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

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

4. SAFE ANESTHESIOLOGIST
‘SAFEST DRUG’

5. SAFEST DRUG?

6. Dexmeditomidine
-Clinician ’s journey

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

8. α2 Agonists
The initiation for the use of α2 agonists in anesthesia resulted from observations made who were receiving clonidine therapy.

9. α2 Agonists -Effects Sedation Anxiolysis Hypnosis Analgesia
Sympatholysis

10. α2 Agonists
α2 Receptors

11. α2 Receptors Alpha2-adrenoceptors are located in CNS & PNS
Vascular smooth muscle
Other organs-Liver ,Platelets,Kidney,Pancreas

12. α2 Receptors Location Action CNS & PNS Pre & Postsynaptic
Produce inhibitory functions

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

14. JOURNEY WITH DEXMEDETOMIDINE

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

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

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

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

19. Pharmacological profile?
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 h
Pharmacokinetics similar in young adults + elderly

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

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

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

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

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

29. Clinical Uses of Dexmeditomidine
SEDATIVE
SOLE ANAESTHETIC
ADJUVANT
OTHERS

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

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:  publication date:  2009 nov 

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

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

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. PREMEDICATION 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

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 (10)

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 Volume 21 Number 1

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

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. 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. 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. 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): , 2009

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 :

44. AS SOLE ANESTHETIC 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

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

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

48. Dr.G.K.Kumar

49. Dr.G.K.Kumar

50. α2 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

52. HYPE?
HOPE?

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

54. a2-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 a2 receptors inhibit the release of noradrenaline and thus serve as an important receptor in the negative feedback control of noradrenaline release.
-Postsynaptic a2 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. a2-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 a2 receptors inhibit the release of noradrenaline and thus serve as an important receptor in the negative feedback control of noradrenaline release.
-Postsynaptic a2 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. α2 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. Mechanism of action of Dexmedetomidine
Activation of postsynaptic alpha2-receptors in the CNS inhibits NE release
Decrease blood pressure , heart rate, sedation , anxiolysis

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