Since the discovery of general anesthesia in the 1840s, opium and its principal analgesic component morphine have been used in conjunction with general anesthetics to produce surgical anesthesia. As preanesthetic medication, morphine-type drugs provided sedation, reduction of anxiety, and analgesia, facilitating the patient's toleration of preanesthetic preparations, including vascular cannulation. Premedication with an opioid facilitates the induction of general anesthesia, and Claude Bernard in 1869 demonstrated that morphine premedication reduced the amount of chloroform required to anesthetize dogs.
In the 1890s, Schneiderlein and other German physicians attempted to produce surgical anesthesia by combining morphine and scopolamine, both in very large doses. The patients had to be restrained for the surgeon to operate, and many died postoperatively from ventilatory depression because mechanical ventilation was unknown at that time. Then, in the 1960s, Lowenstein et al. (1969) combined morphine with d-tubocurarine to produce general anesthesia in critically ill patients undergoing valvular heart surgery. When this anesthetic technique was later extended to physically fit individuals undergoing coronary artery bypass surgery, there was an unacceptably high incidence of hypertension and tachycardia as well as intraoperative awareness and recall of intraoperative events. Because of its side effects, especially those related to histamine release, there were limitations on the doses of morphine that human patients could tolerate.
During World War II, intense efforts were made to discover synthetic morphine like drugs (i.e., opioids). Many of these drugs were investigated and used for preoperative medication and intraoperative supplementation of general and regional anesthesia.