Low-potency Opioids Research Articles

Percutaneous Continuous Radiofrequency Versus Pulsed Radiofrequency Thermorhizotomy for the Treatment of Neuralgia of the Trigeminal Nerve: A Retrospective Observational Study.

Trigeminal neuralgia (TN) represents one of the most powerful manifestations of neuropathic pain. The diagnostic criteria, as well as its therapeutic modalities, stand firmly established. The percutaneous radiofrequency thermorhizotomy of the gasserian ganglion and posterior root of the trigeminal nerve stands as a widely employed procedure in this context. In this retrospective observational investigation, we undertake a comparative analysis of patients subjected to treatment employing continuous radiofrequency (C-rF) versus pulsed radiofrequency (P-rF). A cohort of 128 patients afflicted with essential neuralgia of the trigeminal nerve, all under the care of the distinguished author (JCA), underwent percutaneous radiofrequency thermorhizotomy between the years 2005 and 2022. They were stratified into two cohorts: Group 1 encompassed 76 patients treated with C-rF, while Group 2 comprised 52 patients subjected to P-rF intervention.All participants met the stringent inclusion and exclusion criteria for TN, with a notable concentration in the V2 and V3 territoriesaccounting for 60% and 45%, respectively. The post-procedural follow-up period exhibited uniformity, spanning from six months to 16 years. Preceding the intervention, all patients uniformly reported a visual analog scale (VAS) score surpassing 6/10. Additionally, everyone had been undergoing pharmacological management, involving a combination of antineuropathic agents and low-potency opioids. The evaluation of clinical improvement was conducted across three temporal domains: the immediate short-term (less than 30 days), the intermediate-term (less than one year), and the prolonged-term (exceeding one year). In the short term, a noteworthy alleviation of pain, surpassing the 50% threshold, was evident in most patients (94%), a similarity observed in both cohorts (98% in Group 1 and 90% in Group 2). The VASrevealed an average rating of 3/10 for Group 1 and 2/10 for Group 2. Moving to the intermediate term, more than 50% improvement in pain was registered in 89% of patients (92% in Group 1 and 86% in Group 2). The mean VAS score stood at 3.5/10, marginally higher in Group 2 at 4/10 compared to 3/10 in Group 1. In the final assessment, a 50% or greater reduction in pain was reported by 75% of patients, with no discernible disparity between the two cohorts. Among the cohort, 18 individuals necessitated a subsequent percutaneous intervention (10 in Group 1 and eight in Group 2), while microvascular decompression was performed on six patients (equitably distributed between the two groups), and radiosurgery was administered to three patients in Group 1. Percutaneous radiofrequency thermorhizotomy emerges as an efficacious modality for addressing essential TN. The employment of continuous radiofrequency yields superior long-term outcomes, albeit accompanied by sensitive manifestations that may prove discomforting. Pulsed radiofrequency demonstrates commendable clinical efficacy with a diminished incidence of complications, rendering it a viable option even for other manifestations of facial pain.

Pain Management in Patients with Hepatorenal Syndrome: A Literature Review

Introduction: Patients with cirrhosis often present with pain as a common complaint. Pharmacological pain management safety depends on the excretion and metabolism of drugs by the kidney and the liver. The analgesic choice in cirrhotic patients can be tremendously challenging, especially in patients with hepatorenal syndrome, a potentially reversible renal impairment associated with an increased drug accumulation and a high risk of potential toxicity. Choice and dose of medications depend on various factors, including the severity of the condition, possible drug interactions, drug dependence, and liver transplant status. Ideally, medications should be titrated from the lowest effective dose to higher strength. This review aims to discuss the pharmacodynamic and pharmacokinetics of analgesics used in cirrhotic patients. The metabolism of each drug, route of administration, pathophysiology, and limitations of their use are discussed to better understand their implementation in patients with cirrhosis and HRS. For this purpose, we performed a systematic literature search in PubMed and Google Scholar. Articles were searched via search terms and keywords. Certain high potency opioids like Sufentanil, Fentanyl, Remifentanil, Oxymorphone, and Butorphanol can be used cautiously. Low potency opioids such as Pentazocine, Tramadol, Nalbuphine, and Tapentadol may also be considered with dose adjustments. Albeit less favorable, some other analgesic options include Gabapentin, Pregabalin, acetaminophen, Duloxetine, Venlafaxine, Fluoxetine, Topical Lidocaine, Capsaicin, and Clonidine. Methodology: A systematic literature search in PubMed and google scholar was conducted between March 5 and August 10, 2021. Articles were searched via search terms and keywords relating to International Classification of Diseases: hepatorenal syndrome, pain, opioids, metabolism, renal clearance. Results: One thousand three hundred eighty-seven articles were identified from database searching. After removal of duplicates, 924 studies were screened for eligibility. After review of titles and abstracts, 665 studies were rejected for relevance reasons. Most of these studies were rejected because they were not relevant, did not meet search criteria, case-control article, case series articles, no English translation, articles did not mention adjustments in patients with liver or kidney disease. One hundred forty-two articles were used for the synthesis.

Perioperative pain management in dermatosurgery - current practice in Germany: Data analysis of a Germany-wide online survey among dermatosurgeons.

Adequate pain management should be part of the standard of care in surgical procedures. However, there is a paucity of data in the field of dermatosurgery. In a standardized online survey among dermatosurgeons working in Germany, the current practice of perioperative pain management was investigated. Members of the German Society for Dermatosurgery (DGDC) and heads of dermatosurgical departments were asked to participate. Questions were related to practical implementation of perioperative pain management, pain documentation and personal sources of information on the topic. 116 questionnaires were analyzed. While prophylactic analgesia is rarely used, the vast majority (86%) reported the use of postoperative on-demand medication. The majority of surgeons do not have a fixed regimen. Mostly NSAIDs and occasionally low potency opioids are used. Pain is documented by the majority (59.1%) as free text. Personal experience (69%) and in-house standards (51%) are the most important factors in pain management. The use of guidelines (25%) plays a minor role. Perioperative pain management in dermatosurgery is strongly influenced by personal experience and may vary depending on the surgery performed. Consensus-based standardized recommendations are lacking. For adequate perioperative analgesia, the development of demand-oriented pain concepts is desirable. This requires prospective studies that address the specific patient population and surgical procedures in dermatology.

Osteoarthritis: what's new?

Osteoarthritis (OA) is a very common disease. As a consequence of the ageing society, osteoarthritis prevalence will further increase. Age itself, trauma, unequal load distribution and overweight are risk factors. Cellular senescence and overweight have been in the focus of scientific interest for the last few years. Both risk factors are able to facilitate joint inflammation, independent of a mechanical approach. Senescent chondrocytes as well as adipocytes can produce increased amounts of inflammatory cytokines. Cornerstones of the therapy are patient education including information on the character/course of the disease and intentional weight loss. Although NSAIDs can be recommended as analgesics, their contraindications limit the widespread use. Alternatively, acetaminophen or low-potency opioids such as tramadol might be considered. Topical NSAIDs and intraarticular glucocorticoid injections can be helpful in pain reduction particularly in knee osteoarthritis. There is still no general recommendation for nutritional supplements including chondroitin or glycosaminoglycan, but they might be considered as an accompanying therapy. With the current non-approval of the nerve growth factor (NGF)-antibody tanezumab, a new therapeutical option for OA suffered a setback. Unfortunately, the results of the phase 2 study on the Wnt inhibitor lorecivivint are barely encouraging. However, the results of the according phase 3 study are eagerly awaited.

COMPARISON OF TRAMADOL AND OXACEPROL IN PATIENTS WITH OSTEOARTHRITIS

Introduction: Osteoarthritis (OA) is a chronic, degenerative disease of unknown origin which is characterised by gradual loss of articular cartilage. It is the most prevalent disease with a worldwide distribution. Earlier, osteoarthritis was seen as an inevitably progressive, degenerative disease process. Now it has been suggested that it is a dynamic process that may progress episodically. It is a heterogeneous group of diseases characterised by an adaptive response of synovial joints to a variety of genetic, environmental, aging and biomechanical stresses. NSAIDs intake increases the risk of gastritis and does not a have direct impact on the underlying pathogenesis of articular diseases. Tramadol augments serotonergic and noradrenergic neurotransmission, although it’s main active metabolite, O-desmethyltramadol. Oxaceprol is an atypical inhibitor of inflammation, used as a drug for joint disease without less side-effects with better safety profile than non-steroidal anti-inflammatory drugs (NSAIDs).
 Material and Methods: Participants were randomized in two study groups of 50 patients each sing computer generated random number list. Each group was given either oxaceprol 200 mg capsule or tramadol 50 mg capsule, thrice daily after food, for 12 weeks. The primary efficacy variable for this study was symptom relief stiffness, and physical function, measured on 100 mm Visual analogue scale (VAS) scale. Rescue medication used during the study period was also recorded. Complete blood count, blood glucose, liver function tests, and serum creatinine was recorded at the start of the study and. Vital signs were recorded at each visit and adverse events were reported. 
 Results: A total of 100 patients were included in the study of which 50 each were placed in tramadol group and oxaceprol group. No statistically significant difference was noted in both the group about baseline parameters about sex, age and blood pressure. Blood sugar was higher in Oxaceprol group as compared to tramadol group (P =0.0042) which was statistically significant. No statistically significant difference was observed between groups for WOMAC scores. Significant reduction in pain, stiffness and physical function was observed between oxaceprol and tramadol group at baseline and after 6 months follow-up. None of the adverse events were severe in nature in both the group commonest were dizziness and nausea.
 Conclusion: Oxaceprol efficacy and tolerability was comparable with tramadol and the drug can be considered as an alternative to low-potency opioids in the management of knee osteoarthritis. Further studies are required to confirm the clinical utility of oxaceprol in osteoarthritis.
 Keywords: OA, tramadol, oxaceprol, NSAID, WOMAC

Utilization of transdermal fentanyl in German nursing home residents from 2010 to 2014.

AbstractPurposeTransdermal fentanyl (TF) is the most commonly used opioid in Germany although it is associated with an increased risk for hypoventilation and potentially life‐threatening respiratory depression if used inappropriately. The objective of this study was to characterize nursing home residents newly receiving TF with regards to (1) patients' conditions at patch initiation, (2) previous analgesic treatment, and (3) the initial TF dose.MethodsUsing claims data (2010‐2014), we studied a cohort of new nursing home residents aged greater than or equal to 65 years initiating TF.ResultsTF was the most commonly prescribed opioid in nursing home residents. During their nursing home stay, 8571 persons (median age: 86 years, 79.2% female and 28.6% with a diagnosis of cancer) started TF (6.7% of all residents). Almost half of the new TF users were opioid‐naïve and 56.2% of those who had been treated with opioids in the 180 days before TF initiation had only received low potency opioids such as tilidine/naloxone or tramadol. Opioid‐naïve TF users more often were care dependent and had a higher prevalence of dementia than patients previously treated with opioids. Overall, patients often received anxiolytic/hypnotic (29.7%) or antipsychotic (31.4%) comedication. About 61% of opioid‐naïve users started with the lowest available dose (12.5 μg/h), followed by 32% treated with 25 μg/h.ConclusionsTF as a noninvasive treatment option is the first‐choice opioid in German nursing homes. Although initial doses seemed more appropriate than those identified in previous studies, the large proportion of opioid‐naïve patients in this vulnerable population warrants attention, given the limited controllability of the treatment.

Long-term treatment in chronic noncancer pain: Results of an observational study comparing opioid and nonopioid therapy

Background and aimsRecent studies reveal high prevalence rates of patients receiving long-term opioids. However, well designed studies assessing effectiveness with longer than 3 months follow-up are sparse. The present study investigated the outcomes of long-term opioid therapy compared to nonopioid treatment in CNCP patients with respect to measures of pain, functional disability, psychological wellbeing, and quality of life (QoL). MethodsThree hundred and thirty three consecutive patients at our pain clinic were included and divided into patients with continuous opioid treatment for at least 3 months (51%) and patients receiving nonopioid analgesics (49%). Further, outcome of different doses of opioid (<120mg vs. >120mg morphine equivalents) and differences between high and low potency opioids were examined. ResultsThe opioid and nonopioid groups did not differ with regard to pain intensity or satisfaction with analgesic. Patients with continuous opioids treatment reported higher neuropathic like pain, longer duration of pain disorder, lower functional level, wellbeing, and physical QoL in comparison to patients receiving nonopioid analgesics. Higher opioid doses were associated with male gender, intake of high potency opioids and depression but there were no differences with regard to pain relief or improvement of functional level between high and low doses. Similarly, patients on high potency opioids reported more psychological impairment than patients on low potency opioids but no advantage with regard to pain relief. Overall, remaining level of pain, functional disability and poor QoL were quite high irrespective of the analgesic used or opioid dosing. ConclusionIn the long-term no clear advantage of opioid vs. non-opioid analgesics could be revealed. In terms of remaining pain intensity, functional disability and quality of life, treatment with pain medication proved insufficient. Additionally, with higher doses of opioids the benefit to risk relationship becomes worse and patients on high potency opioids reported more psychological impairment than patients on low potency opioids but no advantage with regard to pain relief. ImplicationsOur results raise questions about the long-term effectiveness of analgesic treatment regimens irrespective of analgesics type employed and call for more multidisciplinary treatment strategies.

Verordnung von starken Opioiden im Jahr 2011

The aim of this study was to analyze the prescription of high-potency (WHO step III) opioids with respect to regional differences and to assess the proportion of opioid-naïve new users of transdermal fentanyl. Prescription claims data of the largest single German health fund (BARMER GEK) with 9.1 million insured persons from the year 2011 were used. For new users of transdermal fentanyl who had had no prescription in the preceding 6 months it was studied whether they had received other high-potency or low-potency opioids before. A total of 18.9 million defined daily doses (DDD) of high-potency opioids were included corresponding to a mean of 208.6DDD per 100 persons. Significant regional differences were found with lower values in the south, ranging from 145.9DDD in Baden-Württemberg to 259.5DDD per 100 persons in Lower Saxony. Fentanyl was the most frequently used step III opioid (40.8% of DDDs) which is nearly only given transdermally. Of the 11,184 patients with new use of transdermal fentanyl 80.7% had received no other high-potency opioid before and 52.9% had received neither low-potency nor high-potency opioids before. The first prescription exceeded the smallest available dose of 12.5μg/h for over half of the patients starting treatment. Although oral morphine, oxycodone and hydromorphone are recommended as first-line step III opioids, transdermal fentanyl seems to be prescribed too often as the first choice and might not be appropriate.

Pharmacokinetics of transdermal buprenorphine patch in the elderly

PurposeTransdermal buprenorphine patches provide comparable pain relief to that of low-potency opioids in elderly individuals. However, specific data on their use in elderly individuals is limited. This study investigated and compared the PK of buprenorphine transdermal patches in elderly (≥75 years) versus younger (50–60 years) individuals.MethodsThis was a multiple-dose, open-label, parallel-group study in healthy volunteers split into two age groups (younger, 50–60 years; elderly, ≥75 years) with 37 individuals in each. Study participants received two consecutive 7-day buprenorphine 5 μg/h transdermal patch applications, and blood samples were collected on the week of the second patch application [day 7 (predose), days 8, 9, 10, 12, and 14] to determine PK at steady state. Pharmacokinetic parameters were determined for buprenorphine and norbuprenorphine. Safety was assessed by analyzing adverse events, hematology, clinical chemistry, urine analysis, vital signs, electrocardiogram (ECG), and physical examinations.ResultsThe area under the plasma concentration-time curve at steady state (AUCtau), measured over one dosing interval, was similar for elderly [mean ± standard deviation (SD) 9,940 pg/h/ml (4,827 pg/h/ml] and younger [mean ± SD 11,309 (3,670 pg/h/ml] individuals. Bioequivalence was not demonstrated between groups, which may be attributable to the relatively high level of variability in individual plasma profiles. More adverse events were reported by younger (216) than elderly (164) study participants.ConclusionsNo dosage alterations are necessary for PK reasons when treating elderly people with buprenorphine transdermal patches.

Prescription opioid use among older adults with arthritis or low back pain

To examine patterns of chronic opioid use in selected groups with arthritis and low back pain and compare them with patterns among persons with ischemic heart disease. The study database consisted of Medicare beneficiaries who were enrolled in a drug benefit program for low-to-moderate income Pennsylvania residents. We identified selected patients who had a diagnosis of rheumatoid arthritis, osteoarthritis, chronic low back pain, or ischemic heart disease since 1995. Chronic opioid use, defined as at least six 30-day prescriptions in a year, was the endpoint of interest. We examined the proportion of patients meeting this definition during the period 1996-2001 and determined predictors based on multivariable Cox proportional hazards models. Four percent of subjects with rheumatoid arthritis used opioids chronically in 2001, compared with <1% in each of the other groups. There was no increase in the chronic use of opioids over the 6-year study period. Low-potency opioids were the most commonly prescribed preparations for chronic users from all patient groups. The prior use of medicines for psychiatric illness, including benzodiazepines or barbiturates, was associated with chronic prescription opioid use across all diagnoses. However, subjects with a prior diagnosis of psychiatric illness were less likely to receive chronic opioids. Chronic opioid use is relatively uncommon, even among older individuals with arthritis or low back pain. The proportion of these individuals receiving such medicines has not increased in the late 1990s. There seems to be a complex relationship between psychiatric medication use, psychiatric diagnoses, and the use of chronic opioids among these individuals.

Association between non-medical and prescriptive usage of opioids

Understanding and managing prescription opioid abuse is one of the major challenges in pain management worldwide. The relationships between prescriptive usage of opioids and reported morbidity at the national level, using data from the Drug Abuse Warning Network (DAWN), were examined. When the major prescription opioids were evaluated, the association between prescriptive medical use in kilograms and reported morbidity, as measured by a ratio between the two, was similar for the intermediate-potency opioids (hydrocodone, methadone, oxycodone, and morphine). This rate was much lower for low-potency opioids (codeine, meperidine, pentazocine, and propoxyphene) and much greater for high-potency opioids (hydromorphone and fentanyl). When the drugs were adjusted by potency (relative to morphine), the rates of reported morbidity per kilogram of morphine equivalent opioid in prescriptive usage were similar among the opioids. Using the potency-adjusted total kilograms of opioid in prescriptive use for all the opioids evaluated, there was a statistically significant association ( r 2 = 0.9791) with the reported morbidity for prescription analgesics as a class, as measured in the DAWN system. These data suggest that non-medical use of opioids is predictable based on potency and extent of prescriptive use.

Analgesics in the elderly

The aim of the study is to investigate whether elderly patients on long-term weak opioid analgesics could suffer the problems of tolerance and dependence. The prevalence of potential dependence amongst long-term users was assessed by a semi-structured questionnaire applying the Diagnostic Criteria for Research (DCR-10) criteria for Dependence Syndrome. The sample consisted of 25 randomly selected elderly patients drawn from four practices in North Cheshire, who had been on continuous repeat prescription of low potency opioid and compound analgesics containing them for a minimum of one year without apparent problem to themselves or their GPs. Approximately 2.8% of the elderly GP practice population were shown to be on opioid analgesics continuously for at a least one year. The study found that an estimated 40% of patients on low potency opioids fulfilled the DCR-10 criteria for Dependence Syndrome. It could be argued however that the finding may be, at least partly, the result of an undetermined specificity of DCR-10 as a screening tool. The finding, in such a small sample, is interesting but requires critical examination, as we believe it to be the first study of the possible effect of long-term use of opioid analgesics in primary care. The unexpectedly high prevalence highlights the need for further research in this area.

A preliminary study of patients on repeat prescriptions of opioid and non-opioid analgesics

BACKGROUND: Available literature suggests that problems due to dependence do not result from the use of low doses of low-potency opioids used for short periods of time, but no studies looked at the effect of their long-term use. OBJECTIVES: The main objective of the study was to discover whether those patients on long-term low-potency opioids, and those on non-opioid analgesics, could suffer the problems of tolerance and dependence. The study also explored the validity of applying DCR-10 criteria to a non-problematic population of analgesic users in identifying drug-dependent patients in primary care. METHOD: The prevalence of potential dependence amongst long-term users was assessed by a semi-structured questionnaire applying the DCR-10 criteria for Dependence Syndrome. The sample consisted of 38 randomly selected patients, drawn from four practices in North Cheshire, who had been on continuous repeat prescriptions of low-potency opioids, compound analgesics containing them and non-opioid analgesics (non-steroidal anti-inflammatory drugs - NSAIDs) for a minimum of one year, without any problems becoming apparent either to the patients or to their GPs. RESULTS: Approximately 3.6% of the North Cheshire GP practice population, predominantly elderly people, were shown to be on either opioid and/or non-opioid analgesics continuously for at least one year. An estimated 31% and 40% of patients on NSAIDs and low-potency opioids respectively fulfilled the DCR-10 criteria for Dependence Syndrome. With the exception of the criterion of 'impaired control' (odds ratio 4; P < 0.05), the DCR-10 criteria are equally likely to be reported in both groups. CONCLUSION: An unexpectedly high incidence of dependence was found, not only on opioids but also within the NSAIDs group. The findings may have resulted, at least in part, from an undetermined DCR-10 specificity.

Efficiency of referral for suspected glaucoma.

Restless legs syndrome (RLS) is a common sensory motor neurological disorder that is characterised by an irresistible urge to move the legs that significantly affects the quality of life of the patient. Prevalence in the general population is 5-25% and it is twice as prevalent in women as in men. RLS is the most common movement disorder in pregnancy with a fourfold increased risk of developing this disorder later in life. The pathophysiology of RLS is centred on dopaminergic dysfunction, reduced central nervous system iron, genetic linkages, or alteration in neurotransmitters such as hypocretins, endorphins levels and immune dysfunction and inflammatory mechanisms. With the emergence of new evidence, there are changes to the previous treatment recommendations for RLS. There is sufficient evidence to conclude that dopamine agonists such as rotigotine transdermal patch, pramipexole, ropinirole, gabapentin enacarbil, pregabalin and gabapentin are effective in the short-term treatment of RLS and rotigotine, followed by gabapentin enacarbil, ropinirole, pramipexole and gabapentin for long-term treatment. Based on expert consensus, the recommendation for daily RLS is dopamine agonists or gabapentin or low-potency opioids. Levodopa is less preferred for treating daily RLS due to its high risk of augmentation. For intermittent RLS, it is levodopa or dopamine agonists or low-potency opioids or benzodiazepines. For refractory RLS, the choice is to change to gabapentin or a different dopamine agonist, addition of a second agent like gabapentin or benzodiazepine to the existing drug or changing to a high-potency opioid or tramadol. Medications with safety record in pregnancy include opioids and antiepileptics such as carbamazepine and gabapentin. There are concerns that patients with RLS are at risk for metabolic deregulation, autonomic dysfunction and cardiovascular morbidity. However, a recent study concluded that RLS is not associated with increased risk of cardiovascular complications.