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Dexmedetomidine
For Intraoperative
Sedation
&
Analgesia
Dr. Mrs. Minnu M. Panditrao
CONSULTANT
DEPARTMENT OF ANESTHESIOLOGY &
INTENSIVE CARE
Public Hospital Authority’s
RAND MEMORIAL HOSPITAL
FREEPORT, GRAND BAHAMA
COMMONWEALTH OF THE BAHAMAS
FORMERLY:
Professor
Department of Anaesthesiology and Critical
Care
Dr. D Y Patil Medical College
Pimpri, Pune, India
alpha 2 Adrenergic Receptor Agonists
• Imidazole class of drugs
• Older drugs : xylazine
detomidine
medetomidine
in veterinary medicine!
• Clonidine : first agent ( in humans)
•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
alpha 2 Adrenergic Receptor Agonists
Dexmedetomidine
What is so special about it?
Dexmedetomidine
• a D – enantiomer of medetomidine
• New Entrant in this class
• approved in 1999 by FDA for clinical
application in humans
• Structure:
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
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
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
CNS ACTIONS
Dexmedetomidine
• Sedation – central, G-proteins (inhibition)
• Analgesia – spinal cord, Substance P
CELLULAR MECHANISM
Ca++
Ca++
Ca++
–
– +
Decrease in
influx of Ca++
Decrease in action
potential due to
hyperpolarization
2A
2AR
Go Gk K+
K+
K+
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
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
Clinical Uses of Dexmedetomidine
• Craniotomy:
aneurysm, AVM
• Cervical spine
surgery
• Conventional CABG
• Off-pump CABG
• Vascular surgery
• Thoracic surgery
• Bariatric surgery
• Back surgery, evoked
potentials
• Head injury
• Burn
• Trauma
• Awake intubation
Clinical Uses of Dexmedetomidine
Sedation in CT and MRI imaging studies
Mason K, Ped Anesth 2008
Koroglu A, Anesth Analg 2006
Outpatient third molar surgery
Ustin Y, J Oral Maxilfac Surg 2006
Cheung C, Anaesthesia 2007
Cataract surgery
Alhashemi J, Br J Anaest 2006
Cardiac catheterization
Tosun Z, J Card Vasc Anesth 2006
Mester R, Am J Therap 2008
GI Procedures
Demiraran Y, Can J Gastroenter 2007
Dex may be a good alternative to midazolam for upper
endoscopy
Dex: Use in Coronary Artery Surgery
Coronary Artery Surgery Patients
Dexmedetomidine : Herr study, n=300: Dex vs. controls [propofol]
• Faster time to extub in dex gp - by 1 hr
• 70% did not require morphine vs. 34% controls
• Dex pts had less Afib (7 vs 12 pts)
Herr DL: Crit Care Med 2000;28:M248. Washington Hospital
CABG and Lung Disease
• RCT, n= 20. Dex started at end of surgery, 0.2 to 0.7 ug/kg/hr, + continued 6
hr after extubation vs. controls (propofol)
Dexmedetomidine
• Faster time to extub: 7.8 + 4.6 h v. 16.5 + 11.8 h
• No difference in PaCO2 between gps 30 min after extub: 37.9 v. 34.9 mmHg
Sumping ST: CCM 2000;28:M249. Duke
Dex: Use in Thoracotomy + Thoracoscopy
Thoracotomy + thoracoscopy patients
• COPD, pleural effusion, marginal pulmonary function, pCO2 + pO2 with opioids
• Thoracic epidural: mainly for thoracotomy, Dex: mainly for thoracoscopy
Dexmedetomidine
• Patients are arousable, but sedated
• Does not ventilatory drive
• Greatly need for opioids
• Alternative to thoracic epidural
• Continue after extubation
Vascular surgery
• Usually at risk for CAD, ischemia, HTN, tachycardia
• Dex attenuates periop stress response
• Dex attenuates BP w AXC, especially thoracic aorta
Dexmedetomidine: RCT, n=41. Dex continued 48 hr postop
• HR in dex gp at emergence- 73 + 11 v. 83 + 20 bpm
• Better control of HR, Plasma NE levels in dex group
Talke et al: Anesth Analg 2000;90:834. Multicenter
Dex: Use in Other Surgical Procedures
Abdominal surgery
• Dexmedetomidine provides analgesia without respiratory depression
• Especially useful in elderly undergoing colon resections, TAH, + other stressful
procedures
Bariatric surgery
• Dexmedetomidine Improves Postop Pain Mgt after Bariatric Surgery
• Morphine use in dex gp
• Pain score better in dex gp: 1.8 vs 3.4 , % time pain free in PACU in dex gp: 44% vs 0
• Better control of HR in dex gp
Neck + back surgery
• Dex causes minimal effect on SSEP monitoring
• Smooth emergence, especially cervical spine
• Easy to evaluate neuro function prior to + after extubation
Ramsay MA, et al: Anesthesiology, 2002: A-910 and A-165. Baylor
Dex: Use in Other Surgical Procedures
Burns patients
• 2 agonist effect assists in the management of burn patients; blunts
catecholamine surge
•Use in intubated and non-intubated burn patients
•Outpatient dressing changes instead of ketamine
Trauma and Alcohol withdrawal patients
•Benzodiazepines typically used- Intubation and ventilation often
required if extreme agitation
•Dexmedetomidine is an alternative to BZD- Spontaneous breathing,
Hemodynamic stability, Adequate sedation, Prevention of autonomic
effects of withdrawal, Pain control
Dex: Use in Neuro anesthesia
Effect of Dexmedetomidine on Cerebral Blood Flow
• Animal models
– Dex causes a reduction in CBF up to 45%
– Dex has no effect on the CMRO2
– Dex produces the concentration-dependent constriction of pial arteries and veins
– Dex limits hypercapnea- and hypoxia-induced cerebral vasodilation
Zornow MH et al, Anesth Analg; 1990
Fale A et al, Anesth Analg; 1994
Karlsson et al, Anesth Analg; 1991
• Human study (TCD)
– Mean CBF velocity decreased with an increase in plasma concentration of Dex
– Pulsatility index increased at higher level of Dex (indicates an increase in CVR)
Zornow MH et al, J Cereb Blood Flow Metab; 1993
Cognitive Function
• There is strong evidence that a2 – agonists improve prefrontal cortical function (PFC)
Arnstein et el. Arch Gen Psychiatry 1996
Dex: Use in Neuro anesthesia
Effect on ICP
• Animal model
– ICP was unchanged despite an increase in systemic blood pressure
in rabbits
– ICP was decreased in the presence of intracranial hypertension
Zornow MH et al, Anesth Analg 1992
• Human study
– Dex has no effect on lumbar CSF pressure in patients undergoing
transphenoidal pituitary tumor resection
Talke P et al. Anesth Analg 1997
Effect on SSEPs and AEP
• There is a lack of effect on cortical AEP
• Dex does not affect cortical (P25-N35) response
• Dex depresses median nerve P15-N20 amplitudes
Thornton C et al. Br J Anaesth 1999
Dex: Use in Neuro anesthesia
Antinociception
· a2 – Agonists attenuate hemodynamic responses to laryngoscopy and intubation
Lawrence CJ et al Anaesthesia 1997
· a2 – Agonists decrease peri operative oxygen consumption Taittonen MT Br J Anaesth
1997
• Dex reduces NE level during emergence from anesthesia (2 to 3 times lower than placebo)
Talke P et al. Anesth Analg 2000
Effect on BIS
• BIS values after Dex infusion for 1 hour were: 65 at 0.2 mg/kg/hr, 60 at 0.6 mg/kg/hr
• Volunteers readily awakened from hypnosis by talking ; BIS returned to awake level
BIS before and after subjects were asked to perform various tasks
Hall JE et al. Anesth Analg 2000
Dex: Use in Neuro anesthesia- Neuro protective effects
• Inhibition of ischemia induced NE release may be associated with
neuroprotection
• Dex prevents delayed neuronal death after focal ischemia
• Dex decreased total ischemic volume by 40% compared to placebo
Jolkkonen J et al. Euro J Pharm 1999
Hoffman WE et al Anesthesiology 1991
• Dex enhances glutamine disposal by oxidative metabolism in
astrocytes
Huang R et al. J Cereb Blood Metab 2000
Dexmedetomidine: Use in Craniotomy
Craniotomy for Aneurysm / AVM
Anesthesia considerations
• Smooth induction + emergence, Prevent rupture
• Avoid cerebral ischemia, Hypothermia (33 oC) CMRO2, CBF, CBV, CSF, ICP
Dexmedetomodine
• sympathetic stimulation
• or no change in ICP
• shivering w/o respiratory depression
• Preserved cognitive function- reliable serial neuro exams
Doufas AG et al: Stroke 2003;34. Louisville, KY
Craniotomy
• Postoperative infusion of Dex in patients recovering from transphenoidal
hypophysectomy reduced plasma catecholamines by 70%
Talke P et al Anesth Analg 1997
Dex Use in Neuro: Clinical Experience
Spinal Fusion
• Intraoperative switching from a propofol infusion to Dex in patients undergoing
cervical fusion resulted in:
– A neurological examination that was successfully performed in the OR on an
intubated patient
– Clinically insignificant hemodynamic changes during and after the switchover
Bloom M et al J Neurosurg Anesth 2001
Dex Use in Neuro: Clinical Experience
Carotid Endartrectomy
• A combination of superficial and deep cervical plexus blocks is the most
common regional anesthetic technique in the NYU medical center
• Sedation with dexmedetomidine (0.2-0.4 mcg/kg/hr) offers a comfortable
and cooperative patient during the operation
• Less agitation and respiratory depression than with a continuous infusion
of propofol or repeated doses of fentanyl and/or midazolam
Functional Neurosurgery
• Dex infusion at 0.1 – 0.2 mcg/kg/hr allowed us to achieve a tranquil state
sufficient to complete neuropsychiatric testing required for mapping of the
cortical speech area, as well as to perform an awake tumor resection
• A lack of respiratory depression offers an advantage over other technique
Bekker A et al. Anesth Analg 2001
Dex Use in Ophthalmology:
Effect of dexmedetomidine premedication on the intraocular pressure
changes after succinylcholine and intubation: BJA
British Journal of Anaesthesia 100 (4): 485–9 (2008) February 19, 2008
Details - 40 patients with no pre-existing eye disease undergoing GA, Random
premedication with Dex 0.6 mcg/kg or saline, HR, MAP, and IOP measured
• IOP- Succinylcholine and intubation increased IOP in both groups.
However, in the Dex group, the IOP rise was not different from the baseline
value and was significantly lower than in the saline group .
• MAP- After intubation, the MAP in the control group was higher than that
in the dex group and exceeded the baseline value
• HR- HR also showed less fluctuation in the dex group than in the saline
group
Result:
• Premedication with a dose dex 0.6 mg/kg over 10 min blunted the ↑IOP
caused by succinylcholine & intubation
• Attenuated the hemodynamic response to laryngoscopy & intubation.
Dex Use in Ophthalmology: Conclusion
  of IOP with succinylcholine & endotracheal intubation can be
blunted with i.v. dexmedetomidine premedication.
 Hemodynamic stability is an additional advantage
 Dex could be a beneficial premedication in open globe injuries
 Single i.v. dose of dexmedetomidine 0.6 mcg/kg  IOP by 34%
 The present study (0.6 mcg/kg) was based on a previous clinical study,
where the selected dose resulted in a significant  IOP and prevented
IOP response to intubation
Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation. Br J Anaesth 1992; 68: 126–31
PROCEDURAL SEDATION
• Koroglu A, Br J Anaesth 2005;94:821
– Dex vs midazolam for MRI sedation
– 80 patients, 1-7 yrs
– Dex: 1ug/kg bolus, then 0.5 ug/kg/hr
– Midazolam: 0.2 mg/kg, then 0.36 mg/kg/hr
– Efficacy: 32/40 (dex) vs 8/40 (midazolam)
– Onset: 19 min (dex) vs 35 min (midazolam)
– Similar CV effects - nothing significant
• Concl: dex > efficacy vs midazolam
• Problem – midaz rarely sole agent for MRI
PROCEDURAL SEDATION
• Koroglu A, Anesth Analg 2006;103:63
– Dex vs propofol for MRI sedation
– 60 patients aged 1-7 yrs
– Dex: 1ug/kg bolus, then 0.5 ug/kg/hr
– Propofol: 3 mg/kg bolus, then 6 mg/kg/min
– Efficacy similar: 83% (dex) vs 90% (propofol)
– Onset – 11 min (dex) vs 4 min (propofol)
– rec time with dex (27 vs 18 min)
– hypoxia with dex (0% vs 13%)
• Concl: Consider as alternative to propofol
Dex Use in MRI
• 80 children aged 1-7 years
• Randomly assigned to either
dexmedetomidine or midazolam
– 10-minute loading doses:
1 mcg/kg dexmedetomidine,
0.2 mg/kg midazolam
– Infusions: 0.5 mcg/kg/h
dexmedetomidine,
6 mcg/kg/h midazolam1
• The quality of MRI was
significantly better (P<.001) and
the rate of adequate sedation was
significantly higher (P<.001) with
dexmedetomidine
Quality of MRI
0
10
20
30
40
1 2 3
NumberofPatients
Midazolam
Dexmedetomidine
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
• Offset of sedative action in 5 minutes, while
midazolam has about 2 to 6 hours and
propofol has 3-8 minutes.
• Duration of analgesic action of about 4 hours
as compared to that of Fentanyl up to 60-80
minutes
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
Indications & Dosage
• In the dose of 0.2 to 0.7 µg/kg/hr, found to
attenuate 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
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
Indications & Dosage
• an intra-operative analgesic in GA as an
alternative to opioids
• 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
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
alpha 2 Adrenergic Receptor
Antagonist
Atipamezole
• Effectively reverses Psychomotor side-
effects
• Reverses Sedation & Sympatholysis
• Reverses Analgesia
• t ½ is 1 ½ - 2 hours.
To compare the efficacy of
Dexmedetomidine vs Fentanyl
as sedative & analgesic in short general
anaesthesia in day care obstetric &
gynaecological surgeries
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 equal doses
METHODOLOGY
• Age group 18 - 65 years of ASA-I & II
•Randomized into two equal groups of 20 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
• Induction done with Inj. Propofol i.v in titrated doses
• Maintained with 66% N2O, 33% Oxygen & Isoflurane ( titrated
concentration) 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
METHODOLOGY
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
0
10
20
30
40
50
60
70
80
90
On table AFT PMD AFT IND At 5 min At 10 min At 15 min At end Post - op
PR
Average
Group A
Group B
P < 0.05 after premedication.
RESULTS
• No significant change in blood pressure
seen in Dex. group whereas continuous
fluctuation of systolic BP seen in
fent.group
• No significant change in diastolic BP &
Respiratory rate seen in any of the groups
• significant fall in saturation was observed
with Fentanyl group
• The time of eye opening is highly
significantly early in Dex. group (p<0.001)
and delayed eye opening seen with
fentanyl group
Line diagram showing comparision of systolic blood pressure in study
groups
90
95
100
105
110
115
120
125
On table AFT PMD AFT IND At 5 min At 10 min At 15 min At end Post - op
SBP (mm Hg)
Average
Group A
Group B
Line diagram showing comparision of SPO2 in study groups
0
10
20
30
40
50
60
70
80
90
100
110
On table AFT PMD AFT IND At 5 min At 10 min At 15 min At end Post - op
SPO2
Average
Group A
Group B
0
1
2
3
4
5
6
7
Average
Eye opening after surgery (min)
Bar chart showing comparison of eye opening after surgery in study
group
Group A
Group B
RESULTS
• The post operative analgesia duration was
more in Dex. group (approx. 4-6 hrs.),
whereas in Fentanyl group patients required
rescue analgesia within 1 – 1.5 hrs of surgery
• The sedation was highly significantly
profound in fentanyl group according to
Ramsay sedation score (p < 0.001) after 15
min of surgery
• The quality of recovery was highly
significantly better (Aldrete score = 9+)was
observed in most of the patients after 30 min
in Dex.group & Similar results were seen
only after 1.5 – 2 hrs. in Fentanyl Group
Line diagram showing comparision of VAS score in study groups
0
2
4
6
8
At End of surgery At 30 min At 1 hr At 1.5 hr At 2 hr
VAS Score
Average
Group A
Group B
Line diagram showing comparision of Ramsay sedation in post operative in study
groups
0
1
2
3
4
End of surgery At 15 min At 30 min At 1 hr At 2 hr
Ramsay sedation
Average
Group A
Group B
P < 0.001 at 1.5 hrs.
P < 0.001 at 15 min.
Line diagram showing comparision of standard aldrete score in post operative in study
groups
0
2
4
6
8
10
12
End of surgery At 15 min At 30 min At 1 hr At 1.5 hr At 2 hr
Standard aldrete score
Average
Group A
Group B
P < 0.001 at 15,30, 60 min.
TO EVALUATE THE EFFECT
OF ADDITION OF
DEXMEDETOMIDINE TO 0.5%
HYPERBARIC BUPIVACAINE
INTRATHECALLY
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
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
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
• No statistically
significant difference
for age, height ,
weight, Sex wise and
ASA distribution in
both groups
RESULTS
• Difference in sensory onset
not statistically significant
• Motor onset significantly
shorter in Dexmedetomidine
Group (t value-2.54,
p value < 0.05)
• Difference in peak sensory
insignificant
• Peak motor significantly
longer in Dex Group(t value-
4.59, p value<0.0001)
RESULTS
0
1
2
3
4
5
6
7
8
Average
Time of Peak sensory (T3) Time of Peak motor(T4)
After spinal anesthesia
Multiple bar diagram showing comparison of time of sensory and motor
Peak after spinal anesthesia in study groups
Group A
Group B
• 2 segment sensory
regression
• motor regression
and
• time of rescue
analgesia
significantly longer
in Dex. Group
RESULTS
Parameters Group A Group B t
Value
P Value
Mean SD
(n=20)
Mean SD
(n=20)
2 segment sensory
regression (T5)
190.3 34.80 98.65 14.95 10.81 <0.000
1
Motor regression
(T6)
265.05 57.50 138.7 14.76 9.51 <0.000
1
Time of rescue
analgesia (T7)
342.75 76.94 189 20.71 8.62 <0.000
1
0
50
100
150
200
250
300
350
Average
2 segment sensory
regression (T5)
Motor regression
(T6)
Time of rescue
analgesia (vas > 7)
(T7)
Level of sensory blockade
Multiple bar diagram showing comparison of level of sensory blockade
in study groups
Group A
Group B
• Both groups with
manageable
Bradycardia &
Hypotension0
1
2
3
4
No.ofcases
Bradycardia Hypotension
Side effect
Multiple bar diagram showing side effect wise distribution of cases in
study groups
Group A
Group B
Line diagram showing comparision of heart rate in study groups
0
10
20
30
40
50
60
70
80
90
100
P
re
–
op
A
t3
m
in
A
t10
m
in
A
t15
m
in
A
t30
m
in
A
t45
m
in
A
t60
m
inE
nd
ofS
urgery
P
ost-op
HR (min)
Average
Group A
Group B
Line diagram showing comparision of systolic blood pressure in study
groups
0
20
40
60
80
100
120
140
P
re
–
op
A
t3
m
in
A
t10
m
in
A
t15
m
in
A
t30
m
in
A
t45
m
in
A
t60
m
inE
nd
ofS
urgery
P
ost-op
SBP (mm Hg)
Average
Group A
Group B
Line diagram showing comparision of diastolic blood pressure in study
groups
0
10
20
30
40
50
60
70
80
90
Pre – op At 3 min At 10
min
At 15
min
At 30
min
At 45
min
At 60
min
End of
Surgery
Post -
op
DBP (mm Hg)
Average
Group A
Group B
Indications: Future plans
• Use of dexmedetomidine as an
adjuvant to Local Anaesthetic Mixture,
in peri- bulbar block
Summarizing
• 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!!!
• It has been successfully employed in Cardiac,
Neuro-surgical, abdominal, Head & Neck
Surgeries and Procedural sedation !!!!
Conclusion!
• Dexmedetomidine can be considered a suitable
agent for providing pre-operative sedation &
pre-anaesthetic anxiolysis
• Useful in the day care procedures like
conscious sedation and procedural sedation
• changing our viewpoint of providing intra &
post operative analgesia, without any potential
and significant side-effects of existing agents
employed for this purpose.
Dr. Minnu Panditrao's Dexmedetomidine for intraoperative sedation & analgesia

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Dr. Minnu Panditrao's Dexmedetomidine for intraoperative sedation & analgesia

  • 2. Dr. Mrs. Minnu M. Panditrao CONSULTANT DEPARTMENT OF ANESTHESIOLOGY & INTENSIVE CARE Public Hospital Authority’s RAND MEMORIAL HOSPITAL FREEPORT, GRAND BAHAMA COMMONWEALTH OF THE BAHAMAS
  • 3. FORMERLY: Professor Department of Anaesthesiology and Critical Care Dr. D Y Patil Medical College Pimpri, Pune, India
  • 4. alpha 2 Adrenergic Receptor Agonists • Imidazole class of drugs • Older drugs : xylazine detomidine medetomidine in veterinary medicine! • Clonidine : first agent ( in humans) •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
  • 5. alpha 2 Adrenergic Receptor Agonists Dexmedetomidine What is so special about it?
  • 6. Dexmedetomidine • a D – enantiomer of medetomidine • New Entrant in this class • approved in 1999 by FDA for clinical application in humans • Structure:
  • 7.
  • 8. 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
  • 9. 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
  • 10.
  • 11. 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
  • 12. CNS ACTIONS Dexmedetomidine • Sedation – central, G-proteins (inhibition) • Analgesia – spinal cord, Substance P
  • 13. CELLULAR MECHANISM Ca++ Ca++ Ca++ – – + Decrease in influx of Ca++ Decrease in action potential due to hyperpolarization 2A 2AR Go Gk K+ K+ K+
  • 14. 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
  • 15. 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
  • 16. Clinical Uses of Dexmedetomidine • Craniotomy: aneurysm, AVM • Cervical spine surgery • Conventional CABG • Off-pump CABG • Vascular surgery • Thoracic surgery • Bariatric surgery • Back surgery, evoked potentials • Head injury • Burn • Trauma • Awake intubation
  • 17. Clinical Uses of Dexmedetomidine Sedation in CT and MRI imaging studies Mason K, Ped Anesth 2008 Koroglu A, Anesth Analg 2006 Outpatient third molar surgery Ustin Y, J Oral Maxilfac Surg 2006 Cheung C, Anaesthesia 2007 Cataract surgery Alhashemi J, Br J Anaest 2006 Cardiac catheterization Tosun Z, J Card Vasc Anesth 2006 Mester R, Am J Therap 2008 GI Procedures Demiraran Y, Can J Gastroenter 2007 Dex may be a good alternative to midazolam for upper endoscopy
  • 18. Dex: Use in Coronary Artery Surgery Coronary Artery Surgery Patients Dexmedetomidine : Herr study, n=300: Dex vs. controls [propofol] • Faster time to extub in dex gp - by 1 hr • 70% did not require morphine vs. 34% controls • Dex pts had less Afib (7 vs 12 pts) Herr DL: Crit Care Med 2000;28:M248. Washington Hospital CABG and Lung Disease • RCT, n= 20. Dex started at end of surgery, 0.2 to 0.7 ug/kg/hr, + continued 6 hr after extubation vs. controls (propofol) Dexmedetomidine • Faster time to extub: 7.8 + 4.6 h v. 16.5 + 11.8 h • No difference in PaCO2 between gps 30 min after extub: 37.9 v. 34.9 mmHg Sumping ST: CCM 2000;28:M249. Duke
  • 19. Dex: Use in Thoracotomy + Thoracoscopy Thoracotomy + thoracoscopy patients • COPD, pleural effusion, marginal pulmonary function, pCO2 + pO2 with opioids • Thoracic epidural: mainly for thoracotomy, Dex: mainly for thoracoscopy Dexmedetomidine • Patients are arousable, but sedated • Does not ventilatory drive • Greatly need for opioids • Alternative to thoracic epidural • Continue after extubation Vascular surgery • Usually at risk for CAD, ischemia, HTN, tachycardia • Dex attenuates periop stress response • Dex attenuates BP w AXC, especially thoracic aorta Dexmedetomidine: RCT, n=41. Dex continued 48 hr postop • HR in dex gp at emergence- 73 + 11 v. 83 + 20 bpm • Better control of HR, Plasma NE levels in dex group Talke et al: Anesth Analg 2000;90:834. Multicenter
  • 20. Dex: Use in Other Surgical Procedures Abdominal surgery • Dexmedetomidine provides analgesia without respiratory depression • Especially useful in elderly undergoing colon resections, TAH, + other stressful procedures Bariatric surgery • Dexmedetomidine Improves Postop Pain Mgt after Bariatric Surgery • Morphine use in dex gp • Pain score better in dex gp: 1.8 vs 3.4 , % time pain free in PACU in dex gp: 44% vs 0 • Better control of HR in dex gp Neck + back surgery • Dex causes minimal effect on SSEP monitoring • Smooth emergence, especially cervical spine • Easy to evaluate neuro function prior to + after extubation Ramsay MA, et al: Anesthesiology, 2002: A-910 and A-165. Baylor
  • 21. Dex: Use in Other Surgical Procedures Burns patients • 2 agonist effect assists in the management of burn patients; blunts catecholamine surge •Use in intubated and non-intubated burn patients •Outpatient dressing changes instead of ketamine Trauma and Alcohol withdrawal patients •Benzodiazepines typically used- Intubation and ventilation often required if extreme agitation •Dexmedetomidine is an alternative to BZD- Spontaneous breathing, Hemodynamic stability, Adequate sedation, Prevention of autonomic effects of withdrawal, Pain control
  • 22. Dex: Use in Neuro anesthesia Effect of Dexmedetomidine on Cerebral Blood Flow • Animal models – Dex causes a reduction in CBF up to 45% – Dex has no effect on the CMRO2 – Dex produces the concentration-dependent constriction of pial arteries and veins – Dex limits hypercapnea- and hypoxia-induced cerebral vasodilation Zornow MH et al, Anesth Analg; 1990 Fale A et al, Anesth Analg; 1994 Karlsson et al, Anesth Analg; 1991 • Human study (TCD) – Mean CBF velocity decreased with an increase in plasma concentration of Dex – Pulsatility index increased at higher level of Dex (indicates an increase in CVR) Zornow MH et al, J Cereb Blood Flow Metab; 1993 Cognitive Function • There is strong evidence that a2 – agonists improve prefrontal cortical function (PFC) Arnstein et el. Arch Gen Psychiatry 1996
  • 23. Dex: Use in Neuro anesthesia Effect on ICP • Animal model – ICP was unchanged despite an increase in systemic blood pressure in rabbits – ICP was decreased in the presence of intracranial hypertension Zornow MH et al, Anesth Analg 1992 • Human study – Dex has no effect on lumbar CSF pressure in patients undergoing transphenoidal pituitary tumor resection Talke P et al. Anesth Analg 1997 Effect on SSEPs and AEP • There is a lack of effect on cortical AEP • Dex does not affect cortical (P25-N35) response • Dex depresses median nerve P15-N20 amplitudes Thornton C et al. Br J Anaesth 1999
  • 24. Dex: Use in Neuro anesthesia Antinociception · a2 – Agonists attenuate hemodynamic responses to laryngoscopy and intubation Lawrence CJ et al Anaesthesia 1997 · a2 – Agonists decrease peri operative oxygen consumption Taittonen MT Br J Anaesth 1997 • Dex reduces NE level during emergence from anesthesia (2 to 3 times lower than placebo) Talke P et al. Anesth Analg 2000 Effect on BIS • BIS values after Dex infusion for 1 hour were: 65 at 0.2 mg/kg/hr, 60 at 0.6 mg/kg/hr • Volunteers readily awakened from hypnosis by talking ; BIS returned to awake level BIS before and after subjects were asked to perform various tasks Hall JE et al. Anesth Analg 2000
  • 25. Dex: Use in Neuro anesthesia- Neuro protective effects • Inhibition of ischemia induced NE release may be associated with neuroprotection • Dex prevents delayed neuronal death after focal ischemia • Dex decreased total ischemic volume by 40% compared to placebo Jolkkonen J et al. Euro J Pharm 1999 Hoffman WE et al Anesthesiology 1991 • Dex enhances glutamine disposal by oxidative metabolism in astrocytes Huang R et al. J Cereb Blood Metab 2000
  • 26. Dexmedetomidine: Use in Craniotomy Craniotomy for Aneurysm / AVM Anesthesia considerations • Smooth induction + emergence, Prevent rupture • Avoid cerebral ischemia, Hypothermia (33 oC) CMRO2, CBF, CBV, CSF, ICP Dexmedetomodine • sympathetic stimulation • or no change in ICP • shivering w/o respiratory depression • Preserved cognitive function- reliable serial neuro exams Doufas AG et al: Stroke 2003;34. Louisville, KY Craniotomy • Postoperative infusion of Dex in patients recovering from transphenoidal hypophysectomy reduced plasma catecholamines by 70% Talke P et al Anesth Analg 1997
  • 27. Dex Use in Neuro: Clinical Experience Spinal Fusion • Intraoperative switching from a propofol infusion to Dex in patients undergoing cervical fusion resulted in: – A neurological examination that was successfully performed in the OR on an intubated patient – Clinically insignificant hemodynamic changes during and after the switchover Bloom M et al J Neurosurg Anesth 2001
  • 28. Dex Use in Neuro: Clinical Experience Carotid Endartrectomy • A combination of superficial and deep cervical plexus blocks is the most common regional anesthetic technique in the NYU medical center • Sedation with dexmedetomidine (0.2-0.4 mcg/kg/hr) offers a comfortable and cooperative patient during the operation • Less agitation and respiratory depression than with a continuous infusion of propofol or repeated doses of fentanyl and/or midazolam Functional Neurosurgery • Dex infusion at 0.1 – 0.2 mcg/kg/hr allowed us to achieve a tranquil state sufficient to complete neuropsychiatric testing required for mapping of the cortical speech area, as well as to perform an awake tumor resection • A lack of respiratory depression offers an advantage over other technique Bekker A et al. Anesth Analg 2001
  • 29. Dex Use in Ophthalmology: Effect of dexmedetomidine premedication on the intraocular pressure changes after succinylcholine and intubation: BJA British Journal of Anaesthesia 100 (4): 485–9 (2008) February 19, 2008 Details - 40 patients with no pre-existing eye disease undergoing GA, Random premedication with Dex 0.6 mcg/kg or saline, HR, MAP, and IOP measured • IOP- Succinylcholine and intubation increased IOP in both groups. However, in the Dex group, the IOP rise was not different from the baseline value and was significantly lower than in the saline group . • MAP- After intubation, the MAP in the control group was higher than that in the dex group and exceeded the baseline value • HR- HR also showed less fluctuation in the dex group than in the saline group Result: • Premedication with a dose dex 0.6 mg/kg over 10 min blunted the ↑IOP caused by succinylcholine & intubation • Attenuated the hemodynamic response to laryngoscopy & intubation.
  • 30. Dex Use in Ophthalmology: Conclusion   of IOP with succinylcholine & endotracheal intubation can be blunted with i.v. dexmedetomidine premedication.  Hemodynamic stability is an additional advantage  Dex could be a beneficial premedication in open globe injuries  Single i.v. dose of dexmedetomidine 0.6 mcg/kg  IOP by 34%  The present study (0.6 mcg/kg) was based on a previous clinical study, where the selected dose resulted in a significant  IOP and prevented IOP response to intubation Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation. Br J Anaesth 1992; 68: 126–31
  • 31. PROCEDURAL SEDATION • Koroglu A, Br J Anaesth 2005;94:821 – Dex vs midazolam for MRI sedation – 80 patients, 1-7 yrs – Dex: 1ug/kg bolus, then 0.5 ug/kg/hr – Midazolam: 0.2 mg/kg, then 0.36 mg/kg/hr – Efficacy: 32/40 (dex) vs 8/40 (midazolam) – Onset: 19 min (dex) vs 35 min (midazolam) – Similar CV effects - nothing significant • Concl: dex > efficacy vs midazolam • Problem – midaz rarely sole agent for MRI
  • 32. PROCEDURAL SEDATION • Koroglu A, Anesth Analg 2006;103:63 – Dex vs propofol for MRI sedation – 60 patients aged 1-7 yrs – Dex: 1ug/kg bolus, then 0.5 ug/kg/hr – Propofol: 3 mg/kg bolus, then 6 mg/kg/min – Efficacy similar: 83% (dex) vs 90% (propofol) – Onset – 11 min (dex) vs 4 min (propofol) – rec time with dex (27 vs 18 min) – hypoxia with dex (0% vs 13%) • Concl: Consider as alternative to propofol
  • 33. Dex Use in MRI • 80 children aged 1-7 years • Randomly assigned to either dexmedetomidine or midazolam – 10-minute loading doses: 1 mcg/kg dexmedetomidine, 0.2 mg/kg midazolam – Infusions: 0.5 mcg/kg/h dexmedetomidine, 6 mcg/kg/h midazolam1 • The quality of MRI was significantly better (P<.001) and the rate of adequate sedation was significantly higher (P<.001) with dexmedetomidine Quality of MRI 0 10 20 30 40 1 2 3 NumberofPatients Midazolam Dexmedetomidine
  • 34. 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 • Offset of sedative action in 5 minutes, while midazolam has about 2 to 6 hours and propofol has 3-8 minutes. • Duration of analgesic action of about 4 hours as compared to that of Fentanyl up to 60-80 minutes
  • 35. 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
  • 36. Indications & Dosage • In the dose of 0.2 to 0.7 µg/kg/hr, found to attenuate 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
  • 37. 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
  • 38. Indications & Dosage • an intra-operative analgesic in GA as an alternative to opioids • 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
  • 39. 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
  • 40. alpha 2 Adrenergic Receptor Antagonist Atipamezole • Effectively reverses Psychomotor side- effects • Reverses Sedation & Sympatholysis • Reverses Analgesia • t ½ is 1 ½ - 2 hours.
  • 41. To compare the efficacy of Dexmedetomidine vs Fentanyl as sedative & analgesic in short general anaesthesia in day care obstetric & gynaecological surgeries
  • 42. 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 equal doses
  • 43. METHODOLOGY • Age group 18 - 65 years of ASA-I & II •Randomized into two equal groups of 20 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
  • 44. • Induction done with Inj. Propofol i.v in titrated doses • Maintained with 66% N2O, 33% Oxygen & Isoflurane ( titrated concentration) 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 METHODOLOGY
  • 45. 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 0 10 20 30 40 50 60 70 80 90 On table AFT PMD AFT IND At 5 min At 10 min At 15 min At end Post - op PR Average Group A Group B P < 0.05 after premedication.
  • 46. RESULTS • No significant change in blood pressure seen in Dex. group whereas continuous fluctuation of systolic BP seen in fent.group • No significant change in diastolic BP & Respiratory rate seen in any of the groups • significant fall in saturation was observed with Fentanyl group • The time of eye opening is highly significantly early in Dex. group (p<0.001) and delayed eye opening seen with fentanyl group Line diagram showing comparision of systolic blood pressure in study groups 90 95 100 105 110 115 120 125 On table AFT PMD AFT IND At 5 min At 10 min At 15 min At end Post - op SBP (mm Hg) Average Group A Group B Line diagram showing comparision of SPO2 in study groups 0 10 20 30 40 50 60 70 80 90 100 110 On table AFT PMD AFT IND At 5 min At 10 min At 15 min At end Post - op SPO2 Average Group A Group B 0 1 2 3 4 5 6 7 Average Eye opening after surgery (min) Bar chart showing comparison of eye opening after surgery in study group Group A Group B
  • 47. RESULTS • The post operative analgesia duration was more in Dex. group (approx. 4-6 hrs.), whereas in Fentanyl group patients required rescue analgesia within 1 – 1.5 hrs of surgery • The sedation was highly significantly profound in fentanyl group according to Ramsay sedation score (p < 0.001) after 15 min of surgery • The quality of recovery was highly significantly better (Aldrete score = 9+)was observed in most of the patients after 30 min in Dex.group & Similar results were seen only after 1.5 – 2 hrs. in Fentanyl Group Line diagram showing comparision of VAS score in study groups 0 2 4 6 8 At End of surgery At 30 min At 1 hr At 1.5 hr At 2 hr VAS Score Average Group A Group B Line diagram showing comparision of Ramsay sedation in post operative in study groups 0 1 2 3 4 End of surgery At 15 min At 30 min At 1 hr At 2 hr Ramsay sedation Average Group A Group B P < 0.001 at 1.5 hrs. P < 0.001 at 15 min. Line diagram showing comparision of standard aldrete score in post operative in study groups 0 2 4 6 8 10 12 End of surgery At 15 min At 30 min At 1 hr At 1.5 hr At 2 hr Standard aldrete score Average Group A Group B P < 0.001 at 15,30, 60 min.
  • 48. TO EVALUATE THE EFFECT OF ADDITION OF DEXMEDETOMIDINE TO 0.5% HYPERBARIC BUPIVACAINE INTRATHECALLY
  • 49. 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
  • 50. 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
  • 51. 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
  • 52. • No statistically significant difference for age, height , weight, Sex wise and ASA distribution in both groups RESULTS
  • 53. • Difference in sensory onset not statistically significant • Motor onset significantly shorter in Dexmedetomidine Group (t value-2.54, p value < 0.05) • Difference in peak sensory insignificant • Peak motor significantly longer in Dex Group(t value- 4.59, p value<0.0001) RESULTS 0 1 2 3 4 5 6 7 8 Average Time of Peak sensory (T3) Time of Peak motor(T4) After spinal anesthesia Multiple bar diagram showing comparison of time of sensory and motor Peak after spinal anesthesia in study groups Group A Group B
  • 54. • 2 segment sensory regression • motor regression and • time of rescue analgesia significantly longer in Dex. Group RESULTS Parameters Group A Group B t Value P Value Mean SD (n=20) Mean SD (n=20) 2 segment sensory regression (T5) 190.3 34.80 98.65 14.95 10.81 <0.000 1 Motor regression (T6) 265.05 57.50 138.7 14.76 9.51 <0.000 1 Time of rescue analgesia (T7) 342.75 76.94 189 20.71 8.62 <0.000 1 0 50 100 150 200 250 300 350 Average 2 segment sensory regression (T5) Motor regression (T6) Time of rescue analgesia (vas > 7) (T7) Level of sensory blockade Multiple bar diagram showing comparison of level of sensory blockade in study groups Group A Group B
  • 55. • Both groups with manageable Bradycardia & Hypotension0 1 2 3 4 No.ofcases Bradycardia Hypotension Side effect Multiple bar diagram showing side effect wise distribution of cases in study groups Group A Group B Line diagram showing comparision of heart rate in study groups 0 10 20 30 40 50 60 70 80 90 100 P re – op A t3 m in A t10 m in A t15 m in A t30 m in A t45 m in A t60 m inE nd ofS urgery P ost-op HR (min) Average Group A Group B Line diagram showing comparision of systolic blood pressure in study groups 0 20 40 60 80 100 120 140 P re – op A t3 m in A t10 m in A t15 m in A t30 m in A t45 m in A t60 m inE nd ofS urgery P ost-op SBP (mm Hg) Average Group A Group B Line diagram showing comparision of diastolic blood pressure in study groups 0 10 20 30 40 50 60 70 80 90 Pre – op At 3 min At 10 min At 15 min At 30 min At 45 min At 60 min End of Surgery Post - op DBP (mm Hg) Average Group A Group B
  • 56. Indications: Future plans • Use of dexmedetomidine as an adjuvant to Local Anaesthetic Mixture, in peri- bulbar block
  • 57. Summarizing • 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!!! • It has been successfully employed in Cardiac, Neuro-surgical, abdominal, Head & Neck Surgeries and Procedural sedation !!!!
  • 58. Conclusion! • Dexmedetomidine can be considered a suitable agent for providing pre-operative sedation & pre-anaesthetic anxiolysis • Useful in the day care procedures like conscious sedation and procedural sedation • changing our viewpoint of providing intra & post operative analgesia, without any potential and significant side-effects of existing agents employed for this purpose.