Skin blood flow changes in response to intradermal injection of bupivacaine and levobupivacaine, assessed by laser Doppler imaging.
OBJECTIVE
The vascular effects of local anesthetics are important determinants of their therapeutic activity. Drugs that vasoconstrict have the potential clinical advantages of limited systemic uptake and prolonged duration of effect. The aim of this study was to assess quantitatively the cutaneous vasoactivity of racemic bupivacaine and one of its enantiomers, levobupivacaine.


METHODS
Four concentrations of each drug (0.1 mL each of 0.125%, 0.25%, 0.5%, and 0.75%), as well as normal saline, were injected intradermally into randomly assigned sites on the forearms of 10 volunteers. We measured skin blood perfusion using laser Doppler imaging before injection and at 2.5, 10, 20, 40, 60, and 90 minutes thereafter.


RESULTS
Both drugs produced a rapid, dose-dependent increase in skin perfusion (P <.001). Saline also caused an increase in perfusion, although less sustained. By 40 minutes, most responses had returned to baseline levels. However, after this time, perfusion continued to decrease, below baseline, for both bupivacaine and levobupivacaine. The exception to this was 0.75% bupivacaine, the response to which was significantly higher than the same concentration of levobupivacaine over this later period (P <.05).


CONCLUSIONS
Bupivacaine and levobupivacaine both have a biphasic effect on skin microvessels. The vasoconstriction observed after 40 minutes may occur when the quantity of drug remaining at the administration site has decreased to a lower level. The continued vasodilatation caused by bupivacaine is more difficult to interpret. The results suggest that these local anesthetics cause vasodilatation at high doses and vasoconstriction at lower, subclinical doses. This hypothesis and the clinical relevance of these effects warrant further investigation.
Newton
D J
DJ
Section of Vascular Medicine and Biology, University Department of Medicine, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland.
Burke
D
D
Khan
F
F
McLeod
G A
GA
Belch
J J
JJ
McKenzie
M
M
Bannister
J
J
D000279:Administration, Cutaneous; D000328:Adult; D000779:Anesthetics, Local / Q000008:administration & dosage*; D002045:Bupivacaine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply*; D013237:Stereoisomerism
D000779:Anesthetics, Local; D002045:Bupivacaine