Prof. Mridul M. panditrao gives detailed pharmacodynamics/ kinetics of alpha 2 agonists, centrally action. especially when given via variuos routes, withb help of evidence in the terms of his own conducted trials.

1. Dexmedetomidine
Why should I make it a Part
of
My anaesthetic Practice ?

2. Dr. Mridul M. Panditrao
CONSULTANT
DEPARTMENT OF ANESTHESIOLOGY AND
INTENSIVE CARE
PUBLIC HOSPITAL AUTHORITY’S
RAND MEMORIAL HOSPITAL
GRAND BAHAMA,THE BAHAMAS

3. • FORMERLY:
PROFESSOR & HEAD
In-charge SURGICAL ICU
DEAN OF THE MEDICAL FACULTY
Department of Anaesthesiology &
Critical Care
D. Y. patil medical college
Pimpri, Pune, Inida

4. For All The Happiness
Mankind can gain.
Is not in pleasure
But in rest from “Pain”
JOHN DRYDEN

5. INTRODUCTION
Receptors
• Classified on the basis of the actions,
potency and specificity of the neuro
transmitters or neuromodulators
influencing them
• adrenergic receptors : on the basis of
effective potency of different naturally
occurring or synthetic catecholamines.

6. Adrenergic Receptors
• Alpha (α) alpha1
A
alpha2
& B
beta1
• Beta (β)
beta2
•Alquist RP. A study of adrenergic receptors. Am j physiol.1948; 153: 586-589
•Langer SZ. Pre Synaptic regulation of catecholamine release. Biochem Pharmacol 1974; 23: 1793-1800

7. Adrenergic Receptors : alpha 2
• pre
• post &
• Extra
synaptic sites of sympathetic terminals
Only the pre-synaptic type of alpha2
receptors are of clinical importance
Drew GM, Whiting SB. Evidence for two distinct types of post synaptic alpha adrenoceptors in vascular smooth
muscle in vivo. Br J Pharmacol. 1979; 67: 207-215

8. Adrenergic Receptors : alpha 2
• regulate the release of nor-adrenaline and
adenosine tri phosphate (ATP), through
negative feedback mechanism
• located in central nervous system,
peripheral nerves, vascular smooth
muscles, platelets and various splanchnic
organs like, liver, kidney, pancreas and eye
•Gertler R, Brown H, Mitchell D and Silvius E. Dexmedetomidine: a novel- sedative – analgesic
agent. Proc (Baylor Univ med Cent) 2001;14(1): 13-21 www.baylorhealth.com

10. Adrenergic Receptors : alpha 2
• Mechanism of action: by modulation of
ion channels causing hyperpolarization of
cell membrane, and suppression of entry
of calcium ions at nerve terminals
• Suppress, both neuronal firing and
release of neurotransmitter, nor-
adrenaline
• useful mechanisms of action of the drugs
which act as alpha2 adrenergic agonists
•Cotechhia S. Kobilka BK, et al. Multiple secondary messenger pathways of alpha adrenergic receptor subtypes expressed
in eukaryotic cells. J Biochem 1990; 103: 163-224
•Birnbaum L. Abramowitz J, Brown AM. Receptor – effector coupling by G- proteins. Biochem Biophys Acta. 1990;1031:
163-224

11. alpha 2 Adrenergic Receptor Agonists
• Imidazole class of drugs
• Older drugs : xylazine
detomidine
medetomidine
in veterinary medicine!
•Clarke KW, Hall LW. “Xylazine” a new sedative for horse and cattle. Vet rec1969; 85: 512-517
•Tamsent A, Gordh T. Epidural clonidine produces analgesia, Lancet1984; 2:231-232

12. alpha 2 Adrenergic Receptor Agonists
Clonidine

13. Clonidine
• first of these drugs for human use
• Introduced as a nasal decongestant
• ‘side-effects’ : prolonged sedation and
severe hypotension.
• It was named as ‚Potent centrally acting
anti-hypertensive agent‛
• Was available only as oral preparation
• Parenteral clonidine: Newer applications
• Various routes: Intravenous, Neuraxially,
regional blocks, peri bulbar etc.

14. Parenteral Clonidine
• Intravenous: obtundation of pressor
response
• As an adjuvant to LAAs :
Neuraxially:
intra-thecally as well as epidurally
Supraclavicular Block
Peribulbar Block

15. Parenteral Clonidine
• Dosages
• I.V. : 4 µg/kg for pressor response
• Neuraxial:
Spinal: 75 µg in 3 ml Bupivacaine
Epidural: 75 µg in 10-12 ml LAAs
• Supra-clavicular block 1-2 µg/kg
• Peri-bulbar block 1-1.5 µg/kg

16. alpha 2 Adrenergic Receptor Agonists
Dexmedetomidine
What is so special about it?

17. Dexmedetomidine
• a D – enantiomer of medetomidine
• New Entrant in this class
• approved in 1999 by FDA for clinical
application in humans
• Structure:

19. Actions
• Central
Sedation, anxiolysis and analgesia
Bradycardia and hypotension
• Peripheral
Decreased GI secretions, inclusive of saliva
Decreased GI motility
Inhibition of rennin-Angiotensin (RA) system and
decreased release of rennin
Increased Glomerular Filtration Rate (GFR),
Increased excretion of Na, water and thus diuresis
Decreased intra-ocular pressure
Decreased insulin release

20. MECHANISM
CLINICAL CNS EFFECTS
• neither the nerve/ terminal is allowed to get
stimulated, nor it can transmit/ propagate the
signal forwards.
• at supra-spinal level as well as at spinal level
Supra-spinal: Locus coeruleus:
– Brainstem center - modulates wakefulness
– Major site for hypnotic actions (sedation,
anxiolysis)
– Mediated via various efferent pathways:
• Thalamus and subthalamus cortex
• Nociceptive transmission via descending spinal tracts
• Vasomotor center and reticular formation

22. MECHANISM
CLINICAL CNS EFFECTS
• Spinal: Spinal cord
 Binding to 2 receptors analgesia
At Substantia gelatinosa (Lamina II),
 closing the gate at the dorsal horn to
stimuli coming from Aδ and C fibers
 Inhibit release of nociceptive humoral
transmitters like Substance P
release of substance P
•Kuraishi Y, Hirota N, Sato Y, et al Noradrenergic inhibition of the release of Substance P from the primary afferents in the rabbit spinal
cord dorsal horn. Brain res.1985; 309: 177- 182

23. CELLULAR MECHANISM
Ca++
Ca++ – Decrease in action
potential due to
Ca++ hyperpolarization
2A
2AR
Go Gk K+
– + K+
K+
Decrease in
influx of Ca++

24. CNS ACTIONS
• Sedation – central, G-proteins (inhibition)
• Analgesia – spinal cord, Substance P
Dexmedetomidine

25. CNS ACTIONS
• Sedation, resembles the physiologic sleep
with less prominent respiratory depression
• Action is supposed to be mediated through
α2A subset of receptors and is very specific
for dexmedetomidine as compared to
clonidine
• Are easily arousable and additional sedative/
adjuvant is not needed to maintain the
sedation
•Hunter JC, Fontana DJ, Hedley LR et al. Assessment of the role of alpha 2 adrenoceptor subtypes in anti nociceptive , sedative and
hypothermic action of dexmedetomidine in transgenic mice Br J Pharmacol1997; 122: 1339-1344
•Venn RM, Bradshaw CJ, Spencer R et al. Preliminary UK experience of dexmedetomidine, a novel agent for post operative sedation
in intensive care unit. Anaesthesia 199; 54: 1136-1142

26. Actions on Cardio-Vascular system
• Totally devoid of any direct effects on
myocardium
• transient increase in BP : attributable to
peripheral vasoconstriction due to
stimulation of α2B adrenoreceptors in
peripheral vascular smooth muscles.
• significant bradycardia & Hypotension
• Secondary to central inhibitory α2A agonist
effect
• all these effects can be offset or overcome
with use of atropine, ephedrine or volume
loading

27. PHARMACOKINETICS
• Intravenous:
– Distribution t1/2 = 6 minutes
– Elimination t1/2 = 2 hrs
– VDSS – 118 liters – 94% protein bound
• Intramuscular (2µg/kg):
– Peak plasma conc 13 18 min (variable)
– 70% bioavailability
• Enteral:
– Buccal - 80% bioavailability
– Gastric - 16-20% bioavailability

28. Biotransformation and Excretion
• Through liver with minimal unchanged
fraction
• 95% of this metabolized portion is excreted
through kidney
• metabolites do not have any significant
pharmacological activity
• Thus liver dysfunction may adversely affect
the clearance of drug
• Impaired renal dysfunction is not known to
change the pharmacokinetics of the drug
•Gertler R, Brown H, Mitchell D and Silvius E Dexmedetomidine: a novel- sedative – analgesic agent.
Proc (Baylor Univ med Cent) 2001;14(1): 13-21 www.baylorhealth.com

29. Clinical Administration
• Onset of 30 minutes as compared to that of
midazolam 3-5 minutes and that of propofol
30-50 seconds
• can be decreased by infusion of standard
loading dose of 1µg/kg, over 10 minutes
• Duration of analgesic action of about 4 hours
as compared to that of Fentanyl up to 60-80
minutes
• Offset of sedative action in 5 minutes, while
midazolam has about 2 to 6 hours and
propofol has 3-8 minutes.

30. Indications & Dosage
• A pre-anaesthetic medication and as a
psychosedation in short outpatient surgical
procedures
• initial loading dose of intra venous infusion
of dexmedetomidine 1- 6 µg / kg for 10
minutes till 3 on Mackenzie’s Sedation
assessment score (till the patient showed
awakening responses to calling in spite of
closed eyes) and maintained on
0.4 µg/kg/hr
•Taniyama K, Oda H, Okawa K et al. Psychosedation with dexmedetomidine hydrochloride during
minor oral surgery. Anesth Prog 2009; 56:n75-80

31. Indications & Dosage
• In the dose of 0.2 to 0.7 µg/kg/hr, found to
atenuate the stress induced sympatho
adrenal responses to laryngoscopy,
endotracheal intubation, surgical stimulation
and provide overall increased hemodynamic
stability & as an adjuvant to other
anaesthetic agents, including inhalational
agents like isoflurane
Bhatia P. Dexmedetomidine: a New agent in Anaesthesia & Critical care Practice. http://dexmedtomidine.com
Aanta R, Jaakola ML, Kallio A, Kanto J. Reduction of minimum alveolar concentration of isoflurane by dexmedetomidine
.Anesthesiology 1997;80 : 1055-1060

32. Indications & Dosage
• Can be used to obtund the autonomic
pressor response due to laryngoscopy and
endotracheal intubation
• In the dose of 1 µg / kg diluted in 100ml of
saline solution, infused over 15 minutes
• After a stabilization period of 5 minutes
• Suitably induced, relaxed & trachea
intubated

33. Indications & Dosage
• an intra-operative analgesic in GA as an
alternative to opioids
• as a post-operative analgesic
• More so used as a sole sedative and analgesic
combined in Critically ill patients on Ventilator
• Infusion of standard loading dose of 1µg/kg,
over 10 minutes followed by maintenance of 0.2-
0.7 µg/kg/hr. diluted in 0.9 % normal saline
Scheinin B, Lindgren L, Bandel T, Scheinin H, Scheinin M. Dexmedomidine attenuates sympatho adrenal responses to
tracheal intubation and reduces need for thiopentone and peri-operative fentanyl Br J Anaesth 1992; 68: 126-131
Menda F, Koner O, Sayin M, Ture H et al. Dexmedetomidine as an adjunct to anaesthetic induction to attenuate
hemodynamic response to endotracheal intubation in patients undergoing fast track CABG. Ann Can J Anaesth 2010’
13: 16-21

34. Indications & Dosage
• It has been found to provide neuro-
protective effect by decreasing cerebral
blood flow without increasing either with
cerebral metabolic rate (CMRO2) or intra
cranial pressure (ICP)
• sole sedating agent with local anesthetic
agents in a high risk patient
• used as anti-shivering and for
thermoregulation
•Zornov MH, Maze M, Dyek JB. Shafer SL. Dexmedetomidine decreases cerebral blood flow velocity in humans J
Cereb Blood Flow Metab 1993; 13: 350-352
•Rich JM. Dexmedetomidine as a sole sedating agent with local anesthesia in a high risk patient for axillo-femoral
bypass graft: a case report. AANA Journal2005; 73:357-360

35. alpha 2 Adrenergic Receptor
Antagonist
Atipamezole
• Effectively reverses Psychomotor side-
effects
• Reverses Sedation & Sympatholysis
• Reverses Analgesia
• t ½ is 1 ½ - 2 hours.

36. To compare the efficacy of
Dexmedetomidine vs Fentanyl
as sedative & analgesic in short general
anaesthesia in day care obstetric &
gynaecological surgeries

37. AIMS AND OBJECTIVES
•To compare the time required for onset and offset
of sedation, quality of intra-operative & post-
operative analgesia and the time required for post-
operative recovery using Inj. Dexmedetomidine
and Inj. Fentanyl
• To evaluate cardio-respiratory and any other
systemic side effects at equi-sedative doses

38. METHODOLOGY
• Age group 18 - 65 years of ASA-I & II
•Randomized into two equal groups of ten each by
computer generated model
•Pre-medicated with Inj. Glycopyrrolate 0.2mg i.v.
• Group A: patients received Inj. Dexmedetomidine
1μg/kg i.v. 10 min. prior to induction by infusion
• Group B: patients received Inj. Fentanyl 1μg/kg i.v.
10 min. prior to induction by infusion

39. METHODOLOGY
• Induction done with Inj. Propofol 2mg/kg i.v in titrated dose
• Maintained with 66% N2O, 33% Oxygen & Isoflurane ( 0.6 –
0.8 %) with the patient breathing spontaneously on Magill circuit
• Time to eye opening at the conclusion of surgery was recorded
• In post anaesthesia care unit patients were evaluated
periodically for
- vitals
- sedation using Ramsay sedation scale
- visual analog scale
- time of rescue analgesia (when VAS >5)
- Standard Aldrete score for post anaesthesia recovery

40. RESULTS
• Demographic profile for Age, Sex and ASA grade had no
statistical significance & hence were comparable
• The requirement of Propofol was significantly reduced in Dex
Group
• Comparison of pulse rate in Dexmedetomidine Group
showed significant fall immediately after pre medication ,
without any intervention it returned to baseline, & remained
equivalent to that in Fentanyl Group throughout surgery
Line diagram showing comparision of pulse rate in study groups
• 90
80 P < 0.05 after premedication.
70
60
Average
50
Group A
Group B
40
30
20
10
0
On table AFT PMD AFT IND At 5 min At 10 min At 15 min At end Post - op
PR

41. RESULTS
Line diagram showing comparision of systolic blood pressure in study
groups
125
120
115
110
Average
No significant change in blood pressure
Group A
• 105
Group B
100
seen in Dex. group whereas continuous 95
90
On table AFT PMD AFT IND At 5 min At 10 min At 15 min At end Post - op
fluctuation of systolic BP seen in SBP (mm Hg)
fent.group 110
Line diagram showing comparision of SPO2 in study groups
100
90
80
• No significant change in diastolic BP & 70
Average
60 Group A
50 Group B
Respiratory rate seen in any of the groups 40
30
20
10
0
On table AFT PMD AFT IND At 5 min At 10 min At 15 min At end Post - op
• significant fall in saturation was observed SPO2
Bar chart showing comparison of eye opening after surgery in study
with Fentanyl group group
7
• The time of eye opening is highly
6
5
Group A
4
Average
significantly early in Dex. group (p<0.001)
Group B
3
2
and delayed eye opening seen with 1
0
fentanyl group Eye opening after surgery (min)

42. RESULTS 8
Line diagram showing comparision of VAS score in study groups
• The post operative analgesia duration was 6
more in Dex. group (approx. 4-6 hrs.),
Average
Group A
4
Group B
whereas in Fentanyl group patients required 2
rescue analgesia within 1 – 1.5 hrs of surgery
0
At End of surgery At 30 m in At 1 hr At 1.5 hr At 2 hr
VAS Score
P < 0.001 at 1.5 hrs.
Line diagram showing comparision of Ramsay sedation in post operative in study
• The sedation was highly significantly
groups
4
profound in fentanyl group according to 3
Average
Group A
Ramsay sedation score (p < 0.001) after 15
2
Group B
1
min of surgery 0
End of surgery At 15 m in At 30 m in At 1 hr At 2 hr
Ram say sedation
• The quality of recovery was highly P < 0.001 at 15 min.
Line diagram showing comparision of standard aldrete score in post operative in study
groups
significantly better (Aldrete score = 9+)was 12
10
observed in most of the patients after 30 min 8
Average
Group A
6
Group B
in Dex.group & Similar results were seen 4
2
only after 1.5 – 2 hrs. in Fentanyl Group 0
End of surgery At 15 m in At 30 m in At 1 hr
Standard aldrete score
At 1.5 hr At 2 hr
P < 0.001 at 15,30, 60 min.

43. TO EVALUATE THE EFFECT
OF ADDITION OF
DEXMEDETOMIDINE TO 0.5%
HYPERBARIC BUPIVACAINE
INTRATHECALLY

44. AIMS & OBJECTIVES
• To study the onset and duration of analgesia with the
addition of 10 µg Dexmedetomidine to 0.5% heavy
Bupivacaine in sub-arachnoid block
• To evaluate the quality of block and post operative
analgesia as compared to control i.e. 0.5% heavy
Bupivacaine
• To observe any side effects of intrathecal administration
of Dexmedetomidine with 0.5% Bupivacaine intra
operatively and post operatively

45. METHODOLOGY
• Patients of ASA I,II and age group 18-65 years were
randomized into two equal groups of 20 each by a
computer generated model
• Group A (Dexmedetomidine Group) were given 3ml of
0.5% heavy Bupivacaine + 0.5ml (10 µg) of
Dexmedetomidine
• Group B (Control Group) were given 3ml of 0.5% heavy
Bupivacaine + 0.5ml of Water for injection
• Patients will be preloaded with Ringer Lactate solution
10 ml/kg body
• Spinal anaesthesia was given using a 26G Quincke’s
needle in sitting position through a midline approach

46. METHODOLOGY
• Sensory block was tested by pinprick method till T6
sensory level
• Degree of motor blockade was assessed by modified
Bromage scale
• Intraoperative vitals were monitored
• Hypotension: SBP < 90 mm Hg or a decrease of >20%
from baseline. Hypotension was treated with a bolus
administration of 250 ml Ringer lactate and 6 mg of i.v.
Mephentermine if required
• Bradycardia was defined as HR < 50 bpm and was
treated with 0.6 mg of i.v. Atropine
• Postoperatively, 2 segment sensory regression, motor
regression and time to rescue analgesia were monitored

47. RESULTS
• No statistically
significant difference
for age, height ,
weight, Sex wise and
ASA distribution in
both groups

48. RESULTS
• Difference in sensory onset
not statistically significant
• Motor onset significantly
shorter in Dexmedetomidine
Group (t value-2.54,
p value < 0.05)
Multiple bar diagram showing comparison of time of sensory and motor
Peak after spinal anesthesia in study groups • Difference in peak sensory
8
insignificant
7
6
• Peak motor significantly
5
Average
4 Group A
Group B
3
2 longer in Dex Group(t value-
1
0
4.59, p value<0.0001)
Time of Peak sensory (T3) Time of Peak motor(T4)
After spinal anesthesia

49. RESULTS
Parameters Group A Group B t P Value
Mean SD Mean SD Value
(n=20) (n=20)
2 segment sensory 190.3 34.80 98.65 14.95 10.81 <0.000
regression (T5) 1
Motor regression 265.05 57.50 138.7 14.76 9.51 <0.000
(T6)
Time of rescue 342.75 76.94 189 20.71 8.62
1
<0.000 • 2 segment sensory
analgesia (T7) 1
regression
• motor regression
Multiple bar diagram showing comparison of level of sensory blockade
in study groups
350
300
and
250
• time of rescue
200
analgesia
Average
150 Group A
significantly longer
Group B
100
50
0
in Dex. Group
2 segment sensory Motor regression Time of rescue
regression (T5) (T6) analgesia (vas > 7)
(T7)
Level of sensory blockade

50. Multiple bar diagram showing side effect wise distribution of cases in
study groups
4
• Both groups with
3
manageable
No. of cases
2 Group A
Bradycardia &
Group B
1
0
Bradycardia
Side effect
Hypotension
Hypotension
Line diagram showing comparision of systolic blood pressure in study Line diagram showing comparision of diastolic blood pressure in study
groups groups
140 90
80
120
70
100
60
80
Average
Group A
50
Average
Group B Group A
60 Group B
40
40
30
20 20
0 10
op
in
in
in
in
in
in
ry
op
0
m
m
m
m
m
m
ge
t-
–
0
5
0
5
0
t3
ur
os
re
t1
t1
t3
t4
t6
Pre – op At 3 min At 10 At 15 At 30 At 45 At 60 End of Post -
S
A
P
P
A
A
A
A
A
of
min min min min min Surgery op
nd
E
DBP (mm Hg)
SBP (mm Hg)
Line diagram showing comparision of heart rate in study groups
100
90
80
70
60
Average
Group A
50
Group B
40
30
20
10
0
op
in
in
in
in
in
in
ry
op
m
m
m
m
m
m
ge
t-
–
0
5
0
5
0
t3
ur
os
re
t1
t1
t3
t4
t6
S
A
P
P
A
A
A
A
A
of
nd
E
HR (min)

51. To compare the Sedation and Analgesia
produced by Dexmedetomidine and
Butorphanol in Critically Ill patients on
Mechanical Ventilation: A Randomized
Double Blind Controlled Trial

52. AIMS AND OBJECTIVES
• To compare inj. Dexmedetomidine with inj. Butorphanol as
sole sedative and analgesic in mechanically ventilated
patients in ICU.
• Compare their effects on hemodynamic parameters,
autonomic system, post extubation agitation, GCS, nausea,
vomiting etc.
• Evaluate whether their use reduces the requirement of
neuromuscular blocking drug: Vecuroneum.
• To compare their cost effectiveness in patients on
mechanical ventilation.

53. MATERIALS AND METHODS
• 20 patients of 20-60 years who needed mechanical ventilation
for post operative or non operative indication.
• As soon as the patient was shifted to the ICU on ventilator
(MAQUET SERVO- S ventilator), vital parameters were noted
and infusion of the specific drug was started using the syringe
pump.
• Inj. Dexmedetomidine was started at the rate of 0.7µg/kg/hr
and Inj. Butorphanol was started at the rate of 5µg/kg/hr.
• Muscle relaxant was given as and when required, while
monitoring pulse , blood pressure, peak airway pressure and
trigger on the ventilator

54. • Vital parameters were recorded at regular intervals
• Time interval between the muscle relaxant doses noted
• The total required dosage of muscle relaxant was
calculated after extubation
• Patient’s score on Glasgow Coma scale and Brussels'
sedation score were noted the next day early morning
when the muscle relaxants were discontinued and
patients were given a trial of weaning
• Infusion of the drug was continued until weaning off of
the patient from the ventilator or for 24 hours
which ever was less

55. RESULTS
Demographically there was no significant difference in the 2 groups.
Bar chart showing comparison of average time interval between M.R
dose in study group
70
Time interval between
65
60
55
the muscle relaxant
doses was nearly
50
45
40 Group A
Average
Group B
double in
35
30
25
20
15
10
Dexmedetomidine
5
0
Average time interval between M.R dose (min) group, hence the
Bar chart showing comparison of total requirement of M.R in study
requirement of muscle
group
relaxant was nearly half,
30
suggesting an excellent
25
quality of sedation and
20
Group A
analgesia.
Average
Group B
15
10
5
0
Total requirement of M.R (mg)

56. RESULTS
Haemodynamically patients in both A and B groups were stable
Bar chart showing comparison of sedation score in study group
0.8
Patients receiving Butorphanol
0.7
were drowsier as assessed by
Brussels’ sedation score but it
0.6
0.5
Group A
Average
Group B
0.4
0.3 was not statistically significant;
0.2
0.1
0
Sedation score
Bar chart showing comparison of total no of hrs on ventilator in
study group
Butorphanol group patients
needed about 30-60 minutes
18
16 more to be weaned off from
the ventilator
14
12
Group A
Average
10
Group B
8
6
4
2
0
Total No of hrs on ventilator (hr)

57. RESULTS
Line diagram showing comparision of respiratory
rate in study groups
16
14
Respiratory rate during weaning
12 and after extubation was
10
significantly low in Butorphanol
Average
Group A
8
Group B
6
Group, suggesting some amount
4
2 of respiratory depression
0
T0 T1 T2
RR
Bar chart showing comparison of Nausea / vomiting in study group Few patients in Butorphanol group
complained of nausea and
6
vomiting during weaning and
5
after extubation where as there
4
Group A was no such complaints in patients
No of cases
Group B
of Dex. group
3
2
1
0
Nausea / vomiting

58. Indications: Under Trial
• Use of dexmedetomidine for post –
operative analgesia given via epidural
route
• Use of dexmedetomidine as an
adjuvant to Local Anaesthetic Mixture
given via supra-clavicular Brachial
Plexus approach

59. Indications: Future plans
• Use of dexmedetomidine as an
adjuvant to Local Anaesthetic Mixture,
in peri- bulbar block

60. MULTI MODAL ANALGESIA
(MMA)
The rationale for multimodal analgesia is
achievement of sufficient analgesia due to
additive or synergistic effects between different
analgesics, with concomitant reduction of side
effects, due to resulting lower doses of
analgesics and differences in side-effect profiles.
1. Kehlet H et al. Anesth Analg 1993;77:1048-56.

61. “Real World”: Multimodal Analgesia
• Reduced doses
Opioids
• Improved pain relief
• Reduce severity
Potentiation of AEs
• Earlier discharge
Non opioids :α2 agonists
NSAIDs, coxibs,
paracetamol, • Decreased costs
nerve blocks
Kehlet et al. Anesth Analg. 1993;77:1048-1056 (B).

62. Preventive Multimodal Analgesia
• Significant improvement in
– Pain reduction
– Opioid use
– Opioid-related AEs
– Recovery or day ward length of stay
– Unplanned admission to the hospital
Reuben et al. Acute Pain. 2004;6:87-93.

63. Multimodal analgesia - methods
• Preemptive analgesia
• Analgesics
– Single shot
– Infusions
– PCA
• Nerve blocks
– Single shot
– Indwelling catheter
• Local wound infiltration

64. Multimodal analgesia should consist of….
Combination of Agents
• Newer ‘Novel’ Centrally acting I. V. Non-Opioid agents
2-agonists
Parenteral Paracetamol
NSAIDs, COX-2 selective inhibitors (coxibs)
Ketamine , Tramadol, Neostigmine
Gabapentin / Pregabalin
• Opioids
• Local anaesthetics: local anaesthetic block
– Local infiltration
– Local nerve block
– Plexus nerve block
– Neuraxial block

65. Proposed Protocols MMA- I
• Pre-medication/ Analgesia with Dexmedetomidine
• Dose: 1 µg/ kg I.V. for 10 minutes
• Induce with small dose of Propofol
• Rocuroneum for Intubation/ Maintenance
• Inhalational iso or sevoflurane
• Near end of surgery I.V. Paracetamol- 15mg/ kg- upto
1g max.
• Continue every 4-6 hourly , till NBM status, switch to
oral NSAID/COXIB
• Dexmedetomidine infusion: Post operative or ICU
sedation/analgesia in ventilated patients: Dex. 0.5
µg/kg/hr infusion

66. Proposed Protocols MMA- II
• Neuraxial Blockade with 0.75% ropivacaine;
3 ml intra-thecal or 12-15 ml epidural
• Sedation with Dexmedetomidine : 0.2 to 0.7
µg/kg/hr.
• Post-op analgesia with : either epidural LAA
with or without adjuvant; like clonidine 75µg,
midazolam 0.5 mg, fentanyl 25-50 µg
• I V Paracetamol &/ or Dexmedetomidine

67. Proposed Protocols MMA- III
Point Modifications
• Addition of clonidine 1 or 1.5 µg/kg to bupi. In
peri-bulbar/ Supraclavicular /axillary block
• Addition of dexmedetomidine 10 µg (0.5 ml) or
fentanyl 0.5 - 1 µg/kg to 3.5 ml Bupivacaine
intra-thecally
• Addition of clonidine 75µg (0.5ml) to 3 ml
bupivacaine intra thecally
• Dex : I.V. 1 µg/kg as an Intraop analgesic for day
care/ short GA Spont. Respn.

68. Summarizing
• Alpha2 adrenoceptor agonists are very unique
class of drugs
• imidazole group
• latest entrant: Dexmedetomidine
• mimics many of the actions of mythical
‘ideal’ sedative/analgesic agent
• wide spectrum of actions encompassing the
entire peri-operative period and then beyond
that, into the critical care services/ as a part of
Multi-Modal Analgesia

69. Conclusion
• Dexmedetomidine is revolutionizing, the intra-
venous anaesthesia
• Changing pre-operative sedation, pre-
anaesthetic anxiolytic medication and even the
day care procedures like conscious sedation
• changing our viewpoint of providing intra and
post- operative analgesia, without any potential
and significant side-effects of existing agents
employed for this purpose.

70. Conclusion
• In critical care setting as a sedative/ analgesic,
without much deleterious effects, morbidity
and dependence of the patients on the
ventilators.
• It’s use via various other routes, than;
conventional intra-venous route such as
neuraxial, regional is taking the drug into New
Frontiers
• All these indications with an enviable safety
profile makes it a very promising, desirable
and dependable drug!!

71. Take Home Message!
• Quest for an ‘Ideal’ peri-operative sedative-
analgesic goes on… &… on…&….on!!
• α2 agonists are unique class of drugs, with
many desirable properties!!
• Clonidine and now dexmedetomidine, are
versatile, multi-faceted and potent drugs!!!
• With more evidence, it’s value is more or less
clearly established, as sole or as part of
MMA!!!!
• It is revolutionizing the modern anaesthetic
practice!!!!!

72. Take Home Message!
On the basis of available evidence &
self experience
• No Hesitation in making it a part of my
Anaesthetic Practice
&
• No Hesitation in recommending it, to
others to do so!!