Double-blind evaluation of buprenorphine hydrochloride for post-operative pain.

In a double-blind, random assignment study of four groups of 40 patients, relief of severe pain with buprenorphine hydrochloride 0.2 mg or 0.4 mg was evaluated and compared with morphine sulphate 5 or 10 mg. Evaluations included pain intensity, pain relief, sedation and other effects for up to 12 hours after drug administration, following recovery of wakefulness from anaesthesia for major abdominal surgery. Analyses of five parameters showed that the four groups were statistically comparable and that buprenorphine hydrochloride is at least 50 times more potent than morphine sulphate and has a substantially longer duration of analgesic action. Further clinical evaluation is, therefore, recommended.

Buprenorphine hydrochloride: determination of analgesic potency.

An open evaluation of relief from severe pain following major abdominal operations was carried out on at least ten patients, who had given written consent, with 0.1 to 0.4 mg doses of buprenorphine hydrochloride administered intramuscularly. Statistical analysis of the data showed that 0.3 mg of this compound provided quite satisfactory relief from pain for up to six hours. Seven more consenting patients were given buprenorphine hydrochloride 0.5 to 0.6 mg, but they did not receive much greater or longer pain relief than those receiving 0.3 to 0.4 mg. However, the latter patients were younger and heavier. It was concluded that buprenorphine hydrochloride 0.2 to 0.4 mg provided relief of severe pain probably as well as is observed with morphine 10 mg for the average-size patient, but the duration of pain relief with the new compound is substantially longer than with other strong analgesics previously tested. The only common side effect noted was drowsiness, which was observed during the analgesic action of the compound. No appreciable alterations were seen in the respiration, pulse rate and blood pressure. On the basis of these tests, buprenorphine hydrochloride appears to be a satisfactory analgesic for severe postoperative pain, and it deserves extensive study.

Butorphanol and pentazocine in patients with severe postoperative pain.

Either butorphanol tartrate (1, 2, or 4 mg) or pentazocine (30 or 60 mg) was given intramuscularly (5 dose groups) to 262 patients, who were scheduled for major operations, if they had severe pain after full awakening in the recovery room, postoperatively under double-blind conditions. There were at least 50 patients in each of the five dosage groups. Pain intensity and relief were scored numerically for each treated patient at 1/2 1, 2, 3 and 4 hr, while under direct surveillance, and the patients were seen again for follow-ups during the first 24 hr postoperatively. Appreciable pain relief developed within 30 min at all dose levels, with a peak analgesic effect apparent at about 1 hr. Satisfactory relief persisted for 4 hr in the majority of patients in each group. With the lowest dose of butorphanol tartrate (1 mg), which gave good pain relief for only 2 to 4 hr, approximately 60% of the patients had to be remedicated within 4 hr. Vital signs were not appreciably affected, but the patients who received the high dose of analgesics (butorphanol tartrate 4 mg or pentazocine lactate 60 mg) were often quite drowsy. The incidence of other side effects was negligible. The relative potency assay showed that butorphanol was approximately 20 times as potent as pentazocine for up to 4 hr.

Uptake of local anaesthetics: movement of ethanol into frog sciatic nerve.

The changes of nerve action potential with time of the excised bullfrog sciaticperoneal nerve were measured at 24 degrees C with the nerve immersed in oxygenated mineral oil containing various concentrations of ethanol. One series of measurements was made with intact nerve and a range of about 20 to 110 millimolar ethanol. Another series was made with nerves in which the epineural sheath was cut open longitudinally and using a range of about 15 to 51 millimolar ethanol. The results were analysed by means of simple diffusion theory, and below applied ethanol concentrations of about 70 millimolar the latent periods and times to total block fitted the theoretical pattern well. Disagreements between theory and measurement of previous workers is explainable by their neglecting to recognize that nerve bundles do not extend to the nerve periphery. It was found that the minimum oil concentration of ethanol capable of producing total block is 15 millimolar. Above 70 millimolar, behaviour was observed consistent with nerve damage. It was found possible, by measuring the ratio latent period: time to total block, to separate the relative contribution of the epineural sheath and epineurium as a diffusion barrier to ethanol from that of the perineurium and perilemma.

The influence of chronic administration of hypnotics and analgesics on rate of recovery from inhalation anesthesia in rats.

A series of groups of Sprague-Dawley rats were given either secobarbital, phenobarbital, morphine, pentazocine, diazepam, methotrimeprazine, or saline (control) intraperitoneally on 4 consecutive days and then, on day 5, anesthetized with chloroform, trichlorethylene, fluroxene, halothane, methoxyflurane, enflurane, isoflurane, bromotrifluorocyclobutane, or chlorotrifluorocyclobutane. One control group received neither pretreatment nor anesthetics and another was given pretreatment but no anesthetics. The factor of "enzyme induction" is also evaluated, as are SGPT elevation and liver and kidney lesions. If enzyme induction occurred with the drugs used for pretreatment, the anesthetics suppressed the expected response. SGPT levels were generally within normal range. The combinations of all pretreatments with enflurane, halothane, or methoxyflurane had the fastest recovery; recovery was slower with the other anesthetic agents, but none of the prior chemotherapeutic drugs accelerated recovery from the inhalation anesthetics.