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The efficacy and neurotoxicity of dexmedetomidine administered via the epidural route

Published online by Cambridge University Press:  01 May 2008

S. Konakci ,
T. Adanir ,
G. Yilmaz  and
T. Rezanko
S. Konakci
Affiliation:
Ataturk Training and Research Hospital, Departments of Anaesthesiology, Izmir, Turkey
T. Adanir*
Affiliation:
Ataturk Training and Research Hospital, Departments of Anaesthesiology, Izmir, Turkey
G. Yilmaz
Affiliation:
Ataturk Training and Research Hospital, Departments of Anaesthesiology, Izmir, Turkey
T. Rezanko
Affiliation:
Ataturk Training and Research Hospital, Departments of Pathology, Izmir, Turkey
*
Tayfun Adanir, P.B. 12 Hatay, 35370 Izmir, Turkey. E-mail: [email protected]; Tel: +90 232 2444444380; Fax: +90 232 2434848
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Summary

Background

α2-Adrenoceptor agonists administered into the intrathecal and epidural space have been found to be effective in the treatment of chronic pain. Moreover, it was shown that they increase the analgesic effects of local anaesthetics and provide sedation, anxiolysis and haemodynamic stability. Dexmedetomidine, a potent and highly selective α2-adrenoceptor agonist, is in current clinical use, particularly in the intensive care unit. Our aim was to investigate whether dexmedetomidine produced motor and sensory blockade and neurotoxic effects when administrated via the epidural catheter in rabbits.

Methods

Twenty-one New Zealand white rabbits were included in the study. Animals were randomized into three groups. In Group L: lidocaine (2%), in Group LD: lidocaine (2%) + dexmedetomidine (5 μg) and in Group D: dexmedetomidine (10 μg) were administered by epidural catheter. Motor and sensory blockade were evaluated. After the evaluation of block, the animals were euthanized and their spinal cords removed for neuropathological evaluations.

Results

Motor and sensory blockade were lower in Group D than in Group L and Group LD (P < 0.01). Although there were no differences between the groups for ischaemia of the medulla spinalis, evidence of demyelinization of the oligodendrocytes in the white matter in Group D was significantly higher than in Group L (P = 0.035).

Conclusions

We observed that dexmedetomidine does not have motor and sensory effects, but it may have a harmful effect on the myelin sheath when administered via the epidural route.

Keywords

ANAESTHETIC TECHNIQUESANAESTHESIA EPIDURALDEXMEDITOMIDINESPINAL CORD ISCHAEMIAMYELIN
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 5 , May 2008 , pp. 403 - 409
Copyright
Copyright © European Society of Anaesthesiology 2007

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References

1.Yaksh, TL. Pharmacology of spinal adrenergic systems which modulate spinal nociceptive processing. Pharmacol Biochem Behav 1985; 22: 845–858.CrossRefGoogle ScholarPubMed
2.Pertovaara, A. Antinociception induced by alpha-2 adrenoceptor agonists, with special emphasis on dexmedetomidine studies. Prog Neurobiol 1993; 40: 691–709.CrossRefGoogle Scholar
3.Kingery, WS, Davies, MF, Maze, M. Molecular mechanisms for the analgesic properties of alpha-2 adrenergic agonists. Prog Pain Res Manage 1997; 9: 275–304.Google Scholar
4.Maze, M, Tranquili, W. Alpha-2 adrenoceptor agonists: defining the role in clinical anesthesia. Anesthesiology 1991; 74: 581–605.CrossRefGoogle ScholarPubMed
5.Drummond, JC, Moore, SS. The influence of dextrose administration on neurological outcome after temporary spinal cord ischemia in the rabbit. Anesthesiology 1989; 70: 64–70.CrossRefGoogle ScholarPubMed
6.Chanimov, M, Cohen, ML, Grinspun, Y et al. Neurotoxicity after spinal anaesthesia induced by serial intrathecal injections of magnesium sulphate. An experimental study in a rat model. Anaesthesia 1997; 52 (3): 223–228.CrossRefGoogle ScholarPubMed
7.Petersson, KH, Pinar, H, Stopa, EG et al. White matter injury after cerebral ischemia in ovine fetuses. Pediatr Res 2002; 51 (6): 768–776.CrossRefGoogle ScholarPubMed
8.Hayashi, Y, Maze, M. Alpha 2 adrenoceptor agonists and anesthesia. Br J Anaesth 1993; 71: 108–118.CrossRefGoogle Scholar
9.Otsuguro, K, Yasutake, S, Ohta, T, Ito, S. Effects of opioid receptor and alpha 2-adrenoceptor agonists on slow ventral root potentials and on capsaicin and formalin tests in neonatal rats. Brain Res Dev Brain Res 2005; 158 (1–2): 50–58.CrossRefGoogle Scholar
10.Wahlander, S, Frumento, RJ, Wagener, G et al. A prospective, double-blind, randomized, placebo-controlled study of dexmedetomidine as an adjunct to epidural analgesia after thoracic surgery. J Cardiothorac Vasc Anesth 2005; 19: 630–635.CrossRefGoogle ScholarPubMed
11.Antti, P, Hong, W. Attenuation of ascending nociceptive signals to the rostroventromedial medulla induced by a novel alpha 2-adrenoceptor agonist, MPV-2426, following intrathecal application in neuropathic rats. Anesthesiology 2000; 92: 1082–2002.Google Scholar
12.Xu, M, Kontinent V, K, Kalso, E. Effects of radolmidine, a novel alpha 2-adrenergic agonist compared with dexmedetomidine in different pain models in the rat. Anesthesiology 2000; 93: 473–481.CrossRefGoogle ScholarPubMed
13.Gabriella, J, Gyöngyi, H, Walter, K et al. The effects of ketamine and its enantiomers on the morphine- or dexmedetomidine-induced antinociception in rats. Anesthesiology 2000; 93: 231–241.Google Scholar
14.Calasans-Maia, JA, Zapata-Sudo, G, Sudo, RT. Dexmedetomidine prolongs spinal anaesthesia induced by levobupivacaine 0.5% in guinea-pigs. J Pharm Pharmacol 2005; 57: 1415–1420.CrossRefGoogle ScholarPubMed
15.Asano, T, Dohi, S, Ohta, S, Shimonaka, H, Iida, H. Antinociception by epidural and systemic alpha 2-adrenoceptor agonists and their binding affinity in rat spinal cord and brain. Anesth Analg 2000; 90: 400–407.Google ScholarPubMed
16.Walker, SM, Howard, RF, Keay, KA, Fitzgerald, M. Developmental age influences the effect of epidural dexmedetomidine on inflammatory hyperalgesia in rat pups. Anesthesiology 2005; 102: 1226–1234.CrossRefGoogle ScholarPubMed
17.Guo, TZ, Jiang, JY, Buttermann, AE, Maze, M. Dexmedetomidine injection into the locus ceruleus produces antinociception. Anesthesiology 1996; 84: 873–881.CrossRefGoogle ScholarPubMed
18.Memis, D, Turan, A, Karamanlioglu, B, Pamukcu, Z, Kurt, I. Adding dexmedetomidine to lidocaine for intravenous regional anesthesia. Anesth Analg 2004; 98: 835–840.Google ScholarPubMed
19.Esmaoglu, A, Mizrak, A, Akin, A, Turk, Y, Boyaci, A. Addition of dexmedetomidine to lidocaine for intravenous regional anesthesia. Eur J Anaesthesiol 2005; 22: 447–451.CrossRefGoogle Scholar
20.Jolkkonen, J, Puurunen, K, Koistinaho, J et al. Neuroprotection by the alpha 2-adrenoceptor agonist, dexmedetomidine, in rat focal cerebral ischemia. Eur J Pharmacol 1999; 372: 31–36.CrossRefGoogle Scholar
21.Vincent, L, Jean, M, Hugo, L, Jean-Marie, D, Philippe, E, Pierre, G. Effects of α2-adrenoceptor agonists on perinatal excitotoxic brain injury: comparison of clonidine and dexmedetomidine. Anesthesiology 2002; 96: 134–141.Google Scholar
22.Ma, D, Hossain, M, Rajakumaraswamy, N et al. Dexmedetomidine produces its neuroprotective effect via α2-adrenoceptor subtype. Eur J Pharmacol 2004; 502: 87–97.CrossRefGoogle Scholar
23.Iida, H, Ohata, H, Iida, M, Watanabe, Y, Dohi, S. Direct effects of alpha 1- and alpha 2-adrenergic agonists on spinal and cerebral pial vessels in dogs. Anesthesiology 2000; 92: 1488–1489.CrossRefGoogle Scholar
24.Canduz, B, Aktug, H, Mavioglu, O et al. Epidural lornoxicam administration-innocent. J Clin Neurosci 2007; 14: 968–974.CrossRefGoogle Scholar
25.Lim, YJ, Sim, WS, Kim, YC, Lee, SC, Choi, YL. The neurotoxicity of epidural hyaluronic acid in rabbits: a light and electron microscopic examination. Anesth Analg 2003; 97: 1716–1720.CrossRefGoogle Scholar