A combination of analgesic and antagonist in postoperative pain.

Clinicians often hesitate to give adequate doses of narcotic analgesics such as morphine and pethidine because these compounds are known to have a marked respiratory depressant effect. As a result there has been considerable interest in the possibility of combining a dose of one of these analgesics with a small quantity of one of the specific narcotic antagonists. The latter substances are known to exert a much greater antagonism to the respiratory depressant effect than to the analgesic action of the narcotics. When deciding on such a combination the first prerequisite is that the antagonist should have few undesirable effects of its own and the second is that the antagonist and the analgesic should have approximately the same length of action. Although the narcotic antagonists nalorphine and levallorphan themselves possess slight respiratory depressant activity, this is insignificant in the doses in which they are used clinically. Levallorphan was chosen for clinical trial because, even in large doses such as are rarely used in therapy, it is tolerated without undesirable side effects by both conscious and unconscious patients (Swerdlow, 1958). Pethidine was selected as the analgesic most likely to have a suitable length of action for combination with levallorphan. Having decided on the combination of drugs we set out to establish whether, using the two drugs together in suitable proportions, the presence of the antagonist influences the following: the respiratory depressant effect of pethidine; the analgesic activity; the incidence of side effects. Accordingly, the following studies were carried out.