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.

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.

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.

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.