The Inspired Median Effective Dose, Brain Concentration at Anesthesia, and Cardiovascular Index for Halothane in Young Rats

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Abstract
It was determined: whether a difference in the inspired ED 50 for halothane exists between 15 day old and 30 day old rats; whether halothane concentrations in the brain and heart, associated with anesthesia and cardiac failure, differ as a function of age; and the cardiovascular index for halothane (the ratio of the halothane concentration in the heart at cardiac failure and the halothane concentration in the heart at anesthesia) for the 2 groups of young rats. Mean ED 50 of halothane was determined in 15, 30 and 60 day old rats by testing for movement and lack of movement (anesthesia) in response to tail clamping using the nonparametric method of Waud. Tissue concentrations of halothane (mg/100 g) were measured by gas chromatography at the end points of anesthesia and cardiovascular failure. Water content in the brain (as a function of age) was determined in separate groups of 15, 30 and 60 day old rats. The ED 50 for halothane was greater in the 15 day old rats than in the 30 day old rats (P < 0.01) or the 60 day old rats (P < 0.05). Anesthesia was attained, with brain concentrations of halothane that were less in 15 day old rats than in either 30 or 60 day old rats (P < 0.01). The estimated nonaqueous halothane concentration in the brain was similar in all 3 age groups of rats. The concentration of halothane in the heart at cardiovascular failure was less in the 15 day old rats than in the 30 day old rats (P < 0.001); likewise the cardiovascular index was lower in the 15 day old rats than in the older rats (P < 0.01). The reduced cardiovascular tolerance to halothane combined with increased anesthetic requirements places the younger rat at a therapeutic disadvantage.

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