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Hypnotic and Antinociceptive Effect of Isoflurane in Young Fischer Rats
Nehal Patel, B.S., Daqing Ma, M.D., Ph.D., Mahmuda Hossain, Ph.D., Mervyn Maze, F.R.C.A.
Department of Anaesthetics and Intensive Care, Imperial College London, C+W Hospital, London, United Kingdom.
Background: Recently, it has been shown that nitrous oxide lacks antinociceptive effects in very young animals (1). Volatile anesthetics are often used in pediatric anesthesia, but their hypnotic and antinociceptive effects in different age population are not yet known. In the present study we compared the hypnotic and antinociceptive efficacy of isoflurane in young vs adult Fischer rats.

Method: 28 days old (28d) and adult rats were used in this study. In the hypnotic study, the percentage of rats that had loss of righting reflex at increasing concentrations of isoflurane was measured (n = 8-10). In the antinociceptive study, the animals (n = 3) were exposed to either 100% oxygen or 0.5% isoflurane delivered with oxygen. After 20 minutes of exposure to the gas, 5% formalin or saline was injected into their left hind paws and then they were returned to the gas chamber for further 90 minutes. The animals were video taped for 60 minutes post-injection, and their behaviour was rated according to the criteria described previously (2) and the area under curve (AUC) was calculated for statistical analysis. The rats were sacrificed and the spinal cords removed. Sections made at the lumbar enlargement were stained for c-Fos (3) and quantitatively analysed.

Results: Isoflurane has a more potent hypnotic effect in 28d rats with a half effective concentration (EC50+/-95%CI) of 0.56% +/-0.01 as compared to that in adults (0.65% +/- 0.03) (p < 0.05). Isoflurane at 0.5% caused a reduction in nociceptive behaviour by 88% (p < 0.01) and 91% (p < 0.01) in 28d and adults rats respectively as calculated from the AUC. Isoflurane also significantly suppressed c-Fos expression by 57% in 28d rats and by 41% in adult rats (NS vs 28d group) as compared with those of formalin control group.

Conclusions: Our results indicate that isoflurane has a more potent hypnotic effect in younger rats when compared to adults but appears to have an equal antinociceptive effect on formalin-induced nociception in both 28d and adult rats. Further studies are needed to investigate the effect in even younger age groups.

References: (1) Ohashi Y, et al, Pain 2002;100:7-18; (2) Teng CJ et al, Pain 1998;76: 337-47; (3) Harris J, Brain Res Bull 1998;45:1-8.

Anesthesiology 2003; 99: A1407