imaging Analg-Anesthesia july 2006

23. 23 Special considerations Hypovolemic patients With other vasodilators or negative chronotropic agents dexmedetomidine have an additive effect With renal or hepatic impairment, metabolites may accumulate and dose reductions may be necessary

24. 24 Dexmedetomidine Contraindications Infusion over 24 hours In obstetric procedures, cesarean section deliveries, as the safety has not been studied Patients with pre-existent severe bradycardia and related bradydysrhythmias (advanced heart block) Patients with impaired ventricular functions (ejection fraction <30%).

25. 25 DOSAGE 2 ml (200µgs) +48 ml NS Loading dose -0.5µg-1µg/kg over 10 min (36-72 ml /hr) Maintenance -0.3µg-0.7µg/kg/hr[4-9ml/hr] Titration ±0.1µg/kg/hr.-1.25ml/hr

26. 26 Administration of Dexmeditomidine Loading dose 1µg/kg 0.5ml[50µg] diluted as10ml ×10min. Maintenance 0.3-0.6µg/kg/hr 1.5ml[150µg] diluted in 500ml NS solution conc-0.3µg/ml infusion-16 to32drops/min Recovery 10-12mins after cessation.

27. 27 Uses of Dexmeditomidine Bariatric surgery Sleep apnea patients Craniotomy: aneurysm, AVM [hypothermia] Cervical spine surgery Off-pump CABG Vascular surgery Thoracic surgery

28. 28 Uses of Dexmeditomidine Conventional CABG Spine surgery, evoked potentials Head injury Burn Trauma Alcohol withdrawal Awake intubation

29. 29 Clinical Uses of Dexmeditomidine SEDATIVE SOLE ANAESTHETIC ADJUVANT OTHERS

30. 30 ICU sedation. Procedural sedation -gynecological -urological -burns patients -pediatric patients Sedation during RA OBESE,OSA Patients SEDATIVE

31. 31 SEDATIVE As sole sedative during percutaneous carotid artery stenting in a patient with severe chronic obstructive pulmonary disease j p cata; e folch minerva anestesiologica volume: 75 issn: 1827-1596 publication date: 2009 nov

32. 32 SEDATIVE Preservation of arousability Respiratory-sparing properties -safer conduct of AWAKE FIBEROPTIC INTUBATIONS in difficult airway cases. Vol. 17, no. 1, 2007 international traumacare (ITACCS FIBROPTIC INTUBATION

33. 33 ENT SURGERIES Analgesia, adequate sedation and surgical comfort without adverse effects for patients undergoing FESS under LA European Journal of Anaesthesiology: January 2008 - Volume 25 - Issue 1 - p 22-28

34. 34 MONITORED ANESTHESIA CARE Effective baseline sedative for a broad range of surgical procedures Better patient co operation Less opioid requirements Less respiratory depression than midazolam and fentanyl Dr. Keith A. Candiotti, department of anesthesiology, perioperative medicine and pain management, university of miami-Anes-anal may2009

35. 35 IV 0.3 - 0.6ug/kg 15mins prior surgery IM 2.5ug/kg 45-90mins prior Effective Stress attenuation Reduces thiopentone doses(±30%) *Miller 7 th edition PREMEDICATION

36. 36 STRESS ATTENUATION Preoperative a single dose(1µg/kg) result in progressive increases in sedation Blunt the haemodynamic responses during laryngoscopy Reduce opioid and anaesthetic requirements Decrease blood pressure and heart rate as well as the recovery time after the operation Drugs in R& DVolume 7, Number 1, 2006, pp. 43-52(10)

37. 37 STRESS ATTENUATION A bolus dose of 1μg/kg over 10 minutes, prior to administration of reversal provided hemodynamic stability associated with extubation D. Jain, R. Khan & M. Maroof The Internet Journal of Anesthesiology. 2009 Volume 21 Number 1

38. 38 ANALGESIC Intravenous Adjuvant in SAB/epidural Intra articular IVRA

39. 39 ANALGESIC The primary site of analgesic action is thought to be the spinal cord Both supra spinal and spinal, modulate the transmission of nociceptive signals in the CNS Systemic use of dexmedetomidine shows narcotic sparing Analgesic property similar to remifentanil

40. 40 AS ADJUVANT Intraoperative infusion of dexmedetomidine reduces perioperative & post op analgesic requirements Dr. Alp Gurbet, Uludag, Department of Anesthesiology and Reanimation, University Faculty of Medicine, GorukleCAN J ANESTH 2006 / 53: 7 / pp 646–652

41. 41 ADJUVANT TO REGIONAL ANAESTHESIA IV administration- prolongs the sensory and motor blocks of bupivacaine spinal analgesia with good sedation effect and hemodynamic stability Mahmoud Al-Mustafa, MD, Department of Anesthesia and Intensive Care, Jordan University Hospital, M.E.J. ANESTH 20 (2), 2009

42. 42 ADJUVANT TO REGIONAL ANAESTHESIA 5 μg with spinal bupivacaine in surgical procedures produces prolongantion of duration & better quality of spinal analgesia. American Journal of Applied Sciences 6 (5): 882-887, 2009

43. 43 ADJUVANT TO REGIONAL ANAESTHESIA Addition of dexmedetomidine to LA in IVRA improve the quality of anaesthesia and decreased analgesic requirement Enhances local anesthetic action via alpha 2A receptors European journal of anestheiology(2005), 22 : 447-451

44. 44 Awake Thyroidectomy Awake Craniotomy, Laminectomy Awake Laryngoplasty Surgeries for Tracheomalacia Militory med jan 2009 Journal of Clinical Anesthesia - Volume 21, Issue 6 (September 2009 Chicago, IL 60612, USASurgical Neurology 63 (2005) 114–117 AS SOLE ANESTHETIC

45. 45 NON ANESTHETIC USES Opioid/BZD withdrawl Alcohol withdrawl Sedative in sleep deprived patients Antishivering

46. 46 Clonidine Vs Dexmedetomidine Clonidine Selectivity:  2:  1 200:1 t1/2  8 hrs1 PO,IV,patch,epidural Antihypertensive Analgesic adjunct Dexmedetomidine Selectivity:  2 :  1 1620:1 t 1/2  2 hrs Intravenous Sedative-analgesic Primary sedative

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48. 48 Dr.G.K.Kumar

49. 49 Dr.G.K.Kumar

50. 50 α 2 Receptors Mediates synaptic transmission in pre- and postsynaptic nerve terminals – Decrease release of acetylcholine – Decrease release of norepinephrine Inhibit norepinephrine system in brain Inhibition of lipolysis in adipose tissue Inhibition of insulin release in pancreas Induction of glucagon release from pancreas platelet aggregation

51. Ropivacaine 51

52. HYPE? HOPE? 52

53. 53 OTHER ALPHA2 AGONISTS INTRODUCED GUANABENZ GUANFACINE Α-METHYLDOPA ROMIFIDINE DETOMIDINE XYLAZINE MEDETOMIDINE DEXMEDETOMIDINE

54. 54 a 2 -adrenoceptors: are found in both the central and peripheral nervous system. They are found both pre- and postsynaptically and serve to produce inhibitory functions. -Presynaptic a 2 receptors inhibit the release of noradrenaline and thus serve as an important receptor in the negative feedback control of noradrenaline release. -Postsynaptic a 2 receptors are located on liver cells, platelets, and the smooth muscle of blood vessels. Activation of these receptors causes platelet aggregation, and blood vessel constriction.

55. 55 a 2 -adrenoceptors: are found in both the central and peripheral nervous system. They are found both pre- and postsynaptically and serve to produce inhibitory functions. -Presynaptic a 2 receptors inhibit the release of noradrenaline and thus serve as an important receptor in the negative feedback control of noradrenaline release. -Postsynaptic a 2 receptors are located on liver cells, platelets, and the smooth muscle of blood vessels. Activation of these receptors causes platelet aggregation, and blood vessel constriction.

56. 56 α 2 Receptors A G protein coupled receptor ALPHA 2a,2b,2c Common effects include: Vasodilation of arteries Vasoconstriction of arteries to heart (coronary artery) Vasoconstriction of veins Decrease motility of smooth muscle in gastrointestinal tract

57. 57 Mechanism of action of Dexmedetomidine Activation of postsynaptic alpha2- receptors in the CNS inhibits NE release Decrease blood pressure, heart rate, sedation, anxiolysis

58. 58 Mechanism of action of Dexmedetomidine Analgesia Dexmedetomidine on alpha2- receptors in the spinal cord. On PNS decrease firing rate of nerve fibres Inhibit substance P & glutamate release

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