Histamine metabolism after adverse reactions due to d-tubocurarine administration

We investigated histamine release in five female patients, submitted for gynaecological surgery, after intravenous administration of the neuromuscular blocking agent d-tubocurarine. In these patients, we measured the plasma levels of histamine and its metabolites, N tau-methylhistamine and N tau-methylimidazoleacetic acid, making use of mass fragmentographic methods. The newly developed determination of plasma N tau-methylimidazoleacetic acid had a within-day coefficient of variation of 2.7% (n = 10). Normal values of N tau-methylimidazoleacetic acid in plasma ranged from 41.3-75.6 nmol/l (n = 13). All five patients developed anaphylactoid reactions: two patients showed severe systemic reactions, one patient a minor systemic reaction and two had skin reactions only. Plasma histamine and N tau-methylhistamine levels appeared to be the most reliable biochemical parameters for confirming both the occurrence and severity of an anaphylactoid reaction. In comparison with plasma histamine, the determination of plasma N tau-methylhistamine is less hampered by artefacts caused by blood collection and plasma preparation. Together with the fact that the increase in plasma N tau-methylhistamine levels after anaphylactoid reactions lasts much longer than the increase in plasma histamine levels, this leads to the conclusion that the determination of plasma N tau-methylhistamine is a useful retrospective parameter for histamine release in this type of pathological state. The plasma N tau-methylimidazoleacetic acid levels fluctuated considerably, showing only a significant increase after administration of d-tubocurarine in the two patients who had severe anaphylactoid reactions. This parameter is, therefore, less useful in such studies.