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

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


1
Dr. G.K.KUMAR MD.,DA.Asst.ProfessorMadras
Medical college Chennai
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  • WOULD YOU LIKE TO SEDATE YOUR PATIENT ?
  • WOULD YOU EXPECT PATIENT SAFETY?
  • SAFE ANESTHESIOLOGIST

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SAFE ANESTHESIOLOGIST
SAFEST DRUG
5
SAFEST DRUG?
6

Dexmeditomidine
-Clinician s journey
7
KEY POINTS
  • JOURNEY WITH DEXMEDETOMIDINE
  • ALPHA2 AGONISTS
  • CLONODINE TO DEXMEDETOMIDINE

8
a2 Agonists
  • The initiation for the use of a2 agonists in
    anesthesia resulted from observations made who
    were receiving clonidine therapy.

9
a2 Agonists-Effects
  • Sedation
  • Anxiolysis
  • Hypnosis
  • Analgesia
  • Sympatholysis

10
a2 Agonists
a2 Receptors
11
a2 Receptors
  • Alpha2-adrenoceptors are located in
  • CNS PNS
  • Vascular smooth muscle
  • Other organs-Liver ,Platelets,Kidney,Pancreas

12
a2 Receptors
  • Location
  • CNS PNS
  • Pre Postsynaptic
  • Action
  • 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

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Dexmedetomidine
  • An intravenous anesthetic agent
  • Selective a2 receptor agonist. (?2?1 16201)
  • 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
  • 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
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
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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

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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 lt30).

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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/hr4-9ml/hr
  • Titration 0.1µg/kg/hr.-1.25ml/hr

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Administration of Dexmeditomidine
  • Loading dose 1µg/kg
  • 0.5ml50µg diluted as10ml 10min.
  • Maintenance 0.3-0.6µg/kg/hr
  • 1.5ml150µg diluted in 500ml NS
  • solution conc-0.3µg/ml
  • infusion-16 to32drops/min
  • Recovery 10-12mins after cessation.

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Uses of Dexmeditomidine
  • Bariatric surgery
  • Sleep apnea patients
  • Craniotomy aneurysm, AVM hypothermia
  • Cervical spine surgery
  • Off-pump CABG
  • Vascular surgery
  • Thoracic surgery

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

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Clinical Uses of Dexmeditomidine
  • SEDATIVE
  • SOLE ANAESTHETIC
  • ADJUVANT
  • OTHERS

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

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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
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

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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

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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

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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)

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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
ANALGESIC
  • Intravenous
  • Adjuvant in SAB/epidural
  • Intra articular
  • IVRA

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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 646652

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)
    882-887, 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
    447-451

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
  • Journal of Clinical Anesthesia - Volume 21, Issue
    6 (September 2009
  • Chicago, IL 60612, USASurgical Neurology 63
    (2005) 114117

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

46
Clonidine Vs Dexmedetomidine
  • Dexmedetomidine
  • Selectivity ?2?1 16201
  • t1/2 ? 2 hrs
  • Intravenous
  • Sedative-analgesic
  • Primary sedative
  • Clonidine
  • Selectivity ?2?1 2001
  • t1/2 ? 8 hrs1
  • PO,IV,patch,epidural
  • Antihypertensive
  • Analgesic adjunct

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Dr.G.K.Kumar
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Dr.G.K.Kumar
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a2 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
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HYPE? HOPE?
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OTHER ALPHA2 AGONISTS INTRODUCED
  • GUANABENZ
  • GUANFACINE
  • ?-METHYLDOPA
  • ROMIFIDINE
  • DETOMIDINE
  • XYLAZINE
  • MEDETOMIDINE
  • DEXMEDETOMIDINE

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  • 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.

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a2 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

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

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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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