Remifentanil-induced Postoperative Hyperalgesia Research Articles

Magnesium Sulfate Prevents Remifentanil-Induced Postoperative Hyperalgesia in Patients Undergoing Thyroidectomy

In a randomized, double-blind, prospective study, we investigated whether an intraoperative high versus low dose of remifentanil increased postoperative hyperalgesia and whether magnesium can prevent remifentanil-induced hyperalgesia. Ninety patients undergoing thyroidectomy were randomly assigned to 1 of 3 groups. Remifentanil was intraoperatively infused at 0.05 μg/kg/min (group LO) or 0.2 μg/kg/min (groups HI and HM). Patients in group HM received MgSO(4) 30 mg/kg at induction followed by an intraoperative infusion of 10 mg/kg/h. Mechanical pain thresholds on the forearm and periincisional area were assessed by von Frey filament the evening before surgery and postoperatively at 24 and 48 hours. Pain measured on a verbal numerical rating scale (VNRS) (0-10) and additional analgesics were recorded in the postanesthesia care unit postoperatively at 6, 24, and 48 hours. There was a significantly greater decrease in pain threshold on the periincisional area at 24 and 48 hours postoperatively in group HI, as compared with the other 2 groups. The 95% confidence intervals for the mean difference in pain thresholds on the periincisional area at 24 and 48 hours postoperatively were 0.31 to 1.11 and 0.36 to 1.14 for group HI versus group LO, 0.45 to 1.26 and 0.54 to 1.32 for group HI versus group HM (values are log(10) of force in milligrams). The change in pain threshold on the forearm was similar among the groups. Group HI had significantly higher VNRS scores (median [interquartile range], 3 [2-4]) than group LO (2 [1-3] and group HM (2 [1-3]) at 48 hours postoperatively. The 95% confidence intervals for median difference in VNRS score at 48 hours postoperatively were 1 to 2 for group HI versus group LO and 0 to 2 for group HI versus group HM. There were no significant differences in the number of patients who requested rescue analgesics in the postoperative anesthesia care unit and general ward during 48 hours postoperatively among the 3 groups. A relatively high dose of intraoperative remifentanil enhances periincisional hyperalgesia. Intraoperative MgSO(4) prevents remifentanil-induced hyperalgesia. However, hyperalgesia did not reach clinical relevance in terms of postoperative pain or analgesic consumption in patients undergoing thyroidectomy.

Magnesium sulphate alleviate remifentanil-induced postoperative hyperalgesia in scoliosis surgery

Department of Anaesthesiology, Drum Tower Hospital, Medical College of Nanjing University, Nanjing, China

Dose-response relationship of ketamine for inhibiting postoperative hyperaigesia after remifentanil-based anesthesia

Objective To investigate the dose-response relationship of ketamine for inhibiting postoperative hyperalgesia after remifentanil-based anesthesia in patients undergoing laparoscopic cbolecystectomy. Methods Fifteen ASA Ⅰ or Ⅱ patients aged 40-60 yr, weighing 45-80 kg undergoing laparuscopic cholecystectomy under remifentanil-based general anesthesia were studied. The patients were premedicated with intramuscular atropine 0.5 mg. Anesthesia was induced with midazolam 0.05 mg/kg, fentanyl 4 μg/kg, propofol ventilated after tracheal intubatiun. Ketamine was given before skin incision for inhibiting remifentanil-induced postoperative hyperalgesia. Pain was assessed using VAS (0 = no pain, 10 = worst pain) at 10 min after tracheal extubation. VAS score < 4 was defined as effective. The optimal dose was determined by Dixon's up-and-down method. If the VAS score was < 4, the next patient received a lower dose of ketamine, or conversely if ineffective, a higher dose was given in the next patient. The up-and-down sequences were analyzed by using probit method to determine the ED50, ED95 and 95% confidence interval (CI). Results The ED50 of ketamine for inhibiting postoperative hyperalgesia after remifentanil-based anesthesia was 0.23 mg/kg (95% CI 0.12-0. 35 mg/kg) and ED95 0.62 mg/kg (95 % CI 0.51-0.68 mg/kg). Conclusion The ED50 and ED95 of ketamine for inhibiting postoperative hyperalgesia after remifentanil-based anesthesia in patients following laparoscopic cholecystectomy are 0.23 mg/kg and 0.62 mg/kg respectively. Key words: Ketamine; Pipefidines; Hyperalgesia; Dose-response relationship,drug

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

BackgroundExperimental and clinical studies showed that intraoperative infusionof remifentanil has been associated with postoperative hyperalgesia. Previous reports suggested that spinal N-methyl-D-aspartate (NMDA) receptors may contribute to the development and maintenance of opioid-induced hyperalgesia. In the present study, we used a rat model of postoperative pain to investigate the role of tyrosine phosphorylation of NMDA receptor 2B (NR2B) subunit in spinal cord in the postoperative hyperalgesia induced by remifentanil and the intervention of pretreatment with ketamine.ResultsIntraoperative infusion of remifentanil (0.04 mg/kg, subcutaneous) significantly enhanced mechanical allodynia and thermal hyperalgesia induced by the plantar incision during the postoperative period (each lasting between 2 h and 48 h), which was attenuated by pretreatment with ketamine (10 mg/kg, subcutaneous). Correlated with the pain behavior changes, immunocytochemical and western blotting experiments in our study revealed that there was a marked increase in NR2B phosphorylation at Tyr1472 in the superficial dorsal horn after intraoperative infusion of remifentanil, which was attenuated by pretreatment with ketamine.ConclusionsThis study provides direct evidence that tyrosine phosphorylation of the NR2B at Tyr1472 in spinal dosal horn contributes to postoperative hyperalgesia induced by remifentanil and supports the potential therapeutic value of ketamine for improving postoperative hyperalgesia induced by remifentanil.

Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine

Remifentanil-induced secondary hyperalgesia has been documented experimentally in both animals and healthy human volunteers, but never clinically. This study tested the hypotheses that increased pain sensitivity assessed by periincisional allodynia and hyperalgesia can occur after relatively large-dose intraoperative remifentanil and that small-dose ketamine prevents this hyperalgesia. Seventy-five patients undergoing major abdominal surgery were randomly assigned to receive (1) intraoperative remifentanil at 0.05 microg x kg(-1) x min(-1) (small-dose remifentanil); (2) intraoperative remifentanil at 0.40 microg x kg(-1) x min(-1) (large-dose remifentanil); or (3) intraoperative remifentanil at 0.40 microg x kg(-1) x min(-1) and 0.5 mg/kg ketamine just after the induction, followed by an intraoperative infusion of 5 microg x kg(-1) x min(-1) until skin closure and then 2 microg x kg(-1) x min(-1) for 48 h (large-dose remifentanil-ketamine). Pain scores and morphine consumption were recorded for 48 postoperative hours. Quantitative sensory tests, peak expiratory flow measures, and cognitive tests were performed at 24 and 48 h. Hyperalgesia to von Frey hair stimulation adjacent to the surgical wound and morphine requirements were larger (P < 0.05) and allodynia to von Frey hair stimulation was greater (P < 0.01) in the large-dose remifentanil group compared with the other two groups, which were comparable. There were no significant differences in pain, pressure pain detection threshold with an algometer, peak flow, cognitive tests, or side effects. A relatively large dose of intraoperative remifentanil triggers postoperative secondary hyperalgesia. Remifentanil-induced hyperalgesia was prevented by small-dose ketamine, implicating an N-methyl-d-aspartate pain-facilitator process.