[Histamine release during induction of combination anesthesia using nalbuphine or fentanyl. Modulation of the reaction by premedication with promethazine/pethidine].

In a controlled clinical trial in patients admitted for general surgery (mainly abdominal and thyroid), histamine release following nalbuphine 1 mg/kg i.v. versus fentanyl 5 micrograms/kg i.v. was studied in the course of an otherwise routine induction with promethazine/pethidine as premedication 30 min before the opioids and alcuronium-flunitrazepam-thiopental 5 min later. Succinylcholine was given before intubation and further analgesia was obtained by repeated administration of either nalbuphine or fentanyl. Plasma histamine levels were measured by a specific fluorometric assay, heart rate and blood pressure were measured for assessing hemodynamics, and clinical signs of anaphylactoid reactions such as skin eruptions and arrhythmias were registered. RESULTS. Nalbuphine and fentanyl both released histamine with an incidence of more than 40%. In addition, nalbuphine potentiated the histamine release evoked by the sequential administration of alcuronium-flunitrazepam-thiopental in one complex of application. The incidence of histamine release in the nalbuphine group was 6/13 = 46%, in the fentanyl group only 1/11 = 9% (chi2 test, P less than 0.05). Furthermore, this study showed high histamine levels after succinylcholine and intubation in a relation to time of administration that suggested histamine release as a stress response to intubation. Finally, the incidence of histamine release after a second injection of the opioids was still 30%. A direct correlation between plasma histamine levels, hemodynamic changes, and skin reactions could not be shown. A detailed causality analysis with histamine release as a contributory determinant showed histamine release less detrimental to hemodynamic stability than the opposite, which had been expected. However, the promethazine administered 30 min before induction of anaesthesia had strong H1- and H2-receptor antagonistic activity and was given with optimum timing for H1- and H2-prophylaxis. CONCLUSION. The study demonstrated that histamine release during anaesthesia and surgery depends strongly on the time sequence of drugs and measures used. Histamine release is not predictable from studies in human volunteers alone; studies in patients have to be added. Histamine release is not always detrimental. H3-receptor-mediated effects after H1- and H2-prophylaxis may help patients to counteract the effects of a series of vasoactive drugs given during induction of anaesthesia.