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1.
Scand J Pain ; 24(1)2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38708610

RESUMEN

OBJECTIVES: Multimodal pain management is one component in enhanced recovery after surgery protocol. Here we evaluate the efficacy of tramadol-paracetamol in acute postoperative pain and pain outcome at 12 months after spine surgery in randomized, double-blind, placebo-controlled trial. METHODS: We randomized 120 patients undergoing spine surgery to receive, for add-on pain management, two tramadol-paracetamol 37.5 mg/325 mg (n = 61) or placebo tablets (n = 59) twice a day for 5 postoperative days. In the hospital, multimodal pain management consisted of dexketoprofen and oxycodone. After discharge, patients were prescribed ibuprofen 200 mg, maximum 1,200 mg/day. Pain, analgesic use, and satisfaction with pain medication were followed up with the Brief Pain Inventory questionnaire before surgery and at 1 and 52 weeks after surgery. The primary outcome was patients' satisfaction with pain medication 1 week after surgery. RESULTS: At 1 week after surgery, patients' satisfaction with pain medication was similarly high in the two groups, 75% [interquartile range, 30%] in the placebo group and 70% [40%] in the tramadol-paracetamol group (p = 0.949) on a scale: 0% = not satisfied, 100% = totally satisfied. At 1 week, ibuprofen dose was lower in the placebo group 200 mg [1,000] compared to the tramadol-paracetamol group, 800 mg [1,600] (p = 0.016). There was no difference in the need for rescue oxycodone. Patients in the tramadol-paracetamol group had more adverse events associated with analgesics during the first postoperative week (relative risk = 1.8, 95% confidence interval, 1.2-2.6). CONCLUSION: Add-on pain treatment with tramadol-paracetamol did not enhance patients' satisfaction with early pain management after back surgery.


Asunto(s)
Acetaminofén , Analgésicos Opioides , Dolor Postoperatorio , Tramadol , Humanos , Dolor Postoperatorio/tratamiento farmacológico , Tramadol/administración & dosificación , Tramadol/uso terapéutico , Método Doble Ciego , Acetaminofén/administración & dosificación , Acetaminofén/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Satisfacción del Paciente , Oxicodona/administración & dosificación , Oxicodona/uso terapéutico , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/uso terapéutico , Adulto , Columna Vertebral/cirugía , Resultado del Tratamiento , Ibuprofeno/administración & dosificación , Ibuprofeno/uso terapéutico , Dimensión del Dolor , Anciano
2.
Dan Med J ; 71(5)2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38704838

RESUMEN

INTRODUCTION: To assess the effect of long-term isolation on the mental state of Danish youth. This study aimed to investigate trends in paracetamol overdoses among people under 18 years of age in Denmark during Covid-19 restrictions as an indicator of mental health. METHODS: All patients under the age of 18 years presenting with paracetamol overdose at one of the 18 paediatric departments in Denmark from 2016 to 2021 were included. They were identified in all Danish hospital databases using specific diagnostic codes. RESULTS: From 2016 to 2021, a total of 3,217 people under 18 years of age were admitted for paracetamol overdose. Among these, 86% (n = 2,755) were girls and 14% (n = 462) were boys. During 2020, a slight (7%) decrease in admissions was observed among both boys and girls compared with the preceding four-year mean value. In 2021, the number of overdoses among girls exceeded by 35% the former all-time high from 2016. Furthermore, the number of overdoses among girls exceeded the pre-four-year period mean value by 43%. Among boys, an 8% increase was seen from the highest ever previous value recorded in 2019 and a 23% increase compared with the previous four-year mean value. CONCLUSIONS: During the first year of restrictions, a slight decrease in paracetamol overdoses was observed, possibly associated with limited accessibility. The second year showed a considerable increase in paracetamol overdoses, which may imply an affected mental state among youth during the prolonged lockdown restrictions as seen in previous epidemics. Therefore, further studies are warranted to develop a pandemic preparedness plan to protect general mental health. FUNDING: None. TRIAL REGISTRATION: Not relevant.


Asunto(s)
Acetaminofén , Analgésicos no Narcóticos , COVID-19 , Sobredosis de Droga , Humanos , Sobredosis de Droga/epidemiología , COVID-19/epidemiología , Acetaminofén/envenenamiento , Adolescente , Femenino , Dinamarca/epidemiología , Masculino , Niño , Analgésicos no Narcóticos/envenenamiento , Preescolar , SARS-CoV-2 , Lactante
3.
Cochrane Database Syst Rev ; 5: CD012361, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695625

RESUMEN

BACKGROUND: Dexmedetomidine is a selective alpha-2 agonist with minimal impact on the haemodynamic profile. It is thought to be safer than morphine or stronger opioids, which are drugs currently used for analgesia and sedation in newborn infants. Dexmedetomidine is increasingly being used in children and infants despite not being licenced for analgesia in this group. OBJECTIVES: To determine the overall effectiveness and safety of dexmedetomidine for sedation and analgesia in newborn infants receiving mechanical ventilation compared with other non-opioids, opioids, or placebo. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and two trial registries in September 2023. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating the effectiveness of dexmedetomidine compared with other non-opioids, opioids, or placebo for sedation and analgesia in neonates (aged under four weeks) requiring mechanical ventilation. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were level of sedation and level of analgesia. Our secondary outcomes included days on mechanical ventilation, number of infants requiring additional medication for sedation or analgesia (or both), hypotension, neonatal mortality, and neurodevelopmental outcomes. We planned to use GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified no eligible studies for inclusion. We identified four ongoing studies, two of which appear to be eligible for inclusion; they will compare dexmedetomidine with fentanyl in newborn infants requiring surgery. We listed the other two studies as awaiting classification pending assessment of full reports. One study will compare dexmedetomidine with morphine in asphyxiated newborns undergoing hypothermia, and the other (mixed population, age up to three years) will evaluate dexmedetomidine versus ketamine plus dexmedetomidine for echocardiography. The planned sample size of the four studies ranges from 40 to 200 neonates. Data from these studies may provide some evidence for dexmedetomidine efficacy and safety. AUTHORS' CONCLUSIONS: Despite the increasing use of dexmedetomidine, there is insufficient evidence supporting its routine use for analgesia and sedation in newborn infants on mechanical ventilation. Furthermore, data on dexmedetomidine safety are scarce, and there are no data available on its long-term effects. Future studies should address the efficacy, safety, and long-term effects of dexmedetomidine as a single drug therapy for sedation and analgesia in newborn infants.


Asunto(s)
Dexmedetomidina , Hipnóticos y Sedantes , Respiración Artificial , Humanos , Dexmedetomidina/uso terapéutico , Dexmedetomidina/efectos adversos , Recién Nacido , Hipnóticos y Sedantes/uso terapéutico , Hipnóticos y Sedantes/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Analgésicos Opioides/uso terapéutico , Morfina/uso terapéutico , Analgesia/métodos , Analgésicos no Narcóticos/uso terapéutico
4.
Scand J Trauma Resusc Emerg Med ; 32(1): 41, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730453

RESUMEN

BACKGROUND: Despite the development of various analgesic concepts, prehospital oligoanalgesia remains very common. The present work examines prehospital analgesia by paramedics using morphine vs. nalbuphine + paracetamol. METHODS: Patients with out-of-hospital-analgesia performed by paramedics from the emergency medical services of the districts of Fulda (morphine) and Gütersloh (nalbuphine + paracetamol) were evaluated with regards to pain intensity at the beginning and the end of prehospital treatment using the Numeric-Rating-Scale for pain (NRS), sex, age, and complications. The primary endpoint was achievement of adequate analgesia, defined as NRS < 4 at hospital handover, depending on the analgesics administered (nalbuphine + paracetamol vs. morphine). Pain intensity before and after receiving analgesia using the NRS, sex, age and complications were also monitored. RESULTS: A total of 1,808 patients who received out-of-hospital-analgesia were evaluated (nalbuphine + paracetamol: 1,635 (90.4%), NRS-initial: 8.0 ± 1.4, NRS-at-handover: 3.7 ± 2.0; morphine: 173(9.6%), NRS-initial: 8.5 ± 1.1, NRS-at-handover: 5.1 ± 2.0). Factors influencing the difference in NRS were: initial pain intensity on the NRS (regression coefficient (RK): 0.7276, 95%CI: 0.6602-0.7950, p < 0.001), therapy with morphine vs. nalbuphine + paracetamol (RK: -1.2594, 95%CI: -1.5770 - -0.9418, p < 0.001) and traumatic vs. non-traumatic causes of pain (RK: -0.2952, 95%CI: -0.4879 - -0.1024, p = 0.002). Therapy with morphine (n = 34 (19.6%)) compared to nalbuphine + paracetamol (n = 796 (48.7%)) (odds ratio (OR): 0.274, 95%CI: 0.185-0.405, p < 0.001) and the initial NRS score (OR:0.827, 95%CI: 0.771-0.887, p < 0.001) reduced the odds of having an NRS < 4 at hospital handover. Complications occurred with morphine in n = 10 (5.8%) and with nalbuphine + paracetamol in n = 35 (2.1%) cases. Risk factors for complications were analgesia with morphine (OR: 2.690, 95%CI: 1.287-5.621, p = 0.008), female sex (OR: 2.024, 95%CI: 1.040-3.937, p = 0.0379), as well as age (OR: 1.018, 95%CI: 1.003-1.034, p = 0.02). CONCLUSIONS: Compared to morphine, prehospital analgesia with nalbuphine + paracetamol yields favourable effects in terms of analgesic effectiveness and a lower rate of complications and should therefore be considered in future recommendations for prehospital analgesia.


Asunto(s)
Acetaminofén , Analgésicos Opioides , Morfina , Nalbufina , Dimensión del Dolor , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Acetaminofén/uso terapéutico , Acetaminofén/administración & dosificación , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/uso terapéutico , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Servicios Médicos de Urgencia/métodos , Morfina/administración & dosificación , Morfina/uso terapéutico , Nalbufina/administración & dosificación , Nalbufina/uso terapéutico , Manejo del Dolor/métodos , Paramédico
5.
J Pak Med Assoc ; 74(5): 857-861, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38783430

RESUMEN

Objectives: To compare the effects of bupivacaine alone and in combination with dexmedetomidine following staging laparoscopies. METHODS: This triple-blinded, prospective study was conducted from June to September 2021 at a tertiary care cancer hospital in Lahore, Pakistan, and comprised adult patients having American Society of Anaesthesiologists grade I-III, weighing >30kg and undergoing diagnostic staging laparoscopy. The subjects were randomised into two equal groups. Group A received 6ml of 2mg/kg bupivacaine at each of the four laparoscopic port sites before skin closure, while group B additionally received 2µg/kg dexmedetomidine. The presence and severity of pain were recorded and assessed at 15 min, 1, 2 and 4 hours as well as at the time of discharge from the post-anaesthesia care unit. The time to first request for rescue analgesia, total morphine consumption, and the occurrence of any side effects during their stay were also recorded. Data was analysed using SPSS 23. RESULTS: Of the 30 patients, 15(50%) were in group A; 10(66.6%) males and 5(33.3%) females with mean age 43.27±7.59 years. There were 15(50%) patients in group B; 12(80%) males and 3(20%) females with mean age 41.36±12.42 years (p>0.05). Of the total, 29(96.66%) patients were classified as American Society of Anaesthesiologists grade II, and 1(3.33%) patient in group A was grade III. There was no significant difference between the groups in any of the outcome measures assessed (p>0.05), and none of the patients experienced any side effect throughout the post-operative stay. CONCLUSIONS: The combination of dexmedetomidine and bupivacaine had no significant improvement in pain relief compared to bupivacaine alone.


Asunto(s)
Anestésicos Locales , Bupivacaína , Dexmedetomidina , Laparoscopía , Dolor Postoperatorio , Humanos , Bupivacaína/administración & dosificación , Femenino , Masculino , Laparoscopía/métodos , Anestésicos Locales/administración & dosificación , Anestésicos Locales/uso terapéutico , Adulto , Dexmedetomidina/administración & dosificación , Dexmedetomidina/uso terapéutico , Persona de Mediana Edad , Estudios Prospectivos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/diagnóstico , Dimensión del Dolor , Pakistán , Analgésicos no Narcóticos/uso terapéutico , Analgésicos no Narcóticos/administración & dosificación , Estadificación de Neoplasias
7.
Minerva Anestesiol ; 90(5): 427-438, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38771166

RESUMEN

INTRODUCTION: Peripheral nerve block, a common technique for managing postoperative pain and providing intraoperative analgesia, often includes adjuncts like dexmedetomidine (DEX) to enhance the effectiveness of local anesthetics. DEX, known for its α2-adrenoceptor agonist properties, extends sensory blockade and improves postoperative analgesia while offering sedative benefits. The objective of this study is to rigorously assess the effectiveness and safety of perineural DEX injection in orthopedic nerve block procedures, focusing on orthopedic surgeries to minimize heterogeneity and provide clearer insights for clinical practice. EVIDENCE ACQUISITION: This meta-analysis, registered on PROSPERO, involved a comprehensive literature search across multiple databases, focusing on RCTs comparing DEX with local anesthetics for peripheral nerve blocks in orthopedic surgery patients. The eligibility criteria included adult participants and various nerve block methods in orthopedic surgeries. Studies were rigorously appraised for methodological quality using Cochrane Handbook guidelines. GRADE profiler 3.6 was used for evidence grading. EVIDENCE SYNTHESIS: Among 1391 documents, 21 studies were included, focusing on DEX with local anesthetics in orthopedic nerve blocks. Findings showed significant improvements in analgesia duration, sensory and motor block duration, and reduced postoperative opioid consumption, with an increased risk of bradycardia. Quality assessments indicated moderate bias risk. CONCLUSIONS: DEX with local anesthetics significantly enhances nerve block effectiveness, extending analgesia and block durations while reducing opioid need. However, it requires careful monitoring due to increased bradycardia risk. These findings highlight the need for cautious use in clinical practice, considering both potential benefits and adverse effects.


Asunto(s)
Anestésicos Locales , Dexmedetomidina , Bloqueo Nervioso , Procedimientos Ortopédicos , Dexmedetomidina/uso terapéutico , Humanos , Bloqueo Nervioso/métodos , Anestésicos Locales/uso terapéutico , Analgésicos no Narcóticos/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Resultado del Tratamiento
9.
BMJ Case Rep ; 17(4)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38688576

RESUMEN

This case describes a rare occurrence of high anion gap metabolic acidosis due to chronic acetaminophen (paracetamol) usage, which can be confirmed by measuring 5-oxoproline (pyroglutamate), an organic acid metabolite. As acetaminophen is an extremely common drug prescribed in both inpatient and outpatient settings, a high degree of clinical suspicion is required to isolate it as the aetiology for metabolic acidosis. Management includes discontinuation of acetaminophen use and at times the supplementation of oral bicarbonate. Metabolic acidosis due to a high anion gap is commonly described by the mnemonic 'MUDPILES' in daily practice. A newer mnemonic, 'GOLD MARK' is proposed to be a more inclusive tool to assist in determining the cause of high anion gap metabolic acidosis, especially with such cases being reported.


Asunto(s)
Acetaminofén , Acidosis , Analgésicos no Narcóticos , Humanos , Acetaminofén/efectos adversos , Acidosis/inducido químicamente , Analgésicos no Narcóticos/efectos adversos , Masculino , Femenino , Equilibrio Ácido-Base/efectos de los fármacos , Ácido Pirrolidona Carboxílico
10.
J Robot Surg ; 18(1): 182, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38668935

RESUMEN

To compare the in-hospital opioid and non-opioid analgesic use among women who underwent robotic-assisted hysterectomy (RH) vs. open (OH), vaginal (VH), or laparoscopic hysterectomy (LH). Records of women in the United States who underwent hysterectomy for benign gynecologic disease were extracted from the Premier Healthcare Database (2013-2019). Propensity score methods were used to create three 1:1 matched cohorts stratified in inpatients [RH vs. OH (N = 16,821 pairs), RH vs. VH (N = 6149), RH vs. LH (N = 11,250)] and outpatients [RH vs. OH (N = 3139), RH vs. VH (N = 29,954), RH vs. LH (N = 85,040)]. Opioid doses were converted to morphine milligram equivalents (MME). Within matched cohorts, opioid and non-opioid analgesic use was compared. On the day of surgery, the percentage of patients who received opioids differed only for outpatients who underwent RH vs. LH or VH (maximum difference = 1%; p < 0.001). RH was associated with lower total doses of opioids in all matched cohorts (each p < 0.001), with the largest difference observed between RH and OH: median (IQR) of 47.5 (25.0-90.0) vs. 82.5 (36.0-137.0) MME among inpatients and 39.3 (19.5-66.0) vs. 60.0 (35.0-113.3) among outpatients. After the day of surgery, fewer inpatients who underwent RH received opioids vs. OH (78.7 vs. 87.5%; p < 0.001) or LH (78.6 vs. 80.6%; p < 0.001). The median MME was lower for RH (15.0; 7.5-33.5) versus OH (22.5; 15.0-55.0; p < 0.001). Minor differences were observed for non-opioid analgesics. RH was associated with lower in-hospital opioid use than OH, whereas the same magnitude of difference was not observed for RH vs. LH or VH.


Asunto(s)
Analgésicos Opioides , Histerectomía , Dolor Postoperatorio , Procedimientos Quirúrgicos Robotizados , Humanos , Femenino , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/administración & dosificación , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricos , Histerectomía/métodos , Estados Unidos , Persona de Mediana Edad , Dolor Postoperatorio/tratamiento farmacológico , Adulto , Enfermedades de los Genitales Femeninos/cirugía , Enfermedades de los Genitales Femeninos/tratamiento farmacológico , Analgésicos no Narcóticos/uso terapéutico , Analgésicos no Narcóticos/administración & dosificación , Laparoscopía/métodos , Laparoscopía/estadística & datos numéricos , Puntaje de Propensión
11.
Swiss Med Wkly ; 154: 3535, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38579298

RESUMEN

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.


Asunto(s)
Analgésicos no Narcóticos , Humanos , Anciano , Adulto , Persona de Mediana Edad , Dipirona/uso terapéutico , Acetaminofén/uso terapéutico , Suiza , Ibuprofeno/uso terapéutico , Diclofenaco/uso terapéutico , Estudios Retrospectivos , Antiinflamatorios no Esteroideos/uso terapéutico , Analgésicos Opioides , Seguro de Salud
12.
JAAPA ; 37(5): 22-27, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38595172

RESUMEN

ABSTRACT: Acute liver failure, commonly caused by acetaminophen overdose, is associated with numerous systemic complications including cerebral edema, hypotension, acute kidney injury, and infection. Management is primarily supportive, with an emphasis on excellent neurocritical care. Although some antidotes and targeted treatments exist, the only definitive treatment remains orthotopic liver transplant.


Asunto(s)
Acetaminofén , Fallo Hepático Agudo , Trasplante de Hígado , Humanos , Fallo Hepático Agudo/terapia , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/diagnóstico , Acetaminofén/efectos adversos , Sobredosis de Droga/terapia , Edema Encefálico/etiología , Edema Encefálico/terapia , Analgésicos no Narcóticos/efectos adversos , Lesión Renal Aguda/terapia , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/etiología , Lesión Renal Aguda/diagnóstico , Antídotos
13.
Zool Res ; 45(3): 478-491, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38682430

RESUMEN

Acetaminophen (APAP), the most frequently used mild analgesic and antipyretic drug worldwide, is implicated in causing 46% of all acute liver failures in the USA and between 40% and 70% in Europe. The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine (NAC); however, its efficacy is limited in cases of advanced liver injury or when administered at a late stage. In the current study, we discovered that treatment with a moderate intensity static magnetic field (SMF) notably reduced the mortality rate in mice subjected to high-dose APAP from 40% to 0%, proving effective at both the initial liver injury stage and the subsequent recovery stage. During the early phase of liver injury, SMF markedly reduced APAP-induced oxidative stress, free radicals, and liver damage, resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione (GSH). During the later stage of liver recovery, application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation. Moreover, the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery, even 24 h post overdose, when the effectiveness of NAC alone substantially declines. Overall, this study provides a non-invasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose. Of note, this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP, and potentially other toxic overdoses.


Asunto(s)
Acetaminofén , Analgésicos no Narcóticos , Enfermedad Hepática Inducida por Sustancias y Drogas , Sobredosis de Droga , Acetaminofén/toxicidad , Animales , Ratones , Analgésicos no Narcóticos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Masculino , Campos Magnéticos , Acetilcisteína/uso terapéutico , Acetilcisteína/farmacología
15.
Mol Biol Rep ; 51(1): 548, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38642142

RESUMEN

INTRODUCTION: Paracetamol (acetaminophen) overdose is a leading cause of acute liver failure in many Western countries. Diagnostic tools for this poisoning may be suboptimal in some cases and new biomarkers have been investigated. We investigated the role of capillary microRNA-122 (miR-122) as a prognostic biomarker of liver injury in the clinical management of patients with paracetamol overdose. METHODS: In a paracetamol overdose patient cohort, miR-122 was measured by quantitative polymerase chain reaction in a blood drop obtained by a finger prick at the end of an antidote cycle treatment with N-acetylcysteine treatment (12 h). Liver injury was defined as serum alanine aminotransferase (ALT) activity > 100 IU/L collected at 10 or 20 h after the start of treatment. Pearson's correlation analyses were performed. RESULTS: In patients with paracetamol overdose, capillary miR-122 was positively correlated with ALT measured at 10 h and at 20 h (r = 0.83, P < 0.0001; r = 0.96, P < 0.0001, respectively). CONCLUSION: This work supports the potential use of capillary miR-122 as a prognostic biomarker of liver injury throughout clinical management of patients with paracetamol overdose. Capillary miR-122 can be measured in a blood drop collected by a finger prick, a minimally invasive diagnostic test for patient stratification.


Asunto(s)
Analgésicos no Narcóticos , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Enfermedad Hepática Inducida por Sustancias y Drogas , MicroARNs , Humanos , Acetaminofén/efectos adversos , Biomarcadores , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , MicroARNs/sangre , MicroARNs/genética , Pronóstico , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/diagnóstico , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/genética
17.
Crit Care ; 28(1): 143, 2024 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-38689310

RESUMEN

BACKGROUND: To determine whether intermittent intravenous (IV) paracetamol as primary analgesic would significantly reduce morphine consumption in children aged 0-3 years after cardiac surgery with cardiopulmonary bypass. METHODS: Multi-center, randomized, double-blinded, controlled trial in four level-3 Pediatric Intensive Care Units (PICU) in the Netherlands and Belgium. Inclusion period; March 2016-July 2020. Children aged 0-3 years, undergoing cardiac surgery with cardiopulmonary bypass were eligible. Patients were randomized to continuous morphine or intermittent IV paracetamol as primary analgesic after a loading dose of 100 mcg/kg morphine was administered at the end of surgery. Rescue morphine was given if numeric rating scale (NRS) pain scores exceeded predetermined cutoff values. Primary outcome was median weight-adjusted cumulative morphine dose in mcg/kg in the first 48 h postoperative. For the comparison of the primary outcome between groups, the nonparametric Van Elteren test with stratification by center was used. For comparison of the proportion of patients with one or more NRS pain scores of 4 and higher between the two groups, a non-inferiority analysis was performed using a non-inferiority margin of 20%. RESULTS: In total, 828 were screened and finally 208 patients were included; parents of 315 patients did not give consent and 305 were excluded for various reasons. Fourteen of the enrolled 208 children were withdrawn from the study before start of study medication leaving 194 patients for final analysis. One hundred and two patients received intermittent IV paracetamol, 106 received continuous morphine. The median weight-adjusted cumulative morphine consumption in the first 48 h postoperative in the IV paracetamol group was 5 times lower (79%) than that in the morphine group (median, 145.0 (IQR, 115.0-432.5) mcg/kg vs 692.6 (IQR, 532.7-856.1) mcg/kg; P < 0.001). The rescue morphine consumption was similar between the groups (p = 0.38). Non-inferiority of IV paracetamol administration in terms of NRS pain scores was proven; difference in proportion - 3.1% (95% CI - 16.6-10.3%). CONCLUSIONS: In children aged 0-3 years undergoing cardiac surgery, use of intermittent IV paracetamol reduces the median weight-adjusted cumulative morphine consumption in the first 48 h after surgery by 79% with equal pain relief showing equipoise for IV paracetamol as primary analgesic. Trial Registration Clinicaltrials.gov, Identifier: NCT05853263; EudraCT Number: 2015-001835-20.


Asunto(s)
Acetaminofén , Morfina , Humanos , Morfina/uso terapéutico , Morfina/administración & dosificación , Acetaminofén/uso terapéutico , Acetaminofén/administración & dosificación , Masculino , Femenino , Lactante , Método Doble Ciego , Dolor Postoperatorio/tratamiento farmacológico , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Bélgica , Países Bajos , Recién Nacido , Administración Intravenosa , Procedimientos Quirúrgicos Cardíacos/métodos , Preescolar , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/uso terapéutico , Unidades de Cuidado Intensivo Pediátrico/organización & administración , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Dimensión del Dolor/métodos
18.
Toxicology ; 504: 153804, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38614205

RESUMEN

Fifty percent of all acute liver failure (ALF) cases in the United States are due to acetaminophen (APAP) overdose. Assessment of canonical features of liver injury, such as plasma alanine aminotransferase activities are poor predictors of acute liver failure (ALF), suggesting the involvement of additional mechanisms independent of hepatocyte death. Previous work demonstrated a severe overdose of APAP results in impaired regeneration, the induction of senescence by p21, and increased mortality. We hypothesized that a discrete population of p21+ hepatocytes acquired a secretory phenotype that directly impedes liver recovery after a severe APAP overdose. Leveraging in-house human APAP explant liver and publicly available single-nuclei RNAseq data, we identified a subpopulation of p21+ hepatocytes enriched in a unique secretome of factors, such as CXCL14. Spatial transcriptomics in the mouse model of APAP overdose confirmed the presence of a p21+ hepatocyte population that directly surrounded the necrotic areas. In both male and female mice, we found a dose-dependent induction of p21 and persistent circulating levels of the p21-specific constituent, CXCL14, in the plasma after a severe APAP overdose. In parallel experiments, we targeted either the putative senescent hepatocytes with the senolytic drugs, dasatinib and quercetin, or CXCL14 with a neutralizing antibody. We found that targeting CXCL14 greatly enhanced liver recovery after APAP-induced liver injury, while targeting senescent hepatocytes had no effect. These data support the conclusion that the sustained induction of p21 in hepatocytes with persistent CXCL14 secretion are critical mechanistic events leading to ALF in mice and human patients.


Asunto(s)
Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas , Quimiocinas CXC , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Hepatocitos , Ratones Endogámicos C57BL , Acetaminofén/toxicidad , Animales , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Masculino , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Femenino , Ratones , Quimiocinas CXC/metabolismo , Quimiocinas CXC/genética , Regeneración Hepática/efectos de los fármacos , Sobredosis de Droga , Analgésicos no Narcóticos/toxicidad
19.
Am J Obstet Gynecol MFM ; 6(5): 101372, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38583715

RESUMEN

BACKGROUND: Scheduled administration of analgesics was proven superior to on-demand dosing following cesarean deliveries. However, this protocol was not compared after vaginal delivery. OBJECTIVE: To compare the efficacy of a fixed- vs on-demand analgesic protocol for the management of pain in the first 24 hours after a vaginal delivery. STUDY DESIGN: This randomized, prospective, controlled trial was conducted at a single tertiary medical center between June 1, 2020 and June 30, 2022. Vaginally delivered patients were randomly assigned to receive oral analgesics (paracetamol 1 g + ibuprofen 400 mg) either every 6 hours for the first 24 hours postpartum (scheduled analgesia group) or as needed (on-demand group). Pain level during the first 24 hours postdelivery was measured using a 10-point visual analog scale. RESULTS: A total of 200 patients were randomized 1:1 to the 2 cohorts. Baseline and delivery characteristics, including oxytocin augmentation, epidural anesthesia, episiotomy rate, and neonatal birthweight, were comparable between groups. Patients in the scheduled group received more paracetamol and ibuprofen doses in the first 24 hours (2.9±1.3 and 2.9±1.2 doses vs 0.8±1.1 and 0.7±1.1 doses, respectively; P<.001). Pain score was comparable between study groups (5.31±1.92 vs 5.29±1.67; P=.626) even after subanalysis for primiparity, episiotomy, and vacuum-assisted delivery (P>.05). However, patients on a fixed treatment schedule were more likely to breastfeed their baby (98% vs 88%; P=.006) as than those receiving treatment on demand. In addition, they were more satisfied with their labor and delivery experience, as evaluated by Birth Satisfaction Scale questionnaires quality control (37.9±4.7 vs 31.1±5.2; P=.0324), patient attributes (35.0±5.1 vs 30.3±6.3; P=.0453), and stress experienced (58.1±8.5 vs 50.1±8.3; P=.0398). No side effects or adverse outcomes were reported in either group. CONCLUSION: A scheduled analgesic protocol for postpartum pain management following vaginal delivery revealed similar pain scores compared with an on-demand protocol, although it was associated with higher breastfeeding rates and higher maternal satisfaction.


Asunto(s)
Acetaminofén , Parto Obstétrico , Ibuprofeno , Dimensión del Dolor , Humanos , Femenino , Adulto , Embarazo , Acetaminofén/administración & dosificación , Ibuprofeno/administración & dosificación , Ibuprofeno/efectos adversos , Parto Obstétrico/métodos , Parto Obstétrico/estadística & datos numéricos , Administración Oral , Estudios Prospectivos , Dimensión del Dolor/métodos , Analgésicos no Narcóticos/administración & dosificación , Esquema de Medicación , Manejo del Dolor/métodos , Analgesia Obstétrica/métodos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/diagnóstico , Satisfacción del Paciente
20.
Ann Ital Chir ; 95(2): 200-205, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38684499

RESUMEN

OBJECTIVE: To investigate the effect of percutaneous balloon compression combined with carbamazepine on patients with Trigeminal Neuralgia (TN). METHODS: The clinical data of 126 patients with TN admitted to our hospital from January, 2021 to January, 2022 were retrospectively analyzed. All patients underwent percutaneous balloon compression in our hospital. The patients were divided into a control group and an observation group, according to whether they continued to take carbamazepine after surgery. The general demographic data of patients, such as gender, age, family income, education level, pain site, diseased nerve, course of disease, and duration of pain were collected. Propensity score matching was used to balance the baseline data of the two groups, and the quality of life, treatment effect, and complications of the two groups were compared after matching. RESULTS: After treatment, the total effective rate of the observation group (95.00%) was higher than that of the control group (70.00%) (p < 0.05). Before treatment, there were no significant differences in the scores for quality of life dimensions between the two groups (p > 0.05). After treatment, the scores for each quality of life dimension in the observation group were higher than those in the control group. After treatment, the incidence of complications in the observation group (7.50%) was lower than that in the control group (30.00%) (p < 0.05). CONCLUSIONS: Percutaneous balloon compression combined with carbamazepine can effectively enhance the treatment of patients by improving their quality of life and reducing the occurrence of complications. These results can improve the clinical management of TN.


Asunto(s)
Analgésicos no Narcóticos , Carbamazepina , Neuralgia del Trigémino , Humanos , Neuralgia del Trigémino/tratamiento farmacológico , Neuralgia del Trigémino/terapia , Carbamazepina/uso terapéutico , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , Anciano , Analgésicos no Narcóticos/uso terapéutico , Calidad de Vida , Terapia Combinada
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