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.

Clinical trial registration: NCT 01702389. EudraCT number 2011-002734-39.

Trial registration: ClinicalTrials.gov NCT01702389.

Keywords: analgesia, postoperative; analgesics, opioid; hyperalgesia; pain, postoperative; remifentanil.

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