Histamine release by propanidid and thiopentone was demonstrated with the use of a highly sensitive and specific method for determining histamine in human plasma. 5 min after i.v. administration of propanidid and 3 min after thiopentone, the plasma histamine level was increased by 350 and 420% respectively. In whole blood, histamine release could be demonstrated only when the basophil content remained constant. This was the case in about 50% of test persons after injection of propanidid, but not after administration of thiopentone where the basophil content decreased in all probands by about 35%. The increase of the histamine concentration in plasma was 3 ng/ml and in whole blood, 24 ng/ml. Half-maximum gastric acid secretion was elicited by injection of propanidid and thiopentone. It was increased by very rapid application of propanidid and diminished by premedication with atropine by about 30%. The changes in plasma histamine and gastric secretion were parallel over 30 min, whereas tachycardia and peripheral arterial hypotension lasted for only 3–4 min.

During i.v. infusion of histamine a correlation could be shown between the doses infused, (15–90 ng/kg)/min, and the elevation of the plasma histamine concentration. 3 ng/ml plasma were measured at a dose of (45 ng/kg)/min, which induced a half-maximum gastric secretion, but was without effect on blood pressure and heart rate. It is concluded that only the increase of plasma histamine concentration, not that of whole blood, represented the release of free, pharmacologically active histamine. In normal test persons, hisramine release by propanidid and thiopentone is without significant clinical consequences, but it is important in anaphylactoid incidents occurring during anesthesia with these substances.