Stanley L. Wallenstein

The memorial pain assessment card. A valid instrument for the evaluation of cancer pain

Effective evaluation and treatment of cancer pain require valid and independent measurement of pain intensity, pain relief, and psychological distress. The Memorial Pain Assessment Card (MPAC) is a simple instrument designed to provide rapid evaluation of these subjective experiences. On the 8.5 by 11 inch card are printed the eight pain intensity descriptors, and three visual analog scales which measure pain intensity, pain relief, and mood. Experienced patients can complete it in less than 20 seconds. The authors administered the MPAC to 50 hospitalized cancer patients within 48 hours of referral to the Pain Service for inadequate pain control, together with standard measures: The McGill Pain Questionnaire, Profile of Mood States, Hamilton Depression Scale, and Zung Anxiety Scale. Correlational and multiple regression analyses revealed that the MPAC can distinguish pain intensity from pain relief and from general psychological distress, and it can provide multidimensional assessment that is practically equivalent to the full assessment battery. We conclude that the MPAC is valid and effective for clinical use, and recommend it for the assessment of individual patients, and as an outcome measure in clinical trials.

SUBLINGUAL ABSORPTION OF SELECTED OPIOID ANALGESICS

Ongoing interest in the improvement of pain management with opioid analgesics has led to the investigation of sublingual opioid absorption. The present report determined the percent absorption of selected opioid analgesics from the oral cavity of normal subjects under conditions of controlled pH and swallowing when a 1.0 ml aliquot of the test drug was placed under the tongue for a 10‐minute period. Compared with morphine sulfate at pH 6.5 (18% absorption), buprenorphine (55%), fentanyl (51%), and methadone (34%) were absorbed to a significantly greater extent (p < 0.05), whereas levorphanol, hydromorphone, oxycodone, heroin, and the opioid antagonist naloxone were not. Overall, lipophilic drugs were better absorbed than were hydrophilic drugs. Plasma morphine concentration‐time profiles indicate that the apparent sublingual bioavailability of morphine is only 9.0% ± 11.9% (SD) of that after intramuscular administration. In the same subjects the estimated sublingual absorption was 22.4% ± 9.2% (SD), indicating that the sublingual absorption method may overestimate apparent bioavailability. When the oral cavity was buffered to pH 8.5, methadone absorption was increased to 75%. Thus, an alkaline pH microenvironment that favors the unionized fraction of opioids increased sublingual drug absorption. Although absorption was found to be independent of drug concentration, it was contact time dependent for methadone and fentanyl but not for buprenorphine. These results indicate that although the sublingual absorption and apparent sublingual bioavailability of morphine are poor, the sublingual absorption of methadone, fentanyl, and buprenorphine under controlled conditions is relatively high.

Analgesic and Mood Effects of Heroin and Morphine in Cancer Patients with Postoperative Pain

We designed a study to determine the relative analgesic potency of intramuscular heroin and morphine and to compare mood and side effects in 166 cancer patients with postoperative pain. Heroin was about twice as potent as morphine (95 per cent confidence limits, 1.6 to 2.6 times) in graded-dose, twin-crossover assays. Heroin provided an analgesic peak effect earlier than morphine (1.2 plus or minus 0.08 and 1.5 plus or minus 0.10 hours, respectively [mean plus or minus S.E.M.]). Doses with equal analgesic effects provided comparable improvements in various elements of mood, particularly feelings of peacefulness. Peak mood improvement occurred earlier after heroin than after morphine (1.2 plus or minus 0.10 and 1.8 plus or minus 0.13 hours, respectively). Both analgesia and mood improvement were less sustained after heroin at doses providing equal peak analgesic effects. The drugs shared the most common side effects, with no marked differences in their occurrence; sleepiness was the most frequent side effect after both drugs (46 per cent with each). Heroin has no apparent unique advantages or disadvantages for the relief pain in patients with cancer.

Sources of variation in analgesic responses in cancer patients with chronic pain receiving morphine

Abstract Our objective was to identify and quantify sources of variation in the relief of chronic pain with morphine. Relief scores were extracted from records obtained during controlled trials of analgesics in cancer patients with chronic pain in which intramuscular morphine was the assay standard. Relief data from 715 patients after 565 8‐mg and 538 16‐mg doses were segregated according to age, race, sex, pre‐drug pain intensity, character and site. Middle‐aged patients obtained relief after 8 mg comparable to relief obtained by younger patients after 16 mg; oldest patients obtained relief after 8 mg comparable to relief obtained by middle‐aged patients after 16 mg. Blacks receiving 8 mg obtained relief comparable to whites receiving 16 mg. Sex‐related differences were not significant. Patients with moderate, as compared to severe, pre‐drug pain obtained significantly greater relief only after 16 mg. Patients reporting dull pain obtained relief after 8 mg comparable to relief obtained with sharp pain after 16 mg. Patients with abdominal pain obtained relief after 8 mg comparable to relief of pain in the chest or arms after 16 mg. These results provide dose‐related evidence of variation in relief with morphine in chronic cancer pain and establish particular patient and pain characteristics as variables for which controls

Measurement of pain and analgesia in cancer patients.

Measurement of pain in cancer patients requires all the procedural safeguards essential for the measurement of subjective responses, including the employment of active and inactive controls, double-blind techniques, randomization, and statistical verification of results. Pain is traditionally measured in analgesic studies by employing verbal descriptors of intensity, but more recently visual analogues of pain intensity have been used and generally provide more sensitive measures of pain intensity. Patients with chronic pain tend to rate the categories representing more intense pain as lower in the visual analogue scale than do patients with postoperative pain. This may well reflect differences in the prior pain experiences of the two groups. Patients with chronic cancer pain have greater positive mood effects after the narcotic, morphine, than after the non-steroidal antiinflammatory analgesic, zomepirac, and this appears to be independent of analgesic activity. It is possible to design crossover analgesic studies in cancer patients so as to minimize carry-over effects, and such studies are more efficient than parallel group assays. Crossover studies also provide the ability to measure carry-over when it occurs.

Relative Analgesic Potency of Oral Zomepirac and Intramuscular Morphine in Cancer Patients with Postoperative Pain

A twin crossover assay of oral zomepirac and intramuscular morphine was completed in 159 cancer patients with postoperative pain. Zomepirac was a surprisingly effective oral analgesic in these patients, 100 mg orally being roughly equivalent to 16 mg intramuscular morphine. Time-effect data indicate that the peak effect for oral zomepirac may occur slightly later than that for morphine but that zomepirac is relatively rapidly effective after oral administration. Side effect occurrence was roughly in the same range for both drugs, with drowsiness, nausea, dry mouth, and feelings of weakness being observed after both drugs while sweating was observed more frequently after zomepirac. The assay further provided a demonstration of the effectiveness of the twin crossover design as a clinical assay method, providing increased sensitivity of crossover data in a patient population available for only a limited number of study treatments.

A clinical comparison of the effects of oral and intramuscular administration of analgesics: Pentazocine and phenazocine

The relative analgesic potency of oral and intramuscular pentazocine was evaluated in a double‐blind crossover comparison of graded single doses in patients with chronic pain due to cancer. When both intensity and duration of effect are considered (total effect), oral pentazocine was one third as potent as the intramuscular form. In terms of peak effect, however, oral pentazocine was only one fourth as potent. Single oral doses of 240 mg. caused psychotomimetic reactions 4 out of 23 times. These reactions were transient and, with the possible exception of one equivocal reaction to the 60 mg. intramuscular dose, were not seen after the intramuscular or lower oral doses. Exclusive of these reactions, adverse effects were not significantly different for equianalgesic doses of oral and intramuscular pentazocine, and were, in general, similar to those associated with the administration of narcotic analgesics. Assuming that the repeated administration of oral pentazocine does not produce adverse effects unanticipated on the basis of this study of single dose administration, the oral form of the drug should be useful in treating moderately severe or severe pain which is now being treated with potent oral or parenteral narcotics.

Clinical analgesic assay of repeated and single doses of heroin and hydromorphone

&NA; A direct comparison of the analgesic activities of heroin and hydromorphone was carried out in cancer patients with postsurgical pain. Intramuscular doses of 5 and 10 mg of heroin were compared with 1 and 2 mg of hydromorphone in a randomized, double‐blind, 4‐point parallel group assay. Design innovations in the study provided that about half the patients would receive prior repeated doses of the same drug as the test medication and half would receive the alternate medication. Both test drugs were found to be potent, relatively short acting analgesics with similar profiles of action. Hydromorphone was about 5 times as potent as heroin on a milligram basis. The comparison of those patients who had repeated doses of the same treatment prior to the test dose and those who had repeated doses of the alternate drug demonstrated no significant effect on the relative potency estimates. Side effect occurrence was similar for both drugs, with sleepiness the most prominent effect. The study supports the view that hydromorphone and heroin produce similar clinical effects and that either drug may adequately substitute for the other. Covariate analysis indicated that time since last analgesic was positively related to analgesia and amount of prior opioid had a negative relationship. To a lesser extent, increase in patient age was associated with an increase in analgesic scores. Taking these covariates into account served to increase the sensitivity of the analysis.

Cocaine and morphine interaction in acute and chronic cancer pain

&NA; An evaluation of the analgesic, mood and side effects of the combination of intramuscular morphine and oral cocaine was conducted in 17 patients with postoperative pain and 19 others with chronic malignant pain for the purpose of assessing the therapeutic merits of so‐called ‘euphoriant’ elixirs in the management of pain in cancer patients. The study was designed as a randomized and double‐blind single dose but complete cross‐over comparison of the combination of 10 mg intramuscular morphine and 10 mg oral cocaine with morphine alone, cocaine alone, and placebo. While patients clearly discriminated between the analgesic effects of morphine and placebo, there were no differences in the analgesic responses to cocaine and placebo, or in responses to morphine and the combination of morphine and cocaine in either patient group. Side effects were predominantly morphine‐like and occurred in 59% of patients after the combination, 43% after morphine, 34% after cocaine and 25% after placebo. Interaction effects between cocaine and morphine were observed in terms of positive changes toward selected aspects of mood (e.g., cheerful, friendly) in postoperative patients but toward negative aspects of mood (e.g., sad, serious) in patients with chronic pain.

Intramuscular meptazinol and morphine in postoperative pain

Meptazinol is an agonist‐antagonist opioid analgesic believed to be unique in its selectivity for µ1 (high affinity) receptors and its cholinergic activity. Our objectives were to determine the relative analgesic potency of intramuscular meptazinol and morphine and to compare mood and side effects in 102 patients with cancer who have postoperative pain. Meptazinol (50, 100, and 200 mg) and morphine (4, 8, and 16 mg) were given for moderate to severe pain in a double‐blind, randomized but balanced, incomplete block design. Serial multiple assessments of pain, relief, mood, and side effects were made. The most precise estimates of relative analgesic potency indicate that meptazinol is equivalent to 10 mg morphine at 120 mg (95% confidence interval 80 to 170 mg) for peak effect and at 175 mg (95% confidence interval 125 to 270 mg) for total effect. Mean (±SE) times to peak effect and to remedication were 0.9 ±0.1 and 3.6 ± 0.2 hours for meptazinol and 1.4 ±0.1 and 4.8 ± 0.4 hours for morphine at equianalgesic peak effects. The percentages of subjects with one or more side effects were 18, 49, and 73 for graded meptazinol doses and 32,49, and 65 for graded morphine doses. Mean numbers of side effects per subject were 0.3, 1.5, and 3.5 for meptazinol and 0.5, 0.7, and 1.7 for morphine. Profiles of side effects differed. Mood improvement and overall satisfaction were dose related and greater for morphine than for meptazinol. Side effects may limit the use of meptazinol in doses that relieve severe postoperative pain.