Pharmacokinetics of fentanyl in lumbar and cervical CSF following lumbar epidural and intravenous administration

Abstract

Fentanyl (1 microgram/kg body weight) was administered intravenously and via a lumbar epidural catheter (in random order) on 2 separate occasions to 6 patients with chronic pain associated with non-terminal disease states. Frequent blood samples were collected from an indwelling intravenous catheter and CSF samples were collected via spinal needles inserted in the cervical (C7-T1 interspace) and lumbar (L3.4 interspace) regions at 0, 5, 10, 20, 30 and 45 min after fentanyl administration. The concentration of fentanyl in blood and CSF samples were quantified by a sensitive and selective gas-liquid chromatography assay. Visual analogue pain scores (VAPS) were recorded every 5 min for the first hour. Coded syringes (one containing the appropriate fentanyl dose while the other contained an equivalent volume of saline) allowed the investigator administering the fentanyl and assessing VAPS to remain blinded as to which route of administration actually contained the fentanyl. There was minimal vascular uptake of fentanyl following epidural administration. Similarly, the permeation of fentanyl into cervical and lumbar CSF following intravenous administration was minimal and erratic such that only 4 of the 60 CSF samples had detectable fentanyl concentrations. In contrast, there was a rapid penetration of fentanyl across the dura mater following lumbar epidural administration. There was significantly fentanyl in lumbar CSF samples by 10 min in 5 patients, and by 20 min in all 6 patients. The mean maximum lumbar CSF concentration was 19.1 ng/ml, while the time associated with these maximum concentrations was 22.5 min. The mean maximum cervical CSF fentanyl concentrations were 10% of the lumbar CSF concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Bupivacaïne intrathécale pure vs hyperbare pour l’analgésie du travail obstétrical: efficacité et effets secondaires

“…21,22 Rapid cephalad spread rather than systemic absorption with redistribution to the brain possibly causes the pruritus and hypotension seen with solutions of lipophilic opioids and plain local anesthetics. 6,7,[23][24][25][26] Both our study and that of Paez et al 27 support this explanation by showing less pruritus when fentanyl is combined with hyperbaric rather than plain bupivacaine. Although hypotension was not statistically different between both groups in our study, a trend towards hypotension requiring treatment was detected in parturients receiving the plain solution.…”

Comparison of combined spinal-epidural and low dose epidural for labour analgesia

“…16 Lipid soluble opioids such as fentanyl also penetrate the dura following lumbar epidural administration and, as such, may reach cerebrospinal fluid (CSF) concentrations similar to those after intrathecal injection. 17 The slower onset of action of fentanyl given by the epidural rather than the intrathecal route may be because it must penetrate the dura to reach its site of action. Even though the CSE group initially obtained greater degree of analgesia, satisfaction was equal and excellent in both sets of mothers from shortly after the initial injection to the end of the study.…”

Can parturients distinguish between intravenous and epidural fentanyl?

“…This pattern characterized by a prompt onset of symptoms followed by a rapid decrease in intensity has been demonstrated in pharrnacokinetic studies of intravenous fentanyl in other patient populations. 25,26 It is essential that blinded observers not only note the presence or absence of symptoms, but that their interpretation of these symptoms facilitate appropriate clinical decisions. We have demonstrated that anaesthestists at various levels of training were able to interpret subjective symptoms and to determine correctly the route of fentanyl administration accurately 92.4% of the time.…”