Ketamine as Treatment for Cluster Headache: A Systematic Review of Literature and a Case Series.

INTRODUCTION: Cluster headache is a severe and debilitating neurological condition characterized by intense, excruciating pain with a significant impact on patients' wellbeing. Although different treatment options are available, many patients continue to experience inadequate relief. Therefore, experimental strategies are increasingly studied. One of the more promising approaches is the use of ketamine. We present the currently available evidence and our own data. METHODS: In this mixed-methods paper, we first summarize the available evidence of ketamine for treatment of cluster headache based on a systematic review of literature in MEDLINE, EMBASE and the Cochrane library of systematic reviews. As the level of evidence is quite limited, we report our own cohort study with ten patients treated with ketamine infusions for cluster headache. They were followed up to investigate the patients' experience of treatment success and quality of life. RESULTS: The search and review of literature identified four reports with a total of 68 patients. All were uncontrolled case series. The current literature suggests that ketamine might decrease cluster headache. However, as the applied regimes and reported outcomes are highly heterogeneous, further analysis was futile. Our own data show high patient satisfaction with ketamine treatment. CONCLUSION: Despite the limited evidence, ketamine might be considered a potential therapeutic approach for cluster headache. Therefore, further research including randomized controlled trials should be encouraged.

This article discusses the potential use of ketamine for the treatment of cluster headache, a severe neurological condition that can have a significant impact on patients' quality of life. The authors conducted a systematic review of the existing literature on ketamine for the treatment of cluster headache. Additionally, they also presented their own cohort study of ten patients receiving ketamine infusions. The review of the literature revealed four reports with a total of 68 patients, all of which were uncontrolled case series. While the current literature suggests that ketamine may be effective in relieving cluster headache symptoms, the heterogeneity of treatment regimens and reported outcomes makes it difficult to draw definitive conclusions. The authors' own cohort study found that patients were very satisfied with ketamine treatment, indicating a potential benefit of this approach. However, due to the limited evidence available, further research, including randomized controlled trials, is needed to better understand the efficacy of ketamine in the treatment of cluster headaches.

Beyond disclaimers: the need for a curation-based model of PubMed.

According to its own description, the biomedical meta-database PubMed exists "with the aim of improving health-both globally and personally." Unfortunately, PubMed contains an increasing amount of low-quality research that may detract from this goal. Currently, PubMed warns its users and protects itself from such problems with a disclaimer stating that the presence of any article, book, or document in PubMed does not imply an endorsement of, or concurrence with, its contents by the NLM, the National Institutes of Health (NIH), or the U.S. Federal Government. However, we are critical of a "disclaimer-only" stance and encourage PubMed to take further action against low-quality research being found and indexed in its database, and thus available for use. To address this problem, we offer two lines of reasoning to argue that PubMed should not function merely as a passive index of health-related research. Instead, we first argue that only trustworthy published research is able to further PubMed's goal of health improvement. Secondly, on the basis of surveys, we argue that researchers place a high level of trust in articles that are referenced in this meta-database. We cannot expect any one set of actors to ensure trustworthy content on PubMed, which requires collective responsibility among authors, peer reviewers, editors, and indexers alike. Instead, we propose a curation-based model that incorporates three mechanisms of collaborative content curation: open expert feedback on indexed content, journal auditing, and constant transparent reassessment of indexed entities.

The Dose-Response Relationship between Opioid Agonist Therapy and Alterations in Pain Pathways in Patients with Opioid Use Disorders: A Cross-Sectional Study.

INTRODUCTION: The administration of opioids can be followed by enduring neuroplastic changes in the peripheral and central nervous systems. This remodeling can lead to opioid-induced hyperalgesia, causing an increased sensitivity to painful stimuli. The description of opioid-induced changes in the somatosensory system has seldom been described in the setting of opioid agonist therapy in the treatment of opioid use disorders, and the few existing reports provide no guidance with respect to the effect of varied doses or substances. OBJECTIVE: The aim of the present study was to assess alterations of pain pathways among patients receiving opioid agonist therapy and to elucidate the dose-response relationship. METHODS: This study was planned as cross-sectional in an outpatient clinic in Graz, Austria. Patients receiving opioid agonist therapy for opioid use disorders (including methadone, levomethadone, buprenorphine, and extended-release morphine) were asked to fill out a questionnaire, including the central sensitization inventory. A battery of somatosensory system assessments was then performed. RESULTS: A total of 120 patients participated (85 men/35 women). The mean oral morphine milligram equivalent (MME) was 694 ± 249 mg/day. Our study found significant alterations in pain perception, conditioned pain modulation, and wind-up. We demonstrated a moderate dose-response relationship between high-dose opioids and markers of central sensitization. CONCLUSION: The present trial demonstrates the clear effects of opioid agonist therapy on the somatosensory system. Both central sensitization and descending pain modulation are negatively affected by high doses of opioids and our data elucidate a moderate dose-response relationship for these phenomena.

Simplified Pain Management Including Fentanyl TTS in PACU Patients With Hip Fracture Surgery to Improve Patients' Well-Being: A Double-Blind Randomized Trial.

PURPOSE: Adequate pain management is eminently relevant for elderly and more vulnerable patients with hip fractures in the setting of pre and postoperative pain. This study compares postoperative hip fracture patients treated with standard pain management with a variety of medications or an approach with only one option in each medication category (nonopioid: acetaminophen; opioid: fentanyl TTS 12,5 mcg/hour; rescue medication: piritramide) to simplify the treatment algorithm for nurses and improve patient well-being. DESIGN: Double-blind randomized controlled trial. METHODS: The sample was cognitively intact patients (N = 141) with hip fractures in a tertiary university hospital. Administration of fentanyl 12 mcg/hour transdermal therapeutic system was administered by the nurses in the postanesthesia care unit (PACU) to address basal wound pain to improve patient well-being and patient treatment in the PACU for 24 hours to better control for early complications. FINDINGS: Well-being was equally increased in both groups in comparison to our preintervention data from 35.7% to over 60% and did not differ significantly between the intervention and control group. No statistically significant differences in numeric rating scale scores, rescue opioid dosage (piritramide i.v.) or in complications were present. CONCLUSIONS: This one-size-fits-all simplified pain management approach did not improve patient well-being or any other outcome but highlighted the importance of adequate pain management and a sufficient nurse-to-patient ratio.

Idiopathic pseudoaneurysm of the popliteal artery with endovascular treatment: A case report.

Popliteal pseudoaneurysms are a rare vascular pathology, usually caused by trauma or iatrogenic interventions. Idiopathic cases are exceptionally uncommon. This case report aims to describe the diagnosis and successful endovascular treatment of an idiopathic pseudoaneurysm of the popliteal artery in a 90-year-old bedridden female patient presented with acute pain and swelling in the left knee at the emergency department. The patient underwent successful endovascular treatment with a covered stent and thrombin injection, leading to complete exclusion of the pseudoaneurysm. Popliteal pseudoaneurysms are a rare pathology, and idiopathic cases are even more uncommon. Endovascular therapy for popliteal pseudoaneurysms is associated with lower morbidity and mortality rates compared to open surgical repair. This case report highlights the importance of interdisciplinary collaboration between vascular surgeons and interventional radiologists in the management of rare vascular pathologies.

Using cardiovascular risk indices to predict mortality in Covid-19 patients with acute respiratory distress syndrome: a cross sectional study.

Covid-19 patients who require admission to an intensive care unit (ICU) have a higher risk of mortality. Several risk factors for severe Covid-19 infection have been identified, including cardiovascular risk factors. Therefore, the aim was to investigate the association between cardiovascular (CV) risk and major adverse cardiovascular events (MACE) and mortality of Covid-19 ARDS patients admitted to an ICU. A prospective cross-sectional study was conducted in a university hospital in Graz, Austria. Covid-19 patients who were admitted to an ICU with a paO2/fiO2 ratio < 300 were included in this study. Standard lipid profile was measured at ICU admission to determine CV risk. 31 patients with a mean age of 68 years were recruited, CV risk was stratified using Framingham-, Procam- and Charlson Comorbidity Index (CCI) score. A total of 10 (32.3%) patients died within 30 days, 8 patients (25.8%) suffered from MACE during ICU stay. CV risk represented by Framingham-, Procam- or CCI score was not associated with higher rates of MACE. Nevertheless, higher CV risk represented by Procam score was significantly associated with 30- day mortality (13.1 vs. 6.8, p = 0.034). These findings suggest that the Procam score might be useful to estimate the prognosis of Covid-19 ARDS patients.

Calcitonin in the Treatment of Phantom Limb Pain: A Systematic Review.

INTRODUCTION: Phantom limb pain (PLP) refers to pain perceived in a part of the body removed by amputation or trauma. Despite the high prevalence of PLP following amputation and the significant morbidity associated with it, robust therapeutic approaches are currently lacking. Calcitonin, a polypeptide hormone, has recently emerged as a novel analgesic with documented benefits in the treatment of several pain-related conditions. METHODS: We present a systematic review that comprehensively evaluates the analgesic effects of calcitonin for patients with PLP. We searched MEDLINE, OLDMEDLINE, and PubMed Central databases with the key words "calcitonin" "phantom limb pain" and "phantom pain" to identify clinical studies evaluating the efficacy or effectiveness of calcitonin administration, in any form and dose, for the treatment of PLP. Additionally, Google Scholar was searched manually with the search term "calcitonin phantom limb pain". All four databases were searched from inception until 1 December 2022. The methodological quality of each included study was assessed using the Downs and Black checklist and the GRADE criteria were used to assess effect certainty and risk of bias. RESULTS: Our search identified 4108 citations, of which six ultimately met the criteria for inclusion in the synthesis. The included articles described a mix of open-label (n = 2), prospective observational cohort (n = 1), and randomized clinical trials (n = 3). The most common treatment regimen in the current literature is a single intravenous infusion of 200 IU salmon-derived calcitonin. CONCLUSION: The available evidence supported the use of calcitonin as either monotherapy or adjuvant therapy in the treatment of PLP during the acute phase, while the evidence surrounding calcitonin treatment in chronic PLP is heterogeneous. Given the limited treatment options for the management of PLP and calcitonin's relatively wide therapeutic index, further research is warranted to determine the role that calcitonin may play in the treatment of PLP and other pain disorders.

Impact of the pandemic and its containment measures in Europe upon aspects of affective impairments: a Google Trends informetrics study.

BACKGROUND: In late 2019, a new virus began spreading in Wuhan, China. By the end of 2021, more than 260 million people worldwide had been infected and 5.2 million people had died because of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Various countermeasures have been implemented to contain the infections, depending on the country, infection prevalence, and political and infrastructural resources. The pandemic and the containment measures have induced diverse psychological burdens. Using internet queries as a proxy, this study examines the psychological consequences on a European level of SARS-CoV-2 containment measures. METHODS: Using informetric analyses, this study reviews within 32 European countries a total of 28 search parameters derived from the International Statistical Classification of Diseases and Related Health Problems (ICD-10) as aspects of affective disorder. RESULTS: Our results show that there are several psychological aspects which are significantly emphasized during the pandemic and its containment measures: 'anxiety', 'dejection', 'weariness', 'listlessness', 'loss of appetite', 'loss of libido', 'panic attack', and 'worthlessness'. These terms are significantly more frequently part of a search query during the pandemic than before the outbreak. Furthermore, our results revealed that search parameters such as 'psychologist', 'psychotherapist', 'psychotherapy' have increased highly significantly (p < 0.01) since the pandemic. CONCLUSIONS: The psychological distress caused by the pandemic correlates significantly with the frequency of people searching for psychological and psychotherapeutic support on the Internet.

Enhanced recovery after cesarean section (ERAC): Where are we in Austria?

OBJECTIVE: Enhanced recovery after surgery (ERAS) recommendations for cesarean section (ERAC), likely the most common reason for laparotomy in women, were issued in 2018-19. We examined how current perioperative management at cesarean section in Austrian hospitals aligns with ERAS recommendations. STUDY DESIGN: We surveyed the 21 largest public obstetric units in Austria for alignment with 20 of the 31 strong ERAS recommendations regarding perioperative maternal care at cesarean section. We also looked at how the German-language clinical guideline for cesarean section (AWMF Guideline Sectio caesarea) aligns with ERAS recommendations. RESULTS: The 21 obstetric units cared for about 51% of all births in Austria in 2019. Cesarean section rates ranged from 17.7% to 50.4%. All 21 units implemented the five strong recommendations regarding patient information and counselling, regional anesthesia, euvolemia and multimodal analgesia. The least implemented strong recommendation was the one for the use of pneumatic compression stockings to prevent thromboembolic disease (0/21 units). Overall, all 21 units implemented ≥11 and 13 (62%) implemented ≥15 (≥75%) of the 20 strong recommendations; no unit implemented all 20 strong recommendations. There were no differences in the implementation of strong recommendations according to hospital volume. CONCLUSIONS: Even in the absence of formal adoption of ERAS program for cesarean section many perioperative ERAS recommendations are already implemented in Austria. The least implemented recommendations were the use of pneumatic compression stockings (0 of 21 units) and immediate catheter removal (4 of 21 units). Only 10 of the 20 ERAS recommendations we looked at are included in the current German-language clinical guideline for cesarean section.

Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.

Chronic pain is a major source of morbidity for which there are limited effective treatments. Palmitoylethanolamide (PEA), a naturally occurring fatty acid amide, has demonstrated utility in the treatment of neuropathic and inflammatory pain. Emerging reports have supported a possible role for its use in the treatment of chronic pain, although this remains controversial. We undertook a systematic review and meta-analysis to examine the efficacy of PEA as an analgesic agent for chronic pain. A systematic literature search was performed, using the databases MEDLINE and Web of Science, to identify double-blind randomized controlled trials comparing PEA to placebo or active comparators in the treatment of chronic pain. All articles were independently screened by two reviewers. The primary outcome was pain intensity scores, for which a meta-analysis was undertaken using a random effects statistical model. Secondary outcomes including quality of life, functional status, and side effects are represented in a narrative synthesis. Our literature search identified 253 unique articles, of which 11 were ultimately included in the narrative synthesis and meta-analysis. Collectively, these articles described a combined sample size of 774 patients. PEA was found to reduce pain scores relative to comparators in a pooled estimate, with a standard mean difference of 1.68 (95% CI 1.05 to 2.31, p = 0.00001). Several studies reported additional benefits of PEA for quality of life and functional status, and no major side effects were attributed to PEA in any study. The results of this systematic review and meta-analysis suggest that PEA is an effective and well-tolerated treatment for chronic pain. Further study is warranted to determine the optimal dosing and administration parameters of PEA for analgesic effects in the context of chronic pain.

The Effect of Smoking Cessation on Acute Pain: A Systematic Review.

Smoking is a known risk factor for developing various pain-related disorders. However, acute pain often triggers the craving for cigarette consumption, resulting in a positive feedback mechanism. In addition, there is evidence of decreased pain tolerance during the early stages of abstinence. Therefore, in this study, we aimed to investigate whether a period of decreased pain tolerance and increased pain intensity occurs during smoking cessation. A systematic literature search was conducted through PubMed and Web of Science databases for controlled studies investigating the influence of smoking cessation on acute (defined as pain presentation of < 3 months) and postoperative pain. The outcomes of interest included pain perception threshold, pain tolerance, pain intensity, and postoperative opioid requirements. The search strategy yielded 1478 studies, of which 13 clinical studies met our inclusion criteria. The included studies collectively represented data from 1721 participants from four countries. Of these, 43.3% of the included individuals were females. The mean age of the included subjects was 44.2 ± 8.2 years. The duration of smoking cessation varied considerably. The shortest duration was 2 h; others investigated the effect after more than 1 month of smoking cessation. Smokers had a history of 14.6 ± 9.9 years of nicotine abuse. The mean number of daily smoked cigarettes was 17.5 ± 10.3. Most studies examined in this systematic review show a negative influence of smoking cessation on acute pain. However, the affected pain modalities, the duration of the altered pain perception, and whether male and female smokers are equally affected could not be ascertained due to high heterogeneity and few available studies.

Palliative Sedation at Home: A Scoping Review.

Palliative Sedation (PS) is an effective measure for the relief of refractory symptoms in end-of-life patients. This intervention can be performed at home, respecting the patients' and their families' decisions. A scoping review was performed to map the available evidence in the literature on the performance of PS at home. This review included 23 studies. Most were conducted in European countries with adult cancer patients. Patients, family members and healthcare providers participated in the decision making regarding the use of PS at home. PS was used primarily to manage refractory symptoms (pain, delirium, dyspnea, and others), and in 1 of the studies PS was mentioned as a possible intervention for shortening life. The most commonly used medication was midazolam and the average duration ranged from 4 h to 7 days. There are few reports on adverse events related to PS. This intervention seems to be a feasible possibility for the management of refractory symptoms in patients at the end of life, despite the fact that it can represent specific challenges for healthcare providers, patients and families. However, the literature is limited regarding PS in children and in people with diseases other than cancer, as well as on the evaluation of possible adverse effects related to this intervention. Furthermore, it is essential to have a broad ethical, clinical and legal debate on whether to consider the use of PS for the purpose of shortening life in specific cases.

The Effect of Palmitoylethanolamide on Pain Intensity, Central and Peripheral Sensitization, and Pain Modulation in Healthy Volunteers-A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial.

Palmitoylethanolamide (PEA) is marketed as a "dietary food for special medical purposes". Its broad-spectrum analgesic, anti-inflammatory, and neuroprotective effects make PEA an interesting substance in pain management. However, the underlying analgetic mechanisms have not yet been investigated in humans. The aim of our study is to provide a deeper understanding of the involved mechanisms, which is essential for differentiating therapeutic approaches and the establishment of mechanism-based therapeutic approaches. In this randomized, placebo-controlled, double-blinded crossover trial, 14 healthy volunteers were included. PEA (3 × 400 mg per day) or placebo were taken for 4 weeks. Our study investigated the mode of action of PEA using an established pain model, "Repetitive phasic heat application", which is well-suited to investigate analgesic and anti-hyperalgesic effects in healthy volunteers. Parameters for peripheral and central sensitization as well as for pain modulation were assessed. Repetitive heat pain was significantly decreased, and the cold pain tolerance was significantly prolonged after the PEA treatment. The pressure pain tolerance and the conditioned pain modulation were increased after the PEA treatment. The wind-up ratio and the average distance of allodynia were significantly decreased after the PEA treatment. The heat pain tolerance was significantly higher after the PEA treatment. The present study has demonstrated that PEA has clinically relevant analgesic properties, acting on both peripheral and central mechanisms as well as in pain modulation.

Evaluation of the usefulness of non-invasive serum haemoglobin measurement in a perioperative setting in a prospective observational study.

Patient Blood Management (PBM) programmes seek to reduce the number of missed anaemic patients in the run-up to surgery. The aim of this study was to evaluate the usefulness of haemoglobin (Hb) measured non-invasively (SpHb) in preoperative screening for anaemia. We conducted a prospective observational study in a preoperative clinic. Adult patients undergoing examination for surgery who had their Hb measured by laboratory means also had their Hb measured non-invasively by a trained health care provider. 1216 patients were recruited. A total of 109 (9.3%) patients (53 men and 56 women) was found to be anaemic by standard laboratory Hb measurement. Sensitivity for SpHb to detect anaemic patients was 0.50 (95% CI 0.37-0.63) in women and 0.30 (95% CI 0.18-0.43) in men. Specificity was 0.97 (95% CI 0.95-0.98) in men and 0.93 (95% CI 0.84-1.0) in women. The rate of correctly classified patients was 84.7% for men and 89.4% for women. Positive predictive value for SpHb was 0.50 (95% CI 0.35-0.65) in men and 0.40 (95% CI 0.31-0.50) in women; negative predictive value was 0.93 (95% CI 0.92-0.94) in men and 0.95 (95% CI 0.94-0.96) in women. We conclude that due to low sensitivity, SpHb is poorly suitable for detecting preoperative anaemia in both sexes under standard of care conditions.

Migraine, interferon ß1a and siponimod immunomodulator therapies.

BACKGROUND: Autoimmunity seems to play a great role in the pathogenesis of migraine headache pain. There is far more evidence that interferon can exacerbate migraines. We report a case where remission of severe comorbid migraine attacks happened with the start of interferon ß1a (Merck, Netherlands) immunomodulation therapy. Therapy for multiple sclerosis was decided according to the severity of the debilitating comorbid migraine headache pain rather than the evolution of multiple sclerosis the far more serious disease. CASE PRESENTATION: A 63-years old patient suffered for 30-years from migraine headache of severe disability assessment scale (MIDAS) Grade-IV = 27. He also suffered for 25-years from optic-sensory relapsing remitting multiple sclerosis (RRMS). Subcutaneous interferon ß1a 44-µg immunomodulation therapy for 4-years resulted in multiple sclerosis complete remission. The start of interferon ß1a therapy for multiple sclerosis seemed to help resolving the comorbid migraine attacks. The visual aura premonitory symptom preceding migraine headache would end up with a feeling of post visual aura clearer field of vision and a feeling of wellbeing. As the patient developed secondary progressive multiple sclerosis (SPMS), oral siponimod 2 mg (Novartis, Ireland), currently the only available therapy for SPMS, replaced his interferon therapy. This was associated with a relapse of migraine severe attacks. Reverting back to interferon therapy was again associated with migraine headache remission. CONCLUSIONS: Interferon ß1a might be an efficic therapy for "autoimmune migraine". With numerous immunomodulators currently available for other systemic autoimmune diseases associated with comorbid migraine; examining the effect of these immunomodulatory therapies on comorbid migraine headache could be beneficial in finding a specific immunomodulator therapy for "autoimmune migraine".

Prospective, randomized, controlled, double-blind, multi-center, multinational study on the safety and efficacy of 6% Hydroxyethyl starch (HES) sOlution versus an Electrolyte solutioN In patients undergoing eleCtive abdominal Surgery: study protocol for the PHOENICS study.

BACKGROUND: Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss and to maintain hemodynamic stability. This study was requested by the European Medicines Agency (EMA) to provide more evidence on the long-term safety and efficacy of HES solutions in the perioperative setting. METHODS: PHOENICS is a randomized, controlled, double-blind, multi-center, multinational phase IV (IIIb) study with two parallel groups to investigate non-inferiority regarding the safety of a 6% HES 130 solution (Volulyte 6%, Fresenius Kabi, Germany) compared with a crystalloid solution (Ionolyte, Fresenius Kabi, Germany) for infusion in patients with acute blood loss during elective abdominal surgery. A total of 2280 eligible patients (male and female patients willing to participate, with expected blood loss ≥ 500 ml, aged > 40 and ≤ 85 years, and ASA Physical status II-III) are randomly assigned to receive either HES or crystalloid solution for the treatment of hypovolemia due to surgery-induced acute blood loss in hospitals in up to 11 European countries. The dosing of investigational products (IP) is individualized to patients' volume needs and guided by a volume algorithm. Patients are treated with IP for maximally 24 h or until the maximum daily dose of 30 ml/kg body weight is reached. The primary endpoint is the treatment group mean difference in the change from the pre-operative baseline value in cystatin-C-based estimated glomerular filtration rate (eGFR), to the eGFR value calculated from the highest cystatin-C level measured during post-operative days 1-3. Further safety and efficacy parameters include, e.g., combined mortality/major post-operative complications until day 90, renal function, coagulation, inflammation, hemodynamic variables, hospital length of stay, major post-operative complications, and 28-day, 90-day, and 1-year mortality. DISCUSSION: The study will provide important information on the long-term safety and efficacy of HES 130/0.4 when administered according to the approved European product information. The results will be relevant for volume therapy of surgical patients. TRIAL REGISTRATION: EudraCT 2016-002162-30 . ClinicalTrials.gov NCT03278548.

Combined femoral and popliteal nerve block is superior to local periarticular infiltration anaesthesia for postoperative pain control after total knee arthroplasty.

INTRODUCTION: After primary total knee arthroplasty (TKA), local periarticular infiltration anaesthesia (LIA) is a fast and safe method for postoperative pain control. Moreover, ultrasound-guided regional anaesthesia (USRA) with femoral and popliteal block is a standard procedure in perioperative care. Two analgesic regimens for TKA-LIA versus URSA with dexmedetomidine-were compared as an additive to ropivacaine. We hypothesised that the use of URSA provides a superior opioid sparing effect for TKA compared with LIA. METHODS: Fifty patients (planned 188 participants; safety analysis was performed after examining the first 50 participants) were randomised. These patients received LIA into the knee capsule during surgery with 60 ml of ropivacaine 0.5% and 1 ml of dexmedetomidine (100 µg ml-1) or two single-shot URSA blocks (femoral and popliteal block) before surgery with 15 ml of ropivacaine 0.5% and 0.5 ml of dexmedetomidine for each block. Postoperative opioid consumption in the first 48 h, pain assessment and complications were analysed. RESULTS: In the safety analysis, there was a significantly higher need for opioids in the LIA group, with a median oral morphine equivalent of 42.0 [interquartile range (IQR) 23.5-57.0] mg versus 27.0 [IQR 0.0-33.5] mg (P = 0.022). Due to this finding, the study was terminated for ethical considerations according to the protocol. CONCLUSION: This is the first study presenting data on LIA application in combination with dexmedetomidine. A superior opioid-sparing effect of URSA was observed when compared with LIA in TKA when dexmedetomidine is added to local anaesthetics. Also, a longer lasting opioid-sparing effect in the LIA group was observed when compared with the recently published literature; this difference could be attributed to the addition of dexmedetomidine. Therefore, multimodal analgesia regimens could be further improved when LIA or USRA techniques are combined with dexmedetomidine.