Journal of Pain Research (2019-01-01)

Effects of low-dose ketamine infusion on remifentanil-induced acute opioid tolerance and the inflammatory response in patients undergoing orthognathic surgery

  • Kido K,
  • Toda S,
  • Shindo Y,
  • Miyashita H,
  • Sugino S,
  • Masaki E

Journal volume & issue
Vol. Volume 12
pp. 377 – 385


Read online

Kanta Kido,1 Shinichi Toda,1 Yuki Shindo,1 Hitoshi Miyashita,2 Shigekazu Sugino,3 Eiji Masaki1 1Department of Dental Anesthesiology and Pain Management, Tohoku University Hospital, Sendai, Miyagi, Japan; 2Department of Oral Medicine and Surgery, Division of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Tohoku University, Sendai, Miyagi, Japan; 3Department of Anesthesiology and Perioperative Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan Purpose: Remifentanil is associated with acute opioid tolerance that can lead to increased postoperative consumption of opioid analgesics. The purpose of this study was to determine whether a low dose of ketamine prevents remifentanil-induced acute opioid tolerance and affects the neutrophil–lymphocyte ratio (NLR), a newly recognized biomarker of inflammation. Materials and methods: Forty patients undergoing orthognathic surgery were enrolled in this prospective, randomized, double-blind study and randomly assigned to intraoperative administration of one of the following anesthetic regimens: high-dose remifentanil (0.6 µg/kg/minute); low-dose remifentanil (0.2 µg/kg/minute); or high-dose remifentanil with ketamine (remifentanil 0.6 µg/kg/minute with 0.5 mg/kg ketamine just after induction followed by an intraoperative infusion of ketamine 5 µg/kg/minute until wound closure). Fentanyl by intravenous patient-controlled analgesia was used for postoperative pain control. Visual Analog Scale pain scores and fentanyl consumption were recorded in the first 24 hours postoperatively. Perioperative serum C-reactive protein level and NLR were also determined. Results: Baseline characteristics were similar in the three study groups. There were no between-group differences in Visual Analog Scale pain scores during the study period. The high-dose remifentanil group had a significantly higher requirement for fentanyl than the other two groups. Addition of ketamine did not affect the C-reactive protein level but increased the NLR; this increase was associated with decreased fentanyl consumption. Conclusion: High-dose intraoperative remifentanil induced postoperative acute opioid tolerance that was prevented by infusion of low-dose ketamine. Ketamine increased the postoperative NLR associated with decreased fentanyl requirement for postoperative pain control. Keywords: acute tolerance, central sensitization, NMDA receptor, neutrophil–lymphocyte ratio, remifentanil