Hs. Feldman et al., COMPARATIVE LOCAL-ANESTHETIC EFFICACY AND PHARMACOKINETICS OF EPIDURALLY ADMINISTERED ROPIVACAINE AND BUPIVACAINE IN THE SHEEP, Regional anesthesia, 22(5), 1997, pp. 451-460
Background and Objectives. Ropivacaine is the S(-) propyl homolog of b
upivacaine and mepivacaine. Studies in humans have confirmed the resul
ts of studies in laboratory animals that ropivacaine is a long-acting
local anesthetic with an anesthetic profile similar to bupivacaine. Ac
ute, intravenous systemic toxicity studies have been conducted in shee
p and dogs. Local anesthetic efficacy has been studied after epidural
administration in the dog. This study was initiated to determine the l
ocal anesthetic efficacy and pharmacokinetics of ropivacaine and bupiv
acaine after epidural administration in an experimental sheep model an
d to evaluate the sheep model as a model of experimental epidural anes
thesia. Methods. Twelve adult nonpregnant ewes were prepared with chro
nically implanted lumbar epidural catheters and arterial lines. Each s
heep received injections of 5.0 mL ropivacaine and bupivacaine (0.5% a
nd 0.75%) in a blinded, random, cross-over fashion. Onset and duration
of sensory and motor blockade were evaluated. Arterial blood samples
were drawn for serum drug concentration determinations and pharmacokin
etic analysis. Results. Onset and duration of motor blockade were simi
lar for comparable concentrations of both drugs. Both concentrations o
f ropivacaine and bupivacaine 0.5% demonstrated differential neural bl
ockade. The peak serum concentrations generally occurred within 8 minu
tes after administration. The terminal elimination half-life in serum
was about 3.5-4.0 hours and 6 hours for ropivacaine and bupivacaine, r
espectively. No signs of systemic toxicity were observed. Results of s
ensory and motor blockade were consistent with previous studies in lab
oratory animals and humans. Conclusion. Ropivacaine produces sensory a
nd motor blockade which is similar to that produced by equal concentra
tions of bupivacaine after epidural administration in the sheep. Peak
serum concentrations produced no signs of systemic toxicity. The resul
ts of this study are consistent with previously published data from st
udies in laboratory animals and humans. The sheep model of experimenta
l epidural anesthesia appears to be a clinically relevant method to ev
aluate experimental local anesthetics.