Hyperalgesia and fentanyl dosing in on-pump coronary artery bypass grafting

Abstract

Introduction Opioids have many known side-effects. However opioid-induced hyperalgesia (OIH), as a result of central sensitization, remains more obscure. The increase in hyperalgesia is dose-related and postoperatively an increased secondary wound hyperalgesia may be a factor in the development of chronic or persistent pain. This prospective, randomized and double-blind clinical trial aims to investigate the effects of fentanyl on secondary wound hyperalgesia in patients undergoing on-pump coronary artery bypass grafting. Methods Secondary wound hyperalgesia was investigated between two study-groups, respectively a low dose bolus group (n = 14, 3mcg/ kg) and a continuous infusion group (n = 17, Shibutani). The primary endpoint of this study was the area of secondary wound hyperalgesia after 24 hours. The area was measured using a Von Frey filament (256mN). Additionally we looked at hyperalgesia after 48 hours and we investigated following secondary endpoints: time to extubation, ICU/hospital length of stay, PONV, pain scores, the need for additional analgesia and the total dose of opioids administered 24 and 48 hours after surgery. This study is a subgroup analysis of a larger study, in which the possible association between the area of secondary wound hyperalgesia and persistent pain at 3, 6 and 12 months after surgery will be investigated. Results The examination of preliminary results showed no statistically significant difference for the area of secondary wound hyperalgesia after 24 hours (p = 0.3268). However the results became significant after 48 hours, where the area of secondary wound hyperalgesia was smaller in the low dose bolus group (p = 0.0389). No significant differences were found for the other secondary endpoints. Discussion There was less secondary wound hyperalgesia in the low dose bolus group after 48 hours, although at 24 hours this was not statistically significant. These findings are the result of preliminary data. We need to wait for the definitive results of hyperalgesia and for the results regarding chronic pain to draw any conclusions about the clinical significance of OIH.