Effect of intraoperative infusion of ketamine on remifentanil-induced hyperalgesia

IntroductionOpioids are a prerequisite for perioperative analgesia in the anesthetic setting, but can be a double-edged sword due to the side effect of opioid-induced hyperalgesia (OIH).OIH is related to high opioid dosage, long duration of opioid use, and abrupt discontinuation of opioids after surgery.Therefore, many mechanism-based combinations of other adjuvant drugs have been used to attenuate sensitization of the central pronociceptive process and reduce the unpleasant hyperalgesic response [1].Ketamine, an N-methyl-D-aspartate (NMDA) antagonist, efficiently decreases the hyperalgesic response induced by opioids.Ketamine modulates the pronociceptive sensitization process Clinical Research ArticleBackground: Opioid induced hyperalgesia (OIH) is related with high opioid dosage, a long duration of opioid administration, and abrupt discontinuation of infused opioids in anesthetic settings.Ketamine is known to attenuate OIH efficiently, but methods of administration and methods to quantify and assess a decrease in OIH vary.We demonstrated the existence of remifentanil-induced hyperalgesia and investigated the ability of ketamine to attenuate OIH.Methods: Seventy-five patients undergoing laparoscopic gynecologic surgery under remifentanil-based anesthesia were assigned to one of the following groups: (1) group RL (remifentanil 0.05 μg/kg/min), (2) group RH (remifentanil 0.3 μg/ kg/min), or (3) group KRH (remifentanil 0.3 μg/kg/min + ketamine 0.5 mg/kg bolus with 5 μg/kg/min infusion intraoperatively).Desflurane was administered for maintenance of anesthesia to target bispectral index scores (40-60) and hemodynamic parameters (heart rate and blood pressure < ± 20% of baseline values).All parameters related to OIH and its attenuation induced by ketamine were investigated.Results: There was no significant difference among the three groups related to demographic and anesthetic parameters except the end-tidal concentration of desflurane.Additional analgesic consumption, numerical rating scale scores at 6 and 24 h, and cumulative fentanyl dose were significantly higher in group RH than in the other two groups.The value difference of the Touch-Test sensory evaluation was significantly higher negative in group RH than in the other two groups.Conclusions: Remifentanil-induced hyperalgesia is significantly attenuated by intraoperative bolus and infusion of ketamine.Ketamine also decreased tactile sensitization, as measured by Touch-Test sensory evaluation.