Sciatic nerve blockade in infant, adolescent, and adult rats: a comparison of ropivacaine with bupivacaine.
BACKGROUND
Ropivacaine is a newly introduced local anesthetic. No data are available regarding its safety, efficacy, or sensory-selectivity in children. The sciatic block duration and systemic toxicity of bupivacaine and ropivacaine were compared among infant, adolescent, and adult rats.


METHODS
Infant, adolescent, and adult rats received blocks with ropivacaine or bupivacaine. Nociceptive, proprioceptive, and motor blockade were assessed. Systemic effects (contralateral leg analgesia, seizures, respiratory distress, apnea) were quantified. Plasma local anesthetic concentrations were measured at terminal apnea.


RESULTS
Nerve blockade for a given absolute dose lasted longer in infants than in older rats for both drugs. Block duration from ropivacaine generally was the same as or slightly shorter than bupivacaine. There was no difference in sensory-selectivity between the drugs. Doses required to induce all systemic toxicity indices were inversely related to age (e.g., the lethal dose in 50% of animals [LD50] of ropivacaine in infants is 155 mg/kg; in adults it is 54 mg/kg). All indices of toxicity occurred at higher doses per kilogram for ropivacaine than bupivacaine, at all ages (e.g., the LD50 of bupivacaine in infants is 92 mg/kg; in adults it is 30 mg/kg). Plasma concentrations at terminal apnea were higher for ropivacaine than for bupivacaine at all ages, and were higher in infants than in older rats.


CONCLUSIONS
Ropivacaine resembles bupivacaine in its local anesthetic effects but has a greater margin of safety. For a given absolute dose, sciatic blockade in infant rats lasts longer than in adolescents or adults. Although the doses (in milligrams per kilogram) causing toxicity were much higher in infants than in adults, this probably does not correspond to a wider therapeutic index.
Kohane
D S
DS
Massachusetts General Hospital and Harvard Medical School, Boston, USA.
Sankar
W N
WN
Shubina
M
M
Hu
D
D
Rifai
N
N
Berde
C B
CB
D000375:Aging / Q000502:physiology*; D000577:Amides / Q000097:blood / Q000494:pharmacology; D000779:Anesthetics, Local / Q000097:blood / Q000494:pharmacology; D000818:Animals; D001049:Apnea / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D002045:Bupivacaine / Q000097:blood / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D009407:Nerve Block; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077212:Ropivacaine; D012584:Sciatic Nerve / Q000187:drug effects* / Q000254:growth & development
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D002045:Bupivacaine