title: Gradual withdrawal of remifentanil infusion may prevent opioid-induced hyperalgesia.
abstract: BACKGROUND
  The aim of this study was to examine if gradual withdrawal of remifentanil infusion prevented opioid-induced hyperalgesia (OIH) as opposed to abrupt withdrawal. OIH duration was also evaluated.
  
  
  METHODS
  Nineteen volunteers were enrolled in this randomized, double-blinded, placebo-controlled, crossover study. All went through three sessions: abrupt or gradual withdrawal of remifentanil infusion and placebo. Remifentanil was administered at 2.5 ng ml(-1) for 30 min before abrupt withdrawal or gradual withdrawal by 0.6 ng ml(-1) every five min. Pain was assessed at baseline, during infusion, 45-50 min and 105-110 min after end of infusions using the heat pain test (HPT) and the cold pressor test (CPT).
  
  
  RESULTS
  The HPT 45 min after infusion indicated OIH development in the abrupt withdrawal session with higher pain scores compared with the gradual withdrawal and placebo sessions (both P<0.01. Marginal mean scores: placebo 2.90; abrupt 3.39; gradual 2.88), but no OIH after gradual withdrawal compared with placebo (P=0.93). In the CPT 50 min after end of infusion there was OIH in both remifentanil sessions compared with placebo (gradual P=0.01, abrupt P<0.01. Marginal mean scores: placebo 4.56; abrupt 5.25; gradual 5.04). There were no differences between the three sessions 105-110 min after infusion.
  
  
  CONCLUSIONS
  We found no development of OIH after gradual withdrawal of remifentanil infusion in the HPT. After abrupt withdrawal OIH was present in the HPT. In the CPT there was OIH after both gradual and abrupt withdrawal of infusion. The duration of OIH was less than 105 min for both pain modalities.
  
  
  BACKGROUND
  NCT 01702389. EudraCT number 2011-002734-39.
authors.affiliation: Division of Emergencies and Critical Care, Department of Anesthesiology Faculty of Medicine, University of Oslo, 0316 Oslo, Norway marlin.comelon@ous-hf.no.
authors.forename: M
authors.initials: M
authors.lastname: Comelon
authors.affiliation: Division of Emergencies and Critical Care, Department of Anesthesiology Faculty of Medicine, University of Oslo, 0316 Oslo, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Raeder
authors.affiliation: Division of Emergencies and Critical Care, Department of Pain Management and Research Faculty of Medicine, University of Oslo, 0316 Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Stubhaug
authors.affiliation: Division of Emergencies and Critical Care, Department of Pain Management and Research Norwegian Institute of Public Health, Department of Mental Health, P.O Box 4404 Nydalen, 0403 Oslo, Norway.
authors.forename: C S
authors.initials: CS
authors.lastname: Nielsen
authors.affiliation: Division of Emergencies and Critical Care, Department of Research and Development, Oslo University Hospital, P.O. Box 4956 Nydalen, 0424 Oslo, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Draegni
authors.affiliation: Division of Emergencies and Critical Care, Department of Anesthesiology.
authors.forename: H
authors.initials: H
authors.lastname: Lenz
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects*; D003080:Cold Temperature; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000517:prevention & control*; D007262:Infusions, Intravenous; D008297:Male; D010147:Pain Measurement; D010149:Postoperative Pain / Q000139:chemically induced / Q000517:prevention & control; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects*; D011312:Pressure; D000077208:Remifentanil; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D010880:Piperidines; D000077208:Remifentanil
keywords: analgesia, postoperative; analgesics, opioid; hyperalgesia; pain, postoperative; remifentanil