Transcript Introduction of two new anaesthetic agents

Dr. G.K.KUMAR MD.,DA.
Asst.Professor
Madras Medical college
Chennai
1
2
• WOULD YOU LIKE TO SEDATE YOUR PATIENT ?
• WOULD YOU EXPECT PATIENT SAFETY?
“SAFE ANESTHESIOLOGIST”
3
SAFE ANESTHESIOLOGIST
‘SAFEST DRUG’
4
SAFEST DRUG?
5
Dexmeditomidine
-Clinician ’s journey
6
KEY POINTS
• JOURNEY WITH DEXMEDETOMIDINE
• ALPHA2 AGONISTS
• CLONODINE TO DEXMEDETOMIDINE
7
α2 Agonists
•The initiation for the use of α2 agonists in
anesthesia resulted from observations made
who were receiving clonidine therapy.
8
α2 Agonists
-Effects
•Sedation
• Anxiolysis
• Hypnosis
• Analgesia
• Sympatholysis
9
α2 Agonists
α2 Receptors
10
α2 Receptors
Alpha2-adrenoceptors are located in
• CNS & PNS
• Vascular smooth muscle
• Other organs-Liver ,Platelets,Kidney,Pancreas
11
α2 Receptors
Location
• CNS & PNS
• Pre & Postsynaptic
Action
• Produce inhibitory functions
12
Action of Dexmedetomidine
CNS
SEDATION,
SYMPATHOLYSIS
SC
ANALGESIA
PNS
ANALGESIA
13
JOURNEY WITH
DEXMEDETOMIDINE
14
Dexmedetomidine
• Dextro (s) isomer of medetomidine
• Introduced 1999
• Approved for short term sedation by
FDA –USA
15
Dexmedetomidine
• An intravenous anesthetic agent
• Selective α2 receptor agonist.
(2:1 1620:1)
• Provides
-Sedation
-Anxiolysis
-Analgesia
• .
16
Dexmedetomidine
• No respiratory depression.
• Mild antihypertensive effects
• Decrease the need for other
analgesic medications such as
opioids
17
Mechanism of Action of
Dexmedetomidine
NE release decreased
SEDATION,
SYMPATHOLYSIS
Binding on
alpha2 receptor
ANALGESIA
Inhibit Firing rate &
Substance P release
ANALGESIA
18
?
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
19
Difference from other sedatives
• Patients sedated, but, arousable, alert, and
to respond without uncomfortable
• They may quickly return to sedation again
20
Hemodynamic effects of
Dexmedetomidine
• Reduces sympathetic activityreduction in HR & BP
• No rebound effects
21
Respiratory effects of
Dexmedetomidine
• NO RESPIRATORY DEPRESSION
A
in
Comparison of the Sedative, Hemodynamic, and
Respiratory Effects of Dexmedetomidine and Propofol
Children Undergoing Magnetic Resonance Imaging
Analg-Anesthesia july 2006
22
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
23
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%).
24
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
25
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.
26
Uses of Dexmeditomidine
•
•
•
•
•
•
•
Bariatric surgery
Sleep apnea patients
Craniotomy: aneurysm, AVM [hypothermia]
Cervical spine surgery
Off-pump CABG
Vascular surgery
Thoracic surgery
27
Uses of Dexmeditomidine
•
•
•
•
•
•
•
Conventional CABG
Spine surgery, evoked potentials
Head injury
Burn
Trauma
Alcohol withdrawal
Awake intubation
28
Clinical Uses of Dexmeditomidine
•
•
•
•
SEDATIVE
SOLE ANAESTHETIC
ADJUVANT
OTHERS
29
SEDATIVE
•
•
•
•
•
•
•
•
ICU sedation.
Procedural sedation
-gynecological
-urological
-burns patients
-pediatric patients
Sedation during RA
OBESE,OSA Patients
30
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
date: 2009 nov
volume: 75
issn: 1827-1596 publication
31
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
32
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
33
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,
34
university of miami-Anes-anal may2009
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
35
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)
36
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
37
ANALGESIC
•
•
•
•
Intravenous
Adjuvant in SAB/epidural
Intra articular
IVRA
38
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
39
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
40
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
41
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
42
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
43
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) 114–117
44
NON ANESTHETIC USES
• Opioid/BZD withdrawl
• Alcohol withdrawl
• Sedative in sleep deprived patients
• Antishivering
45
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
• t1/2  2 hrs
• Intravenous
• Sedative-analgesic
• Primary sedative
46
47
Dr.G.K.Kumar
48
Dr.G.K.Kumar
49
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
50
Ropivacaine
51
HYPE?
HOPE?
52
OTHER ALPHA2 AGONISTS
INTRODUCED
•
•
•
•
•
•
•
•
GUANABENZ
GUANFACINE
Α-METHYLDOPA
ROMIFIDINE
DETOMIDINE
XYLAZINE
MEDETOMIDINE
DEXMEDETOMIDINE
53
• 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
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
55
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
56
Mechanism of action of
Dexmedetomidine
• Activation of postsynaptic alpha2receptors in the CNS inhibits NE
release
• Decrease blood pressure , heart
rate, sedation , anxiolysis
57
Mechanism of action of
Dexmedetomidine
Analgesia
• Dexmedetomidine on alpha2receptors in the spinal cord.
• On PNS
decrease firing rate of nerve
fibres
Inhibit substance P &
glutamate release
58
59
60