Abstract: BACKGROUND: To assess the adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison with slow release oral morphine. METHODS: A systematic review of the literature in the MEDLINE and EMBASE databases from 1966 to June 2007 was independently performed by two authors. All phase 3 randomized trials comparing transdermal opiates and slow-release oral morphine in the treatment of moderate-severe cancer pain were considered eligible and included in the analysis. The primary end point was the overall adverse effects odds ratio (OR); secondary end points were the overall gastrointestinal adverse effects, constipation, nausea, somnolence, patients' preference, and trial withdrawal. Heterogeneity was analyzed using the Mantel-Haenszel test, and outcome analysis was performed using a random effect model; an alpha error lower than 5% was assumed as statistically significant. RESULTS: Four trials met the selection criteria. The safety of transdermal opiates (fentanyl and buprenorphine) and slow-release oral morphine was analyzed in 425 patients. A significant difference in favor of transdermal opiates was observed for constipation (OR=0.38, p<0.001), and patients' preference (OR=0.43, p=0.014, in the three trials investigating transdermal fentanyl). No significant differences were observed for overall adverse effects, overall gastrointestinal adverse effects, overall neurologic adverse effects, nausea, somnolence, hypoventilation, trial withdrawal, and changes in opiate treatments. CONCLUSION: Although no difference in the overall adverse effect profile exists between transdermal opiates and slow release oral morphine, the difference in some adverse effects (mainly constipation) seems to favor transdermal opiates in the preference of patients with moderate-severe cancer pain.
Abstract: Objective. To assess long term follow up of efficacy and quality of life (QOL) for 34 geriatric patients (10 male, 24 female, mean age 72,3 ± 11,6 years) with IT drug delivery systems (IDDS), implanted between 1994 to 2002, for the treatment of severe non-cancer chronic pain.
Methods. Patients equal to or older than 64 years, who had no-pain relief after administration of a placebo injection(subcutaneous saline), and who responded positively to an IT trial (morphine and bupivacaine at low doses) with pain relief greater 70% without intolerable adverse effects were included into our study. Clinical assessment forms and questionnaires assessing pain intensity, adverse events, complications, concommittent use of analgesics and doses of IT drugs administered were filled out by our patients prior to and after IT drug delivery implantation.
Results. Pain intensity was substantially reduced (60%) at 3 month’s follow-up after commencing IT therapy and was consistently reduced at 48-month’s follow-up. The mean Visual Analog Scale (VAS) value decreased from 8,09 (±1,25) before implantation to 1,68 (±0,63) after implantation at 48 month’s follow-up. This benefit, at 48 months, was achieved using mean low doses of IT morphine and bupivacaine, 1.03±0.61 mgs and 1.15±0.58 mgs, respectively. Only 2/34 patients (5.9%) had complications related to the implantation procedure, itself. Side effects of therapy were reported by 50% of the patients, the most frequent being constipation (34,4%), drowsiness (21,9%), nausea (21,9%) and urinary retention (18,8%). No side effects of therapy resulted in removal of the IDDS.
Conclusion. The use of IT drug delivery through IDDS for the treatment of non-cancer and cancer related pain in geriatric patients is successful.
Abstract: BACKGROUND: Despite the widespread belief that patients should be given full information about their disease and prognosis, they actually they know very little. The purpose of this study was to evaluate the awareness of 100 patients (from the Hospices of Rimini and Savignano-Rubicone) about their diagnoses and prognoses. It is also investigated staff and relatives perceptions of patients' awareness. METHODS: A semistructured interview of patients was performed by psychologists to evaluate their awareness about diagnosis and prognosis. Then psychologists completed a questionnaire about their own evaluation of patients' disease awareness. Moreover, the same questionnaire was completed by family members and by staff members (doctors and nurses) about their perceptions of patients' awareness. Doctors and nurses gave their answers based on their routine interactions with patients. RESULTS: Despite the fact that patients in hospice were in the terminal phase of disease, 30% of patients had no diagnosis awareness, and an even higher percentage of patients (62%) who had no prognosis awareness.
Abstract: BACKGROUND AND OBJECTIVE: The aim of this prospective, randomized, double-blind investigation was to assess the dose-effect characteristics of postoperative nausea and vomiting after intrathecal administration of small doses of morphine (from 0.015 to 0.25 mg) in opioid-naïve, non-surgical patients. METHODS: With Ethic Committee approval and written informed consent 144 opioid-naïve patients suffering from non-cancerous chronic back-pain, and receiving intrathecal morphine as diagnostic test for their chronic pain, were randomly allocated to receive intrathecal injection of 0.015 mg (Group I, n=25), 0.03 mg (Group II, n=30), 0.06 mg (Group III, n=31) or 0.25 mg (Group IV, n=33) morphine. The control group consisted in 25 further patients not included in the dose-effect study and receiving a placebo injection of normal saline in the interspinous ligament. A blinded observer recorded the occurrence of pruritus, nausea, vomiting, urinary retention and respiratory depression (respiratory rate<6 bpm) at 2, 4 and 24 h after injection. RESULTS: Clinically significant pain relief was observed in all patients receiving intrathecal morphine but only six patients (25%) of the control group (P=0.0005). The incidence of pruritus was lower in patients of Groups III (6%) and IV (3%) than in Groups I (12%) and II (20%) (P=0.002). The incidence of nausea and vomiting was higher at 2- and 4-h observation times, and decreased 24 h after intrathecal injection. Surprisingly, nausea was more frequent in Groups I (56%) and II (50%) than in Groups III (33%) and IV (24%) (P=0.0005). Vomiting was higher in patients receiving morphine than in control group, but without differences among the four doses. No urinary retention was observed in the control group, while 2 h after intrathecal injection urinary retention was observed in 20-40% of cases, and decreased to less than 10% 24 h after spinal injection without differences among the four doses. CONCLUSIONS: The onset and incidence of minor opioid-related side-effects after intrathecal morphine administration do not depend on its dose, occurring with even very small doses of morphine. Accordingly, they can be considered as a patient-dependent effect of the drug, suggesting the presence of a primary dose-independent excitatory component that might be related to the theory of the bimodal activation of opioid receptors. The very low incidence major respiratory depression prevents us from drawing any conclusion about the dose-effect relationship for this side-effect, and further properly powered studies should be advocated to evaluate major respiratory depression after spinal morphine.
Abstract: The neuropeptide nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the opioid-like receptor ORL-1 and is thought to be involved in pain transmission and modulation. Human studies have not yet defined its role in pain patients. The aims of this study were 1) to verify the presence of N/OFQ in the cerebrospinal fluid (CSF) of human controls and patients with chronic noncancer pain, including those treated with intrathecally administered morphine, and 2) to determine whether pain or treatment with long-term intrathecal morphine influences its levels. The CSF of 27 patients (nine controls and 18 with chronic noncancer pain, of whom 12 were treated chronically with intrathecally administered morphine and six were opioid naïve) was analyzed, blindly, with radioimmunoassay methods. N/OFQ was detected in all patients. Mean CSF concentrations were lowest in the morphine-treated group and highest in the untreated chronic pain patients (12.06+/-1.19 and 57.41+/-10.06 fmol/ml, respectively), and the difference between the morphine-treated group and controls was statistically significant (44.72+/-13.56 fmol/ml, P<0.05). The presence of N/OFQ peptide in human CSF may correlate with biological activities that are influenced by different pain states and long-term intrathecal-morphine treatment. Further studies should verify whether the determination of this peptide CSF level may provide information on opioid treatment efficacy and on the presence of opioid tolerance.
Abstract: The most frequently discussed ethical issue within the context of cancer treatment is whether patients should be told their diagnosis and
prognosis.This work analyses results of studies published from 1993 to 2004, in order to assess physicians’ attitudes and their opinions
about disclosure of diagnosis and prognosis, to evaluate illness awareness in cancer patients and to explore its relationship with other
factors.
Abstract: Failed back surgery syndrome represents a heterogeneous situation that suggests a fibrosis or neuroinflammatory genesis. The social cost related to this issue are enormous. Several surgical techniques have been applied to FBSS patients with controversial effectiveness. In 1998 we evaluated the efficiency and limits of epiduroscopy treatment; it proved to be effective in 75% of cases, but in 45% of cases it needed to be repeated after 12 months. Therefore we subjected 14 patients, who had previously experienced a short temporary benefit by using a traditional epiduroscopic approach, to a new epiduroscopy fibrolysis using a radio-frequency device named "R-Resablator Epiduroscopy". Clinical evaluation was performed before myeloscopy and after 1-3-6 months. After myeloscopy, 93% of patients reported a general improvement. Among the latter, pain was reduced by 90% in 8 patients, by 60-70% in 5, and by less than 30% in 1. CONCLUSION: It can be concluded that RF-Epiduroscopy offers greater therapeutic benefit than traditional epiduroscopy or other surgical techniques. Furthermore, RF-Epiduroscopy is more easily performed and repeated.
Abstract: In a previous work we demonstrated that chronic in vivo antalgic therapy of cancer patients with morphine reduced the endogenous cytotoxic activity of natural killer (NK) cells, while increasing the development of lymphokine activated killer (LAK) cell cytotoxicity. In order to investigate the mechanisms by which morphine affects NK and LAK cell function further, we evaluated the modulation exerted by short- or long-term morphine administration on either NK/LAK cell cytotoxicities or plasma levels of prolactin (PRL) and other immunomodulating neurohormones. An intravenous morphine injection (10 mg) significantly increased the plasma levels of PRL, reduced the cytotoxic activity of NK cells, and increased the development of LAK cell activity 30 min after drug injection in neoplastic patients. The administration of bromocriptine before the injection of morphine prevented both PRL augmentation and the increase in LAK cell activation, although it did not prevent the inhibition of NK cytotoxicity. The chronic oral administration of morphine (90 +/- 30 mg/day for 1 month) also resulted in higher PRL levels; the NK and LAK cell activities were, respectively, lower than or higher than those found in neoplastic patients untreated with morphine. The plasma levels of thyrotropin (TSH), adrenocorticotropic hormone (ACTH) and cortisol were not significantly modified in either short- or long-term experiments. The absolute number and the percentages of lymphocyte populations, as well as the percentage of IL-2 receptors, were not modified after short-term morphine administration whereas little changes of T lymphocyte populations and NK cell number were observed after oral treatment with morphine. In vitro morphine did not affect the development of LAK cell activity. In conclusion, our findings indicate that morphine reduces NK cytotoxicity and increases the development of LAK cell cytotoxicity after short- and long-term administration. The effect of morphine on LAK cell activation but not on NK cell reduction is related to the modulation of PRL levels determined by the opioid drug.
Abstract: The cytotoxic activity of Natural Killer (NK) and Lymphokine Activated Killer (LAK) cells in neoplastic patients with or without antalgic treatment was studied. NK cell activity was found reduced in untreated neoplastic patients when compared to healthy subjects. The atalgic treatment with morphine (orally or intrathecally administered) was able to significantly reduce the mean values of NK cell activity found in cancer patients. In three patients the cytotoxicity of NK cells significantly decreased during transfer from oral to intrathecal administration of morphine. In contrast to the NK cell function, the development of LAK cell activity significantly increased in neoplastic patients when compared to healthy controls. Further increments were obtained during treatment with morphine. The oral treatment with morphine was able to determine a higher induction of LAK cells than the intrathecal administration of the drug. Besides providing new knowledge on the effect of morphine on immune system our findings suggest that, in order to include neoplastic patients in clinical trials of adoptive immunotherapy with LAK cells and interleukin-2 (IL-2), the antalgic therapy with oral administration of morphine may represent a better solution than the intrathecal administration of the drug.
