Acute Tolerance to and Distribution of Hexobarbital in Relation to Depth and Duration of Anaesthesia in Rats

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Abstract
The development of acute tolerance to hexobarbital was investigated with an EEG‐threshold method in rats. Hexobarbital was infused in a tail vein and the effect was monitored either by continous EEG‐recording (using the criterion “silent second”) or by continous observation. Anaesthesia was maintained at the level of “the silent second” for periods of up to 120 min. After different time intervals the last infusion period to the EEG‐criterion was followed by decapitation and samples from blood, brain, muscle and fat were analysed for hexobarbital content. Brain concentrations at the EEG criterion increased and were notable after 10 min. but statistically significant at 30 min. when a 40% increase in concentration was needed to reach the criterion. Another group of rats kept at a lower level of anaesthesia (i.e. the righting reflex) showed a slight but not always significant increase in concentration when measured in different parts of the brain at “silent second”. The dose of hexobarbital needed to maintain anaesthesia for intervals up to 120 min. increased almost linearly with time. Analysis of serum, muscle and fat tissue showed that concentration in fat tissue increased linearly during this whole interval and served as the final depot in redistribution. Muscle tissue shows an increase up to 60 min. but a very small increase thereafter, which is consistent with a function as temporary storage compartment.