Porphyrin metabolism and barbiturate poisoning: observations on cases of acute and chronic poisoning.

The connexion between acute porphyria and barbiturate poisoning was pointed out by Waldenstrom (1939), who stated that practically all fatal cases of acute porphyria had been treated with large doses of barbiturates; on the other hand, the less severe cases as a rule received no such treatment, and further (Waldenstrom, 1940) in the majority of cases of acute porphyria large quantities of, for example, isophen, veronal, luminal, or dial, had been taken immediately preceding an attack of severe porphyria with pareses, and he mentioned further that cases with paralytic attacks of this disease without a history of taking barbiturates were in his experience very rare. In his two brief communications Waldenstrom presented no material in support of these important statements, but his monograph (1937) on acute porphyria includes some cases where attacks of porphyria were provoked by barbiturates. No systematic studies on the connexion between the drugs taken and the acute attacks of porphyria were carried out on the clinical material of 103 cases presented in Waldenstrom's classic monograph. Later several writers presented clinical observations supporting Waldenstrom's statements (e.g., Hug, 1945; J0rgensen and With, 1945, 1947; Dalseth, 1955), and moreover animal experiments have shown that barbiturates and allied substances may cause conditions much like acute porphyria in rodents and chick embryos (Schmid and Schwartz, 1952; Goldberg, 1954; Talman, Case, Neve, Labbe, and Aldrich, 1955). The reports of Nielsen (1953) and Plum (1954) from a Danish mental hospital, where several cases of acute porphyria developed among the patients during a short period, are, however, brief and preliminary and not entirely satisfactory from a clinical point of view (cf. With, 1953, 1955). On the other hand some investigators have questioned Waldenstrom's hypothesis. Thus Nilsson (1946) was unable to find any connexion between attacks of acute porphyria and barbiturate intake, and J0rgensen and Voldby (1949) report a case of acute porphyria where high doses of barbiturates were tolerated both during attacks and free periods for years, apparently without influence on the porphyria. Because of this controversial evidence it seemed important to study the influence of acute and chronic barbiturate poisoning on the porphyrin excretion in man, and especially to decide whether barbiturates are capable of producing acute porphyria in normal subjects as they seem to do in certain rodents. If this were correct one would expect a significant rise in the porphyrin excretion or an excretion of porphobilinogen in acute and chronic barbiturate poisoning in man, and failing such an increase one would be inclined to regard the occasional cases of acute porphyria provoked by barbiturates and allied substances as instances of latent porphyria rendered manifest by the poisoning.