Plasma concentration profile of epidural alfentanil. Bolus followed by continuous infusion technique in the parturient: effect of epidural alfentanil and fentanyl on fetal heart rate.

BACKGROUND AND OBJECTIVES: A combined bolus and continuous epidural infusion technique of opioid and bupivacaine mixture has been described, although no pharmacokinetic data for this technique exists. The study documents the plasma concentration profile of epidural alfentanil in parturients using this technique, and evaluates the fetal heart rate tracing for associated changes following opioid administration.

METHODS: Twenty-four subjects were randomized to receive epidural alfentanil 500 micrograms in 10 mL 0.125% bupivacaine, group A, or fentanyl 50 micrograms in 10 mL 0.125% bupivacaine, group B, as a bolus dose, followed by continuous infusions of alfentanil 20 micrograms/mL in 0.125% bupivacaine (group A) or fentanyl 2 micrograms/mL in 0.125% bupivacaine (group B) for labor analgesia. Plasma drug levels for each group were examined using repeated measures analysis of covariance.

RESULTS: Fetal heart rate tracings were recorded throughout the study and were retrospectively analyzed by a "blinded" perinatologist. Data from fetal heart rate tracings were examined by repeated measures analysis of variance. Mean infusion rates were 9.3 +/- 2.1 mL/hour and 9.6 +/- 1.7 mL/hour for groups A and B, respectively. Mean study duration was 3.7 hours in group A, and 3.0 hours in group B. Low plasma levels precluded analysis of fentanyl data. Group A subjects exhibited stability of drug levels over time. Fetal heart rate tracings in 21 patients demonstrated no changes associated with epidural opioid infusion in either group.

CONCLUSIONS: With the dosage regimen used in this study, an initial epidural bolus with continuous infusion technique generates a steady state plasma concentration of alfentanil that is below levels associated with direct respiratory depression.