title: The interaction between epidural 2-chloroprocaine and morphine: a randomized controlled trial of the effect of drug administration timing on the efficacy of morphine analgesia.
abstract: BACKGROUND
  The efficacy and duration of epidural morphine analgesia is diminished when administered after 2-chloroprocaine compared with lidocaine. The mechanism of the interaction between 2-chloroprocaine and morphine is unknown. Possible explanations include differences in the latency and duration of action of the two drugs or opioid receptor antagonism. We hypothesized that administration of epidural morphine 30 min before the initiation of 2-chloroprocaine anesthesia would result in postoperative analgesia of similar duration and quality to that achieved by epidural morphine after the initiation of lidocaine anesthesia in patients undergoing postpartum tubal ligation.
  
  
  METHODS
  Subjects undergoing bilateral postpartum tubal ligation after vaginal delivery with epidural analgesia were randomized to one of three groups. Subjects received epidural morphine or saline 30 min before the initiation of analgesia with 3% 2-chloroprocaine (two groups) or 2% lidocaine (one group), and at the time of surgical incision, they received either epidural saline or morphine. The duration of analgesia was defined as the time from morphine administration until the first request for supplemental analgesia. Duration of epidural morphine analgesia was compared among groups using Kaplan-Meier survival analysis and the log-rank test.
  
  
  RESULTS
  Administration of epidural morphine 30 min before the initiation of 2-chloroprocaine anesthesia (n = 29) resulted in a longer median duration of analgesia (28.6 h [95% CI 4.4-52.7]) compared with the administration of morphine after 2-chloroprocaine anesthesia (n = 30) (2.2 h [95% CI 0-4.8]) (P = 0.006). The median duration of analgesia observed when morphine was administered before 2-chloroprocaine was similar to that observed when morphine was administered after initiation of lidocaine anesthesia (n = 28) (25.8 h [95% CI 10.7-40.9]) (P = 0.83). Pain scores were not different in the postanesthesia care unit, but were higher on admission to the postpartum unit in the subjects receiving morphine after 2-chloroprocaine. Supplemental morphine equivalents administered in the first 48 h were similar among groups and there were no differences in opioid-related side effects.
  
  
  CONCLUSIONS
  This study demonstrates that administration of epidural morphine 30 min before epidural anesthesia with 2-chloroprocaine provides a similar duration of analgesia as epidural morphine after epidural lidocaine anesthesia. This suggests that the observed interaction between epidural morphine and 2-chloroprocaine is a result of differences in latency and duration of action of the two drugs, or that the administration of morphine before 2-chloroprocaine effectively blocks a receptor site antagonism.
authors.affiliation: Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Paloma
authors.initials: P
authors.lastname: Toledo
authors.forename: Robert J
authors.initials: RJ
authors.lastname: McCarthy
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Ebarvia
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Huser
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Wong
mesh_terms: D000328:Adult; D015360:Analgesia, Epidural / Q000379:methods*; D004311:Double-Blind Method; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D009020:Morphine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011247:Pregnancy; D011343:Procaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D011343:Procaine; C004616:chloroprocaine; D009020:Morphine