The site of action of epidural fentanyl infusions in the presence of local anesthetics: a minimum local analgesic concentration infusion study in nulliparous labor.
We have previously demonstrated that continuous epidural infusions of fentanyl without local anesthetics elicit analgesia by a systemic mechanism. In this study, we examined the hypothesis that, in the presence of epidural bupivacaine, continuous infusions of epidural fentanyl elicit analgesia by a spinal mechanism. Forty-eight nulliparous women in active labor participated in this prospective, randomized, double-blinded study. Women received lumbar epidural analgesia with 20-30 mL bupivacaine 0.125% until pain free. Subjects were then randomized to either IV or epidural (EPI) fentanyl infusion groups. Each infusion delivered fentanyl 30 microg/h. All women received an epidural infusion of bupivacaine at a rate of 20 mL/h, the concentration of which was determined by the response of the previous woman in the same group to the analgesic regimen used. Unlike previous studies that assessed the minimum local analgesic concentration (MLAC) for bolus administration at the initiation of analgesia, this study assessed MLAC(infusion) for the maintenance of analgesia throughout the first stage of labor. MLAC(infusion) was determined using the up-down sequential analysis described by Dixon and Massey. The MLAC(infusion) of epidural bupivacaine was 0.063% (95% confidence interval, 0.058-0.068) and 0.019% (95% confidence interval, 0.000-0.038) in the IV and EPI groups respectively. A continuous infusion of fentanyl was more than three times as potent when administered by the epidural than by the IV route. This marked increase in potency for the epidural route is highly suggestive for a predominantly spinal mechanism of action for infused epidural fentanyl under the conditions of this study.


CONCLUSIONS
This study determined the median effective concentration for epidural infusions of bupivacaine during labor analgesia. Coadministered epidural fentanyl infusions were more than three times more potent than IV fentanyl infusions, suggesting a predominantly spinal mechanism of opioid action under these study conditions.
*Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University School of Medicine, Jerusalem, Israel, the †Department of Anaesthesia and Intensive Care Medicine, South Manchester University Hospitals, Wythenshawe, UK, and the ‡Department of Anesthesia, Stanford University, Stanford, California.
Yehuda
Y
Ginosar
Malachy O
MO
Columb
Sheila E
SE
Cohen
Edward
E
Mirikatani
Martha S
MS
Tingle
Emily F
EF
Ratner
Martin S
MS
Angst
Edward T
ET
Riley
D000293:Adolescent; D000328:Adult; D015360:Analgesia, Epidural; D016362:Analgesia, Obstetrical; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000779:Anesthetics, Local; D002045:Bupivacaine; D004311:Double-Blind Method; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage*; D006801:Humans; D007267:Injections; D007275:Injections, Intravenous; D010147:Pain Measurement; D010298:Parity; D011247:Pregnancy
D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D005283:Fentanyl; D002045:Bupivacaine