Residual analgesic effects of morphine in 55 four-period crossover analgesic studies.

Subjective response data from 55 postoperative pain studies were examined for the residual analgesic effects of morphine. The studies were planned as four-period crossover designs for four treatments. Each patient received 5 and 10 mg of morphine and two doses of a test preparation. Two measures of analgesia were used: Sum of the Pain Intensity Difference (SPID) and Total Pain Relief (TOTPAR). To facilitate analysis, two two-period groups were defined. Morphine data for periods 1 and 2 were designated as group A, and morphine data for periods 3 and 4 were designated as group B. Residual analgesic effects were 0.12 for both SPID and TOTPAR in group A and were 0.65 and 0.17 for SPID and TOTPAR, respectively, in group B. In these 55 studies, there was no evidence of significant residual analgesic effects. Thus the crossover design is an appropriate method for the evaluation of selected parenteral analgesics in the postoperative pain model.

Crossover and noncrossover designs in four-point parallel line analgesic assays.

Fifty-nine analgesic investigations designed as four-point parallel line crossover assays were examined. Sum of pain intensity differences (SPID) and total pain relief (TOTPAR) were the subjective response measures. Separate analyses with four-point crossover data and first-dose data (noncrossover) allowed comparison within each study of these two approaches. The crossover analysis allows for removal of the subject component of variance, which in these studies was a substantial fraction of the error variance (0.49 for SPID; 0.56 for TOTPAR). For this type of study, 2.4 times as many subjects would have to be recruited in a noncrossover design to obtain precision equivalent to that of the crossover design. Thus efficiency considerations argue for the crossover design in cases in which a treatment carryover effect may be assumed to be negligible.

Effectiveness in professional organizations: the impact of surgeons and surgical staff organizations on the quality of care in hospitals.

In this research, we examine the relative importance of different structural units in a professional organization, the hospital, as they affect organizational effectiveness. The difficulties of measuring effectiveness in a complex professional organization are discussed, and an adjusted measure of surgical outcome is developed. Data are drawn from a prospective study of over 8,000 surgical patients treated by more than 500 surgeons in 15 hospitals throughout the nation. Two different types of analyses are presented, both indicating that hospital features have more impact on surgical outcomes than do surgeon characteristics. The second analysis assesses the relative importance of specific attributes of the hospital, surgical staff organization, and surgeon characteristics on surgical outcomes.

Orally administered zomepirac and parenterally administered morphine. Comparison for the treatment of postoperative pain.

A double-blind study comparing the analgesic efficacy of orally administered zomepirac sodium with intramuscularly (IM) administered morphine sulfate was conducted in 109 patients with acute postoperative pain. Single treatments were administered within 48 hours of surgery, and subjective responses were obtained from patients by specially employed trained nurses. Pain relief achieved with both doses of orally administered zomepirac sodium at 100 mg and 200 mg was similar, and analgesia with each dose of zomepirac was significantly better than that obtained with IM administered morphine sulfate at 8 mg. There were no unusual side effects with either drug.

Measuring the complexity and uncertainty of surgery and postsurgical care.

This article reports the results of a survey of a nationwide sample of more than 900 surgeons and post-surgical nurses, who were asked to rate the relative complexity and uncertainty of 71 surgical procedures frequently performed in hospitals. Average scores assigned to each surgical procedure by both types of raters are reported and the extent of agreement is assessed across indicator questions and types of raters. A surprisingly high level of agreement was observed. Explanations for the extent of agreement are discussed and uses for these scores are described.

Dextroamphetamine with morphine for the treatment of postoperative pain.

In a double-blind, single-dose study, dextroamphetamine combined with morphine was compared with morphine alone to determine the relative efficacy of the combination given intramuscularly for postoperative pain. Each of 450 patients received one treatment of morphine sulfate (3, 6 or 12 mg) with dextroamphetamine (0, 5 or 10 mg). Analgesia, as measured by the patients' subjective responses to questions about relief of pain, was augmented when dextroamphetamine was given with morphine; the combination of dextroamphetamine, 10 mg, with morphine was twice as potent as morphine alone, and the combination with 5 mg was 1 1/2 times as potent as morphine. In simple performance tests, and in measures of side effects, dextroamphetamine generally offset undesirable effects of morphine (sedation and loss of alertness) while increasing analgesia. Effects on blood pressure, pulse and respiratory rate were minimal.

Combined routes of administration to assay oral analgesia in postoperative pain.

To increase the sensitivity of the method for evaluating oral analgesics in postoperative patients, we designed a combined oral/parenteral bioassay. Drugs studied were parenteral morphine, parenteral propiram, and oral codeine at two dose levels each and oral propiram at four dose levels. Results from data on 308 patients suggest that future studies designed to establish the relative potencies of oral analgesics should use parenteral morphine as the standard in a combined oral/parenteral study because this approach provides a very sensitive measure of analgesia. Further, with one drug as the reference compound, results from many sources would be more readily compared.

Assay of aspirin and naproxen analgesia.

To establish the relative potency of naproxen and aspirin for oral analgesia, a 4-point, noncrossover bioassay with placebo control was undertaken with 197 patients. Subjective-response methods were used to determine two measures of postoperative analgesia over a period of 6 hr. With reasonable confidence for an oral analgesic assay, we found 220 mg of naproxen to be equivalent to 600 mg of aspirin for pain relief and 330 mg of naproxen to be equivalent to 600 mg of aspirin for decreased pain intensity.

Lorazepam compared with pentobarbital for nighttime sedation.

Lorazepam (0.5, 1, 2, and 4 mg) was compared with pentobarbital (60 and 180 mg) for its effect on sleep in "hospital insomnia." Subjective-response data were collected by research nurses. Lorazepam was found to be a potent nighttime sedative: 1 to 1.25 mg of lorazepam is equivalent to 100 mg sodium pentobarbital for measures of sleep quality and duration. At this dose level it is less effective than 100 mg of pentobarbital as a sleep inducer. Studies at higher doses (up to 4 mg) indicate that lorazepam has a wide therapeutic index.

Relative analgesic potencies of morphine and hydromorphone in postoperative pain.

Because of discrepancies in the estimates of the relative analgesic potencies of hydromorphone and morphine, the drugs were compared in two four-point, double-blind bioassays. In the first study, hydromorphone, 1 and 2 mg, was compared with morphine, 5 and 10 mg, in 31 postoperative patients; in the second, hydromorphone, 0.5 and 1 mg, was compared with morphine, 5 and 10 mg, in 112 postoperative patients. Subjective responses to nurse-observer questions were used to quantitate analgesia for postoperative pain. Hydromorphone is more potent than commonly believed: approximately 0.9 to 1.2 mg is equianalgesic with 10 mg of morphine, with a similar incidence of side effects.

Hypnotic efficacy of diphenhydramine, methapyrilene, and pentobarbital.

The antihistamines diphenhydramine and methapyrilene were compared with pentobarbital for hypnotic effect in two Veterans Administration Hospital populations using subjective-response methods. In the first part of the study, 60 mg and 180 mg of pentobarbital were compared with 50 mg and 150 mg of diphenhydramine. A positive dose-response relationship was obtained only for pentobarbital; neither dose of diphenhydramine was significantly different from 60 mg of pentobarbital for any response variable. In the second part of the study, 100 mg of pentobarbital, 50 mg of diphenhydramine, and 50 mg of diphenhydramine, and 50 mg of methapyrilene were compared with placebo. One hundred mg of pentobarbital and 50 mg of diphenhydramine were significantly different from placebo, but 50 mg of methapyrilene was not.