Comparable analgesic efficacy of transdermal buprenorphine in patients over and under 65 years of age.

OBJECTIVES: To compare the efficacy and tolerability of transdermal buprenorphine in elderly patients and 2 younger populations, all requiring analgesic treatment for moderate-to-severe chronic pain. METHODS: Three equally sized age-groups (A>/=65, n=30; B=51 to 64, n=27; C

Transdermal buprenorphine patches applied in a 4-day regimen versus a 3-day regimen: a single-site, Phase III, randomized, open-label, crossover comparison.

BACKGROUND: In 2001, a transdermal matrix patch formulation of buprenorphine was approved for the treatment of moderate to severe cancer pain and severe pain that is unresponsive to nonopioid analgesics. The primary recommendation contained in the prescribing information was that transdermal patches be worn for a 3-day period before application of a new patch. OBJECTIVE: This study was conducted to evaluate the potential for extending the time the buprenorphine patch is worn from 3 to 4 days. METHODS: This single-center, randomized, open-label, crossover Phase III study compared the efficacy and tolerability of the buprenorphine transdermal patch applied for different durations, with patch changes every 3 days versus every 4 days (12 days each), in patients with chronic moderate or severe pain of malignant or nonmalignant origin. Study participants were aged >18 years, had already responded to at least 4 weeks of transdermal buprenorphine, and had achieved steady-state conditions for at least 2 weeks before enrollment. The primary end point was patients' rating of the quality of treatment (analgesic efficacy and tolerability, rated on a 5-point scale: very good, good, satisfactory, poor, and inadequate) at the completion of each treatment regimen. Also recorded were physicians' ratings of the quality of treatment; pain intensity, rated on an 11-point numerical rating scale (from 0 = no pain to 10 = worst pain imaginable) and on the McGill Pain Questionnaire (MPQ) (maximum pain = 3.0); health status, assessed using the 36-item Short Form Health Survey (SF-36), expressed as a percentage of the best health condition (100%); and pain relief (5-point scale: complete, good, satisfactory, slight, and none). Local skin tolerability was evaluated for objective and subjective dermatologic symptoms at the patch application sites. Patients recorded daily pain intensities at specified times of day and night, pain relief (5-point verbal rating scale), and sleep duration (2-3 hours, >3-<6 hours, or >or=6 hours) in a diary. The safety profile was evaluated based on standard monitoring of adverse events, vital signs, and routine laboratory tests. RESULTS: Forty-nine white patients (25 women, 24 men) were enrolled; their mean (SD) age was 61.6 (11.5) years, and their mean weight was 74.7 (16.7) kg. The most common source of pain was musculoskeletal disorders (40 patients), followed by nervous system disorders (10), neoplasms (9), injuries (5), and other causes (6). Forty-one patients completed the study; 2 patients discontinued because of adverse events, 1 because of lack of efficacy, and 5 for nonmedical reasons. Thirty-three patients provided data per protocol. Patients in the perprotocol population received a mean (SD) transdermal buprenorphine dose of 49.9 (38.9) microg/h. The proportion of patients in the per-protocol population rating the quality of treatment as adequate (combined ratings of very good, good, and satisfactory) was 93.9% (31/33) for both regimens. The physicians' ratings indicated adequate quality of treatment in 93.8% (30/32) of patients applying 4 patches for 3 days each and 97.0% (32/33) of patients applying 3 patches for 4 days each. Mean (SD) pain intensity scores on the numerical rating scale were similar after completion of the 3- and 4-day regimens (3.73 [1.88] and 3.88 [1.75] points, respectively), as were MPQ scores (0.79 [0.67] and 0.79 [0.78]). The mean (SD) proportion of days with at least satisfactory pain relief was 83.9% (26.1%) and 85.6% (24.4%) for the 3- and 4-day regimens; the corresponding proportions of nights with at least satisfactory pain relief were 85.2% (26.6%) and 88.1% (21.4%). Continuously assessed pain intensities at specified times of day and night (numerical rating scale) did not differ significantly between regimens. Mean SF-36 health status scores did not differ significantly between regimens (total score: 37.7% [17.0%] and 37.7% [17.3%]). Mean rates of nights with good sleep quality were 28.5% (39.9%) for the 3-day regimen and 36.0% (42.6%) for the 4-day regimen. Local skin tolerability was comparable for the 3- and 4-day regimens, with objective findings (mainly erythema) at the patch-application sites in 17 of 32 and 11 of 33 patients, respectively, and subjective symptoms (mainly itching) in 16 of 32 and 13 of 33 patients. The most common adverse events in the safety population were nausea, dizziness/giddiness, and malaise/fatigue (3/49 [6.1%] each). CONCLUSION: Analgesic efficacy, patients' satisfaction with the quality of treatment, and skin tolerability did not differ significantly between 3 and 4 days of patch application in these patients with chronic pain who had been previously stabilized on transdermal buprenorphine.

Withdrawal following sufentanil/propofol and sufentanil/midazolam. Sedation in surgical ICU patients: correlation with central nervous parameters and endogenous opioids.

PURPOSE: Patients in the ICU after long-term administration of an opioid/hypnotic often develop delirium. To assess the nature of this phenomenon, patients in a surgical ICU following ventilatory support and sedation with an opioid/hypnotic/sedative were studied. METHODOLOGY: Following sufentanil/midazolam (group 1; n =14) or sufentanil/propofol (group 2; n =15) sedation, patients were evaluated for changes in mean arterial blood pressure and heart rate, the activity of the central nervous system (sensory evoked potentials, spectral edge frequency of EEG), and the endogenous opioids plasma concentrations (beta-endorphin, met-enkephalin). Data obtained were correlated with the individual intensities of withdrawal symptoms 6-, 12-, and 24 h following sedation. RESULTS: Following a mean duration of ventilation of 7.7 days (+/-3.6 SD) in groups 1 and 3.5 (+/-1.7 SD) in group 2, withdrawal intensities peaked within the 6th hour after cessation. Plasma beta-endorphin and met-enkephalin levels were low during sedation, and only the sufentanil/midazolam group demonstrated a postinhibitory overshoot. Withdrawal symptom intensities demonstrated an inverse correlation with beta-endorphin and met-enkephalin levels, a direct linear correlation with amplitude height of the evoked potential, and blood pressure and heart rate changes. Withdrawal intensities did not correlate with EEG power spectral edge frequency. CONCLUSION: The endorphinergic system is suppressed when a potent exogenous opioid like sufentanil is given over a long period of time. Following sedation, abstinence symptoms seem to be related to postinhibitory increased endorphin synthesis. This is mostly seen in the combination of sufentanil/midazolam. In addition, an increase in the amplitude of the sensory-evoked potential suggests a postinhibitory excitatory state within the nociceptive system.