Pharmacokinetics of Epidural Fentanyl

To the Editor: Harukuni et al. [1] compared patients receiving epidural fentanyl (EP-F) and intravenous fentanyl (IV-F) combined with isoflurane and N2 O for gastrectomy. EP-F patients received a bolus of fentanyl epidurally followed by an hourly dose of 1 micro gram/kg. IV-F patients received the same bolus intravenously and an infusion of 1 micro gram centered dot kg-1 centered dot h-1 fentanyl. Hormonal responses to surgical trauma were more attenuated in the EP-F group. Isoflurane concentrations required to control blood pressure during surgery as well as the postoperative analgesic needs in EP-F patients were lower than in IV-F patients. The authors therefore concluded that EP-F may have a more potent analgesic effect than IV-F. These conclusions do not take into consideration that two different routes and methods of drug delivery were used, viz. an hourly bolus (for EP-F) versus a constant rate infusion (for IV-F), although the doses were equal. Analgesic effects of epidural opioids are influenced by a number of pharmacokinetic factors including the mode of drug delivery, with infusions resulting in lower dose requirements [2,3]. The high lipophilicity of fentanyl, its rapid penetration across the dura [4], its nonspecific binding in the spinal cord [5], its possible uptake by dural fat tissues, and its systemic absorption make its pharmacokinetics very complex when administered epidurally [6]. The different methods of fentanyl delivery may have inappropriately influenced their results. Jose Eduardo Tanus dos Santos, MD Department of Pharmacology Faculty of Medical Sciences University of Campinas 13081-970 Campinas, Sao Paulo, Brazil