Retention of nociceptor responses during deep barbiturate anesthesia in frogs

Bullfrogs (Rana catesbeiana) anesthetized with a large dose of thiopental ( 42.8 mg/kg) retained movement responses to nociceptor stimuli despite an av erage plasma drug level of 51 mg/l, of which 63% was bound to plasma protei ns. This concentration, when corrected to include only unbound and uncharge d drug, was 2-fold greater than those reported to abolish nociceptor respon se (NR) during surgical anesthesia in man. The median anesthetic dose (AD(5 0)) for loss of the righting reflex was 11.2 mg/kg by s.c. injection into t he abdominal lymph sac; however, at 54.0 mg/kg, all frogs retained NRs, alt hough otherwise deeply anesthetized. The ratio of NR-blocking dose to light AD was thus > 4.8, as compared to < 2 in mammalian studies. Whole body lev els of thiopental determined at 3 h after intralymphatic injection showed t hat about half the injected drug had been eliminated by this time and that termination of anesthesia was chiefly due to drug elimination. Even though the pharmacokinetics of thiopental appears to differ markedly in frogs and men, the poor analgesia seen in the present study frequently has been repor ted during clinical barbiturate anesthesia. Since this deficiency is much m ore pronounced in the bullfrog than in man, its neurophysiological basis mi ght profitably be studied using the bullfrog as a model; however, the high mortality associated with deep thiopental anesthesia in the frog should pre clude its use as a practical anesthetic in amphibia. (C) 1999 Elsevier Scie nce Inc. All rights reserved.