Systemic dextromethorphan and dextrorphan are less toxic in rats than bupivacaine at equianesthetic doses.
OBJECTIVE
Dextrorphan, a major metabolite of dextromethorphan, produces the duration of spinal and cutaneous anesthesia similar to bupivacaine. The purpose of this study was to test the central nervous system and cardiovascular toxicity of bupivacaine, dextromethorphan, and dextrorphan.


METHODS
First, dose-response curves for dextromethorphan, dextrorphan, and bupivacaine (n = 8 at each testing point) were determined for cutaneous analgesia on the rat back, and equipotent doses were calculated. Next, during continuous intravenous infusion of equipotent doses of bupivacaine, dextromethorphan, and dextrorphan (n = 8 in each group), we observed the time to seizure, apnea, and complete cardiac arrest. A saline group (n = 7) was used for comparison. Mean arterial blood pressure (MAP), heart rate (HR), stroke volume (SV), and cardiac output (CO) were also monitored.


RESULTS
Bupivacaine, dextromethorphan, and dextrorphan produced dose-dependent cutaneous anesthesia. A longer duration of equipotent infusion doses was required to produce seizures in the dextromethorphan group (10.6 ± 1.3 min) than in the bupivacaine group (7.6 ± 2.1 min) (P = 0.005). Dextrorphan did not produce any seizures. Compared with bupivacaine, time to apnea and complete cardiac arrest was longer with dextrorphan (P < 0.001) and with dextromethorphan (P = 0.001). Cardiovascular collapse, defined as a decline in MAP, HR, CO, and SV, was slower in the dextromethorphan and dextrorphan groups than in the bupivacaine group (P < 0.001 for both comparisons).


CONCLUSIONS
At equipotent doses for local anesthesia, dextromethorphan and dextrorphan were less likely than bupivacaine to induce central nervous system and cardiovascular toxicity.
Department of Physical Therapy, China Medical University, Taichung, Taiwan.
Yu-Wen
YW
Chen
Jhi-Joung
JJ
Wang
Tzu-Ying
TY
Liu
Yu-Chung
YC
Chen
Ching-Hsia
CH
Hung
D000779:Anesthetics, Local / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001049:Apnea / Q000139:chemically induced; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D003915:Dextromethorphan / Q000008:administration & dosage / Q000633:toxicity*; D003917:Dextrorphan / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000633:toxicity; D006323:Heart Arrest / Q000139:chemically induced; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced; D013997:Time Factors
D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D003917:Dextrorphan; D003915:Dextromethorphan; D002045:Bupivacaine