Cephalad movement of morphine and fentanyl in humans after intrathecal injection.
BACKGROUND
Despite decades of use, controversy remains regarding the extent and time course of cephalad spread of opioids in cerebrospinal fluid (CSF) after intrathecal injection. The purpose of this study was to examine differences between two often used opioids, morphine and fentanyl, in distribution in the CSF after intrathecal injection.


METHODS
Eight healthy volunteers received intrathecal injection of morphine (50 microg) plus fentanyl (50 microg) at a lower lumbar interspace. CSF was sampled through a needle in an upper lumbar interspace for 60-120 min. At the end of this time, a sample was taken from the lower lumbar needle, and both needles were withdrawn. CSF volume was determined by magnetic resonance imaging. Pharmacokinetic modeling was performed with NONMEM.


RESULTS
Morphine and fentanyl peaked in CSF at the cephalad needle at similar times (41 +/- 13 min for fentanyl, 57 +/- 12 min for morphine). The ratio of morphine to fentanyl in CSF at the cephalad needle increased with time, surpassing 2:1 by 36 min and 4:1 by 103 min. CSF concentrations did not correlate with weight, height, or lumbosacral CSF volume. The concentrations of morphine and fentanyl at both sampling sites were well described by a simple pharmacokinetic model. The individual model parameters did not correlate with the distance between the needles, CSF volume, patient height, or patient weight.


CONCLUSIONS
Fentanyl is cleared more rapidly from CSF than morphine, although their initial distribution in the first hour after injection does not differ greatly. The pharmacokinetic model demonstrates that mixing is the primary determinant of early concentrations and is highly variable among individuals.
Eisenach
James C
JC
Department of Anesthesiology and Center for the Study of Pharmacologic Plasticity in the Presence of Pain, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. eisenach@wfubmc.edu
Hood
David D
DD
Curry
Regina
R
Shafer
Steven L
SL
D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics; D006801:Humans; D007278:Injections, Spinal; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics
D000701:Analgesics, Opioid; D009020:Morphine; D005283:Fentanyl