Epidural fentanyl, adrenaline and clonidine as adjuvants to local anaesthetics for surgical analgesia: meta-analyses of analgesia and side-effects

Background: The risk/benefit ratio of adding fentanyl, adrenaline and clonidine to epidural local anaesthetics for improving intraoperative analgesia is unclear. This meta-analysis was performed to clarify this issue.
Methods: Trials retrieved by search were considered if they were prospective, controlled, epidural analgesia (without combining general anaesthesia) was planned and occurrence of pain during surgery or side-effects were reported. Papers entered meta-analysis if they reached a predefined minimum quality score. Pooled odds ratios (OR) and confidence intervals (CI) were computed. P <0.05 was considered as significant.
Results: Eighteen trials were included in the analysis for fentanyl. Fentanyl decreased the likelihood of pain (OR=0.21, 95% CI=0.15–0.30, P <0.001) and increased the incidence of pruritus (OR=5.59, 95% CI=3.12–10.05, P <0.001) and sedation (OR= 1.88, 95% CI=1.19–2.98, P =0.003), compared to control (local anaesthetic without fentanyl). Fentanyl had no effect on respiratory depression, nausea, vomiting and Apgar score. One case of respiratory depression of a newborn was observed. Because of the very low number of trials selected, evaluation of adrenaline and clonidine was not feasible.
Conclusion: The analysis of current literature shows that the addition of fentanyl to local anaesthetics for intraoperative epidural analgesia is safe and advantageous. The reduction in the incidence of pain during surgery is quantitatively high and therefore clinically significant. Side-effects are mild. Randomized, controlled trials have to be performed in order to clarify the role of adrenaline and clonidine as epidural adjuvants for surgical analgesia.