1. Intraoperative Use of
α2− Agonists in Neuroanesthesia
Alex Bekker M.D., Ph.D.
Director of Neuroanesthesia
New York University School of
Medicine

2. Progress may have been all right once,
but it went on too long.
Ogden Nash

3. Activation of α2−receptors leads to:
• Dose dependent sedation and anxiolysis
• Analgesia (supraspinal and spinal sites)
• Decrease plasma catecholamines
• Centrally mediated bradycardic and
hypotensive effects
• Diuresis due to inhibition of ADH release and
antagonism of ADH tubular effects
• Decongestant and antisialogogue effects

4. Qualifications for inclusion into
the neuroanesthesia drug club:
• Controllability (e.g. rapid onset and offset
of effect)
• Stability of intracranial homeostasis
• Hemodynamic stability
• Noninterference with neurophysiologic
monitoring
• Neuroprotection
• Antinonociception

5. Pharmacokinetics of IV agents
Dex Propofol Fentanyl Alfenta
Vdcc, l 16 16 30 10
Vdss, l 200 350 330 30
Cl, l/min 0.6 1.8 0.8 0.3
T1/2α, min 6 4 6 4
T1/2β, hr 2 1.5 2.5 1

6. Context-sensitive Dexmedetomidine recovery
times as a function of duration of infusion

7. 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

8. Effect of Dexmedetomidine on
Cerebral Blood Flow
• 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

9. Effect of Dexmedetomidine 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

10. Dexmedetomidine 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

11. Median nerve SSEPs tracings after
switching from propofol to
Dexmedetomidine infusion
Left
Right

12. Amplitudes of early and late SSEP waves at
various stages of the surgery
EP Amplitudes
0
1
2
3
4
5
6
7
8
10:17 11:33 11:39 11:49 12:11 12:16 12:21 13:06 13:09 13:19
Time
uV
R P25-N35
L P25-N35
R N20-P25
L N20-P25
R P15-N20
L P15-N20
d
d

13. Dexmedetomidine effect on the EEG
• Dex decreased MPF and
95% PF in cats
• Dex increased delta band
power
• Halothane 2% produced
similar EEG changes
• Animals on Dex
responded to tail clamping
purposefully
• BIS values after Dex
infusion for 1 hour were:
65 at 0.2 µg/kg/hr
60 at 0.6 µg/kg/hr
• The volunteers were
readily awakened from
hypnosis by talking to
them; BIS returned to
awake level
Farber NE et al. Brain Research 1997 Hall JE et al. Anesth Analg 2000

14. BIS before and after subjects were asked to
perform various tasks
Hall et al. Anesth Analg 2000

15. Neuroprotective effects of
Dexmedetomidine
• 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 oxydative metabolism
in astrocytes
Huang R et al. J Cereb Blood Metab 2000

16. Dexmedetomidine and
Antinociception
• α2 – Agonists attenuate hemodynamic responses to
laryngoscopy and intubation
Lawrence CJ et al Anaesthesia 1997
• α2 – Agonists decrease perioperative oxygen consumption
Taittonen MT Br J Anaesth 1997
• Dex reduces NE level during emergence from anesthesia
(2 to 3 times lower than in placebo group)
Talke P et al. Anesth Analg 2000

17. Law of Conservation of Tsouris
The amount of aggravation in the universe
is a constant. If things are going well in one area,
they are going wrong in another.

18. Dexmedetomidine: Side Effects
• Hypotension
• Transient hypertension
• Bradycardia
• Dry mouth
• Limited amnestic effect
• Animal studies show reduction in the
CBF/CMRO2 ratio
• Excessive sedation

19. Clinical Experience: Craniotomy
• In patient undergoing craniotomy, premedication with
clonidine:
reduced anesthetic requirements
attenuated hemodynamic responses to intubation and
pin fixation
Costello T et al Anesth Analg 1998
• Postoperative infusion of Dex in patients recovering from
transphenoidal hypophysectomy reduced plasma
catecholamines by 70%
Talke P et al Anesth Analg 1997

20. Clinical Experience: Spinal Fusion
• Perioperative administration of clonidine reduced
postoperative morphine requirements by a factor of 3 in
patients undergoing spinal fusion
Bernard et al Anesthesiology 1991
• 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

21. α2 – Agonists and Cognitive Function
• There is strong evidence that α2 – agonists improve
prefrontal cortical function (PFC)
• PFC shares reciprocal projections with:
– Parietal association cortex specialized for visuospatial processing
– Medial temporal lobe important to memory abilities
– Anterior cingulate cortex involved in organizing complex cognitive
function
– Caudate nucleus that regulates motor behavior
• NE’s beneficial action in the PFC appear to result from
stimulation of α2 (A) – receptors postjunctional to NE
terminals
Arnstein et el. Arch Gen Psychiatry 1996

22. 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

23. Clinical Experience: Functional Neurosurgery
• Dex infusion at 0.1 – 0.2 µg/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

24. Is there a reason to add
Dexmedetomidine to our practice?
• Dex properties include:
– Reversible sedation without respiratory depression
– Analgesia
– Anesthetic sparing effect
– Cardiovascular stability
– Has minimal effect on ICP
– May offer neuroprotection
– A unique type of sedation in which a patient could be aroused
readily
• Theoretical advantages have to be objectively justified in
clinical studies