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1.
Notas enferm. (Córdoba) ; 25(43): 34-43, jun.2024.
Artigo em Espanhol | LILACS, BDENF - Enfermagem, UNISALUD, InstitutionalDB, BINACIS | ID: biblio-1561186

RESUMO

Introducción: en la unidad de cuidados intensivos (UCI), las personas asistidas con patologías relevantes se encuentran bajo sedación, una vez que estas se encuentran bajo los principios de supresión de la sedación, es importante identificar cuáles son las manifestaciones que presentan, propias de las sedaciones. Objetivo: describir las manifestaciones clínicas del síndrome de supresión de la sedoanalgesia presentes en pacientes asistidos en un Hospital Público de la Ciudad de Corrientes de enero a diciembre del 2022. Metodología: estudio cuantitativo, descriptivo, transversal y observacional. La muestra incluyó pacientes adultos de UCI. El cálculo del tamaño muestral se realizó a través del método probabilístico aleatorio simple resultando de éste una muestra de 100 historias clínicas. Para la recolección de datos se utilizó la observación y como instrumento un formulario semiestructurado, de carácter anónimo. Cada formulario contenía datos específicos donde se categorizan las variables en estudio como ser edad, sexo, comorbilidades, tiempo de sedoanalgesia, tipo de sedación, sedoanalgesia utilizada, agitación, confusión, alucinación, diaforesis, taquicardia. Resultados: en cuanto a la edad se obtuvo un promedio de 49 años, el sexo predominante fue el masculino con 52%, en cuanto a las comorbilidades más frecuentes, el 20% presentó Insuficiencia Respiratoria Aguda y el 16% Insuficiencia renal. El motivo de ingreso a UCI en mayor medida con el 33% fue por dificultad respiratoria y Post Quirúrgicos complicados 32%. Los fármacos de mayor elección fueron midazolam 94%, seguido del fentanilo 80%. En cuanto al tiempo de sedación de los pacientes, se encontró una media de 1265 horas. Las manifestaciones clínicas que se observaron en la muestra en mayor medida corresponden a taquicardia 70%, agitación 52%, un 37% confusión e hipertensión y un 24% alucinación. Conclusión: las manifestaciones que se presentaron con mayor frecuencia fueron taquicardia, agitación, confusión, hipertensión y con menor frecuencia alucinación[AU]


Introduction: in the intensive care unit (ICU), people treated with relevant pathologies are under sedation. Once they are under the principles of sedation suppression, it is important to identify the manifestations they present, typical of sedations. Objective: To describe the clinical manifestations of sedation suppression syndrome present in patients treated at a Public Hospital in the City of Corrientes from January to December 2022. Methodology: quantitative, descriptive, cross-sectional and observational study. The sample included adult ICU patients. The calculation of the sample size was carried out through the simple random probabilistic method, resulting in a sample of 100 medical records. Manifestaciones clínicas post supresión de sedoanalgesia en pacientes adultos de una terapia intensiva. Observation was used to collect data and a semi-structured, anonymous form was used as an instrument. Each form contained specific data where the variables under study were categorized, such as age, sex, comorbidities, sedation time, type of sedation, sedation used, agitation, confusion, hallucination, diaphoresis, tachycardia. Results: regarding age, an average of 49 years was obtained, the predominant sex was male with 52%, regarding the most frequent comorbidities, 20% presented Acute Respiratory Failure and 16% Renal failure. The reason for admission to the ICU to a greater extent with 33% was due to respiratory difficulty and complicated Post-Surgeries 32%. The drugs of greatest choice were midazolam 94%, followed by fentanyl 80%. Regarding the sedation time of the patients, an average of 1265 hours was found. The clinical manifestations that were observed in the sample to a greater extent correspond to tachycardia 70%, agitation 52%, confusion and hypertension 37% and hallucination 24%. Conclusion: the manifestations that occurred most frequently were tachycardia, agitation, confusion, hypertension and, less frequently, hallucination[AU]


Introdução: na unidade de terapia intensiva (UTI), as pessoas tratadas com patologias relevantes estão sob sedação. Uma vez sob os princípios da supressão da sedação, é importante identificar as manifestações que apresentam, típicas das sedações. Objetivo: Descrever as manifestações clínicas da síndrome de supressão da sedação presentes em pacientes atendidos em um Hospital Público da Cidade de Corrientes no período de janeiro a dezembro de 2022. Metodologia: estudo quantitativo, descritivo, transversal e observacional. A amostra incluiu pacientes adultos internados em UTI. O cálculo do tamanho amostral foi realizado pelo método probabilístico aleatório simples, resultando em uma amostra de 100 prontuários. A observação foi utilizada para a coleta de dados e um formulário semiestruturado e anônimo foi utilizado como instrumento. Cada formulário continha dados específicos onde foram categorizadas as variáveis em estudo, como idade, sexo, comorbidades, tempo de sedação, tipo de sedação, sedação utilizada, agitação, confusão, alucinação, sudorese, taquicardia. Resultados: em relação à idade obteve-se uma média de 49 anos, o sexo predominante foi o masculino com 52%, quanto às comorbidades mais frequentes, 20% apresentavam Insuficiência Respiratória Aguda e 16% Insuficiência Renal. O motivo de internação na UTI em maior proporção com 33% foi por dificuldade respiratória e pós-cirúrgicos complicados 32%. Os medicamentos de maior escolha foram midazolam 94%, seguido de fentanil 80%. Quanto ao tempo de sedação dos pacientes, foi encontrada uma média de 1265 horas. As manifestações clínicas mais observadas na amostra correspondem a taquicardia 70%, agitação 52%, confusão e hipertensão 37% e alucinação 24%. Conclusão: as manifestações que ocorreram com maior frequência foram taquicardia, agitação, confusão, hipertensão e, menos frequentemente, alucinação[AU]


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Midazolam/uso terapêutico , Fentanila/uso terapêutico
2.
BMC Anesthesiol ; 24(1): 223, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965492

RESUMO

BACKGROUND: This study investigated the optimal concentration of ropivacaine epidural anesthesia for clinical use in percutaneous transforaminal endoscopic discectomy (PTED) by comparing the effects of different concentrations. METHODS: Seventy patients scheduled for their first PTED procedure were enrolled in this randomized controlled trial. Patients were randomized to receive ropivacaine at varying concentrations (0.3% or 0.4%). Primary outcome measures included the numeric rating scale (NRS) and hip extension level (HEL). Secondary outcome measures included intraoperative fentanyl dosage and postoperative complications. RESULTS: One patient withdrew due to severe postoperative complications. The remaining 69 patients were allocated to the 0.3% (n = 34) and 0.4% (n = 35) groups, respectively. Baseline characteristics showed no significant differences between the two groups (P > 0.05). The NRS score was significantly lower in the 0.4% group than in the 0.3% group (P < 0.01), whereas the HEL score was significantly higher (P < 0.001). The average fentanyl dose in the 0.4% group was significantly lower than that in the 0.3% group (P < 0.01). Postoperative complications occurred in five and two patients in the 0.3% and 0.4% groups, respectively. CONCLUSION: Although 0.4% ropivacaine (20 mL) impacts muscle strength, it does not impede PTED surgery. Given its effective analgesic properties and few postoperative complications, 0.4% ropivacaine can be considered a preferred dose for PTED. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trials Registry (Registration number: ChiCTR2200060364; Registration Date: 29/5/2022) and on chictr.org.cn ( https://www.chictr.org.cn/showproj.html?proj=171002 ).


Assuntos
Anestesia Epidural , Anestésicos Locais , Ropivacaina , Humanos , Ropivacaina/administração & dosagem , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Anestésicos Locais/administração & dosagem , Anestesia Epidural/métodos , Discotomia Percutânea/métodos , Fentanila/administração & dosagem , Endoscopia/métodos , Relação Dose-Resposta a Droga , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico
3.
MMWR Morb Mortal Wkly Rep ; 73(26): 594-599, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38959171

RESUMO

Xylazine has been increasingly detected in illegally manufactured fentanyl (IMF) products and overdose deaths in the United States; most xylazine-involved overdose deaths involve IMF. A convenience sample of U.S. adults aged ≥18 years was identified from those evaluated for substance use treatment during July 2022-September 2023. Data were collected using the Addiction Severity Index-Multimedia Version clinical assessment tool. Among 43,947 adults, 6,415 (14.6%) reported IMF or heroin as their primary lifetime substance-use problem; 5,344 (12.2%) reported recent (i.e., past-30-day) IMF or heroin use. Among adults reporting IMF or heroin as their primary lifetime substance-use problem, 817 (12.7%) reported ever using xylazine. Among adults reporting recent IMF or heroin use, 443 (8.3%) reported recent xylazine use. Among adults reporting IMF or heroin use recently or as their primary lifetime substance-use problem, those reporting xylazine use reported a median of two past nonfatal overdoses from any drug compared with a median of one overdose among those who did not report xylazine use; as well, higher percentages of persons who reported xylazine use reported other recent substance use and polysubstance use. Provision of nonjudgmental care and services, including naloxone, wound care, and linkage to and retention of persons in effective substance use treatment, might reduce harms including overdose among persons reporting xylazine use.


Assuntos
Usuários de Drogas , Fentanila , Centros de Tratamento de Abuso de Substâncias , Xilazina , Adulto , Centros de Tratamento de Abuso de Substâncias/estatística & dados numéricos , Fentanila/química , Usuários de Drogas/estatística & dados numéricos , Overdose de Drogas/epidemiologia , Overdose de Drogas/prevenção & controle , Estudos Transversais , Dependência de Heroína , Humanos , Masculino , Feminino , Estados Unidos/epidemiologia
4.
PLoS One ; 19(7): e0306395, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38980856

RESUMO

We conduct this research with a two-fold aim: providing a quantitative analysis of the opioid epidemic in the United States (U.S.), and exploring the impact of the COVID-19 pandemic on opioid-related mortality. The duration and persistence of the opioid epidemic lends itself to the need for an overarching analysis with extensive scope. Additionally, studying the ramifications of these concurrent severe public health crises is vital for informing policies to avoid preventable mortality. Using data from CDC WONDER, we consider opioid-related deaths grouped by Census Region spanning January 1999 to October 2022 inclusive, and later add on a demographic component with gender-stratification. Through the lens of key events in the opioid epidemic, we build an interrupted time series model to reveal statistically significant drivers of opioid-related mortality. We then employ a counterfactual to approximate trends in the absence of COVID-19, and estimate excess opioid-related deaths (defined as observed opioid-related deaths minus projected opioid-related deaths) associated with the pandemic. According to our model, the proliferation of fentanyl contributed to sustained increases in opioid-related death rates across three of the four U.S. census regions, corroborating existing knowledge in the field. Critically, each region has an immediate increase to its opioid-related monthly death rate of at least 0.31 deaths per 100,000 persons at the start of the pandemic, highlighting the nationwide knock-on effects of COVID-19. There are consistent positive deviations from the expected monthly opioid-related death rate and a sizable burden from cumulative excess opioid-related deaths, surpassing 60,000 additional deaths nationally from March 2020 to October 2022, ∼70% of which were male. These results suggest that robust, multi-faceted measures are even more important in light of the COVID-19 pandemic to prevent overdoses and educate users on the risks associated with potent synthetic opioids such as fentanyl.


Assuntos
COVID-19 , Epidemia de Opioides , Pandemias , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , Estados Unidos/epidemiologia , Masculino , Feminino , Transtornos Relacionados ao Uso de Opioides/mortalidade , Transtornos Relacionados ao Uso de Opioides/epidemiologia , SARS-CoV-2 , Analgésicos Opioides/efeitos adversos , Fentanila/efeitos adversos , Overdose de Drogas/mortalidade , Overdose de Drogas/epidemiologia
5.
Sci Rep ; 14(1): 16075, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38992157

RESUMO

Orthognathic surgery has a high incidence of postoperative nausea (PON) and vomiting (POV), delaying mobility initiation and postoperative recovery. Bleeding is another risk associated with this surgical procedure. We aimed to compare total intravenous anesthesia (TIVA) and volatile anesthesia in patients undergoing orthognathic surgery in terms of postoperative nausea and vomiting (PONV) incidence and hemodynamic changes. This retrospective study included 82 patients who underwent bilateral sagittal split ramus osteotomies at Saga University Hospital between April 2016 and April 2021. We compared the effects of TIVA and volatile anesthesia on PONV onset after surgery, acute postoperative hemodynamic changes (blood pressure and heart rate), and factors contributing to PONV. PON was significantly lower in the TIVA group than in the volatile anesthesia group. The total dose of fentanyl contributed to the onset of POV, while the onset of PON was associated with low volumes of fluid infusion and urine in the TIVA and volatile anesthesia groups, respectively. Furthermore, post-extubation hemodynamic change was significantly smaller in the TIVA group than in the volatile anesthesia group. Therefore, TIVA could have a reduced risk of PONV and hemodynamic changes in patients undergoing orthognathic surgery. Employing TIVA could mitigate perioperative complications and enhance patient safety.


Assuntos
Anestesia Geral , Anestesia Intravenosa , Procedimentos Cirúrgicos Ortognáticos , Náusea e Vômito Pós-Operatórios , Humanos , Feminino , Masculino , Estudos Retrospectivos , Adulto , Anestesia Intravenosa/efeitos adversos , Anestesia Intravenosa/métodos , Anestesia Geral/efeitos adversos , Anestesia Geral/métodos , Náusea e Vômito Pós-Operatórios/epidemiologia , Náusea e Vômito Pós-Operatórios/etiologia , Procedimentos Cirúrgicos Ortognáticos/efeitos adversos , Procedimentos Cirúrgicos Ortognáticos/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Cirurgia Ortognática/métodos , Adulto Jovem , Anestesia por Inalação/efeitos adversos , Anestesia por Inalação/métodos , Hemodinâmica/efeitos dos fármacos , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/efeitos adversos , Osteotomia Sagital do Ramo Mandibular/efeitos adversos , Osteotomia Sagital do Ramo Mandibular/métodos , Fentanila/administração & dosagem , Fentanila/efeitos adversos
6.
AMA J Ethics ; 26(7): E527-533, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38958421

RESUMO

Evidence of harm reduction interventions' morbidity and mortality benefits is abundant and of high quality, so there are good reasons for regional and national groups to advocate for more widespread distribution of legally regulated "drug paraphernalia," including needles, syringes, and fentanyl test strips. But lack of consistency among states' laws means that patients' interstate travel can subject them to being charged with possession of illegal items. This commentary on a case offers guidance to clinicians looking to help patients understand legal risks of interstate travel with supplies that are prescribed or recommended to reduce harms of their drug use and explores the ethical responsibilities of physicians in jurisdictions that legally prohibit these harm reduction interventions.


Assuntos
Redução do Dano , Humanos , Redução do Dano/ética , Fentanila , Seringas/ética , Agulhas , Estados Unidos , Equipamentos e Provisões/ética , Equipamentos e Provisões/provisão & distribuição
7.
J Mass Spectrom ; 59(8): e5070, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38989742

RESUMO

Recently, our group has shown that fentanyl and many of its analogues form prototropic isomers ("protomers") during electrospray ionization. These different protomers can be resolved using ion mobility spectrometry and annotated using mobility-aligned tandem mass spectrometry fragmentation. However, their formation and the extent to which experimental variables contribute to their relative ratio remain poorly understood. In the present study, we systematically investigated the effects of mixtures of common chromatographic solvents (water, methanol, and acetonitrile) and pH on the ratio of previously observed protomers for 23 fentanyl analogues. Interestingly, these ratios (N-piperidine protonation vs. secondary amine/O = protonation) decreased significantly for many analogues (e.g., despropionyl ortho-, meta-, and para-methyl fentanyl), increased significantly for others (e.g., cis-isofentanyl), and remained relatively constant for the others as solvent conditions changed from 100% organic solvent (methanol or acetonitrile) to 100% water. Interestingly, pH also had significant effects on this ratio, causing the change in ratio to switch in many cases. Lastly, increasing conditions to pH ≥ 4.0 also prompted the appearance of new mobility peaks for ortho- and para-methyl acetyl fentanyl, where all previous studies had only showed one single distribution. Because these ratios have promise to be used qualitatively for identification of these (and emerging) fentanyl analogues, understanding how various conditions (i.e., mobile phase selection and/or chromatographic gradient) affect their ratios is critically important to the development of advanced ion mobility and mass spectrometry methodologies to identify fentanyl analogues.


Assuntos
Fentanila , Espectrometria de Mobilidade Iônica , Solventes , Fentanila/análogos & derivados , Fentanila/química , Fentanila/análise , Solventes/química , Espectrometria de Mobilidade Iônica/métodos , Concentração de Íons de Hidrogênio , Espectrometria de Massas por Ionização por Electrospray/métodos , Isomerismo , Metanol/química , Acetonitrilas/química , Espectrometria de Massas em Tandem/métodos , Água/química
8.
J Opioid Manag ; 20(3): 243-253, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39017616

RESUMO

OBJECTIVE: This study assessed the impact of erector spinae plane block (ESPB) and intravenous (IV) dexmedetomidine in reduction of perioperative opioid consumption following bariatric surgery and their impact on post-operative recovery, analgesia, and pulmonary functions. DESIGN: A randomized controlled trial. SETTING: Tanta University Hospitals, Tanta, Gharboa, Egypt. PATIENTS: Forty obese patients with obstructive sleep apnea syndrome (OSAS), aged 20-55 years, and eligible for bariatric surgery were included. INTERVENTIONS: Patients randomized into group I (received general anesthesia [GA] with opioid, sham ESPB, and IV normal saline) or group II (received GA [without opioid], ESPB [at T7 level] using 20 mL bupivacaine 0.25 percent and bolus IV dexmedetomidine 1 µg/kg and then 0.25 µg/kg/h). MAIN OUTCOME MEASURES: Fentanyl consumption (primary outcome), sevoflurane consumption, recovery time, Visual Analog Scale (VAS), and pulmonary functions (secondary outcomes) were recorded. RESULTS: Perioperative fentanyl (intraoperative, post-operative, and total) consumption and sevoflurane consumption were substantially lower in group II compared to group I (p = 0.010, <0.001, <0.001, and <0.001, respectively). Moreover, recovery time was shorter in group II (p < 0.001). At 2, 4, 8, and 24 hours after surgery, group I patients had VAS values considerably higher. Relative to preoperative values, pulmonary function did not significantly alter after surgery. Oxygen desaturation was significantly lower in group II (p = 0.001). CONCLUSIONS: The ESPB with IV dexmedetomidine is advantageous for OSAS patients having bariatric surgery as it provides anesthesia and opioid-sparing effect with short recovery, adequate analgesia, and nonsignificant complications. Yet, it had no effect on post-operative pulmonary function.


Assuntos
Analgésicos Opioides , Dexmedetomidina , Bloqueio Nervoso , Obesidade , Dor Pós-Operatória , Apneia Obstrutiva do Sono , Humanos , Dexmedetomidina/administração & dosagem , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/complicações , Masculino , Adulto , Analgésicos Opioides/administração & dosagem , Pessoa de Meia-Idade , Bloqueio Nervoso/métodos , Feminino , Obesidade/complicações , Obesidade/cirurgia , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico , Adulto Jovem , Fentanila/administração & dosagem , Cirurgia Bariátrica , Egito , Músculos Paraespinais/inervação , Resultado do Tratamento , Método Duplo-Cego , Administração Intravenosa , Medição da Dor
9.
J Opioid Manag ; 20(3): 260-262, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39017618

RESUMO

Transitioning a patient with chronic pain from a fentanyl patch to a buprenorphine patch has not been well described in the literature. Even after a patient removes their fentanyl patch, the residual fentanyl in the skin continues to be absorbed for hours. Due to the risk of precipitated withdrawal when initiating buprenorphine, this transition is a more challenging opioid rotation to plan safely. We report a case of a patient who had been using a fentanyl patch for over 10 years and was successfully rotated directly to a buprenorphine patch.


Assuntos
Analgésicos Opioides , Buprenorfina , Dor Crônica , Fentanila , Adesivo Transdérmico , Humanos , Buprenorfina/administração & dosagem , Buprenorfina/efeitos adversos , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Dor Crônica/tratamento farmacológico , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Administração Cutânea , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Tratamento de Substituição de Opiáceos , Feminino
10.
Mikrochim Acta ; 191(8): 463, 2024 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995455

RESUMO

The intensifying global opioid crisis, majorly attributed to fentanyl (FT) and its analogs, has necessitated the development of rapid and ultrasensitive remote/on-site FT sensing modalities. However, current approaches for tracking FT exposure through wastewater-based epidemiology (WBE) are unadaptable, time-consuming, and require trained professionals. Toward developing an extended in situ wastewater opioid monitoring system, we have developed a screen-printed electrochemical FT sensor and integrated it with a customized submersible remote sensing probe. The sensor composition and design have been optimized to address the challenges for extended in situ FT monitoring. Specifically, ZIF-8 metal-organic framework (MOF)-derived mesoporous carbon (MPC) nanoparticles (NPs) are incorporated in the screen-printed carbon electrode (SPCE) transducer to improve FT accumulation and its electrocatalytic oxidation. A rapid (10 s) and sensitive square wave voltammetric (SWV) FT detection down to 9.9 µgL-1 is thus achieved in aqueous buffer solution. A protective mixed-matrix membrane (MMM) has been optimized as the anti-fouling sensor coating to mitigate electrode passivation by FT oxidation products and enable long-term, intermittent FT monitoring. The unique MMM, comprising an insulating polyvinyl chloride (PVC) matrix and carboxyl-functionalized multi-walled carbon nanotubes (CNT-COOH) as semiconductive fillers, yielded highly stable FT sensor operation (> 95% normalized response) up to 10 h in domestic wastewater, and up to 4 h in untreated river water. This sensing platform enables wireless data acquisition on a smartphone via Bluetooth. Such effective remote operation of submersible opioid sensing probes could enable stricter surveillance of community water systems toward timely alerts, countermeasures, and legal enforcement.


Assuntos
Analgésicos Opioides , Técnicas Eletroquímicas , Fentanila , Estruturas Metalorgânicas , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Fentanila/análise , Fentanila/sangue , Analgésicos Opioides/análise , Estruturas Metalorgânicas/química , Eletrodos , Águas Residuárias/análise , Monitoramento Ambiental/métodos , Limite de Detecção , Carbono/química , Nanopartículas/química , Tecnologia de Sensoriamento Remoto/métodos
11.
Sci Rep ; 14(1): 16250, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009645

RESUMO

[11C]Carfentanil ([11C]CFN) is the only selective carbon-11 labeled radiotracer currently available for positron emission tomography (PET) imaging of mu opioid receptors (MORs). Though used extensively in clinical research, [11C]CFN has not been thoroughly characterized as a tool for preclinical PET imaging. As we were occasionally observing severe vital sign instability in rat [11C]CFN studies, we set out to investigate physiological effects of CFN mass and to explore its influence on MOR quantification. In anesthetized rats (n = 15), significant dose-dependent PCO2 increases and heart rate decreases were observed at a conventional tracer dose range (IV, > 100 ng/kg). Next, we conducted baseline and retest [11C]CFN PET scans over a wide range of molar activities. Baseline [11C]CFN PET studies (n = 27) found that nondisplaceable binding potential (BPND) in the thalamus was positively correlated to CFN injected mass, demonstrating increase of MOR availability at higher injected CFN mass. Consistently, when CFN injected mass was constrained < 40 ng/kg (~ 10% MOR occupancy in rats), baseline MOR availability was significantly decreased. For test-retest variability (TRTV), better reproducibility was achieved by controlling CFN injected mass to limit the difference between scans. Taken together, we report significant cardiorespiratory depression and a paradoxical influence on baseline MOR availability at conventional tracer doses in rats. Our findings might reflect changes in cerebral blood flow, changes in receptor affinity, or receptor internalization, and merits further mechanistic investigation. In conclusion, rat [11C]CFN PET requires stringent quality assurance of radiotracer synthesis and mass injected to avoid pharmacological effects and limit potential influences on MOR quantification and reproducibility.


Assuntos
Encéfalo , Radioisótopos de Carbono , Fentanila , Tomografia por Emissão de Pósitrons , Receptores Opioides mu , Animais , Receptores Opioides mu/metabolismo , Fentanila/análogos & derivados , Fentanila/metabolismo , Fentanila/farmacologia , Ratos , Tomografia por Emissão de Pósitrons/métodos , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Masculino , Ratos Sprague-Dawley , Compostos Radiofarmacêuticos/farmacocinética
12.
BMC Pulm Med ; 24(1): 301, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926768

RESUMO

BACKGROUND: Sedation during flexible bronchoscopy (FB) should maintain an adequate respiratory drive, ensure maximum comfort for the patient, and warrant that the objectives of the procedure are achieved. Nevertheless, the optimal sedation method for FB has yet to be established. This study aimed to compare the standard recommended combination of midazolam-fentanyl (MF) with that of dexmedetomidine-ketamine (DK) for patient sedation during FB. METHODS: Patients subjected to FB were randomly assigned to a DK (n = 25) and an MF group (n = 25). The primary outcome was the rate of critical desaturation events (arterial oxygen saturation < 80% with nasal oxygen supply 2 L/min). Secondary outcomes included sedation depth, hemodynamic complications, adverse events, and patient and bronchoscopist satisfaction. RESULTS: The incidence rates of critical desaturation events were similar between the two groups (DK: 12% vs. MF: 28%, p = 0.289). DK achieved deeper maximum sedation levels (higher Ramsay - lower Riker scale; p < 0.001) and was associated with longer recovery times (p < 0.001). Both groups had comparable rates of hemodynamic and other complications. Patient satisfaction was similar between the two groups, but bronchoscopist satisfaction was higher with the DK combination (p = 0.033). CONCLUSION: DK demonstrated a good safety profile in patients subjected to FB and achieved more profound sedation and better bronchoscopist satisfaction than the standard MF combination without increasing the rate of adverse events.


Assuntos
Broncoscopia , Dexmedetomidina , Fentanila , Hipnóticos e Sedativos , Ketamina , Midazolam , Satisfação do Paciente , Humanos , Dexmedetomidina/administração & dosagem , Dexmedetomidina/efeitos adversos , Broncoscopia/métodos , Fentanila/administração & dosagem , Masculino , Midazolam/administração & dosagem , Midazolam/efeitos adversos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Método Simples-Cego , Idoso , Adulto , Sedação Consciente/métodos
13.
JAMA Netw Open ; 7(6): e2417377, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38916892

RESUMO

Importance: Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are limited. Objective: To assess the effectiveness of sublingual or extended-release injection formulations of buprenorphine for the treatment of OUD among patients with and without fentanyl use. Design, Setting, and Participants: Post hoc analysis of a 24-week, randomized, double-blind clinical trial conducted at 35 outpatient sites in the US from December 2015 to November 2016 of sublingual buprenorphine-naloxone vs extended-release subcutaneous injection buprenorphine (CAM2038) for patients with OUD subgrouped by presence vs absence of fentanyl or norfentanyl in urine at baseline. Study visits with urine testing occurred weekly for 12 weeks, then 6 times between weeks 13 and 24. Data were analyzed on an intention-to-treat basis from March 2022 to August 2023. Intervention: Weekly and monthly subcutaneous buprenorphine vs daily sublingual buprenorphine-naloxone. Main Outcomes and Measures: Retention in treatment, percentage of urine samples negative for any opioids (missing values imputed as positive), percentage of urine samples negative for fentanyl or norfentanyl (missing values not imputed), and scores on opiate withdrawal scales and visual analog craving scales. Results: Of 428 participants, 123 (subcutaneous buprenorphine, n = 64; sublingual buprenorphine-naloxone, n = 59; mean [SD] age, 39.1 [10.8] years; 75 men [61.0%]) had evidence of baseline fentanyl use and 305 (subcutaneous buprenorphine, n = 149; buprenorphine-naloxone, n = 156; mean [SD] age, 38.1 [11.1] years; 188 men [61.6%]) did not have evidence of baseline fentanyl use. Study completion was similar between the fentanyl-positive (60.2% [74 of 123]) and fentanyl-negative (56.7% [173 of 305]) subgroups. The mean percentage of urine samples negative for any opioid were 28.5% among those receiving subcutaneous buprenorphine and 18.8% among those receiving buprenorphine-naloxone in the fentanyl-positive subgroup (difference, 9.6%; 95% CI, -3.0% to 22.3%) and 36.7% among those receiving subcutaneous buprenorphine and 30.6% among those receiving buprenorphine-naloxone in the fentanyl-negative subgroup (difference, 6.1%; 95% CI, -1.9% to 14.1%), with significant main associations of baseline fentanyl status and treatment group. In the fentanyl-positive subgroup, the mean percentage of urine samples negative for fentanyl during the study was 74.6% among those receiving subcutaneous buprenorphine vs 61.9% among those receiving sublingual buprenorphine-naloxone (difference, 12.7%; 95% CI, 9.6%-15.9%). Opioid withdrawal and craving scores decreased rapidly after treatment initiation across all groups. Conclusions and Relevance: In this post hoc analysis of a randomized clinical trial of sublingual vs extended-release injection buprenorphine for OUD, buprenorphine appeared to be effective among patients with baseline fentanyl use. Patients with fentanyl use had fewer opioid-negative urine samples during the trial compared with the fentanyl-negative subgroup. These findings suggest that the subcutaneous buprenorphine formulation may be more effective at reducing fentanyl use. Trial Registration: ClinicalTrials.gov Identifier: NCT02651584.


Assuntos
Buprenorfina , Preparações de Ação Retardada , Fentanila , Transtornos Relacionados ao Uso de Opioides , Humanos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Fentanila/administração & dosagem , Fentanila/uso terapêutico , Masculino , Feminino , Administração Sublingual , Adulto , Método Duplo-Cego , Buprenorfina/administração & dosagem , Pessoa de Meia-Idade , Injeções Subcutâneas , Antagonistas de Entorpecentes/administração & dosagem , Antagonistas de Entorpecentes/uso terapêutico , Analgésicos Opioides/administração & dosagem , Tratamento de Substituição de Opiáceos/métodos , Combinação Buprenorfina e Naloxona/administração & dosagem , Combinação Buprenorfina e Naloxona/uso terapêutico , Resultado do Tratamento
14.
Anal Chim Acta ; 1312: 342686, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38834256

RESUMO

BACKGROUND: Fentanyl and its derivatives are a type of potent opioid analgesics, with the characteristics of diverse structure, high toxicity, extremely low content, and high fatality rate. Currently, they have become one of the most serious problems in international drug abuse control due to their extensive use in drug production and use. Therefore, the development of a rapid, sensitive, and accurate method for detecting trace fentanyl is of great significance. In this study, in view of its complex structure and trace concentration, a new molecular imprinting electrochemical sensor was developed through molecular simulations followed by experimental validation to detect trace fentanyl. RESULTS: The process consisted of first obtaining the optimal functional monomer and its molar ratio through molecular simulations. The recognition sites of fentanyl-imprinted polymers were predicted to guide the synthesis of imprinted membranes with precision approach to ensure an efficient and accurate reaction process. Reduced graphene oxide (ErGO) was then deposited on glassy carbon electrode surface by electrochemical reduction to yield large numbers of active sites suitable for catalyzing reactions of fentanyl piperidine for promoted efficient electron transfer and amplified sensitivity of the sensor. Accordingly, fentanyl molecularly imprinted film was formed through one-step electropolymerization to yield greatly improved sensing selectivity due to the specific recognition of molecularly imprinted polymer. Under optimal experimental conditions, the fentanyl sensor showed an extended detection range of 3.84 × 10-9 mol L-1-1.72 × 10-6 mol L-1 and a detection limit of 1.28 × 10-9 mol L-1. SIGNIFICANCE: A distinctive feature of this sensor is its molecularly imprinted polymerized membrane, which offers excellent specific recognition, thereby boosting the sensor's selectivity. Throughout the sensor's development process, molecular simulations were employed to steer the synthesis of molecularly imprinted polymers and predict the recognition sites of fentanyl-imprinted polymers. The experimental outcomes proved to align with the simulation data. The final sensor exhibited outstanding selectivity, repeatability, stability, and high sensitivity. The sensor was effectively used to reliably track fentanyl in human serum samples, with acceptable analytical reliability, suggesting its potential for practical applications.


Assuntos
Técnicas Eletroquímicas , Fentanila , Impressão Molecular , Fentanila/análise , Fentanila/sangue , Fentanila/química , Polímeros Molecularmente Impressos/química , Eletrodos , Limite de Detecção , Grafite/química , Simulação de Dinâmica Molecular , Analgésicos Opioides/sangue , Analgésicos Opioides/análise , Analgésicos Opioides/química , Humanos
15.
BMC Vet Res ; 20(1): 253, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851722

RESUMO

BACKGROUND: When inhalant anesthetic equipment is not available or during upper airway surgery, intravenous infusion of one or more drugs are commonly used to induce and/or maintain general anesthesia. Total intravenous anesthesia (TIVA) does not require endotracheal intubation, which may be more difficult to achieve in rabbits. A range of different injectable drug combinations have been used as continuous infusion rate in animals. Recently, a combination of ketamine and propofol (ketofol) has been used for TIVA in both human patients and animals. The purpose of this prospective, blinded, randomized, crossover study was to evaluate anesthetic and cardiopulmonary effects of ketofol total intravenous anesthesia (TIVA) in combination with constant rate infusion (CRI) of midazolam, fentanyl or dexmedetomidine in eight New Zealand White rabbits. Following IV induction with ketofol and endotracheal intubation, anesthesia was maintained with ketofol infusion in combination with CRIs of midazolam (loading dose [LD]: 0.3 mg/kg; CRI: 0.3 mg/kg/hr; KPM), fentanyl (LD: 6 µg/kg; CRI: 6 µg/kg/hr; KPF) or dexmedetomidine (LD: 3 µg/kg; CRI: 3 µg/kg/hr; KPD). Rabbits in the control treatment (KPS) were administered the same volume of saline for LD and CRI. Ketofol infusion rate (initially 0.6 mg kg- 1 minute- 1 [0.3 mg kg- 1 minute- 1 of each drug]) was adjusted to suppress the pedal withdrawal reflex. Ketofol dose and physiologic variables were recorded every 5 min. RESULTS: Ketofol induction doses were 14.9 ± 1.8 (KPM), 15.0 ± 1.9 (KPF), 15.5 ± 2.4 (KPD) and 14.7 ± 3.4 (KPS) mg kg- 1 and did not differ among treatments (p > 0.05). Ketofol infusion rate decreased significantly in rabbits in treatments KPM and KPD as compared with saline. Ketofol maintenance dose in rabbits in treatments KPM (1.0 ± 0.1 mg/kg/min) and KPD (1.0 ± 0.1 mg/kg/min) was significantly lower as compared to KPS (1.3 ± 0.1 mg/kg/min) treatment (p < 0.05). Ketofol maintenance dose did not differ significantly between treatments KPF (1.1 ± 0.3 mg/kg/min) and KPS (1.3 ± 0.1 mg/kg/min). Cardiovascular variables remained at clinically acceptable values but ketofol infusion in combination with fentanyl CRI was associated with severe respiratory depression. CONCLUSIONS: At the studied doses, CRIs of midazolam and dexmedetomidine, but not fentanyl, produced ketofol-sparing effect in rabbits. Mechanical ventilation should be considered during ketofol anesthesia, particularly when fentanyl CRI is used.


Assuntos
Anestesia Intravenosa , Anestésicos Intravenosos , Estudos Cross-Over , Dexmedetomidina , Fentanila , Ketamina , Midazolam , Propofol , Animais , Coelhos , Fentanila/administração & dosagem , Fentanila/farmacologia , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacologia , Midazolam/administração & dosagem , Midazolam/farmacologia , Ketamina/administração & dosagem , Ketamina/farmacologia , Anestesia Intravenosa/veterinária , Propofol/administração & dosagem , Propofol/farmacologia , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/farmacologia , Masculino , Feminino , Frequência Cardíaca/efeitos dos fármacos , Estudos Prospectivos , Pressão Sanguínea/efeitos dos fármacos , Anestésicos Combinados/administração & dosagem , Infusões Intravenosas/veterinária , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia
16.
Drug Des Devel Ther ; 18: 2347-2356, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915865

RESUMO

Background: The novel short-acting benzodiazepine drug, remimazolam tosilate, has been employed for sedation during endoscopic procedures. The optimal loading dosage of remimazolam tosilate in gastroscopy for elderly patients when co-administered with fentanyl remains unclear. Therefore, the primary objective of our research was to ascertain the median effective dose (ED50) and the 95% effective dose (ED95) of remimazolam tosilate in combination with various fentanyl dosages for elderly patients undergoing painless gastroscopy. Methods: Seventy-five patients aged ≥65 years and American Society of Anesthesiologists (ASA) class I-III were recruited to undergo elective painless gastroscopy. All patients were randomized assigned to group F1, group F2, and group F3, and were injected intravenously with different doses of fentanyl (0.5 ug/kg, 1 ug/kg, and 1.5 ug/kg) 3 minutes prior to the administration of remimazolam tosilate, respectively. The initial preset dose of remimazolam tosilate was 0.3 mg/kg in group F1, 0.2 mg/kg in group F2, 0.15 mg/kg in group F3. The dose gradient was 0.02 mg/kg per group according to the up-and-down sequential method. Probibt regression model was employed to determine the ED50 and ED95 of remimazolam tosilate. Results: The ED50 of remimazolam tosilate in group F3 was lower than that in group F1 and F2 (0.095 [0.088-0.108] mg/kg vs 0.162 [0.153-0.171] mg/kg; 0.258 [0.249-0.266] mg/kg, p < 0.05). The ED95 of remimazolam tosilate was 0.272 mg/kg (95% CI: 0.264-0.295 mg/kg) in group F1, 0.175 mg/kg (95% CI: 0.167-0.200 mg/kg) in group F2 and 0.109 mg/kg (95% CI: 0.101-0.135 mg/kg) in group F3. The total dosage of remimazolam tosilate decreased gradually with the increasing of fentanyl (p < 0.001). The frequency of injection pain was higher in group F1 compared to groups F2 and F3 (p < 0.05). The patients in group F3 had a lower incidence of hypotension than in groups F1 and F2 (p < 0.05). There was no respiratory depression, intraoperative consciousness, dizziness or delirium in the three groups. Conclusion: The concurrent use of fentanyl reduces the dosage of remimazolam tosilate required for sedative gastroscopy in elderly patients in a dose-dependent manner. Moreover, 1.5 ug/kg fentanyl combined with remimazolam tosilate may reduce the incidence of hypotension and injection pain. These findings should be confirmed in a large-scale study.


Assuntos
Benzodiazepinas , Relação Dose-Resposta a Droga , Fentanila , Gastroscopia , Humanos , Idoso , Benzodiazepinas/administração & dosagem , Masculino , Feminino , Fentanila/administração & dosagem , Idoso de 80 Anos ou mais
17.
Ups J Med Sci ; 1292024.
Artigo em Inglês | MEDLINE | ID: mdl-38863729

RESUMO

Background: Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses need to be better examined. The purpose of this study was to describe daily dosages, measured blood concentrations, and clinical responses in critically ill patients. The purpose was also to contribute to establishing whole blood concentration reference values of the drugs investigated. Methods: A descriptive study of prospectively collected data from 302 admissions to a general intensive care unit (ICU) at a university hospital. Ten drugs (clonidine, fentanyl, morphine, dexmedetomidine, ketamine, ketobemidone, midazolam, paracetamol, propofol, and thiopental) were investigated, and daily dosages recorded. Blood samples were collected twice daily, and drug concentrations were measured. Clinical responses were registered using Richmond agitation-sedation scale (RASS) and Numeric rating scale (NRS). Results: Drug dosages were within recommended dose ranges. Blood concentrations for all 10 drugs showed a wide variation within the cohort, but only 3% were above therapeutic interval where clonidine (57 of 122) and midazolam (38 of 122) dominated. RASS and NRS were not correlated to drug concentrations. Conclusion: Using recommended dose intervals for analgesic and sedative drugs in the ICU setting combined with regular monitoring of clinical responses such as RASS and NRS leads to 97% of concentrations being below the upper limit in the therapeutic interval. This study contributes to whole blood drug concentration reference values regarding these 10 drugs.


Assuntos
Analgésicos , Hipnóticos e Sedativos , Unidades de Terapia Intensiva , Midazolam , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacocinética , Hipnóticos e Sedativos/sangue , Analgésicos/administração & dosagem , Analgésicos/farmacocinética , Analgésicos/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Adulto , Midazolam/administração & dosagem , Midazolam/farmacocinética , Midazolam/sangue , Cuidados Críticos/métodos , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacocinética , Dexmedetomidina/sangue , Fentanila/administração & dosagem , Fentanila/sangue , Fentanila/farmacocinética , Estado Terminal , Propofol/administração & dosagem , Propofol/farmacocinética , Propofol/sangue , Clonidina/administração & dosagem , Clonidina/farmacocinética , Clonidina/sangue , Ketamina/administração & dosagem , Ketamina/sangue , Ketamina/farmacocinética , Morfina/administração & dosagem , Morfina/sangue , Morfina/farmacocinética , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Tiopental/administração & dosagem , Tiopental/farmacocinética , Acetaminofen/administração & dosagem , Acetaminofen/sangue , Acetaminofen/farmacocinética
18.
BMC Palliat Care ; 23(1): 150, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877477

RESUMO

BACKGROUND: Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains inadequate. This study aimed to evaluate the efficacy of FBSF proportional to the around-the-clock (ATC) opioid regimens in rapidly relieving the intensity of BTcP episodes by determining the percentage of patients requiring further dose titration. METHODS: The study procedure included a dose-finding period followed by a 14-day observation period. Pain intensity was recorded with a Numeric Rating Scale (NRS) at onset and 5, 10, 15, and 30 min after FBSF self-administration. Meaningful pain relief was defined as the final NRS score ≤ 3. Satisfaction survey was conducted for each patient after treatment using the Global Satisfaction Scale. RESULTS: A total of 63 BTcP episodes occurred in 30 cancer patients. Only one patient required rescue medication at first BTcP episode and then achieved meaningful pain relief after titrating FBSF by 200 µg. Most BTcP episodes relieved within 10 min. Of 63 BTcP episodes, 30 (47.6%), 46 (73.0%), and 53 (84.1%) relieved within 5, 10, and 15 min after FBSF administration. Only grade 1/2 adverse events were reported, including somnolence, malaise, and dizziness. Of the 63 BTcP episodes, 82.6% were rated as excellent/good satisfaction with FBSF. CONCLUSION: FBSF can be administrated "on demand" by cancer patients at the onset of BTcP, providing rapid analgesia by achieving meaningful pain relief within 10 min. TRIAL REGISTRATION: This study was retrospectively registered 24 December, 2021 at Clinicaltrial.gov (NCT05209906): https://clinicaltrials.gov/study/NCT05209906 .


Assuntos
Analgésicos Opioides , Dor Irruptiva , Fentanila , Humanos , Fentanila/uso terapêutico , Fentanila/administração & dosagem , Feminino , Masculino , Dor Irruptiva/tratamento farmacológico , Dor Irruptiva/etiologia , Pessoa de Meia-Idade , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/administração & dosagem , Idoso , Administração Bucal , Adulto , Medição da Dor/métodos , Dor do Câncer/tratamento farmacológico , Manejo da Dor/métodos , Manejo da Dor/normas , Manejo da Dor/estatística & dados numéricos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Idoso de 80 Anos ou mais
19.
Harm Reduct J ; 21(1): 115, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38877522

RESUMO

BACKGROUND: Fentanyl test strips (FTS) are lateral flow immunoassay strips designed for detection of ng/mL levels of fentanyl in urine. In 2021, the US Centers for Disease Control and the Substance Abuse and Mental Health Administration stated that federal funds could be used for procurement of FTS for harm reduction strategies approved by the government such as drug checking. The market for FTS has expanded rapidly in the US and Canada. However, there is no regulatory oversight by either government to ensure proper function of FTS that are being marketed for drug checking. MAIN BODY: Many brands of FTS have rapidly entered the harm reduction market, creating concerns about the reproducibility and accuracy of their performance from brand to brand and lot to lot. Some examples are provided in this Comment. Similar problems with product quality were observed in the mid 2000's when lateral flow immunoassays for malaria were funded in many countries and again in 2020, when COVID-19 tests were in huge demand. The combination of high demand and low levels of regulation and enforcement led some manufacturers to join the goldrush without adequate field testing or quality assurance. We argue that the harm reduction community urgently needs to set a lot checking program in place. A set of simple protocols for conducting the tests and communicating the results have been developed, and are described in the following Perspectives paper in this issue. CONCLUSION: In the absence of governmental regulation and enforcement, the harm reduction community should implement a FTS lot checking program. Based on previous experience with the malaria diagnostic lot checking program, this inexpensive effort could identify products that are not suitable for harm reduction applications and provide valuable feedback to manufacturers. Dissemination of the results will help harm reduction organizations to ensure that FTS they use for drug checking are fit for the purpose.


Assuntos
Fentanila , Redução do Dano , Fitas Reagentes , Humanos , Fentanila/urina , Fentanila/análise , Reprodutibilidade dos Testes , Detecção do Abuso de Substâncias/métodos , Imunoensaio/métodos , Analgésicos Opioides/urina , Analgésicos Opioides/análise , COVID-19 , América do Norte
20.
Int J Mol Sci ; 25(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38891855

RESUMO

Melatonin influences arterial biomechanics, and its absence could cause remodeling of the arterial wall, leading to increased stiffness. Direct effects of fentanyl on the aortic wall have also been observed previously. This study aimed to evaluate in vitro the effects of fentanyl on aortic viscoelasticity in a rat model of melatonin deficiency and to test the hypothesis that melatonin deficiency leads to increased arterial wall stiffness. The viscoelasticity was estimated in strip preparations from pinealectomized (pin, melatonin deficiency) and sham-operated (sham, normal melatonin) adult rats using the forced oscillations method. In the untreated aortic wall pin, the viscoelasticity was not significantly altered. However, combined with 10-9 M fentanyl, the pin increased the natural frequency (f0) and modulus of elasticity (E') compared to the sham-operated. Independently, fentanyl treatment decreased f0 and E' compared separately to untreated sham and pin preparations. The effects of fentanyl were neither dose-dependent nor affected by naloxone, suggesting a non-opioid mechanism. Furthermore, an independent effect of naloxone was also detected in the normal rat aortic wall, resulting in reduced E'. Additional studies are needed that may improve the clinical decisions for pain management and anesthesia for certain patients with co-occurring chronic low levels of blood plasma melatonin and some diseases.


Assuntos
Aorta , Elasticidade , Fentanila , Melatonina , Animais , Fentanila/farmacologia , Melatonina/farmacologia , Ratos , Masculino , Aorta/efeitos dos fármacos , Aorta/metabolismo , Elasticidade/efeitos dos fármacos , Viscosidade , Modelos Animais de Doenças , Rigidez Vascular/efeitos dos fármacos , Analgésicos Opioides/farmacologia , Naloxona/farmacologia
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