Dexmedetomidine by tushar chokshi

1. Dr. Tushar Chokshi
Anesthesiologist
Vadodara
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Non Opioid Sedative Analgesic
and Anesthetic

2. From all kind of Happiness
available to Mankind,
Relief from pain is number one
Proud to be Anaesthesiologist 2
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3. How many of you are using Dexmedetomidine?
What is your experience of Dexmedetomidine ?
Will you give Dexmedetomidine in your practice ?
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4. Lecture Outline
- History of Dex
- Mechanism of Action of Dex
- What is Ideal Anesthetic Agent
- Different Systemic Actions of Dex
- Clonidine and Dexmedetomidine
- Pharmacokinetics and Pharmacodynemics
- Indications and Dosage
- Contraindications
- Commercially available preparations
- Antagonist of Dex
- Journal Articles
- My Experience
- Future of Dex
- Take Home message
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5. > Developed by Orion Pharma, as Precedex <
> Approved in December 1999 by FDA <
> Available in Market from August 2000 <
> Agonist of α2-adrenergic receptors <
> Also used in veterinary anaesthesia for dogs and cats <
> Most ideal anesthetic agent available in this era <
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6. • It is the dextrorotatory S-enatiomer of medetomidine and
is chemically described as (+)-4-(2, 3-dimethyle phenyl)
ethyl-1 H-imidazole monohydrochloride with molecular
weight as 236.7 The empirical formula is C13H16HCl.
• Introduced as a short-term sedative and analgesic
(<24 hours) for critically ill or injured people on
mechanical ventilation in the intensive care
unit (ICU)
• In 2008 the FDA expanded its indication to include
nonintubated people requiring sedation for
surgical or non-surgical procedures, such as
colonoscopy
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7. Dexmedetomidine induces sedation by
decreasing activity of noradrenergic neurons
in the locus ceruleus in the brain stem,
thereby increasing the activity of
inhibitory gamma-aminobutyric acid (GABA)
neurons in the ventrolateral preoptic nucleus
Mechanism of Action
* Dex binds the α2 receptors of locus ceruleus and spinal cord
causing sedation and analgesia respectively
* In contrast, other sedatives like propofol and benzodiazepines
directly increase the activity of gamma-aminobutyric
acid neurons causing only sedation 7
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The locus coeruleus is a nucleus
In the pons of the brainstem
Involved with physiological
responces to stress and panic. It is a
Part of reicular activating system

9. Mechanisms of action
Dexmedetomidine (From Textbook)
An imidazole compound, is the pharmacologically active
dextroisomer of medetomidine that displays specific and selective α2-
adrenoceptor agonism.
The mechanism of action is unique and differs from those of
currently used sedative agents, including clonidine.
Activation of the receptors in the brain and spinal cord inhibits
neuronal firing, causing hypotension, bradycardia, sedation, and
analgesia.
The responses to activation of the receptors in other areas
include decreased salivation, decreased secretion, and decreased
bowel motility in the gastrointestinal tract; contraction of vascular and
other smooth muscle; inhibition of rennin release, increased
glomerular filtration, and increased secretion of sodium and water in
the kidney; decreased intraocular pressure; and decreased insulin
release from the pancreas 9
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These α2-Adrenoreceptor subtypes α2A, α2B, and
α2C are found every where in the central,
peripheral, and autonomic nervous systems, as well
as in vital organs and blood vessels

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15. Rapid onset of action
Rapid and predictable
recovery
Potent and lipid-soluble
Water-soluble to minimize
toxicity associated with
the solvent
Stable in solution
Chemically compatible
with other drugs
No perivascular
sloughing if
extravasated
Not absorbed by
plastics
Does not promote
bacterial growth
Devoid of adverse
side effects
Low cost
Most important it can
be mixed with other
anesthetic agents without
any complication
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16. Dexmedetomidine
fulfils
almost
80 % criteria's
of
Ideal Anesthetic Agent
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17. Dex Differs from other sedatives
• Patients sedated, but, arousable, alert and
respond without uncomfortable
• They may quickly return to sedation again
• Conscious Sedation as natural sleep
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22. The adverse effects of dexmedetomidine include
Hypotension
Hypertension
Dry Mouth
Nausea
Bradycardia
Atrial fibrillation,
Hypoxia
Overdose may cause
First-degree or
Second-degree atrioventricular block. 22
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-- Nasal - ~ 84 % bioavailability
The pharmacokinetic profile of dexmedetimidine is not altered by age

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and faeces 4%

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From Textbook
Dex Routes and Doses

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(MMA)

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34. So Dexmedetomidine used as
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35. / TIVA
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37. ICU
Fentanyl
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Use of Dex in the Elderly
In patients more than 65 y of age,
a higher incidence of bradycardia and
hypotension was
observed following dexmedetomidine
administration.
Hence a dose reduction is needed and renal
function should be monitored

41. Dexmedetomidine Relative 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%).
There is no absolute contraindication
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Available as Ampoules
50 mcg / 0.5ml
100 mcg / 1 ml
200 mcg / 2ml

43. Dexmedetomidine is compatible when administered
with the following intravenous fluids
0.9% sodium chloride in water
5% dextrose in water
20% mannitol
Lactated Ringer's solution
100 mg/ml magnesium sulfate solution
0.3% potassium chloride solution
With other Anesthetic agents like Propofol, Ketamine, Etomidate, & Midaz
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α2 adrenergic receptor antagonist
Released in 1996
Also use as Anti-Parkinsonian
Supplied at -20 degree and stable for two years
Of
Dex

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46. KPD TIVA (Ketamine, Propofol and Dex)
Mixture in 1:1:1 Dose for TIVA
Combination of all these drugs permit lower dose
of each individual agent for TIVA and reducing
their adverse hemodynamic and respiratory
effects which is very safe and important for
patient and anesthesiologist
The advantage is low dose of each agent as
compared to full dose
Excellent analgesia and anesthesia
 dose of individual
agents
 airway complications
Stable haemodynamics Rapid recovery 46
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47. KPD
• In my 80 % practice I use this mixture
• In all TIVA cases
• For maintenance intraop I use Dex infusion
depends upon surgery, surgical time and vital
parameters
• I put 100 mcg Dex in RL 500 ml during intraop
• Maximum user of Dex
• Started concepts of Opioid Free Multi Model
Analgesia and Anesthesia with Dex in TIVA
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48. Ketodex
Ketamine 1mg / kg + Dex 1 mcg / kg
Useful in Pediatric patients
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Dex is primary Agent for sedation and Analgesia

50. Dex in S/A
• I have completed almost 200 patients adding Dex in
S/A
• The effect is extended doubled and analgesia is
lasting for 10 to 15 hrs
• I usually add 20 mcg Dex in S/A drugs
• Usually patient is consciously sedated and no need to
give other sedation
• I keep Atropine or Diluted Adrenaline ready if heart
rate goes below 45/minute
• No major or minor side effects noted
• Selection of patients are most important and I avoid
patient with baseline heart rate of 50 or below 50 per
minute
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Dex and Bradycardia
Because of double effect

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Exp Ther Med. 2016 Jan; 11(1): 360–366.
Published online 2015 Nov
17. doi: 10.3892/etm.2015.2872
PMCID: PMC4726941
PMID: 26889269
Effects of different doses of
dexmedetomidine on heart rate and blood
pressure in intensive care unit patients
XIAOYAN ZHANG, RUILAN WANG, JIAN
LU, WEI JIN, YONGBIN QIAN, PEIJIE
HUANG, RUI TIAN, and YAN LI
Loading dose of Dex is 0.5 mcg/Kg over 10 minute
Maintenance dose of Dex 0.4 mcg/kg/hr

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There was a correlation between the change in heart rate during natural sleep
and dexmedetomidine sedation. The bradycardia that occurs when using
dexmedetomidine may be one of the normal changes, and this may be observed
rather than corrected

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J Clin Anesth. 2016 Dec;35:13-19. doi:
10.1016/j.jclinane.2016.07.012. Epub 2016 Aug 4.
Anticholinergic premedication to prevent bradycardia in
combined spinal anesthesia and dexmedetomidine sedation: a
randomized, double-blind, placebo-controlled study.
Ahn EJ, Park JH, Kim HJ, Kim KW, Choi HR, Bang SR.
CONCLUSION:
Prophylactic atropine reduces the incidence of bradycardia in
patients undergoing spinal anaesthesia with
dexmedetomidine sedation. However, DBP and MBP showed
significant increases in patients when prophylactic atropine
was administrated. Therefore, atropine premedication should
be administered cautiously

55. Dex and Blood Pressure
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Second Effect due to Dex Vasodilatation caused by relaxation of smooth muscle cells in
arteries causes an increase in blood flow. When blood vessels dilate, the blood flow is
increased due to a decrease in vascular resistance. Therefore, dilation of arteries and
arterioles leads to an immediate decrease in arterial blood pressure and heart rate
First Effect due to Dex Vasoconstriction reduces the volume or space inside affected blood
vessels. ... This causes higher blood pressure
Peripheral Effect
Increase
BP
Central Effect
Decrease
BP

56. • The hypertension is to be due to an initial, direct
stimulation of alpha-1 or alpha-2b receptors
peripherally, resulting in vasoconstriction. This
phenomenon resolves with subsequent central alpha-
2a receptor stimulation, which exerts a stronger effect
causing hypotension and bradycardia. This is known as
a biphasic blood pressure response
• The hypertension associated with dexmedetomidine is
usually mild, transient and not requiring treatment
• This effect is only seen when Dex is given in bolus dose
and not seen in slow infusion over 10 to 30 minutes
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Total around 5000 Articles on Dexmedetomidine
From 2000 to 2018 in PUBMED

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The potent and highly selective α 2 adrenergic dexmedetomidine
not only provides unique type of sedation and analgesia with minimal
side effect, but also have a special antiarrhythmic effect. It can be used
as an adjunct to other conventional antiarrhythmics.
DEX appears to be a useful antiarrythmic agents for the prevention
and treatment of arrhythmias especially those of supraventricular in
origin.
Conclusions

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Dexmedetomidine is not currently
approved by the Food and Drug
Administration (FDA) for the paediatric
population, but findings have shown it
to be effective in various clinical
scenarios for sedation and more than
200 journal articles are there

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Dexmedetomidine in Children: Current Knowledge and Future
Applications
Mason, Keira P. MD*; Lerman, Jerrold MD, FRCPC, FANZCA†
Anesthesia & Analgesia: November 2011 - Volume 113 - Issue 5 - p
1129–1142
doi: 10.1213/ANE.0b013e31822b8629
Pediatric Anesthesiology: Review Article
More than 200 studies and reports have been published regarding
the use of dexmedetomidine in infants and children
REVIEW ARTICLES
Dexmedetomidine: review, update, and future
considerations of paediatric perioperative and
periprocedural applications and limitations
M. Mahmoud1,* and K. P. Mason2
1Department of Anesthesiology, Cincinnati Children’s Hospital Medical
Center, 3333 Burnet Avenue, Cincinnati,
OH 45229, USA, and 2Department of Anesthesiology, Perioperative, and
Pain Medicine, Boston Children’s Hospital
and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115,
USA

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Saudi J Anaesth 2016 Oct-Dec; 10(4): 390–394.
doi: 10.4103/1658-354X.177333
PMCID: PMC5044721
PMID: 27833480
A comparison of oral midazolam and oral dexmedetomidine as premedication in
pediatric anesthesia
V Jannu, RS Mane, MG Dhorigol, and CS Sanikop
Conclusions:
In this study, premedication with oral dexmedetomidine produced equally
effective preoperative sedation and a better recovery from anesthesia in children
in comparison to oral midazolam.
Anesth Pain Med. 2015 Jun 22;5(3):e25032. doi: 10.5812/aapm.5(3)2015.25032.
eCollection 2015 Jun.
Oral Dexmedetomidine Versus Midazolam as Anesthetic Premedication in
Children Undergoing Congenital Heart Surgery.
Faritus SZ1, Khazaee-Koohpar M1, Ziyaeifard M, Mehrabanian MJ
CONCLUSIONS:
It appears reasonable to apply oral premedication with dexmedetomidine 45
minutes before transferring the patient to the operating room when he or she is
more prone to resist inhalation anesthesia induction.

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65. Dex as Anti shivering agent
Post S/A shivering, Dex is given in dose of 15
to 20 mcg, either IV or Intrathecal gives
excellent result to control shivering
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Intranasal Dex
More than 132 Journal articles
Nasal - 84 % bioavailability

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Dex combined with L/A blocks
0.5 mcg/kg Dex is ideal dose

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Dex and Intravenous Regional Anesthesia

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0.5 mcg/kg Dex is ideal dose

71. Future of Dex
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72. Dexmedetomidine TCI model
Hannivoort and Dyck
Will be launched in 2019
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DEX
Analgesia
Anesthesia
Given
By
All Routes
Combine
With
Any Drug
Conscious
Sedation

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78. Sileo Gel for Dogs
(Dexmedetomidine Oromucosal Gel)
0.09 mg/ml, 3 ml syringe. Sileo
is the first and only FDA-approved
prescription medication for the treatment
of canine noise aversion
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79. Patient wants Analgesia with Anesthesia
Start Using Dex

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USE
USE
USE
USE
USE
USE
USE
USED
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