DIURESIS AND INDIVIDUAL TOLERANCE IN EXPERIMENTAL BARBITAL POISONING

Since the introduction of barbital into clinical use as a hypnotic by Fischer and v. Mering in 1903-1905 (1), considerable litera-ture on its clinical and experimental toxicology has accumulated. From these reports it is evident that there is a wide variation in individual susceptibility to barbital and to its derivatives. Thus, estimates of the average fatal dose for man vary from 3.25 to 10 grams (2) (3), yet a death has been reported following the inges-tion of 1 gram (4). At the other extreme, Littell has reported a case in which recovery occurred after the taking of over eighty grams of barbital within twelve days (5). Where death occirs in acute barbital poisoning, it usually appears to be the result of respiratory failure or of effects secondary to prolonged coma, such as bronchopneumonia, or impairment of circulation with pul-monary edema and cyanosis. As in man so also in laboratory animals are there wide varia-tions in the snscptibility to the various members of the barbi-turic acid group. Nielsen, Higgins, and Spruth (6) found cats and dogs unsatisfactory for making a comparative study of these drugs on account of the wide individual variations in toler-ance. In their researches the rat reacted more consistently. Eddy (7) noted that the cats which tolerated high doses of on barbituric acid derivative were likely to exhibit a high tolerance to other members of the series. Pertinent to the question of natural resistance is the distribu-tion of barbital in tissues, which has been found to be unequal. Relative1ly high concentrations are found in the nervous system (8) (9), and Paolini (10) furthermore finds that the concentra-tions in various parts of the nervous system differ markedly