title: Remifentanil tolerance and hyperalgesia: short-term gain, long-term pain?
abstract: The unique pharmacology of remifentanil makes it a popular intra-operative analgesic. Short-acting opioids like remifentanil have been associated with acute opioid tolerance and/or opioid-induced hyperalgesia, two phenomena which have different mechanisms and are pharmacologically distinct. Clinical studies show heterogeneity of remifentanil infusion regimens, durations of infusion, maintenance of anaesthesia, cumulative dose of remifentanil and pain measures, which makes it difficult to draw conclusions about the incidence of acute tolerance or hyperalgesia. However, it appears that intra-operative remifentanil infusion rates of above 0.25 μg.kg-1.min-1are associated with higher postoperative opioid consumption, suggesting tolerance. Infusion rates greater than 0.2 μg.kg-1.min-1are characterised by lower mechanical/pressure/cold/pain thresholds, which suggests hyperalgesia. The use of concurrent multimodal analgesia, especially N-methyl-D-aspartate receptor antagonists, may be an effective preventive strategy. The clinical significance and long-term consequences of these entities is still uncertain.
authors.affiliation: Department of Anaesthesiology, Queen Mary Hospital, Pokfulam, Hong Kong.
authors.forename: E H Y
authors.initials: EH
authors.lastname: Yu
authors.affiliation: Department of Anaesthesiology, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: D H D
authors.initials: DH
authors.lastname: Tran
authors.affiliation: Department of Anaesthesiology, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: S W
authors.initials: SW
authors.lastname: Lam
authors.affiliation: Department of Anaesthesiology, The University of Hong Kong, Hong Kong Special Administrative Region, China. mgirwin@hku.hk.
authors.forename: M G
authors.initials: MG
authors.lastname: Irwin
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced* / Q000517:prevention & control; D007430:Intraoperative Care / Q000009:adverse effects / Q000379:methods; D010149:Postoperative Pain / Q000517:prevention & control*; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D000077208:Remifentanil
chemical_list: D000701:Analgesics, Opioid; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D000077208:Remifentanil
keywords: hyperalgesia; operative; opioid; remifentanil; surgery; tolerance