Long-term effect of oxycodone/naloxone on the management of postoperative pain after hysterectomy: a randomized prospective study.

BACKGROUND: The analgesic efficacy of oxycodone prolonged-release (PR) combined with naloxone PR (OXN) in postoperative pain management is recognized, however, few studies have examined the efficacy of OXN on pain relief and bowel function following hysterectomy. This study compared the effect of OXN vs. standard treatment for post-operative pain management and bowel function following hysterectomy. METHODS: This randomized prospective study included 83 women who underwent laparoscopic/laparotomic hysterectomy. General anesthesia was induced by propofol (1.5-2 mg/kg), fentanyl (50-100 µg) and rocuronium (0.6-1 mg/kg) and maintained with sevoflurane (MAC 0.8-1) and fentanyl (1-2 µg/kg). Intraoperative analgesia was performed with ketorolac (30 mg), paracetamol (1 g) and morphine (0.1 mg/kg). Postoperative analgesia in the control group (N.=41) included morphine (0.2-0.4 mg/kg/day), whereas the OXN (N.=42) group only received oxycodone (10 mg)/naloxone (5 mg) for the first 48 hours. As rescue analgesic, both groups received paracetamol (3 mg). Bowel Function Index (BFI) and pain numeric rating scales (NRS) were measured at day 0, 1, 2, 3, 5 and 7, whereas vital parameters, rescue medication and side effects were recorded for the first three days only. RESULTS: Bowel function indices were significantly improved in OXN-treated patients at all time points compared to morphine-treated patients. Mean static pain NRS was significantly decreased at day 2 and day 3 and dynamic pain NRS at day 3 in the OXN group. Side effects, rescue analgesic and antiemetics were more frequent in the control group. CONCLUSIONS: Improved pain control, bowel function and reduced side effects were observed with OXN compared to morphine in patients who underwent hysterectomy.

Oral prolonged-release Oxycodone-Naloxone: analgesic response, safety profile, and factors influencing the response in advanced cancer patients.

BACKGROUND: Oxycodone-Naloxone (OXN) aims to reduce opioid-related constipation while being successfully analgesic. METHODS: We evaluated the analgesic response, prevalence, and severity of side effects in 176 cancer patients with moderate to severe pain and treated with OXN. Patients were followed for 28 days and evaluated every seven. Pain intensity, changes of therapy, and adverse drug reactions were recorded at each visit. The primary efficacy endpoint was the proportion of responders (≥30% reduction of pain intensity from baseline to final) and final average pain score ≤4 on a 0-10 scale. RESULTS: Average and worst pain intensity, and breakthrough pain (BTP) prevalence decreased over time and 81.3% of patients were responders. The starting daily dose of OXN was raised from 25.1±13.0 mg to 44.1±29.9 mg, and dose escalation >5%/day was observed in 19.4% of patients; 40.8-46.2% and 11.0-17.0% experienced any and severe grade of constipation during the follow-up visit, respectively. Digestive system tumor, thyroid endocrinopathies, psychological irritability, and BTP increased the risk of analgesic non-response. CONCLUSIONS: OXN had strong analgesic effect in moderate to severe cancer pain patients: the safety profile is in line with the common adverse effects of opioids and severe constipation was uncommon. This article is protected by copyright. All rights reserved.

Effects of opioid therapy on human natural killer cells.

Opioid compounds, such as morphine, induce powerful analgesic effects and are extensively used clinically to treat a wide variety of pain. The aim of our study was to evaluate the impact of opioid therapy on phenotype and function peripheral blood NK cells. The patients were referred to three Italian pain therapy centers (Milan, Pavia, Piacenza) for chronic pain in neuropathic or mixed somatic components. The patients were between 18 and 75 years old and were of Caucasian ethnicity. We studied the expression of activating and inhibitory NK receptors to discriminate NK subsets with different CD56 surface expression intensities (CD56(bright) and CD56(dull) NK cells). The flow cytometry analysis of the NK cells was at normal levels in peripheral blood lymphocytes with fewer CD56(bright) compared to the CD56(dull) NK cell subset when compared to blood from drug free donors. Furthermore, the cytolytic activity of in vitro patient NK cells analyzed was not lower, as would be expected from the regular expression of activating NK receptors for both subsets. Taken together, these data indicate that NK cells from opioid treated patients do not show any signs of NK cell immune-suppression.

Comparison of intravenous ketorolac with or without paracetamol in postoperative pain control following ambulatory surgery.

OBJECTIVE: The aim of this randomized, patient-blinded study was to compare efficacy and safety of oral paracetamol plus intra-venous (i.v.) ketorolac with i.v. ketorolac alone after ambulatory uterine evacuation. RESEARCH DESIGN AND METHODS: Women were randomly assigned to receive either oral paracetamol (1 g), in a melt-in-the mouth, without-water formulation plus ketorolac (30 mg i.v. once daily (o.d.)) or ketorolac (30 mg i.v. o.d.) as monotherapy. The mean duration of uterine evacuation was 11 minutes in the paracetamol + ketorolac group and 13 minutes in the ketorolac-only group. Paracetamol was administered 15 minutes before surgery, on discharge from hospital (mean 6 hours after surgery) and in the morning the day after surgery, while ketorolac was administered at the end of the surgical intervention. MAIN OUTCOME MEASURES: The numeric rating scale (NRS) was used by patients to rate their pain on an 11 point scale. RESULTS: Overall, 60 women received paracetamol plus ketorolac (group 1) and 60 ketorolac alone (group 2). There were significant differences in pain levels (NRS 0.92 and 2.08; p < 0.01) at T0 (when patients left the operating room 30 minutes after the end of surgery). At T1 (before discharge from hospital but before the next administration of paracetamol) there were no significant differences between NRS scores in the two groups (3.7 vs. 3.5, respectively, p = 0.3453). At T2 (in the morning after surgery; data collected by phone interview), following administration of the next dose of paracetamol, significant differences in pain scores were recorded (1.58 vs. 1.98; p = 0.01). Only a case of dizziness was reported in the paracetamol + ketorolac group, and no other unexpected adverse events were recorded. CONCLUSION: Despite the small sample size and the monocentric nature of the study being taken into account, this study suggests, for the first time to our knowledge, that oral paracetamol t.i.d. in combination with i.v. ketorolac o.d. is effective and well tolerated in the control of postoperative pain after ambulatory uterine evacuation.

Randomised phase II trial (NCT00637975) evaluating activity and toxicity of two different escalating strategies for pregabalin and oxycodone combination therapy for neuropathic pain in cancer patients.

PURPOSE: Neuropathic pain is commonly associated with cancer. Current treatments include combination opioid and adjuvant therapies, but no guidelines are available for dose escalation strategies. This phase II study compared the efficacy and tolerability of two dose escalation strategies for oxycodone and pregabalin combination therapy. METHODS: Patients (N = 75) with oncological neuropathic pain, previously untreated with pregabalin, were recruited in 5 Italian institutions between 2007 and 2010. Patients were randomised to two different dose escalation strategies (arm A; N = 38) oxycodone at a fixed dose with increasing pregabalin doses; (arm B; N = 37) pregabalin at a fixed dose with increasing oxycodone doses. Patients were evaluated from daily diaries and follow-ups at 3, 7, 10, and 14 days after beginning treatment with a numerical rating scale (NRS), neuropathic pain scale (SDN), and well-being scale (ESAS). The primary endpoint was a ≥1/3 reduction in pain (NRS); secondary endpoints included the time to analgesia and adverse effects. The study had a 90% probability of detecting the best strategy for a true difference of at least 15%. RESULTS: More patients in arm A (76%) than arm B (64%) achieved ≥1/3 overall pain reduction even after controlling for baseline factors (gender, baseline pain). Group A reported fewer side effects than group B; constipation 52.8% vs. 66.7%; nausea: 27.8% vs. 44.4%; drowsiness: 44.4% vs. 55.6%; confusion: 16.7% vs. 27.8%; itching: 8.3% vs. 19.4%. CONCLUSIONS: Both strategies effectively controlled neuropathic pain, but according to the adopted selection design arm A is preferable to arm B for pain control. TRIAL REGISTRATION: ClinicalTrials.gov NCT00637975.

Beyond the traditional definition of breakthrough pain: an observational study.

INTRODUCTION: Breakthrough pain (BTP) is traditionally defined as a transitory pain flare in opioid-treated patients with chronic background pain. This definition has, however, been challenged in recent years. This study aimed to analyze BTP prevalence in different pain conditions. METHODS: This was a prospective, non-interventional, observational study conducted from June to September 2011 in two Italian pain treatment reference centres. Consecutive patients aged >18 years with oncological or non-oncological pain were eligible for this study; background pain was acute/ subacute (<3 months) or chronic (>3 months). The characteristics of pain were evaluated by means of a structured interview by physicians, and patients were asked to complete a dedicated clinical study form. The following outcomes were assessed: chronic pain duration (in patients with chronic pain), BTP prevalence, and number and severity of daily BTP episodes. All outcomes were assessed in four populations of patients with: (a) chronic oncological pain; (b) chronic non-oncological pain; (c) non-chronic oncological pain; (d) non-chronic non-oncological pain. The correlation between BTP and gender was also investigated. RESULTS: Of 1,270 patients with chronic pain, 1,086 had non-oncological pain (85.5%). Most patients (68.6%) with non-oncological pain were female (P = 0.001). Pain duration was significantly longer in non-oncological pain versus oncological pain groups (P = 0.002). BTP prevalence was lower in non-oncological patients (P < 0.001). No differences were reported in terms of number and severity of daily BTP episodes. BTP was more frequent in females with non-oncological pain (P = 0.04). Females had a significantly higher pain severity (P = 0.02) than males. CONCLUSION: BTP is frequently reported in patients who do not have BTP according to the traditional definition. BTP frequency and severity is similar in oncological and non-oncological pain.

Scrambler therapy may relieve chronic neuropathic pain more effectively than guideline-based drug management: results of a pilot, randomized, controlled trial.

CONTEXT: Neuropathic pain is common, disabling, and often difficult to treat. OBJECTIVES: To compare guideline-based drug management with Scrambler therapy, a patient-specific electrocutaneous nerve stimulation device. METHODS: A clinical trial with patients randomized to either guideline-based pharmacological treatment or Scrambler therapy for a cycle of 10 daily sessions was performed. Patients were matched by type of pain including postsurgical neuropathic pain, postherpetic neuralgia, or spinal canal stenosis. Primary outcome was change in visual analogue scale (VAS) pain scores at one month; secondary outcomes included VAS pain scores at two and three months, pain medication use, and allodynia. RESULTS: Fifty-two patients were randomized. The mean VAS pain score before treatment was 8.1 points (control) and 8.0 points (Scrambler). At one month, the mean VAS score was reduced from 8.1 to 5.8 (-28%) in the control group, and from 8 to 0.7 points (-91%) in the Scrambler group (P<0.0001). At two and three months, the mean pain scores in the control group were 5.7 and 5.9 points, respectively, and 1.4 and 2 points in the Scrambler group, respectively (P<0.0001). More relapses were seen in polyradicular pain than monoradicular pain, but retreatment and maintenance therapy gave relief. No adverse effects were observed. CONCLUSION: In this pilot randomized trial, Scrambler therapy appeared to relieve chronic neuropathic pain better than guideline-based drug management.