Intraoperative Use of a2- Agonists in Neuroanesthesia

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
Context-sensitive Dexmedetomidine recovery times as a function of duration of infusion
Effect of Dexmedetomidine on Cerebral Blood Flow
• Animal models
Dexmedetomidine: Side Effects
Hypotension Transient hypertension Bradycardia Dry mouth Limited amnestic effect Animal studies show reduction in the CBF/CMRO2 ratio • Excessive sedation • • • • • •
Zornow MH et al, J Cereb Blood Flow Metab; 1993
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
Thornton C et al. Br J Anaesth 1999
Median nerve SSEPs tracings after switching from propofol to Dexmedetomidine infusion
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Amplitudes of early and late SSEP waves at various stages of the surgeth Analg 1992
• Human study – Dex has no effect on lumbar CSF pressure in patients undergoing transphenoidal pituitary tumor resection
Pharmacokinetics of IV agents
Dex Vdcc, l Vdss, l Cl, l/min T1/2α, min T1/2β, hr 16 200 0.6 6 2 Propofol Fentanyl 16 350 1.8 4 1.5 30 330 0.8 6 2.5 Alfenta 10 30 0.3 4 1
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
• 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)
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.
Intraoperative Use of α2− Agonists in Neuroanesthesia
Alex Bekker M.D., Ph.D. Director of Neuroanesthesia New York University School of Medicine
Progress may have been all right once, but it went on too long. Ogden Nash
Dexmedetomidine and Antinociception
• α2 – Agonists attenuate hemodynamic responses to laryngoscopy and intubation
Lawrence CJ et al Anaesthesia 1997
• α2 – Agonists decrease perioperative oxygen consumption
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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
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
Bernard et al Anesthesiology 1991
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
Hall JE et al. Anesth Analg 2000
BIS before and after subjects were asked to perform various tasks
Hall et al. Anesth Analg 2000
Neuroprotective effects of Dexmedetomidine
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
Clinical Experience: Spinal Fusion
• Perioperative administration of clonidine reduced postoperative morphine requirements by a factor of 3 in patients undergoing spinal fusion
Zornow MH et al, Anesth Analg; 1990 Fale A et al, Anesth Analg; 1994 Karlsson et al, Anesth Analg; 1991
Effect of Dexmedetomidine on Cerebral Blood Flow
Farber NE et al. Brain Research 1997