Real-time and video-recorded pain assessment in beef cattle: clinical application and reliability in young, adult bulls undergoing surgical castration.

Bovine pain assessment relies on validated behavioral scales related to normal and pain-related behaviors. This study investigated the reliability and applicability of real-time and video-recorded pain assessment, and their agreement, in young, adult bulls undergoing surgical castration. Ten Nelore and nine Angus bulls underwent general anesthesia and surgical castration. Three-minute real-time observations and simultaneous videos were recorded at - 48 h (M0), before sedation, under fasting (M1), after surgery, 3 h after sternal recumbency (M2), after rescue analgesia (M3) and at 24 h (M4). Animals received morphine (after M2), dipyrone (after M3), and flunixin meglumine after surgical castration (M4). Two trained evaluators assessed real-time (n = 95) and video-recorded time-points (n = 95) using the Unesp-Botucatu Cattle Pain Scale (UCAPS). Both assessment methods inferred 'very good' reliability (≥ 0.81) with minimal bias, however, video-recorded assessment (4.33 ± 2.84) demonstrated slightly higher scores compared to real-time (3.08 ± 2.84). The results from this study suggest that UCAPS can be used in real-time or video-recorded to assess pain and guide analgesic therapy in cattle.

[New manifestation of a type 2-inflammation in the upper respiratory tract with nasal polyposis under treatment with an asthma biologic]. / Neumanifestation einer Typ-2-Inflammation im Bereich der oberen Atemwege mit Polyposis nasi unter einem Asthmabiologikum.

INTRODUCTION: For 7 years we gained experience of how asthma and chronic rhinosinusitis with nasal polyposis respond to biologics. In contrast, it is much less known, how ASA/NSAID intolerance (Widal's disease) behaves under biologicals. We therefore describe the case of a patient with both clinical conditions who reacted with a severe intolerance reaction under perioperative metamizole administration.

Use of metamizole and other non-opioid analgesics in Switzerland between 2014 and 2019: an observational study using a large health insurance claims database.

OBJECTIVE: To investigate claims patterns for metamizole and other non-opioid analgesics in Switzerland. To characterise users of these non-opioid analgesics regarding sex, age, comedications and canton of residence. METHODS: We conducted a retrospective descriptive study using administrative claims data of outpatient prescribed non-opioid analgesics of the Swiss health insurance company Helsana between January 2014 and December 2019. First, we evaluated the number of claims and defined daily doses  per year of metamizole, ibuprofen, diclofenac and paracetamol in adults aged 18 years or over. Second, we characterised new users of these non-opioid analgesics in terms of sex, age, claimed comedications and canton of residence. RESULTS: From 2014 to 2019, among the investigated non-opioid analgesics, metamizole showed the highest increase in claims (+9545 claims, +50%) and defined daily doses (+86,869 defined daily doses, +84%) per 100,000 adults. Metamizole users had the highest median age (62 years [IQR: 44-77]) compared to ibuprofen (47 years [IQR: 33-62]), diclofenac (57 years [IQR: 43-71]) and paracetamol (58 years [IQR: 39-75]) users. Metamizole users also more frequently claimed proton pump inhibitors, anticoagulants, platelet aggregation inhibitors and antihypertensive drugs than users of other non-opioid analgesics. While metamizole was most frequently claimed in German-speaking regions of Switzerland, ibuprofen and paracetamol were most frequently claimed in the French-speaking regions and diclofenac in German- and Italian-speaking regions. CONCLUSION: In Switzerland, metamizole was increasingly claimed between 2014 and 2019. Metamizole was most frequently claimed by older adults and patients with comedications suggestive of underlying conditions, which can be worsened or caused by use of nonsteroidal anti-inflammatory drugs. The lack of studies regarding the effectiveness and safety of metamizole in this population warrants further investigation.

Management of analgesia in acute pancreatitis: Results of a national survey. / Manejo de la analgesia en la pancreatitis aguda. Resultados de una encuesta nacional.

INTRODUCTION: Acute pancreatitis is one of the main reasons for digestive admissions. Adequate pain treatment is crucial in its management. However, there are hardly any descriptions of the analgesic guidelines used in our setting. METHODS: On-line survey on analgesic management in acute pancreatitis, aimed at attending physicians and residents practising in Spain. RESULTS: Two hundred and nine physicians from 88 centres responded to the survey. Ninety percent were specialists in gastrointestinal medicine and 69% worked in a tertiary centre. The majority (64.4%) do not routinely use scales to measure pain. When choosing a drug, experience in its use was the most important factor. The most commonly prescribed initial treatments are: combination of paracetamol and metamizole (53.5%), paracetamol alone (19.1%) and metamizole alone (17.4%). As rescue: meperidine (54.8%), tramadol (17.8%), morphine chloride (17.8%) and metamizole (11.5%). Continuous perfusion is used in 8.2% of initial treatments. Physicians with >10 years of service use more metamizole as monotherapy (50%), while residents and attending physicians with <10 years of service prescribe it in combination with paracetamol (85%). If progression is needed, morphine chloride and meperidine are mainly used. The speciality of the respondent, the size of the work centre and the unit/service where the patients were admitted did not influence the analgesia prescribed. Satisfaction with pain management reached 7.8/10 (SD 0.98). CONCLUSION: In our setting, metamizole and paracetamol are the most commonly used analgesics as initial pain treatment in acute pancreatitis, and meperidine is the most commonly used rescue analgesic.

Increased Use and Large Variation in Strong Opioids and Metamizole (Dipyrone) for Minor and Major Musculoskeletal Injuries Between 2008 and 2018: An Analysis of a Representative Sample of Swiss Workers.

PURPOSE: Musculoskeletal (MSK) injuries are a major contributing factor for chronic pain. To date, little is known how pain medication use in MSK injuries has changed over time. We assessed pain medication prescription for MSK injuries in a representative sample of Swiss workers between 2008 and 2018. METHODS: Retrospective analysis of the Swiss Accident Insurance Fund (Suva) data. We calculated annual pain medication use, treatment days, and costs associated with pain medication use in minor and major MSK injuries. RESULTS: In total, 1,921,382 cases with MSK injuries with ≥ 1 pain medication were analyzed. Whereas MSK injuries with ≥ 1 pain medication increased by 9.4%, we observed a larger increase in metamizole (+ 254%), strong opioids (+ 88.4%), coxibs (+ 85.8%), and paracetamol (+ 28.1%). Strong opioids were increasingly used in minor (+ 91.4%) and major (+ 88.3%) injuries. The increase in metamizole (+ 390.6%) and coxibs (+ 115.5%) was larger in minor injuries compared to major injuries (+ 238.7% and + 80.6%, respectively). Medical expenses decreased in all medications except for strong opioids where a substantial increase was observed (+ 192.4% in minor; + 34% in major injuries). CONCLUSIONS: We observed a disproportionate increase in metamizole, strong opioids, coxibs, and paracetamol prescriptions even in minor MSK injuries between 2008 and 2018. Whereas treatment costs decreased for all pain medications, there was a substantial increase in strong opioids. A more liberal prescription practice of opioids conflict with current evidence-based practice recommendations and need to be addressed by physicians and policy makers.

Assessment of local pain and analgesia in envenoming by wandering spiders (Phoneutria spp.).

Phoneutrism (bites by wandering spiders of the genus Phoneutria) frequently results in local pain. We describe a retrospective cohort study of a case series of phoneutrism admitted to our Emergency Department (ED), in which we used the Numeric Pain Rating Scale (NPRS 0-10) to assess the intensity of local pain upon admission, and recorded the analgesic measures used to control this pain. Other criteria for inclusion were: (1) An age ≥8 years, (2) Treatment exclusively at our ED, and (3) Visualization or photographing the spider at the time of the bite and/or bringing the spider for identification. The patients were classified into three groups based on the intensity of pain at admission: group 1 - mild or no pain (NPRS: 0-3), group 2 - moderate pain (NPRS: 4-6), and group 3 - intense or severe pain (NPRS: 7-10). Fifty-two patients fulfilled the inclusion criteria (n = 11, 14 and 27 in groups 1, 2, and 3, respectively), with a median age of 37 years. The median NPRS upon admission was 7 (interquartile range: 5-8). In patients with an NPRS <7 (groups 1 and 2), only dipyrone was used to alleviate the pain, with six cases in group 1 requiring no analgesia. Most of the cases in group 3 (19/27) were treated with a local anesthetic infiltration (2% lidocaine), in association with analgesics given i.v. in 16 cases (dipyrone, 14; tramadol, 2); additional analgesic treatment was required in seven cases, six of which were treated with tramadol i.v. The median time spent in the ED was 18, 58 and 120 min for groups 1, 2 and 3, respectively. These findings show that most cases of envenoming by Phoneturia spp. involved intense local pain (NPRS ≥7), with local anesthetics being used only in these cases, often in association with dipyrone i.v.

Pain Management and Analgesics Used in Small Mammals during Post-Operative Period with an Emphasis on Metamizole (Dipyrone) as an Alternative Medication.

Metamizole (dipyrone) is a widely used non-opioid analgesic in both human and animal medicine. Metamizole's safety has been the topic of numerous opposing debates, given the fact that in certain countries metamizole is frequently used as an over-the-counter (OTC) medicine, while in others it is banned due to the risk of agranulocytosis. Further, small mammals such as rabbits, ferrets, rodents, and hedgehogs have become some of the most common pets present in veterinary practice, and each of these species has specific analgesic needs due to their anatomy and physiology. The key to providing appropriate medical care is in finding a substance that has minimal negative effects. In small mammals, analgesia is an important factor and, it happens frequently that, pain in these patients is not well managed. Post-operative pain management is an important topic in the welfare of animals. The objectives of this review, thus, were to provide a concise overview of analgesics that are used in the treatment of postoperative pain in small mammals (e.g., rabbits and rodents) and to highlight the importance of this product, metamizole, in veterinary medicine, as well as the potential of this substance as an alternative analgesic for the treatment of postoperative pain in small mammals.

Efficacy of single-shot adductor canal block before Versus after primary total knee arthroplasty - Does timing make a difference? A randomized controlled trial.

BACKGROUND: Total knee arthroplasty (TKA) is associated with severe postoperative pain. Multimodal analgesia, including peripheral nerve block, is recommended for post-operative pain relief. Administration of some pain medications prior to surgery has shown to be more effective than after the operation. This is a prospective, randomized controlled trial designed to compare the analgesic efficacy of the adductor canal block (ACB) performed immediately before or immediately after primary total knee arthroplasty (TKA). We hypothesized that ACB before the surgery will reduce postoperative pain and improve knee function. METHODS: A total of 50 patients were enrolled and randomized into 2 groups, with 26 patients receiving a preoperative ACB and 24 receiving a postoperative ACB. RESULTS: Treatment groups were similar in terms of gender (p = .83), age (p = 0.61) weight (p = .39) and ASA score. Average visual analogue scale (VAS) on arrival to the post-anesthesia care unit (PACU) were 4.9 ± 3.2 in the preoperative ACB versus 3.4 ± 2.8 for the postoperative ACB (p = .075). VAS scores at different time points as well as the mean, minimal and maximal reported VAS scores were not significantly different between the two groups. The cumulative quantities of Fentanyl administered by the anesthesia team was comparable between the groups. Similarly, the dosage of Morphine, Tramadol, Acetaminophen and Dipyrone showed only small variations. The Quality of Recovery Score, Knee Society Scores and knee range of motion did not differ between the groups. CONCLUSIONS: Our findings demonstrate no significant differences in patient total narcotics consumption, pain scores and functional scores, between preoperative and postoperative ACB in patients undergoing TKA. TRIAL REGISTRATION: The trial was registered at www.clinicaltrials.gov and was assigned the registration number NCT02908711. LEVEL OF EVIDENCE: level I randomized controlled trial.

Analgesic Medication in Fibromyalgia Patients: A Cross-Sectional Study.

There is no approved drug for fibromyalgia syndrome (FMS) in Europe. In the German S3 guideline, amitriptyline, duloxetine, and pregabalin are recommended for temporary use. The aim of this study was to cross-sectionally investigate the current practice of medication in FMS patients in Germany. We systematically interviewed 156 patients with FMS, while they were participating in a larger study. The patients had been stratified into subgroups with and without a decrease in intraepidermal nerve fiber density. The drugs most commonly used to treat FMS pain were nonsteroidal anti-inflammatory drugs (NSAIDs) (41.0% of all patients), metamizole (22.4%), and amitriptyline (12.8%). The most frequent analgesic treatment regimen was "on demand" (53.9%), during pain attacks, while 35.1% of the drugs were administered daily and the remaining in other regimens. Median pain relief as self-rated by the patients on a numerical rating scale (0-10) was 2 points for NSAIDS, 2 for metamizole, and 1 for amitriptyline. Drugs that were discontinued due to lack of efficacy rather than side effects were acetaminophen, flupirtine, and selective serotonin reuptake inhibitors. Reduction in pain severity was best achieved by NSAIDs and metamizole. Our hypothesis that a decrease in intraepidermal nerve fiber density might represent a neuropathic subtype of FMS, which would be associated with better effectiveness of drugs targeting neuropathic pain, could not be confirmed in this cohort. Many FMS patients take "on-demand" medication that is not in line with current guidelines. More randomized clinical trials are needed to assess drug effects in FMS subgroups.

Intravenous Morphine Infusion versus Thoracic Epidural Infusion of Ropivacaine with Fentanyl after the Ravitch Procedure-A Single-Center Cohort Study.

OBJECTIVE: To compare the efficacy of analgesia with intravenous infusion of morphine and thoracic epidural infusion of ropivacaine with fentanyl in pediatric patients after the Ravitch procedure. METHODS: Postoperative analgesia was achieved by intravenous morphine infusion with a dose of 0.02-0.06 mg/kg per hour (intravenous group, n = 56) or thoracic epidural infusion of 0.2% ropivacaine and fentanyl 5 µg/mL with a flow rate of 0.1 mL/kg per hour (epidural group, n = 40). Furthermore, the multimodal pain management protocol included paracetamol, non-steroidal anti-inflammatory drugs, and metamizole as a rescue drug. The primary outcomes included pain scores (according to the Numerical Rating Scale, range 0-10), while the secondary outcomes included consumption of the rescue drug, anxiety, postoperative side effects, and patient satisfaction. The observation period lasted from postoperative day 0 to postoperative day 3. RESULTS: Median average and maximal pain scores at rest, during deep breathing, and coughing were significantly lower in the intravenous group compared to the epidural group (p < 0.05). The effect size was medium (Cohen's d ranged from 0.5 to 0.7). Patients receiving morphine required significantly lower numbers of metamizole doses than in the epidural group (median 1 vs. 3; p = 0.003; Cohen's d = 0.6). Anxiety, postoperative side effects, and patient satisfaction were similar in both groups (p > 0.05). CONCLUSIONS: An intravenous infusion of morphine may offer better postoperative analgesia than a thoracic epidural infusion of ropivacaine with fentanyl.

Real world evidence of the use of metamizole (dipyrone) by the Brazilian population. A retrospective cohort with over 380,000 patients.

OBJECTIVE: To determine under which health conditions metamizole (dipyrone) is used as a single drug or as fixed-dose combination. METHODS: Two retrospective cohorts of Brazilian patients treated with metamizole between January 2015 and December 2017 were analyzed: a metamizole-based cohort (Cohort 1) and a symptoms-based cohort (Cohort 2). Anonymized patient data was obtained from Amil Clinical Data Warehouse. The number of patients with symptoms was described by age and sex. RESULTS: The sample size of the two cohorts consisted of 384,668 patients. In patients using metamizole (Cohort 1), the most common reason for medication was the treatment of some form of pain (81%), followed by fever (19%). Headache was the most common (19%) specified pain class, followed by sore throat (8%), muscular pain (6%), and abdominal pain (5%). In adult patients (n=276,279; 71.8%), metamizole was used as a monotherapy or associated with another drug, for any sort of pain, in over 88% of the patients. General pain was the main reason for metamizole use in children (61%). CONCLUSION: Real world evidence to evaluate Brazilian patients' therapeutic options is unusual and yet to be more explored using digital tools enabling better data registration. The present study confirmed that metamizole is widely used as a non-anti-inflammatory drug, and also showed the management of pain and fever as the most frequent indications in all age groups studied.Registry in Clinical Trials Database: REBEC Database: 10507.

Analgesic benefit of metamizole and ibuprofen vs. either medication alone: a randomized clinical trial.

BACKGROUND: Postoperative pain relief remains a key problem after surgery. Multimodal pain therapy has proven beneficial in alleviating pain to a certain extent. However, when combining non-opioids, the focus has been on NSAIDs and paracetamol, but effects of combined use are only moderate. Metamizole could be a potent adjunct, due to its preclusion in several countries, data on its combined use are sparse, despite its common use in many countries. The aim of this study was to examine whether the combination of metamizole and ibuprofen is superior in relieving postoperative pain to either drug alone. METHODS: For this randomized, placebo-controlled, cross-over study, 35 patients undergoing bilateral lower third molar extraction were randomized. Each patient received three applications of 1000 mg metamizole + 400 mg ibuprofen for surgery on one side and either 1000 mg metamizole + placebo or 400 mg ibuprofen + placebo on the other side. Pain ratings, rescue-medication (tramadol), and sleep were assessed for 18 hours. RESULTS: The combined treatment of metamizole and ibuprofen showed lower mean pain scores over 12 hours than ibuprofen (2.4±1.3 vs 3.8±1.6; P=0.005). Further, combined treatment showed lower mean pain scores over 6 hours than ibuprofen (2.0±1.2 vs. 3.1±1.6; P=0.022) or metamizole alone (2.0±1.2 vs. 3.3±1.7; P=0.015). Consumption of rescue medication was lowest in the combination-group (25% vs. 46%-metamizole; 50%-ibuprofen). The trial was stopped prematurely as the COVID-pandemic halted elective surgeries. CONCLUSIONS: Combined use enables superior pain control compared to ibuprofen after molar extraction and tends to be superior to metamizole alone. The premature study-termination may overestimate this effect.

The antipyretic effectiveness of dipyrone in the intensive care unit: A retrospective cohort study.

INTRODUCTION: Dipyrone (metamizol) is regularly used in critical care for pain and fever treatment, especially in Germany and Spain. However, indication for antipyretic therapy in critically ill patients is currently unclear and data for both the risk and benefit of dipyrone treatment in the intensive care environment are scarce. We hypothesized that antipyretic efficiency of dipyrone would not exceed antipyretic efficiency of acetaminophen. We therefore aimed to compare temperature courses in critically ill patients receiving either intravenous dipyrone, acetaminophen or no antipyretic medication. MATERIAL AND METHODS: We included 937 intensive care unit (ICU) patients with body temperature recordings of at least 37.5°C. We investigated temperature decrease associated with dipyrone or acetaminophen and additionally compared it to an untreated control group. RESULTS: Within the eight-hour study interval, maximum body temperature decrease in patients without antipyretic medication was -0.6°C (IQR: -1.0 to -0.4°C; n = 315). Maximal decrease in body temperature was higher both with dipyrone (-0.8°C (IQR: -1.2 to -0.4°C); p = 0.016; n = 341) and acetaminophen (-0.9°C (IQR: -1.6 to -0.6°C); p<0.001; n = 71), but did not differ between dipyrone and acetaminophen (p = 0.066). As compared to untreated patients, dipyrone only led to a marginal additional decrease in body temperature of only -0.1°C. Maximum of antipyretic effectiveness was reached four hours after administration. CONCLUSION: Antipyretic effectiveness of dipyrone in ICU patients may be overestimated. Given the lack of prospective data, clinical evidence for antipyretic dipyrone therapy in the ICU is insufficient and warrants further critical evaluation.

Efficacy of metamizole versus ibuprofen and a short educational intervention versus standard care in acute and subacute low back pain: a study protocol of a randomised, multicentre, factorial trial (EMISI trial).

INTRODUCTION: Low back pain (LBP) is among the top three most common diseases worldwide, resulting in a life with pain-related disability. To date, no study has assessed the efficacy of metamizole (dipyrone), a non-opioid analgesic and antipyretic prodrug compared with the conventional non-steroidal anti-inflammatory drug ibuprofen, in patients with an acute LBP episode. Further, it is unclear, whether a short educational intervention is superior to usual care alone. OBJECTIVES: The objective of this study is to assess first, whether metamizole is non-inferior to ibuprofen in a new episode of acute or subacute LBP. Second, we aim to assess whether a short educational intervention including evidence-based patient information on the nature of LBP is superior to usual care alone. METHODS AND ANALYSIS: An investigator-initiated multicentre, randomised, double blind trial using a factorial design will be performed. A total of 120 participants with a new episode of LBP will be recruited from GP practices, outpatient clinics and from emergency departments, and randomised into four different treatment groups: ibuprofen alone, ibuprofen and short intervention, metamizole alone, metamizole and short intervention. The primary endpoint for the medical treatment will be change in pain assessed on an 11-point Numeric Rating Scale after 14 days. The primary outcome for the short intervention will be change in the Core Outcome Measures Index assessed after 42 days. ETHICS, DISSEMINATION AND FUNDING: This study has been approved by the responsible Ethics Board (Ethikkommission Bern/2018-01986) and the Swiss Agency for Therapeutic Products (Swissmedic/2019DR4002). Results will be published in open access policy peer-reviewed journals. The study is funded by the Swiss National Science Foundation (grant number 32 003B-179346). TRIAL REGISTRATION NUMBER: NCT04111315.

Cyclooxygenases 1 and 2 inhibition and analgesic efficacy of dipyrone at different doses or meloxicam in cats after ovariohysterectomy.

OBJECTIVE: To evaluate the cyclooxygenases (COX) inhibition, adverse effects and analgesic efficacy of dipyrone or meloxicam in cats undergoing elective ovariohysterectomy. STUDY DESIGN: Prospective, blinded, randomized, clinical study. ANIMALS: A total of 30 healthy young cats. METHODS: The cats were randomly assigned to three postoperative groups: D25 (dipyrone 25 mg kg-1 every 24 hours), D12.5 (dipyrone 12.5 mg kg-1 every 12 hours) and M (meloxicam 0.1 mg kg-1 every 24 hours). In the first 24 hours, the drugs were administered intravenously (IV), and then orally for 6 (dipyrone) or 3 days (meloxicam). Prostanoids thromboxane B2 and prostaglandin E2 concentrations served as indicators of COX activity and, with physiological variables and pain and sedation scores, were measured for 24 hours after first analgesic administration. Rescue analgesia (tramadol, 2 mg kg-1 IV) was provided if Glasgow feline composite measure pain scale (CMPS-Feline) ≥5. Laboratory tests included symmetric dimethylarginine and adverse effects were evaluated regularly up to 7 and 10 days after surgery, respectively. Parametric and nonparametric data were analyzed with two-way anova and Kruskal-Wallis tests, respectively (p < 0.05). RESULTS: In the first half hour after analgesic administration, COX-1 activity was close to zero and remained significantly lower than before drug administration for 24 hours in all groups. The inhibition of COX-2 activity was significant for 30 minutes in all groups and up to 4 hours in group M. No alterations in laboratory tests or significant adverse effects were observed. Pain scores and need for rescue analgesia did not differ statistically among groups. CONCLUSIONS: Dipyrone at both doses and meloxicam provided a nonselective inhibition of COX-1 and -2 activities and effective analgesia without causing significant adverse effects or laboratory tests alterations. CLINICAL RELEVANCE: Dipyrone at both doses provides equally effective analgesia without causing adverse effects in cats undergoing ovariohysterectomy.

Migraine Treatment in Emergency Departments of Brazil: A Retrospective Study of 2 Regions.

OBJECTIVE: This study describes the approaches, medications used, and time of care for migraineurs, who have been in emergency departments (ED) from 2 different regions of Brazil. METHODS: Retrospective, cross-sectional, observational, non-randomized study of migraine patients seen at 2 headache centers in Brazil. RESULTS: Eighty-four migraine patients (15 men and 69 women) were divided into 2 groups: chronic (19%, n = 16) and episodic migraineurs (81%, n = 68). In the ED, medications were used in the following order of frequency: dipyrone or metamizole (89.3%, 75/84), nonsteroidal anti-inflammatory drugs (57.1%; 48/84) opioids (51.1%; 43/84), metoclopramide (29.8%; 25/84), dexamethasone (28.6%; 24/84), chlorpromazine (13.1%; 11/84), and subcutaneous sumatriptan (7.1%; 6/84). The average time in the care center was 8.2 hours, but only 23 patients (27.4%) left the hospital with greater than 50% relief in headache severity. CONCLUSIONS: Dipyrone and nonsteroidal anti-inflammatories were the most used drugs, but nearly half received opioids. More efficient drugs were poorly used. Considering the number of patients leaving the hospital with headache relief, a changing treatment paradigm should be carried out in Brazil.

Use of metamizole as an additional analgesic during umbilical surgery in calves.

OBJECTIVE: To investigate the effect of metamizole on physiologic variables in calves undergoing surgical extirpation of the navel during anaesthesia using xylazine, ketamine and isoflurane. STUDY DESIGN: Double-blind, randomized trial. ANIMALS: A total of 26 calves. METHODS: Calves with uncomplicated umbilical hernias and otherwise clinically healthy were randomly allocated to one of two groups: the control group (CG) and metamizole group (MG). All calves were administered meloxicam (0.5 mg kg-1) intravenously (IV) 150 minutes before skin incision (SI). Animals were premedicated with xylazine (0.2 mg kg-1) intramuscularly 50 minutes before SI. Anaesthesia was induced with ketamine (2 mg kg-1) IV 30 minutes before SI and maintained with isoflurane in oxygen. MG calves were given metamizole (40 mg kg-1) IV 60 minutes before SI. CG calves were administered an equivalent volume of saline. Heart rate (HR) and mean arterial blood pressure (MAP) were recorded from 5 minutes before SI until the end of anaesthesia (60 minutes after SI). Blood samples for determination of the plasma cortisol concentration (PCC) were drawn 60 minutes before SI and at 5, 30, 60, 150, and 510 minutes after SI. RESULTS: In both groups, PCC increased during surgery and decreased after surgery. PCC was consistently lower in MG than in CG and was significantly (p = 0.0026) lower at 150 minutes after SI in the MG. Overall, the mean PCC in MG was 10.9 nmol L-1 lower than that in CG (p = 0.01). In both groups, HR decreased during anaesthesia, whereas MAP increased, albeit with no statistically significant (p > 0.05) differences between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Our study results suggest that a single preoperative dose of metamizole may have a positive impact on intra- and immediate postoperative analgesia by reducing PCC when used as an indicator of nociception.

Pain severity and analgesics use in the community-dwelling older population: a drug utilization study from Germany.

PURPOSE: Chronic pain is common in the older population and a significant public health concern. However, comprehensive studies on analgesics use in this age group from Germany are scarce. This study aims to give a comprehensive overview on the use of the most common therapeutic groups of analgesics in community-dwelling older adults from Germany. METHODS: A cross-sectional study was carried out using data from a German cohort of 2038 community-dwelling adults aged 63-89 years. Descriptive statistics and logistic regression models were applied to assess the utilization of analgesics by age, sex, pain severity, pain duration, and locations. RESULTS: One out of four study participants was suffering from high-intensity or disabling pain. Approximately half of those taking analgesics still reported to suffer from high-intensity or disabling pain. Among analgesics users, occasional non-steroidal anti-inflammatory drugs (NSAIDs) use was the most frequent pain therapy (in 43.6% of users), followed by metamizole (dipyrone) use (16.1%), regular NSAIDs use (12.9%), strong opioids use (12.7%), and weak opioids use (12.0%). In multivariate logistic regression models, higher age, higher pain severity, longer pain duration, abdominal pain, and back pain were statistically significantly associated with opioids use. Metamizole use was also statistically significantly associated with higher pain severity but inversely associated with pain duration. CONCLUSIONS: A significant number of older German adults are affected by high-intensity and disabling chronic pain despite receiving analgesics. Long-term studies are needed to compare the effectiveness and safety of different treatments for chronic pain in older adults.

Non-opioid Analgesics and the Endocannabinoid System

Non-steroidal anti-inflammatory drugs produce antinociceptive effects mainly through peripheral cyclooxygenase inhibition. In opposition to the classical non-steroidal anti-inflammatory drugs, paracetamol and dipyrone exert weak anti-inflammatory activity, their antinociceptive effects appearing to be mostly due to mechanisms other than peripheral cyclooxygenase inhibition. In this review, we classify classical non-steroidal anti-inflammatory drugs, paracetamol and dipyrone as "non-opioid analgesics" and discuss the mechanisms mediating participation of the endocannabinoid system in their antinociceptive effects. Non-opioid analgesics and their metabolites may activate cannabinoid receptors, as well as elevate endocannabinoid levels through different mechanisms: reduction of endocannabinoid degradation via fatty acid amide hydrolase and/or cyclooxygenase-2 inhibition, mobilization of arachidonic acid for the biosynthesis of endocannabinoids due to cyclooxygenase inhibition, inhibition of endocannabinoid cellular uptake directly or through the inhibition of nitric oxide synthase production, and induction of endocannabinoid release.