Efficacy and safety of sublingual fentanyl tablets for the management of breakthrough pain in patients with chronic musculoskeletal pain with neuropathic component: multicenter prospective study.

BACKGROUND AND OBJECTIVE: Despite its prevalence and impact, breakthrough pain (BTP) in chronic non-cancer pain with neuropathic component, has not been well studied and is sometimes unrecognized and often undertreated. We evaluated the efficacy of sublingual fentanyl tablet (SLF) for the treatment of BTP in opioid-tolerant patients with chronic musculoskeletal pain with neuropathic component in terms of relief of pain intensity and assessed whether hypothetical pain relief impacts on quality of life (QoL). METHODS: A multicenter, prospective, open-label study was conducted over a 30-day period. Efficacy was evaluated using a visual analogue scale (VAS) and time to onset of action of SLF. The incidence of dependence was assessed by the Leeds Dependence Questionnaire (LDQ). Changes in QoL were evaluated using the Brief Pain Questionnaire (BPI) and the EuroQol (EQ-5D). Adverse events (AE) were recorded throughout. RESULTS: 106 patients were enrolled and 105 completed the study. The average pain reduction across the study was -3.30 points [95 % confidence interval (CI) 2.9-3.7; P < 0.0001]. Pain intensity improvement from baseline was statistically significant at first assessment and all subsequent assessments (P < 0.0001). The most common AEs included nausea (33.87 %), constipation (33.06 %), somnolence (19.35 %) and vomiting (6.45 %). No significant differences were observed on LDQ (P = 0.71). QoL as measured by BPI showed statistically significant improvement in all four severity items and all interference items (P < 0.0001) and a significant improvement in the percentage of pain relief reported by patients (P < 0.0001). EQ-5D results showed a trend towards improvement. Mean self-rate health status, as measured by the EQ VAS scale increased significantly (P < 0.0001). CONCLUSION: SLF provides significant reductions in BTP intensity. The results of the BPI and EQ-5D assessments indicate that pain relief is associated with improvement of functioning and enhancement of QoL.

Esmolol versus ketamine-remifentanil combination for early postoperative analgesia after laparoscopic cholecystectomy: a randomized controlled trial.

PURPOSE: Controversy surrounds the optimal technique to moderate pain after laparoscopic cholecystectomy (LC). Opioid analgesics, sympatholytic drugs, and adjuvants, such as ketamine, have all been used. We compared esmolol with a combination of remifentanil plus ketamine in patients undergoing LC to determine the impact of these drugs on morphine requirements and pain control. METHODS: Sixty American Society of Anesthesiologists physical status I-II patients undergoing LC and anesthetized with sevoflurane were randomized to one of two groups. Group E patients received a bolus of esmolol 0.5 mg·kg(-1) iv at induction followed by an infusion of 5-15 µg·kg(-1)·min(-1), and Group R-K patients received a bolus of ketamine 0.5 mg·kg(-1) iv and remifentanil 0.5 µg·kg(-1) iv at induction followed by a remifentanil infusion titrated over a range of 0.1-0.5 µg·kg(-1)·min(-1). All patients received paracetamol, dexketoprofen, and levobupivacaine via infiltration of laparoscopic port sites. After surgery, a predetermined bolus of morphine was administered according to a verbal numerical rating scale (VNRS) for pain intensity. The primary outcome of interest was postoperative morphine requirement. RESULTS: Median consumption of morphine was higher in Group R-K than in Group E (5 mg [4-6] vs 0 mg [0-2], respectively; P < 0.001). In the postanesthesia care unit, patients in Group R-K had higher pain scores than patients in Group E (difference in maximum VNRS, -11; 95% confidence interval (CI), -19 to -3). The concentration of sevoflurane to maintain a bispectral index~40 was higher in Group E than in Group R-K (between-group difference 0.3%; 95% CI, 0.15 to 0.40). The incidence of postoperative nausea and vomiting was similar between the two groups. CONCLUSION: Intraoperative esmolol infusion reduces morphine requirements and provides more effective analgesia compared with a combination of remifentanil-ketamine given by infusion in patients undergoing LC.