Antihyperalgesic effects of dexmedetomidine on high-dose remifentanil-induced hyperalgesia

Cheol Lee, Yeon-Dong Kim, Ji-Na Kim, Cheol Lee, Yeon-Dong Kim, Ji-Na Kim

Abstract

Background: Dexmedetomidine is a highly selective α2 adrenergic agonist that has been shown to decrease the intensity of opioid-induced hyperalgesia (OIH). We aimed to investigate the antihyperalgesic effects of dexmedetomidine on high-dose remifentanil-induced hyperalgesia.

Methods: Ninety American Society of Anesthesiologists physical status I-II patients undergoing laparoscopically assisted vaginal hysterectomy (LAVH) were randomly assigned to one of the following three groups, each of which received either dexmedetomidine (an initial dose of 1.0 µg/kg for 10 min, followed by a continuous infusion of 0.7 µg/kg/hr) or placebo saline 15 min before the induction of anesthesia and intraoperative remifentanil infusion: group C received a placebo and 0.05 µg/kg/min remifentanil; group RH received a placebo and 0.3 µg/kg/min remifentanil; and group DRH received dexmedetomidine and 0.3 µg/kg/min remifentanil.

Results: The mechanical hyperalgesia threshold 24 hr after surgery was significantly lower in group RH than in the other two groups. Postoperative pain intensity using visual analog scale (VAS) and cumulative volume of a patient-controlled analgesia (PCA) containing morphine over 24 hr were significantly greater in group RH than in group DRH. The time to the first postoperative analgesic requirement was significantly shorter in group RH than in the other two groups. The desflurane requirement was significantly greater in group C than in the other groups. The frequency of hypotension and bradycardia was significantly higher, but shivering and postoperative nausea and vomiting were significantly lower in group DRH than in the other two groups.

Conclusions: High-doses of remifentanil induced hyperalgesia, which presented a decreased mechanical hyperalgesia threshold, enhanced pain intensity, a shorter time to first postoperative analgesic requirement, and greater morphine consumption, but dexmedetomidine efficiently alleviated those symptoms. Dexmedetomidine may be a novel and effective treatment option for preventing or attenuating OIH.

Keywords: Dexmedetomidine; Opioid-induced hyperalgesia; Remifentanil.

Figures

Fig. 1
Fig. 1
The COSORT flowchart.

References

    1. Virtanen R, Savola JM, Saano V, Nyman L. Characterization of the selectivity, specificity and potency of medetomidine as an alpha 2-adrenoceptor agonist. Eur J Pharmacol. 1988;150:9–14.
    1. Belgrade M, Hall S. Dexmedetomidine infusion for the management of opioid-induced hyperalgesia. Pain Med. 2010;11:1819–1826.
    1. Koppert W, Sittl R, Scheuber K, Alsheimer M, Schmelz M, Schuttler J. Differential modulation of remifentanil-induced analgesia and postinfusion hyperalgesia by S-ketamine and clonidine in humans. Anesthesiology. 2003;99:152–159.
    1. Zhang WS, Xu H, Xu B, Sun S, Deng XM, Zhang YQ. Antihyperalgesic effect of systemic dexmedetomidine and gabapentin in a rat model of monoarthritis. Brain Res. 2009;1264:57–66.
    1. Zheng Y, Cui S, Liu Y, Zhang J, Zhang W, Zhang J, et al. Dexmedetomidine prevents remifentanil-induced postoperative hyperalgesia and decreases spinal tyrosine phosphorylation of N-methyl-d-aspartate receptor 2B subunit. Brain Res Bull. 2012;87:427–431.
    1. Bürkle H, Dunbar S, Van Aken H. Remifentanil: a novel, short-acting, mu-opioid. Anesth Analg. 1996;83:646–651.
    1. Chu LF, Angst MS, Clark D. Opioid-induced hyperalgesia in humans: molecular mechanisms and clinical considerations. Clin J Pain. 2008;24:479–496.
    1. Singler B, Tröster A, Manering N, Schüttler J, Koppert W. Modulation of remifentanil-induced postinfusion hyperalgesia by propofol. Anesth Analg. 2007;104:1397–1403.
    1. Lee C, Song YK, Jeong HM, Park SN. The effects of magnesium sulfate infiltration on perioperative opioid consumption and opioid-induced hyperalgesia in patients undergoing robot-assisted laparoscopic prostatectomy with remifentanil-based anesthesia. Korean J Anesthesiol. 2011;61:244–250.
    1. Mori H, Mishina M. Structure and function of the NMDA receptor channel. Neuropharmacology. 1995;34:1219–1237.
    1. Boyce S, Wyatt A, Webb JK, O'Donnell R, Mason G, Rigby M, et al. Selective NMDA NR2B antagonists induce antinociception without motor dysfunction: correlation with restricted localisation of NR2B subunit in dorsal horn. Neuropharmacology. 1999;38:611–623.
    1. Gu X, Wu X, Liu Y, Cui S, Ma Z. Tyrosine phosphorylation of the N-Methyl-D-Aspartate receptor 2B subunit in spinal cord contributes to remifentanil-induced postoperative hyperalgesia: the preventive effect of ketamine. Mol Pain. 2009;5:76.
    1. Chu LF, Cun T, Ngai LK, Kim JE, Zamora AK, Young CA, et al. Modulation of remifentanil-induced postinfusion hyperalgesia by the β-blocker propranolol in humans. Pain. 2012;153:974–981.
    1. Tröster A, Sittl R, Singler B, Schmelz M, Schüttler J, Koppert W. Modulation of remifentanil-induced analgesia and postinfusion hyperalgesia by parecoxib in humans. Anesthesiology. 2006;105:1016–1023.
    1. Blaudszun G, Lysakowski C, Elia N, Tramèr MR. Effect of perioperative systemic α2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials. Anesthesiology. 2012;116:1312–1322.
    1. Maze M, Birch B, Vickery RG. Clonidine reduces halothane MAC in rats. Anesthesiology. 1987;67:868–869.
    1. Segal IS, Vickery RG, Walton JK, Doze VA, Maze M. Dexmedetomidine diminishes halothane anesthetic requirements in rats through a postsynaptic alpha 2 adrenergic receptor. Anesthesiology. 1988;69:818–823.
    1. Aantaa R, Jaakola ML, Kallio A, Kanto J. Reduction of the minimum alveolar concentration of isoflurane by dexmedetomidine. Anesthesiology. 1997;86:1055–1060.
    1. Khan ZP, Munday IT, Jones RM, Thornton C, Mant TG, Amin D. Effects of dexmedetomidine on isoflurane requirements in healthy volunteers. 1: Pharmacodynamic and pharmacokinetic interactions. Br J Anaesth. 1999;83:372–380.
    1. Correa-Sales C, Rabin BC, Maze M. A hypnotic response to dexmedetomidine, an alpha 2 agonist, is mediated in the locus coeruleus in rats. Anesthesiology. 1992;76:948–952.
    1. Andrade R, Aghajanian GK. Opiate- and alpha 2-adrenoceptor-induced hyperpolarizations of locus ceruleus neurons in brain slices: reversal by cyclic adenosine 3':5'-monophosphate analogues. J Neurosci. 1985;5:2359–2364.
    1. Aho M, Lehtinen AM, Erkola O, Kallio A, Korttila K. The effect of intravenously administered dexmedetomidine on perioperative hemodynamics and isoflurane requirements in patients undergoing abdominal hysterectomy. Anesthesiology. 1991;74:997–1002.
    1. Aho M, Erkola O, Kallio A, Scheinin H, Korttila K. Dexmedetomidine infusion for maintenance of anesthesia in patients undergoing abdominal hysterectomy. Anesth Analg. 1992;75:940–946.
    1. Tufanogullari B, White PF, Peixoto MP, Kianpour D, Lacour T, Griffin J, et al. Dexmedetomidine infusion during laparoscopic bariatric surgery: The effect on recovery outcome variables. Anesth Analg. 2008;106:1741–1748.
    1. Bloor BC, Ward DS, Belleville JP, Maze M. Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anesthesiology. 1992;77:1134–1142.
    1. Watcha MF, White PF. Postoperative nausea and vomiting. Its etiology, treatment, and prevention. Anesthesiology. 1992;77:162–184.
    1. Komatsu R, Turan AM, Orhan-Sungur M, McGuire J, Radke OC, Apfel CC. Remifentanil for general anaesthesia: a systematic review. Anaesthesia. 2007;62:1266–1280.
    1. Bajwa SJ, Gupta S, Kaur J, Singh A, Parmar S. Reduction in the incidence of shivering with perioperative dexmedetomidine: a randomized prospective study. J Anaesthesiol Clin Pharmacol. 2012;28:86–91.

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