Thoracotomy Patients Under General Anesthesia: A Comparison on Intra-Operative Anesthetic and Analgesic Requirements, When Combined with Either Epidural Analgesia or Continuous Unilateral Paravertebral Analgesia.

BACKGROUND AND OBJECTIVE: Regional analgesia is effective for post-thoracotomy pain. The primary objective of the study is to compare the intraoperative requirement of isoflurane and fentanyl between general anaesthesia (GA) with epidural analgesia and GA with paravertebral analgesia. METHODS AND MATERIAL: A prospective observational comparative study was conducted on 56 patients undergoing open thoracotomy procedures. The patients were divided into two groups of 28 by assigning the study participants alternatively to each group: Group GAE - received thoracic epidural catheterization with GA, and Group GAP - received ultrasound guided thoracic paravertebral catheterization on the operative side with GA. Intraoperative requirement of isoflurane, fentanyl, postoperative analgesia, stress response, need of rescue analgesics and adverse effects were observed and analysed. RESULTS: 25 patients in each group were included in the data analysis. The intraoperative requirement of isoflurane (32.28 ± 1.88 vs 48.31 ± 4.34 ml; p < 0.0001) and fentanyl (128.87 ± 25.12 vs 157 ± 30.92 µg; p = 0.0009) were significantly less in the GAE group than in the GAP group. VAS scores and need of rescue analgesics and blood glucose levels were not statistically significant during the postoperative period (p > 0.05). The incidence of adverse effects was comparable except for hypotension and urinary retention which were significantly higher in the GAE group. CONCLUSION: GA with epidural analgesia resulted in significant reduction in the intraoperative consumption of isoflurane and fentanyl in comparison to GA with paravertebral analgesia. However, both the techniques were equally effective in the postoperative period.

Low-dose short infusion ketamine as adjunct to morphine for acute long bone fracture in the emergency department: a randomized controlled trial.

BACKGROUND: Ketamine is recognized as an alternative for pain management; however, concerns about emergent adverse reactions have limited its widespread adoption. This study aimed to assess the efficacy of a short infusion of low-dose ketamine (LDK) compared to intravenous morphine (MOR) as adjunctive analgesia for acute long bone fracture pain. METHODS: This single-blinded, randomized controlled trial was conducted in a single emergency department. Patients with acute long bone fractures and numerical rating scale (NRS) pain scores ≥ 6 following an initial dose of intravenous morphine were assigned to receive either a LDK (0.3 mg/kg) over 15 min or intravenous MOR at a dose of 0.1 mg/kg administered over 5 min. Throughout a 120-min observation period, patients were regularly evaluated for pain level (0-10), side effects, and the need for additional rescue analgesia. RESULTS: A total of 58 subjects participated, with 27 in the MOR group and 31 in the LDK group. Demographic variables and baseline NRS scores were comparable between the MOR (8.3 ± 1.3) and LDK (8.9 ± 1.2) groups. At 30 min, the LDK group showed a significantly greater mean reduction in NRS scores (3.1 ± 2.03) compared to the MOR group (1.8 ± 1.59) (p = 0.009). Similarly, at 60 min, there were significant differences in mean NRS score reductions (LDK 3.5 ± 2.17; MOR mean reduction = 2.4, ± 1.84) with a p-value of 0.04. No significant differences were observed at other time intervals. The incidence of dizziness was higher in the LDK group at 19.4% (p = 0.026). CONCLUSION: Short infusion low-dose ketamine, as an adjunct to morphine, is effective in reducing pain during the initial 30 to 60 min and demonstrated comparability to intravenous morphine alone in reducing pain over the subsequent 60 min for acute long bone fractures. However, it was associated with a higher incidence of dizziness. TRIAL REGISTRATION: NMRR17318438970 (2 May 2018; www.nmrr.gov.my ).

[Pharmacological pain management in cancer patients]. / Medikamentöse Schmerztherapie bei Patienten mit Tumorerkrankungen.

Pharmacological pain therapy in cancer patients is based on guideline recommendations, which, however, do not fully coincide in all aspects due to varying weighting of evidence. The present article discusses current issues including the decreasing significance of the World Health Organization (WHO) analgesic ladder, with its distinction between step 2 and 3 being increasingly questioned. Risks of nonopioid analgesics such as paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs), particularly in older populations, are discussed. Paracetamol may potentially reduce the effectiveness of immunotherapies. Aspects of administering analgesics via a feeding tube are considered. Recommendations for the treatment of episodic pain, transitioning between different opioids, and some relevant interactions are also discussed.

[Topical Use of Cannabis in Inflammatory Diseases in patients of the IPS Salud Social in Barranquilla, Colombia]. / Uso tópico de Cannabis para enfermedades inflamatorias, en pacientes de la IPS Salud Social de Barranquilla.

OBJECTIVE: To relate the topical use of cannabis as an analgesic therapeutic alternative in patients with some inflammatory diseases in Salud Social I.P.S during May to July 2023. METHODS: An analytical, retrospective study was carried out. The population from which the sample was obtained corresponds to patients diagnosed with Arthrosis, Unspecified, Non-Toxic Multinodular Goiter, Epilepsy, Unspecified Type Venous Insufficiency (Chronic) (Peripheral), Unspecified Lumbago, Secondary Gonarthrosis, Rotator Cuff Syndrome, Carpal Tunnel Syndrome, in Salud Social I.P.S of Barranquilla, Atlántico. A sample of 23 patients diagnosed with these pathologies was obtained by non-probabilistic convenience sampling. RESULTS: All patients showed pain relief after two months of follow-up, two experienced adverse effects. Some studies suggest that cannabinoids present in cannabis, such as CBD and THC, may have analgesic and anti-inflammatory properties that could alleviate pain and inflammation associated with these conditions. This is consistent with the present study. CONCLUSION: Topical cannabis is presented as a therapeutic alternative in inflammatory diseases, however, it is important to highlight that research on the use of cannabis in these diseases is limited and more studies are needed to fully understand its effects and potential benefits.

OBJETIVO: Relacionar el uso tópico de cannabis como alternativa terapéutica analgésica en pacientes con algunas enfermedades inflamatorias, de la IPS Salud Social, entre mayo y julio de 2023. MÉTODOS: Se realizó un estudio analítico, retrospectivo. La población de donde se obtuvo la muestra, corresponde a pacientes diagnosticados con Artrosis no especificada, bocio multinodular no tóxico, Epilepsia tipo no especificado, insuficiencia venosa crónica y periférica, Lumbago no especificado, gonartrosis secundaria, síndrome de manguito rotador, síndrome del túnel carpiano, de la IPS Salud Social de Barranquilla, Atlántico. Se obtuvo una muestra de 23 pacientes diagnosticados con estas patologías mediante muestreo no probabilístico por conveniencia. RESULTADOS: Todos los pacientes mostraron alivio del dolor, después de dos meses de seguimiento; dos experimentaron efectos adversos. Algunos estudios sugieren que los cannabinoides presentes en el cannabis, como el CBD y el THC, podrían tener propiedades analgésicas y antiinflamatorias que podrían aliviar el dolor y la inflamación asociados con estas afecciones, lo que es coherente con el presente estudio. CONCLUSIÓN: El cannabis tópico se presenta como una alternativa terapéutica para enfermedades inflamatorias, sin embargo, es importante destacar que la investigación sobre el uso del cannabis en estas enfermedades es limitada y se necesitan más estudios para comprender completamente sus efectos y beneficios potenciales.

The Effect of Preprocedural Low-Dose Ketamine for Pain and Anxiety in Patients during Thoracic Epidural Catheterization.

Background and Objectives: Thoracic epidural catheterization (TEC) can be both uncomfortable and fearful for patients when performed awake with the thought that the procedure may be painful. The aim of this study was to assess the effect of low-dose intravenous ketamine administration on pain and anxiety during the TEC procedure. Materials and Methods: Sixty patients were randomly divided into two groups to receive intravenous (IV) placebo (Group P) and IV low-dose (0.15 mg/kg) ketamine (LDK) (Group K) 3 min before the procedure in a double-blind manner. A visual analog scale (VAS) was used to measure anxiety (VAS-A) and pain (VAS-P) scores. Vital parameters were monitored before premedication (T1), 20 min after premedication (T2), during skin anesthesia (T3), during TEC (T4), and 5 min after TEC (T5). VAS-A values were recorded at T1, T3, T4, and T5 periods, and VAS-P levels were noted at T3, T4, and T5 periods. Results: During TEC (T4), both VAS-P and VAS-A were significantly lower in Group K (p < 0.001). The mean VAS-A value was 10.6 mm lower, and the mean VAS-P value was 9 mm lower in Group K than in Group P at the T4 time point. Additionally, the mean VAS-P value was 7.7 mm lower in Group K compared to Group P at the T3 time point (p < 0.001). Both groups showed a statistically significant difference in VAS-A measurements when compared at their respective time points (p < 0.001). However, only Group P demonstrated a statistically significant difference in VAS-P measurements (p < 0.001). VAS-P values remained stable in Group K. The number of patients who did not recall the procedure was significantly higher in Group K (p < 0.001). Furthermore, the number of patients who would consent to the same procedure in the future was significantly higher in Group K (p = 0.007). Conclusions: A preprocedural LDK (0.15 mg/kg) can effectively prevent anxiety and pain experienced by patients during the TEC procedure. Administration of LDK may provide a more comfortable procedure process without causing ketamine-induced side effects (hemodynamic, respiratory, and psychological).

High uptake of menstrual health information, products and analgesics within an integrated sexual reproductive health service for young people in Zimbabwe.

BACKGROUND: Despite being integral to women's well-being, achieving good menstrual health (MH) remains a challenge. This study examined MH services uptake (including information, analgesics, and a choice of MH products - the menstrual cup and reusable pads) and sustained use of MH products within an integrated sexual and reproductive health intervention for young people in Zimbabwe. METHODS: This mixed-methods study was nested within a cluster randomised trial of integrated sexual and reproductive health services (CHIEDZA) for youth in three provinces (Harare, Mashonaland East, and Bulawayo). The study collected qualitative and quantitative data from 27,725 female clients aged 16-24 years, who accessed CHIEDZA from April 2019 - March 2022. Using a biometric (fingerprint recognition) identification system, known as SIMPRINTS, uptake of MH information, products, and analgesics and other services was tracked for each client. Descriptive statistics and logistic regression were used to investigate MH service uptake and product choice and use over time, and the factors associated with these outcomes. Thematic analysis of focus group discussions and interviews were used to further explore providers' and participants' experiences of the MH service and CHIEDZA intervention. RESULTS: Overall, 36,991 clients accessed CHIEDZA of whom 27,725 (75%) were female. Almost all (n = 26,448; 95.4%) took up the MH service at least once: 25433 took up an MH product with the majority (23,346; 92.8%) choosing reusable pads. The uptake of cups varied across province with Bulawayo province having the highest uptake (13.4%). Clients aged 20-24 years old were more likely to choose cups than reusable pads compared with those aged 16-19 years (9.4% vs 6.0%; p < 0.001). Over the implementation period, 300/1819 (16.5%) of clients swapped from the menstrual cup to reusable pads and 83/23346 (0.4%) swapped from reusable pads to the menstrual cup. Provision of the MH service encouraged uptake of other important SRH services. Qualitative findings highlighted the provision of free integrated SRH and MH services that included a choice of MH products and analgesics in a youth-friendly environment were key to high uptake and overall female engagement with SRH services. CONCLUSIONS: High uptake demonstrates how the MH service provided much needed access to MH products and information. Integration of MH within an SRH intervention proved central to young women accessing other SRH services.

The effectiveness of parenteral agents for pain reduction in patients with migraine presenting to emergency settings: A systematic review and network analysis.

OBJECTIVES: To assess the comparative effectiveness and safety of parenteral agents for pain reduction in patients with acute migraine. BACKGROUND: Parenteral agents have been shown to be effective in treating acute migraine pain; however, the comparative effectiveness of different approaches is unclear. METHODS: Nine electronic databases and gray literature sources were searched to identify randomized clinical trials assessing parenteral agents to treat acute migraine pain in emergency settings. Two independent reviewers completed study screening, data extraction, and Cochrane risk-of-bias assessment, with differences being resolved by adjudication. The protocol of the review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42018100096). RESULTS: A total of 97 unique studies were included, with most studies reporting a high or unclear risk of bias. Monotherapy, as well as combination therapy, successfully reduced pain scores prior to discharge. They also increased the proportion of patients reporting pain relief and being pain free. Across the pain outcomes assessed, combination therapy was one of the higher ranked approaches and provided robust improvements in pain outcomes, including lowering pain scores (mean difference -3.36, 95% confidence interval [CI] -4.64 to -2.08) and increasing the proportion of patients reporting pain relief (risk ratio [RR] 2.83, 95% CI 1.74-4.61). Neuroleptics and metoclopramide also ranked high in terms of the proportion of patients reporting pain relief (neuroleptics RR 2.76, 95% CI 2.12-3.60; metoclopramide RR 2.58, 95% CI 1.90-3.49) and being pain free before emergency department discharge (neuroleptics RR 4.8, 95% CI 3.61-6.49; metoclopramide RR 4.1, 95% CI 3.02-5.44). Most parenteral agents were associated with increased adverse events, particularly combination therapy and neuroleptics. CONCLUSIONS: Various parenteral agents were found to provide effective pain relief. Considering the consistent improvements across various outcomes, combination therapy, as well as monotherapy of either metoclopramide or neuroleptics are recommended as first-line options for managing acute migraine pain. There are risks of adverse events, especially akathisia, following treatment with these agents. We recommend that a shared decision-making model be considered to effectively identify the best treatment option based on the patient's needs.

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

Introducción La pancreatitis aguda constituye uno de los principales motivos de ingreso por causa digestiva. En su manejo resulta crucial un adecuado tratamiento del dolor. Pero apenas existen descripciones sobre las pautas analgésicas empleadas en nuestro medio. Métodos Encuesta on-line sobre el manejo de analgésicos en la pancreatitis aguda, dirigida a médicos adjuntos y residentes con ejercicio en España. Resultados Un total de 209 facultativos de 88 centros respondieron la encuesta. El 90% eran especialistas en Aparato Digestivo y el 69% trabajaba en un centro terciario. La mayoría (64,4%) no utilizan habitualmente escalas para medir el dolor. Al elegir un fármaco se valora sobre todo la experiencia en su uso. Los tratamientos más prescritos inicialmente son: combinación de paracetamol y metamizol (53,5%), paracetamol solo (19,1%) y metamizol solo (17,4%). Como rescate: meperidina (54,8%), tramadol (17,8%), cloruro mórfico (17,8%) y metamizol (11,5%). Se utiliza perfusión continua en el 8,2% de los tratamientos iniciales. Los médicos con >10años de servicio utilizan más metamizol en monoterapia (50%), mientras que médicos residentes y adjuntos con <10años de servicio lo prescriben asociado a paracetamol (85%). Si se necesita progresar, se usan fundamentalmente cloruro mórfico y meperidina. La especialidad del encuestado, el tamaño del centro de trabajo y la unidad/servicio donde ingresaban los pacientes no influyeron sobre la analgesia pautada. El grado de satisfacción con el tratamiento del dolor alcanzó el 7,8/10 (DE 0,98). Conclusión En nuestro medio, el metamizol y el paracetamol son los analgésicos más empleados como tratamiento inicial del dolor en la pancreatitis aguda, y la meperidina, el analgésico de rescate más utilizado (AU)

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. (AU)

Subhypnotic Intravenous Ketamine Improves Patient Satisfaction With Burn Wound Care: A Quality Improvement Project.

Despite advancements in pain management for burn injuries, analgesia often fails to meet our patients' needs. We hypothesized that low doses of intravenous (IV) ketamine as an adjunct to our current protocol would be safe, improving both nurse and patient satisfaction with analgesia during hydrotherapy. Burn patients admitted who underwent hydrotherapy from June 1, 2021, to June 30, 2023 were surveyed. Ketamine was administered with the standard opioid-midazolam regimen. Demographics, oral morphine equivalents, midazolam, ketamine doses and time of administration, and adverse events were collected. Patient and nurse satisfaction scores were collected. The ketamine and no-ketamine groups were compared. P < .05 was considered significant. Eighty-five hydrotherapies were surveyed, 47 without ketamine, and 38 with ketamine. Demographics, comorbidities, %TBSA, and hospital length of stay were not different. The median amount of ketamine given was 0.79 mg/kg [0.59-1.06]. Patients who received ketamine were more likely to receive midazolam (100% vs 61.7%; P < .001), and both oral and IV opioids (94.7% vs 68.1%; P = .002) prior to hydrotherapy and less likely to receive rescue opioids or midazolam during hydrotherapy. Two patients in the ketamine group had hypertension (defined as SBP > 180) that did not require treatment. Nurses tended to be more satisfied with patient pain control when ketamine was used (10 [8-10] vs 9 [7-10], P = .072). Patient satisfaction was higher in the ketamine group (10 [8.8-10] vs 9 [7-10], P = .006). Utilizing subhypnotic dose of IV ketamine for hydrotherapy is safe and associated with increased patient satisfaction.

Experience from a single-center study on multimodal medication therapy for patients with complex regional pain syndrome.

BACKGROUND: Despite the application of various therapeutic methods, pain caused by complex regional pain syndrome (CRPS) is not sufficiently managed and often progresses to a chronic stage. For the systematic and effective treatment of CRPS, we developed an algorithm for multimodal medication therapy based on the established pathophysiology of CRPS to control CRPS-related pain. OBJECTIVE: In this study, we present the outcomes of our novel algorithm for multimodal medication therapy for patients with CRPS, consisting of three major components: multimodal oral medication, intravenous ketamine, and intravenous lidocaine therapy. METHODS: We retrospectively investigated patients with CRPS who received multimodal therapy. Pain severity scores were evaluated using a numerical rating scale at four time points (P1, pain at initial consultation; P2, pain after oral medication; P3, pain after ketamine treatment; and P4, pain after lidocaine treatment). The effect of the multimodal medication therapy algorithm on pain management was evaluated at each time point. RESULTS: In patients with CRPS, multimodal oral medication, intravenous ketamine, and intravenous lidocaine therapies led to significantly improved pain control (p< 0.05). Additionally, the combination of these three therapies (through the multimodal medication therapy algorithm) resulted in significant pain relief in patients with CRPS (p< 0.05). CONCLUSIONS: Our multimodal medication therapy algorithm effectively controlled pain in patients with CRPS. However, further prospective studies with large sample sizes and randomized controlled trials are needed for more accurate generalization.

Topical Nonprescription Pain Medications for Adults.

This JAMA Patient Page describes the types of topical nonprescription pain medications and tips for using them.

Implicaciones de los diferentes modelos analgésicos en los marcadores inflamatorios tras colecistectomía laparoscópica / Implications of Different Analgesic Models on Inflammatory Markers after Laparoscopic Cholecystectomy

Antecedentes: Las cirugías laparoscópicas inducen dolores de hombro y abdominales significativos, que fluctúan entre 35 y 80% de los pacientes, a pesar de sus ventajas. La causa del dolor posterior a la laparoscopia no se comprende plenamente, suponiéndose que es multifactorial y posiblemente un tipo de dolor referido. Objetivo del estudio Evaluar el efecto de los diferentes modelos analgésicos en el dolor posterior a la laparoscopia y en las modulaciones del marcador inflamatorio. Métodos Se asignó aleatoriamente a los pacientes programados para colecistectomía laparoscópica electiva, para recibir una infiltración local en la fosa hepática y el área subdiafragmática derecha con uno de los cuatro tipos de mezcla analgésica de fármacos siguientes: grupo 1 (G1) con 20 mL de bupivacaína al 0,25%; grupo 2 (G2) con 20 mL de bupivacaína al 0,25% + 3 mg de sulfato de morfina; grupo 3 (G3) con 20 mL de bupivacaína al 0,25% + 3 mg de sulfato de morfina + 200 mcg/kg de ketamina; y grupo 4 (G4) con 20 mL de solución salina isotónica como grupo control. Resultados El G3 demostró unos niveles significativamente bajos en la escala de calificación numérica oral del dolor de hombro y marcadores inflamatorios, en contraste con los tres grupos restantes. Los altos niveles de marcadores inflamatorios, estadísticamente significativos, fueron registrados en el grupo control en la comparación entre los grupos de estudio. No se documentaron efectos secundarios ni complicaciones en los cuatro grupos. Conclusión La adición de ketamina y morfina a bupivacaína para insuflado hepático y subdiafragmático produjo buena analgesia y redujo los niveles de los marcadores inflamatorios tras colecistectomía laparoscópica. (AU)

Background: Despite the advantages of laparoscopic surgeries, its induced shoulder and abdominal pain are significant, ranging from 35% to 80%. The cause of post laparoscopic pain is not fully understood and supposed to be multifactorial and possibly referred to as pain. Aim of the study Evaluate the effect of different analgesic models on post-laparoscopic pain and inflammatory markers modulation. Methods Patients scheduled for elective laparoscopic cholecystectomy randomLy assigned to receive local infiltration of the hepatic and right subdiaphragmatic fossae with one of four types of the analgesic mixture of drugs:-Group-1 (G1): 20 mL of (bupivacaine 0.25%) Group-2 (G2): 20 mL of (bupivacaine 0.25% + 3 mg of Morphine sulphate) Group-3 (G3): 20 mL of (bupivacaine 0.25% + 3 mg of Morphine sulphate + 200 microgram/kg ketamine). Group-4 (G4): 20 mL of isotonic saline as the control group. Results Group 3 demonstrated significant low VNRS of shoulder pain and significantly low levels of inflammatory marker compared with the other three groups. Highest statistically significant levels of inflammatory markers recorded in the control group among the study groups. No side effects or complications documented in the four study groups. Conclusión The addition of Ketamine and Morphine to the Bupivacaine for hepatic and subdiaphragmatic insufflation produced good analgesia and reduced the levels of inflammatory markers after Laparoscopic cholecystectomy. (AU)

Use of analgesics in professional soccer players: A systematic review

Objective: Use of painkillers appears to have become a widespread issue in the sporting environment as athletes pursue successful pain relief during competitions. We conducted a systematic review on the prevalence of analgesics use in soccer, using literature from January 1980 to July 2021. Methods: The systematic review followed PRISMA guidelines. Studies were obtained from the Cochrane Library, PubMed, Scopus, and Web of Science (WOS) databases. In total, 213 articles were found where 14 were selected. The risk of bias was assessed using the NIH scale for prevalence studies and the PEDro quality scale for randomized control trials (RCTs). Results: Less than 3% of the literature were randomized studies (n=10 observational; n=4 double-blind trials) and only 2 studies included females. At least 54% of the research subjects consumed analgesic drugs during the course of their tournaments, and nearly half of them (39-67%) did so before each match, mostly in the form of non-steroidal anti-inflammatory drugs (NSAIDs) (15% of daily use). Conclusion: Given that short-term observational studies indicated high consumption of analgesics despite limited evidence of their pain control effectiveness, the question is raised whether this potential drug abuse affects the sexes at the same rates and in the same ways. Further investigation into these specific cohorts is needed. (AU)

Oral Nonprescription Pain Medications for Adults.

This JAMA Patient Page describes the common oral nonprescription pain medications acetaminophen, aspirin, ibuprofen, and naproxen sodium.

Association of FDA Mandate Limiting Acetaminophen (Paracetamol) in Prescription Combination Opioid Products and Subsequent Hospitalizations and Acute Liver Failure.

Importance: In January 2011, the US Food and Drug Administration (FDA) announced a mandate to limit acetaminophen (paracetamol) to 325 mg/tablet in combination acetaminophen and opioid medications, with manufacturer compliance required by March 2014. Objective: To assess the odds of hospitalization and the proportion of acute liver failure (ALF) cases with acetaminophen and opioid toxicity prior to and after the mandate. Design, Setting, and Participants: This interrupted time-series analysis used hospitalization data from 2007-2019 involving ICD-9/ICD-10 codes consistent with both acetaminophen and opioid toxicity from the National Inpatient Sample (NIS), a large US hospitalization database, and ALF cases from 1998-2019 involving acetaminophen and opioid products from the Acute Liver Failure Study Group (ALFSG), a cohort of 32 US medical centers. For comparison, hospitalizations and ALF cases consistent with acetaminophen toxicity alone were extracted from the NIS and ALFSG. Exposures: Time prior to and after the FDA mandate limiting acetaminophen to 325 mg in combination acetaminophen and opioid products. Main Outcomes and Measures: Odds of hospitalization involving acetaminophen and opioid toxicity and percentage of ALF cases from acetaminophen and opioid products prior to and after the mandate. Results: In the NIS, among 474 047 585 hospitalizations from Q1 2007 through Q4 2019, there were 39 606 hospitalizations involving acetaminophen and opioid toxicity; 66.8% of cases were among women; median age, 42.2 (IQR, 28.4-54.1). In the ALFSG, from Q1 1998 through Q3 2019, there were a total of 2631 ALF cases, of which 465 involved acetaminophen and opioid toxicity; 85.4% women; median age, 39.0 (IQR, 32.0-47.0). The predicted incidence of hospitalizations 1 day prior to the FDA announcement was 12.2 cases/100 000 hospitalizations (95% CI, 11.0-13.4); by Q4 2019, it was 4.4/100 000 hospitalizations (95% CI, 4.1-4.7) (absolute difference, 7.8/100 000 [95% CI, 6.6-9.0]; P < .001). The odds of hospitalizations with acetaminophen and opioid toxicity increased 11%/y prior to the announcement (odds ratio [OR], 1.11 [95% CI, 1.06-1.15]) and decreased 11%/y after the announcement (OR, 0.89 [95% CI, 0.88-0.90]). The predicted percentage of ALF cases involving acetaminophen and opioid toxicity 1 day prior to the FDA announcement was 27.4% (95% CI, 23.3%-31.9%); by Q3 2019, it was 5.3% (95% CI, 3.1%-8.8%) (absolute difference, 21.8% [95% CI, 15.5%-32.4%]; P < .001). The percentage of ALF cases involving acetaminophen and opioid toxicity increased 7% per year prior to the announcement (OR, 1.07 [95% CI, 1.03-1.1]; P < .001) and decreased 16% per year after the announcement (OR, 0.84 [95% CI, 0.77-0.92]; P < .001). Sensitivity analyses confirmed these findings. Conclusions and Relevance: The FDA mandate limiting acetaminophen dosage to 325 mg/tablet in prescription acetaminophen and opioid products was associated with a statistically significant decrease in the yearly rate of hospitalizations and proportion per year of ALF cases involving acetaminophen and opioid toxicity.

Determination of the Dose-Response Relationship of Epidural Dexmedetomidine Combined with Ropivacaine for Labor Analgesia.

Background: The safety and efficacy of dexmedetomidine for epidural labor analgesia have been reported in numerous literatures, but the optimal dose has not been fully determined. The objective of this study was to determine the dose-response relationship of epidural dexmedetomidine (combined with ropivacaine) for labor analgesia. Methods: A total of 120 full-term laboring parturients requesting epidural labor analgesia were enrolled in the study from July 5, 2020 to September 22, 2021. The parturients were randomly assigned to receive 0, 0.1, 0.2, 0.3, 0.4 or 0.5 µg/mL dexmedetomidine combined with 0.075% ropivacaine epidurally. An effective dose was defined as numerical rating scale (NRS) pain score ≤3 at 30-minutes of epidural drug injection. The dose-response relationship of dexmedetomidine (with ropivacaine) for epidural labor analgesia was performed using probit regression. The median effective dose (ED50) and the 95% effective dose (ED95) values for epidural dexmedetomidine combined with 0.075% ropivacaine with 95% confidence intervals (CIs) were derived by interpolation. Results: The estimated values of ED50 and ED95 with 95% CIs for epidural dexmedetomidine (combined with 0.075% ropivacaine) were 0.085 (0.015 to 0.133) µg/mL and 0.357 (0.287 to 0.493) µg/mL, respectively. No differences were found among groups for sensory block level, number of parturients with Bromage score >0, total dosage of analgesics, cesarean delivery rate, fetal birth weight, Apgar score at 1-minute, Apgar score at 5-minutes and adverse effects. Compared with other groups, group dexmedetomidine 0.5 µg/mL had a longer duration of the first stage of labor. Conclusion: The ED50 and ED95 values of dexmedetomidine for epidural labor analgesia was 0.085 and 0.357 µg/mL under the conditions of this study. Dexmedetomidine is a suitable adjuvant for epidural labor analgesia.

Effectiveness of Ultrasound-Guided Canal Adductor Blockade for Chronic Pain and Functioning in Knee Osteoarthritis: A Prospective Longitudinal Observational Study.

METHODS: Seventy-seven patients with chronic knee osteoarthritis pain received ultrasound-guided ACB with 14 ml 0.25% levobupivacaine and 100 mcg clonidine. At baseline and 1 month after the blockade, we assessed maximal and minimal pain intensity in the knee using a numeric rating scale (NRS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS). The range of motion in extension and flexion (ROMext and ROMflex) and quadriceps muscle strength of both knees (QS), Timed Up and Go Test (TUG), and 30-Second Chair Stand Test (30CST) results were determined at baseline, 1 hour, 1 week, and 1 month after the blockade. RESULTS: ACB with levobupivacaine and clonidine appeared to decrease pain severity (NRSmax 8.13 to 4.2, p < 0.001 and NRSmin 3.32 to 1.40, p < 0.001). Similarly, knee ROMext decreased from 3.90 preintervention to 2.89 postintervention at 1 month, p < 0.001; ROMflex decreased from 5.70 to 3.29, p < 0.001; TUG time decreased from 3.22 to 2.93, <0.001; QS increased from 18.43 to 22.77, p < 0.001; CST increased from 8.23 to 10.74, p < 0.001. The KOOS for pain (36.40 to 58.34), symptoms (52.55 to 64.32), activities of daily living functions (ADLs, 36.36 to 60.77), and quality of life (QoL, 17.87 to 30.97) also increased, all p < 0.001. CONCLUSION: ACB appeared to decrease pain and increase ambulation. If our preliminary results are reproducible in a planned randomized controlled trial, ACB could be a useful adjunctive pain therapy in patients with disabling pain due to knee OA.

The analgesic properties of Yu-Xue-Bi tablets in the inflammatory pain mice: By the inhibition of CCL3-mediated macrophage transmigration into the spinal cord.

ETHNOPHARMACOLOGICAL RELEVANCE: Until now, inflammatory pain, especially ones with central sensitization in the spinal cord, is far from effectively treated. Yu-Xue-Bi Tablets (YXB) is a patented medicine, which has been widely applied for inflammatory pain. However, its therapeutic characteristics and mechanism remain unknown. AIM OF THE STUDY: This study is designed to evaluate the analgesic characteristics and explore the underlying mechanism of YXB in the inflammatory pain model induced by Complete Freund's Adjuvant (CFA). MATERIALS AND METHODS: The analgesic effects were measured by Von Frey test. The expression of calcitonin gene-related peptide (CGRP) was quantified by immunofluorescence. The expression of immune factors was analyzed via Luminex assay. The further quantifications of C-C Motif chemokine ligand 3 (CCL3) were verified by Enzyme-linked immunosorbent assay (ELISA). The transmigration of macrophage and activation of microglia were evaluated by immunofluorescence. Spinal injections of purified CCL3, CCR1 antagonist (J113863) and CCR5 antagonist (Maraviroc) were used to clarify roles of CCL3 assumed in the pharmacological mechanism of YXB. RESULTS: In CFA mice, YXB ameliorated the mechanical allodynia in dose and time dependent way, suppressed the central sensitization in dose dependent way. In the L5 spinal cord, YXB downregulated the expression of macrophage M1 pro-inflammatory factors TNFRI and CCL3, inhibited the transmigration of circulating macrophage and the activation of microglia. Purified CCL3 led to the transmigration of macrophage, activation of microglia, central sensitization, and mechanical allodynia in the Sham mice. Inhibitors of CCR1 and CCR5 attenuated above symptoms in CFA mice. Purified CCL3 blocked YXB mediated down regulation of CCL3, inhibition of macrophage transmigration, but not activation of microglia. CONCLUSION: YXB exerts the analgesic effects by inhibiting CCL3-mediated peripheral macrophage transmigrate into spinal cord. This study provided a novel approach for inflammatory pain treatment and new insight into the pharmacological action of YXB.