title: Vasoactive characteristics of bupivacaine and levobupivacaine with and without adjuvant epinephrine in peripheral human skin.
abstract: BACKGROUND
  Epinephrine is added to local anaesthetic preparations to prolong their action and reduce their systemic absorption. Bupivacaine and levobupivacaine cause vasodilatation at clinical doses, but lower doses appear to cause vasoconstriction. The aim of this study was to characterize fully the vasoactive effects of these anaesthetics, using an objective measure of blood flow, and to assess the influence of adding epinephrine.
  
  
  METHODS
  Laser Doppler imaging was used to measure the forearm skin blood flow responses to intradermal injection of eight doses of bupivacaine and levobupivacaine in 10 healthy male volunteers. The doses tested ranged from 0.008% to 0.75%, and the five highest doses were administered both with and without adjuvant epinephrine 2.5 microg ml(-1).
  
  
  RESULTS
  The cumulative responses to the lower subclinical concentrations (0.008-0.0625%) of both anaesthetics were smaller than or similar to that produced by saline alone, indicating a net vasoconstrictive effect. Higher doses caused net vasodilatation, and the levobupivacaine responses were generally lower than the corresponding bupivacaine responses (P=0.022). Epinephrine 2.5 microg ml(-1) significantly reduced the responses to clinical doses of both drugs (P<0.001), producing net vasoconstriction.
  
  
  CONCLUSIONS
  Bupivacaine and levobupivacaine have a biphasic vascular effect when injected intradermally, with subclinical doses causing net vasoconstriction. The addition of epinephrine 2.5 microg ml(-1) decreases these responses markedly.
authors.affiliation: Vascular Diseases Research Unit, The Institute of Cardiovascular Research, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. d.j.newton@dundee.ac.uk
authors.forename: D J
authors.initials: DJ
authors.lastname: Newton
authors.forename: G A
authors.initials: GA
authors.lastname: McLeod
authors.forename: F
authors.initials: F
authors.lastname: Khan
authors.forename: J J F
authors.initials: JJ
authors.lastname: Belch
mesh_terms: D000759:Adjuvants, Anesthesia / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000779:Anesthetics, Local / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002045:Bupivacaine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D017078:Laser-Doppler Flowmetry; D000077554:Levobupivacaine; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000759:Adjuvants, Anesthesia; D000779:Anesthetics, Local; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000077554:Levobupivacaine; D002045:Bupivacaine; D004837:Epinephrine