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

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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
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SAFEST DRUG?
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Dexmeditomidine
-Clinician s journey
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KEY POINTS

• JOURNEY WITH DEXMEDETOMIDINE
• ALPHA2 AGONISTS
• CLONODINE TO DEXMEDETOMIDINE

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a2 Agonists

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

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a2 Agonists-Effects

• Sedation
• Anxiolysis
• Hypnosis
• Analgesia
• Sympatholysis

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a2 Agonists
a2 Receptors
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a2 Receptors

• Alpha2-adrenoceptors are located in
• CNS PNS
• Vascular smooth muscle
• Other organs-Liver ,Platelets,Kidney,Pancreas

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a2 Receptors

• Location
• CNS PNS
• Pre Postsynaptic
• Action
• Produce inhibitory functions

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Action of Dexmedetomidine
CNS
SEDATION, SYMPATHOLYSIS
SC
ANALGESIA
PNS
ANALGESIA
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• JOURNEY WITH DEXMEDETOMIDINE

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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
• .

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Dexmedetomidine

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

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

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Difference from other sedatives

• Patients sedated, but, arousable, alert, and to
  respond without uncomfortable
• They may quickly return to sedation again

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Hemodynamic effects of Dexmedetomidine

• Reduces sympathetic activity-reduction in HR BP
  
• No rebound effects

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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 

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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.

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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.

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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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