Histamine and antihistamines in anaesthesia and surgery: from experimental pharmacology to clinical decision making.

The problem of whether antihistamines (histamine H1 + H2-antagonists) should be administered prophylactically before surgical interventions rose after animal experiments with hypnotics, opioids, muscle relaxants and plasma substitutes. It could, however, not be solved by classical biomedical research, but needed a heuristic problem-solving strategy. This strategy was formalized and in this way changed into a scientific structure by the thinking-aloud technique and the building of a decision tree with 9 nodes and various study designs to answer questions at particular decision nodes. The first question, whether the incidence of the reactions was high, was answered by several controlled clinical trials. The second question of life-threatening degrees of severity in single cases, was answered by a drug surveillance study. The third question, of whether severe incidents could always be avoided was answered by medical audit. The same was the case if death had to be considered as the final therapeutic failure. The fifth question was, "are the risks of histamine release comparable to other risks in the perioperative period?" They were--if thromboembolism, infection and stress ulcers were considered. The sixth and seventh questions referred to an experimentally and clinically effective prophylaxis. They were answered by animal and clinical studies with histamine antagonists, mainly with dimetindene and cimetidine. Undesired, adverse reactions to prophylaxis are rare since the drugs are given only once. Prophylaxis was calculated to be fairly cost-effective. Problem-solving strategies are very helpful in transferring facts and conclusions from experimental basic research to clinical decision making. This was convincingly demonstrated in antihistamine prophylaxis in anaesthesia and surgery.