title: The effect of prior dural puncture on cerebrospinal fluid sufentanil concentrations in sheep after the administration of epidural sufentanil.
abstract: Sufentanil is a highly lipid soluble opioid that provides potent analgesia when administered in the subarachnoid space. Unfortunately, the penetration of sufentanil into the cerebrospinal fluid (CSF) after epidural administration is poor, and limits its effectiveness for epidural analgesia. Dural puncture may enhance the movement of epidural sufentanil into the subarachnoid space and increase its effectiveness. To determine whether the administration of epidural sufentanil adjacent to a dural puncture results in significantly greater CSF concentrations, 18 adult ewes were studied. Animals in the control group had an epidural catheter placed at the superior border of the pelvis without dural puncture. Animals in the study group had an epidural catheter placed, followed by a dural puncture performed using an 18-gauge Touhy needle. The dural puncture was performed one interspace cephalad to the epidural catheter. One hour after dural puncture, each animal received a loading dose of 0.35 microg/kg of sufentanil (5 microg/mL) through the epidural catheter, followed by an infusion of epidural sufentanil 0.15 microg x kg(-1) x h(-1) for a period of 4 h. After 4 h, CSF was sampled from a site one interspace caudad to the epidural catheter as well as at the cisterna magna. The mean CSF concentration of sufentanil at the level of the pelvis for animals with a dural puncture was 12.1 +/- 3.0 ng/mL compared with 1.8 ng/mL in controls with intact dura. Sufentanil concentrations at the cisterna magna were below the level of detection (0.08 ng/mL) for all animals in both groups. We conclude that an 18-gauge dural puncture significantly increases movement of sufentanil from the epidural to the intrathecal space. This increase in sufentanil concentration at the level of the pelvis was not associated with detectable levels of sufentanil at the brainstem.
  
  
  CONCLUSIONS
  This study addresses the effect of dural puncture on spinal fluid concentrations of sufentanil after epidural administration. A sheep model was used to measure drug concentrations in the spinal fluid at the levels of the pelvis and brainstem after epidural administration. Dural puncture significantly enhanced movement of sufentanil into the spinal fluid at the level of the pelvis, but brainstem concentrations were below the level of detection. Analgesic concentrations of spinal sufentanil in the clinical setting, as well as brainstem concentrations associated with respiratory depression, have yet to be defined.
authors.affiliation: Department of Anesthesiology, University of Utah Medical Center, Salt Lake City 84132, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Swenson
authors.forename: T H
authors.initials: TH
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: McJames
mesh_terms: D015360:Analgesia, Epidural; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000134:cerebrospinal fluid*; D000818:Animals; D001933:Brain Stem / Q000378:metabolism; D002946:Cisterna Magna / Q000378:metabolism; D004388:Dura Mater; D005260:Female; D005500:Follow-Up Studies; D007268:Injections, Epidural; D009339:Needles; D010384:Pelvic Bones; D012756:Sheep; D013129:Spinal Puncture / Q000295:instrumentation; D013346:Subarachnoid Space; D017409:Sufentanil / Q000008:administration & dosage / Q000134:cerebrospinal fluid*
chemical_list: D000701:Analgesics, Opioid; D017409:Sufentanil