REDISTRIBUTION OF SUFENTANIL TO CEREBROSPINAL-FLUID AND SYSTEMIC CIRCULATION AFTER EPIDURAL ADMINISTRATION IN DOGS

Due to its higher lipid solubility, sufentanil may be less likely than morphine to migrate rostrally in the cerebral spinal fluid (CSF) and cause delayed respiratory depression following epidural administration . However, early respiratory depression has been reported in patients after relatively large doses of epidural sufentanil. This has been att ributed to systemic drug uptake. We used a dog model to investigate th e pharmacokinetics and rostral spread of epidural sufentanil in CSF. S ampling catheters were placed in the lumbar subarachnoid space, the ci sterna magna, and femoral arteries of six mongrel dogs. Samples of cis ternal CSF, lumbar CSF, and blood were drawn at 0, 1, 5,15, 30, 60, 90 , 120, and 180 min after lumbar epidural sufentanil injection. We meas ured sufentanil concentrations by gas chromatography-mass spectrometry and used the least squares method to a fit tri-exponential function t o each sufentanil concentration versus time data set. Paired t-test wa s used to test for statistical significance. After epidural sufentanil , lumbar CSF concentrations were significantly higher than plasma or c isternal CSF sufentanil concentrations at all assessment times, Sufent anil concentrations were significantly higher in cisternal CSF than in plasma at 30 and 60 min after injection. Sufentanil appeared rapidly in lumbar CSF, reaching a maximum concentration (C(max)) of 57 ng/mL a t 6.5 min. In cisternal CSF, a C(max) of 1.2 ng/mL was reached at 21 m in, and C(max) in plasma was 0.35 ng/mL at 6 min. The area under the c oncentration-time curve (AUC) of sufentanil in cisternal CSF was appro ximately six times higher than the plasma AUC (P < 0.05). We conclude that after a large epidural bolus dose, systemic redistribution of suf entanil is inadequate to explain the magnitude of sufentanil ultimatel y appearing in cisternal CSF.