Search

Abstract: 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 hours, >2–3 hours, >3-<6 hours, 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) pg/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. [Copyright &y& Elsevier]

Abstract: Background:: Tramadol is widely prescribed, even to the eldest patients. Although age-related differences in pharmacologic responsiveness are to be expected, the pharmacodynamic and pharmacokinetic (PK) properties of tramadol have not been systematically compared between patients of various ages. Objective:: The aim of this study was to explore the effectiveness, PK properties, and safety profile of 2 galenic tramadol formulations in 3 similarly sized age groups with malignant and nonmalignant pain of moderate to severe intensity. Methods:: This prospective, age-group-controlled study was conducted at the ambulatory pain clinic of the Landeskrankenhaus Kärnten, Klagenfurt, Austria. Male and female adults with malignant and nonmalignant pain of moderate to severe intensity were eligible. Patients were stratified into similarly sized age groups, as follows: ≥75, 65-<75, and <65 years. Patients first received the immediate-release galenic formulation of tramadol (tramadol IR) until steady state was achieved, followed by the sustained-release formulation (tramadol SR) until steady state. Serum concentrations of tramadol and its active metabolite (O-desmethyl-tramadol [M1]) were measured using gas chromatography to estimate the age-related PK handling of the analgesic drug. Three validated scales were used to measure pain intensity during the study: a 100-mm visual analog scale (VAS), an 11-point numeric analog scale (NAS), and a 4-point verbal rating scale (VRS). Tolerability was assessed by evaluating daily answers about the potential occurrence of adverse events (and respective details such as type and severity) from baseline until the end of the observation period. Results:: A total of 100 patients were enrolled (58 women, 42 men; mean [SD] age, 65.2 [15.0] years; ≥75, 30 patients; 65-<75, 31 patients; and <65 years, 39 patients). Predominant causes of pain were neoplasms (27.4% of causes) and injury and other external causes (20.8%), and diseases of the musculoskeletal and connective-tissues systems (19.8%). Fifty-five patients completed the study and provided all data as planned. Mean (SEM) steady-state tramadol IR doses were 250 (20.2), 277 (39.8), and 325 (33.1) mg/d in patients aged ≥75, 65-<75, and 65 years, respectively (P = NS); tramadol SR, 278 (27.5), 306 (39.7), and 340 (35.1) mg/d (P = NS). Serum concentrations of tramadol and M1 were statistically similar across all 3 age groups. Overall, mean pain intensity scores, as measured using the VAS and NAS, were decreased from baseline (62.4 [2.0] mm and 6.22 [0.22] points, respectively) to steady state with tramadol IR (23.6 [2.9] mm and 2.65 [0.30] points) and tramadol SR (16.9 [2.5] mm and 1.91 [0.26] points) (all, P < 0.001). Pain intensity before and improvements during both treatment phases were similar across all 3 age groups. Results:: for pain intensity on the VRS also did not find age-related differences. The predominant adverse effects were nausea (27.0% of patients), dizziness and giddiness (18.0%), and malaise and fatigue (15.0%); no significant differences in adverse events were found between age groups. Conclusions:: The fate of tramadol and its active metabolite, and their clinical effects, have been examined here for the first time in a prospective cohort study, which compared patients aged <65 years, 65-<75 years, and ≥75 years. In contrast to expecta tions, it was concluded that tramadol IR and tramadol SR were both generally well tolerated and effective in the treatment of moderate to severe pain in any of the 3 age groups in these patients. Although the eldest group of patients consumed, on average, 20% less tramadol (P = NS) than the youngest group, the PK properties of both drugs were not changed when given to elderly patients. [Copyright &y& Elsevier]

Introduction: Ganglionic local opioid analgesia (GLOA) at the superior cervical ganglion (SCG) is performed for pain control and is known to be an effective procedure. In this study, we evaluated the spread of the injectate in the area of the SCG. Our expectation was that there would be a correlation between the area and volume of the injectate spread and post-procedural outcome measures. Methods: This was a retrospective blinded review of magnetic resonance imaging (MRI) scans. Assessors evaluated the anatomical area of fluid spread, the furthermost spread from midline, any hampered spread and contact of contrast fluid with other structures. The efficacy of GLOA and complications were estimated. Results: The main solution spread reached from the C1 to C3 vertebrae. The furthest spread in the lateral and sagittal planes was 21.2 and 15.2 mm, respectively. The furthest craniocaudal spread was 63.5 mm. In 53.3% and 33% of interventions, the solution was found in the parapharyngeal space and in its "medial compartment," respectively. A correlation was found between pain relief and both solution spread and volume of solution spread. No hampered spread was recorded. A negative correlation between pain reduction and number of GLOA was observed. Higher pre-procedural pain intensity was correlated with higher pain reduction. We estimated pain relief in 93% of procedures correctly. No correlation between post-procedural Numerical Rating Scale (NRS) scores and different needle approaches was found. Conclusion: For the transoral blocking technique, a strict laterodorsal needle direction is recommended to prevent possible block failures. A total volume of 2 ml injected into the parapharyngeal space and its "medial compartment" is recommended. Higher volumes may lead to uncontrolled distribution patterns. Trial registration: Clinicaltrials.gov identifier NCT05257655; date of registration 2022-02-25; patient enrollment date from 2023-01-09 to 2023-08-31. Plain Language Summary: The injection of low-dose opioids (mainly buprenorphine or sufentanil) to different sympathetic ganglia has been termed "ganglionic local opioid analgesia" (GLOA). This form of therapy has been successfully used for numerous, often protracted diseases that severely impair the patient's quality of life, such as trigeminal neuralgia. For example, as part of a multimodal approach for pain management, GLOA at the superior cervical ganglion should be considered for pain treatment in patients suffering from trigeminal neuralgia with high pre-procedural pain scores. [ABSTRACT FROM AUTHOR]

Introduction: Computed tomography (CT)-guided coeliac plexus neurolysis (CPN) is considered effective at controlling pain in patients with intra-abdominal malignancies. The primary objective was to correlate pain outcomes with the spread of neurolytic solution in the coeliac area and to evaluate the predictive value for the spread of injectate for pain outcomes and side effects. Methods: Blinded CT scans were reviewed. The coeliac area was divided into nine quadrants. Assessors evaluated quadrants according to contrast spread, needle tip position, and the contact between the injectate and other organs and plexuses. Efficacy of CPN and complications were estimated. Results: In 54.9% there was complete spread of the neurolytic in the coeliac area with no correlation between pain relief and spread of injectate. In 85% the neurolytic had contact with viscera with no correlation with pain relief or complications. There was no correlation between needle tip position and spread of the neurolytic and contact of the neurolytic with viscera. In 71.6% the injectate was found to have spread into "other" plexuses. In 13.3% hampered spread of the injectate was observed. There was no correlation between patterns of injectate spread and pain relief, pain relief and spread of injectate in any particular quadrants, and expected and documented post-procedural pain scores. Conclusions: Based on the spread of contrast medium clinicians can neither correctly anticipate the pain relief or post-procedural NRS, nor the duration of pain relief and complications. It is not essential to have the perfect sickle-shaped spread of the injectate for adequate pain control. Plain language summary: CT-guided coeliac plexus neurolysis is considered effective at controlling pain in patients with intra-abdominal malignancies. Based on the spread of contrast medium clinicians can neither correctly anticipate the pain relief or post-procedural NRS, nor the duration of pain relief and complications. It is not essential to have the perfect sickle-shaped spread of the injectate for adequate pain control. [ABSTRACT FROM AUTHOR]

Introduction: Prevalence rates of chronic abdominal pain (CAP) and breakthrough cancer pain (BTcP) are high in patients with intra-abdominal malignancies. As part of a multimodal approach, CT-guided coeliac plexus blockade (CPB) and CT-guided coeliac plexus neurolysis (CPN) are commonly used pain management strategies. The aim of this study was to evaluate pain outcomes among patients with intra-abdominal malignancies who underwent CPB and/or CPN. Methods: Patients with intra-abdominal malignancies who underwent CPB and/or CPN for pain control at the general hospital Klagenfurt am Wörthersee from 2010 to 2019 were enrolled. Results: A total of 84 procedures (24 CPB and 60 CPN) were performed on 52 patients; 62% of these patients had pancreatic cancer. CPN led to significant pain reduction and decreased BTcP intensity. Patients receiving repeated CPN showed higher individual pain reduction. Higher pre-procedural pain intensity was correlated with higher pain reduction. No difference in pain reduction in patients receiving a diagnostic CPB prior to CPN compared to patients without a diagnostic CPB was found. Higher pain reduction after CPN led to longer-lasting pain relief. The time frame from diagnosis to CPN was 472 (± 416) days. Patients experienced a mean duration of pain prior to CPN of 330 (± 53) days. The time frame from diagnosis to CPN was shorter in patients with pancreatic cancer compared to other intra-abdominal malignancies. In 58% of patients pain medication was stable or was reduced after CPN; 16% of patients complained about pain during the procedure; no major complications occurred. There was no correlation between median survival after CPN and pain outcomes. Conclusions: In patients with intra-abdominal malignancy-related CAP, CPN is a safe and effective procedure which can provide long-lasting significant relief of background pain and BTcP. As part of a multimodal approach, CPN should be considered as an earlier option for pain management in these patients. Plain Language Summary: In patients with intra-abdominal malignancy-related abdominal pain, CT-guided coeliac plexus neurolysis is a safe and effective procedure. It can provide long-lasting significant relief of background pain and breakthrough cancer pain. As part of a multimodal approach, coeliac plexus neurolysis should be considered as an earlier option for pain management in patients with intractable abdominal cancer pain. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the applicability of US-guided rectus sheath block and to find out the efficacy of analgesia provided using this method without the need for opioids in conventional Hypertrophic pyloric stenosis (HPS) surgery in infants. Background: This study describes the provision of intra- as well as postoperative analgesia by the use of an ultrasound-guided rectus sheath block in infants undergoing conventional HPS surgery under general anesthesia. Methods/Materials: The anesthetic protocols of 26 infants undergoing HPS surgery were reviewed retrospectively. Results: The weight of the infants ranged from 2.6 to 4.6 kg. The rectus sheath block was regarded as successful in all patients as there was no heart rate increase upon surgical skin incision in any of the patients. Two out of 26 (7.6%) babies needed additional intraoperative rescue analgesia and were administered fentanyl at 20 and 40 min after skin incision. Two more (a total of 4; 15.3%) babies required postoperative analgesia and were administered tramadol droplets and liquid ibuprofen at 15, 120 and 150 min postoperatively. Duration of surgery was significantly longer in those two patients who required intraoperative rescue analgesia (Wilcoxon-Mann-Whitney test: P < 0.05). These were also the only two patients who received one intra- and one postoperative dose of opioid each (7.6%). Conclusion: US-guided rectus sheath block seems to be a simple and quick method for the provision of intra- and postoperative analgesia in infants undergoing conventional HPS surgery. [ABSTRACT FROM AUTHOR]

Despite the increasing clinical use of transdermal buprenorphine, questions have persisted about the possibility of a ceiling effect for analgesia, its combination with other μ-opioid agonists, and the reversibility of side effects. In October 2008, a consensus group of experts met to review recent research into the pharmacology and clinical use of buprenorphine. The objective was to achieve consensus on the conclusions to be drawn from this work. It was agreed that buprenorphine clearly behaves as a full μ-opioid agonist for analgesia in clinical practice, with no ceiling effect, but that there is a ceiling effect for respiratory depression, reducing the likelihood of this potentially fatal adverse event. This is entirely consistent with receptor theory. In addition, the effects of buprenorphine can be completely reversed by naloxone. No problems are encountered when switching to and from buprenorphine and other opioids, or in combining them. Buprenorphine exhibits a pronounced antihyperalgesic effect that might indicate potential advantages in the treatment of neuropathic pain. Other beneficial properties are the compound's favorable safety profile, particularly in elderly patients and those with renal impairment, and its lack of effect on sex hormones and the immune system. The expert group agreed that these properties, as well as proven efficacy in severe pain and favorable tolerability, mean that buprenorphine can be considered a safe and effective option for treating chronic cancer and noncancer pain. [ABSTRACT FROM AUTHOR]

The aim of our study was to compare postoperative analgesic efficacy, analgesic duration and motor blockade of levobupivacaine, ropivacaine and bupivacaine administered caudally in equal concentrations to children undergoing elective minor surgery.In the study, 182 children, aged 1–7 years, undergoing either inguinal hernia repair or orchidopexy, were randomly allocated to one of the three groups. They received via a caudal extradural either 1 ml·kg−1 levobupivacaine 0.2% (Group L) or 1 ml·kg−1 ropivacaine 0.2% (Group R) or 1 ml·kg−1 bupivacaine 0.2% (Group B).No statistically significant difference was noted in age, weight, duration of the operation or level of the caudal block between the groups. The onset of analgesia was significantly later after levobupivacaine. Postoperative pain scoring evaluated with Children's and Infant's Postoperative Pain Scale observational scale showed no statistical difference between groups. Median postoperative analgesia was 5.75 h (SEMed:± 0.65) in Group L, 5.7 h (SEMed:± 0.8) in Group R and 5.35 h (SEMed:± 1.3) in Group B the difference being statistically nonsignificant.The degree of motor block was significantly less after ropivacaine and levobupivacaine during the first 2 h postoperatively. [ABSTRACT FROM AUTHOR]