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

Abstract

BackgroundDexmedetomidine 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.MethodsNinety 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.ResultsThe 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.ConclusionsHigh-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.

Randomized Controlled Trial on the Influence of Intraoperative Remifentanil versus Fentanyl on Acute and Chronic Pain after Cardiac Surgery

“…Our finding that chronic pain was especially observed in patients receiving a higher dose of remifentanil further supports this. A dose‐dependent relationship is also in line with previous reports …”

The influence of dexmedetomidine on remifentanil‑induced hyperalgesia and the sex differences

“…Furthermore, VAS scores were significantly lower in groups with either high or low dose of dexmedetomidine compared with the groups receiving placebo. Our data correspond with other supporting evidence indicated that dexmedetomidine infusion efficiently alleviated RIH symptoms (35,36). …”

“…This result was consistent with other animal studies that suggested combination of α2 adrenergic receptor agonist with an opioid can increase analgesic potency to some extent (33,34). Moreover, by effectively suppressing glial cell proliferation and activate the adjacent nerve cells involved in peripheral and central sensitization, dexmedetomidine has been shown effectively decreasing hyperalgesia by increasing acetylcholine levels in the spinal cord (35). Several clinical trials and case reports have confirmed that dexmedetomidine as an α2 adrenergic agonist has the potential to synergize with opioids (4,15,35).…”

“…Moreover, by effectively suppressing glial cell proliferation and activate the adjacent nerve cells involved in peripheral and central sensitization, dexmedetomidine has been shown effectively decreasing hyperalgesia by increasing acetylcholine levels in the spinal cord (35). Several clinical trials and case reports have confirmed that dexmedetomidine as an α2 adrenergic agonist has the potential to synergize with opioids (4,15,35). Therefore, dexmedetomidine was set out as an adjuvant to reduce RIH and improving pain control in patient undergoing thyroidectomy.…”

Efficacy of dexmedetomidine on postoperative shivering: a meta-analysis of clinical trials

“…3,9,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] Other control agents included fentanyl, [33][34][35][36] remifentanyl, 37,38 meperidine, 15 midazolam, [39][40][41] propofol, 43,44 ketamine, 45,46 tramadol, 24,47 clonidine, 42 propacetamol, 48 and buprenorphine 49 ( 8 were reported in the 39 included trials, and all studies reported every endpoint mentioned in the Methods section (reporting bias). 8 however, some bias 8 may exist in of the two trials, 27,32 as the length of surgery was not clear.…”