Prior epidural lidocaine alters the pharmacokinetics and drug effects of extended-release epidural morphine (DepoDur(R)) after cesarean delivery.
Author(s): Atkinson Ralls L, Drover DR, Clavijo CF, Carvalho B
Affiliation(s): Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA.
Publication date & source: 2011-08, Anesth Analg., 113(2):251-8. Epub 2011 Jun 3.
Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't
BACKGROUND: A potential physicochemical interaction between epidural local anesthetics and extended-release epidural morphine (EREM) could negate the sustained release. In this study, we sought to determine the pharmacokinetic and drug effects of prior epidural lidocaine administration on EREM. METHODS: Thirty healthy women undergoing cesarean delivery were enrolled in this randomized study. Patients received 8 mg EREM 1 hour after either a combined spinal-epidural (intrathecal bupivacaine and fentanyl 20 mug with no epidural medication; group SE) or an epidural anesthetic (epidural 2% lidocaine with fentanyl 100 mug; group E). Maximal concentration (Cmax), time to Cmax (Tmax), and AUC(0-last) (area under the concentration-time curve until the last plasma concentration that was below the limit of quantitation) for morphine levels were determined from a plasma sample at 0, 5, 10, 15, and 30 minutes, and 1, 4, 8, 12, 24, 36, 48, and 72 hours. Drug effects including pain, analgesic use, and side effects were measured for 72 hours after cesarean delivery. RESULTS: Epidural lidocaine administration (20-35 mL) 1 hour before epidural EREM administration increased the Cmax in group E (11.1 +/- 4.9) compared with group SE (8.3 +/- 7.1 ng/mL) (P = 0.038). There were no significant effects on Tmax and AUC(0-last) of venous morphine between the groups (P > 0.05). There was an increased incidence in vomiting, oxygen use, and hypotension in group E (patients who received lidocaine before EREM). CONCLUSION: A large dose of epidural lidocaine 1 hour before EREM administration alters the pharmacokinetics and drug effects of EREM. Clinicians must apply caution when EREM is administered even 1 hour after an epidural lidocaine "top-up" for cesarean delivery.