The systemic toxicity of equipotent proxymetacaine, oxybuprocaine, and bupivacaine during continuous intravenous infusion in rats.
BACKGROUND
Although proxymetacaine and oxybuprocaine produce topical ocular and spinal anesthesia, they have never been tested as cutaneous anesthetics. We compared cutaneous analgesia of proxymetacaine and oxybuprocaine with bupivacaine and tested their central nervous system and cardiovascular toxicity.


METHODS
After blockade of cutaneous trunci muscle reflex with subcutaneous injections, we evaluated the local anesthetic effect of proxymetacaine and oxybuprocaine on cutaneous analgesia in rats. After i.v. infusions of equipotent doses of oxybuprocaine, proxymetacaine, and bupivacaine, we observed the onset time of seizure, apnea, and impending death and monitored mean arterial blood pressure and heart rate.


RESULTS
Proxymetacaine and oxybuprocaine acted like bupivacaine and produced dose-related cutaneous analgesia. On a 50% effective dose basis, the ranks of potencies were proxymetacaine > oxybuprocaine > bupivacaine (P < 0.01). Under equipotent doses, the infusion times of proxymetacaine or oxybuprocaine required to cause seizure, apnea, and impending death were longer than that of bupivacaine (P < 0.05). The decrease in mean arterial blood pressure and heart rate was slower with oxybuprocaine and proxymetacaine compared with bupivacaine (P < 0.05 for the differences) at equipotent doses.


CONCLUSIONS
Oxybuprocaine and proxymetacaine were more potent at producing cutaneous anesthesia but were less potent than bupivacaine at producing central nervous system and cardiovascular toxicity.
Hung
Ching-Hsia
CH
Department of Physical Therapy, National Cheng Kung University, Tainan, Taiwan.
Liu
Kuo-Sheng
KS
Shao
Dong-Zi
DZ
Cheng
Kuang-I
KI
Chen
Yu-Chung
YC
Chen
Yu-Wen
YW
D000698:Analgesia; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D020258:Neurotoxicity Syndromes / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D011343:Procaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D011430:Propoxycaine / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced
D000779:Anesthetics, Local; D011343:Procaine; C005298:benoxinate; C005717:proxymetacaine; D011430:Propoxycaine; D002045:Bupivacaine