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

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

Received 19 June 2018

Accepted for publication 17 December 2018

Published 17 January 2019 Volume 2019:12 Pages 377—385

DOI https://doi.org/10.2147/JPR.S177098

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 5

Editor who approved publication: Dr Michael Schatman


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

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