title: The effect of the addition of epinephrine on early systemic absorption of epidural ropivacaine in humans.
abstract: The addition of epinephrine to ropivacaine has not been recommended because ropivacaine has intrinsic vasoconstrictor properties. However, few pharmacokinetic data are available on the addition of epinephrine to epidural ropivacaine in humans. In this prospective, double-blinded study, we randomized patients having elective abdominal hysterectomy to receive epidural ropivacaine 1.5 mg/kg, diluted in 15 mL, either with (epinephrine group, n = 12) or without (plain group, n = 12) epinephrine 5 microg/mL and then measured arterial and venous plasma concentrations of ropivacaine at intervals up to 180 min. We found that arterial and venous plasma ropivacaine concentrations were smaller in the epinephrine group compared with the plain group in the first 60 min after the drug administration (P < 0.01). Mean (+/- SD) maximum total plasma ropivacaine concentration was smaller in the epinephrine group (arterial, 0.92 +/- 0.32 microg/mL; venous, 0.82 +/- 0.33 microg/mL) compared with the plain group (1.31 +/- 0.39 microg/mL and 1.31 +/- 0.50 microg/mL, respectively; P = 0.01). Time to maximum total plasma ropivacaine concentration was not significantly different between groups (mean +/- SD; arterial, 16 +/- 2 min; venous, 23 +/- 2 min in the epinephrine group versus 9 +/- 2 min and 12 +/- 3 min, respectively, in the plain group; P = 0.08). Arterial plasma ropivacaine concentrations were larger than venous concentrations during the first hour (P < 0.01); the arterio-venous difference decreased exponentially, and the rate and magnitude of this decrease was unaffected by epinephrine. We conclude that the addition of epinephrine 5 microg/mL to ropivacaine reduced the early systemic plasma concentrations of ropivacaine after epidural injection and may be useful for decreasing the risk of toxicity from systemic absorption of epidural ropivacaine.
  
  
  CONCLUSIONS
  The addition of epinephrine 5 microg/mL to epidural ropivacaine reduced the systemic arterial and venous plasma concentrations of ropivacaine in the first hour and the maximum plasma concentration of ropivacaine. Epinephrine may be a useful additive for reducing the risk of systemic toxicity when large doses of ropivacaine are given epidurally.
authors.affiliation: Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China. bblee@cuhk.edu.hk
authors.forename: Bee B
authors.initials: BB
authors.lastname: Lee
authors.forename: Warwick D
authors.initials: WD
authors.lastname: Ngan Kee
authors.forename: John L
authors.initials: JL
authors.lastname: Plummer
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Karmakar
authors.forename: April S Y
authors.initials: AS
authors.lastname: Wong
mesh_terms: D000328:Adult; D000368:Aged; D000577:Amides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000767:Anesthesia, Epidural; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008875:Middle Aged; D011446:Prospective Studies; D000077212:Ropivacaine; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D014662:Vasoconstrictor Agents; D000077212:Ropivacaine; D004837:Epinephrine