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1.
J Zoo Wildl Med ; 50(4): 868-873, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926517

RESUMO

Blue poison dart frogs (Dendrobates tinctorius azureus) are commonly maintained in zoological institutions and are becoming popular in the pet trade industry. Sedation or light anesthesia is required for safe and effective handling of this species. In this study, the sedative effects of subcutaneously administered alfaxalone-midazolam-dexmedetomidine (AMD) (20, 40, 5 mg/kg, respectively) and ketamine-midazolam-dexmedetomidine (KMD) (100, 40, 5 mg/kg, respectively) were compared in a prospective, randomized, blinded, crossover study in juvenile blue poison dart frogs (n = 10). Both protocols were partially reversed 45 min after administration of either protocol with subcutaneously administered flumazenil (0.05 mg/kg) and atipamezole (50 mg/kg). Heart rate, pulmonic respiratory rate, various reflexes, and behavioral parameters were monitored after drug administration. Both protocols resulted in rapid loss of righting reflex [median (range): AMD, 5 min (5-5 min); KMD, 5 min (5-10 min)]. Time to complete recovery was similar with both protocols (mean ± SD: AMD, 97.5 ± 11.4 min; KMD, 96.5 ± 25.4 min). The AMD protocol resulted in pulmonic respiratory depression, whereas no significant difference in heart rate was found between the two protocols. All frogs were observed eating within 24 hr of chemical restraint. Gastric prolapses occurred in four frogs (AMD 3, KMD 1) that were easily reduced with a cotton-tip application. No other adverse reactions were observed. The results of this study provide two different subcutaneous chemical restraint protocols in juvenile blue poison dart frogs.


Assuntos
Dexmedetomidina/farmacologia , Midazolam/farmacologia , Pregnanodionas/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Envelhecimento , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Anestésicos/administração & dosagem , Anestésicos/farmacologia , Animais , Antídotos/administração & dosagem , Antídotos/farmacologia , Anuros , Sedação Consciente , Estudos Cross-Over , Dexmedetomidina/administração & dosagem , Quimioterapia Combinada , Flumazenil/administração & dosagem , Flumazenil/farmacologia , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Ketamina/administração & dosagem , Ketamina/farmacologia , Midazolam/administração & dosagem , Pregnanodionas/administração & dosagem
2.
J Zoo Wildl Med ; 50(4): 988-992, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926533

RESUMO

Five free-ranging male (subadults, n = 3; adults, n = 2) plains zebras (Equus quagga) were immobilized using a combination of etorphine (0.017 mg/kg), medetomidine (0.017 mg/kg), and azaperone (0.24 mg/kg) by means of a blank cartridge-fired projector. Time to recumbency was recorded and a descriptive score used to assess the quality of immobilization, manipulation, maintenance, and recovery. Physiological parameters were recorded at 5-min intervals for 20 min. At the end of the procedure, naltrexone (0.23 mg/kg) was administered intramuscularly and time to standing documented. The combination evaluated in this study allowed for successful immobilization and safe recovery of all animals, including during the subsequent 15 days. Despite the good outcome in this pilot study, as a result of the periodic apneic events and hypercapnia documented in the zebras, the authors suggest that physiological parameters be thoroughly monitored when using this protocol. Further studies are needed to improve upon chemical immobilization protocols in free-ranging plains zebras.


Assuntos
Azaperona/farmacologia , Equidae , Etorfina/farmacologia , Imobilização/veterinária , Medetomidina/farmacologia , Animais , Animais Selvagens , Azaperona/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Combinação de Medicamentos , Etorfina/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Masculino , Medetomidina/administração & dosagem , Projetos Piloto , Taxa Respiratória/efeitos dos fármacos
3.
J Zoo Wildl Med ; 50(4): 993-996, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926534

RESUMO

Seven anesthesia events were performed over 6 wk on a 1.5-yr-old female okapi (Okapia johnstoni) being managed for a fetlock injury. A combination of butorphanol (B) (median; range) (0.045; 0.031-0.046 mg/kg), medetomidine (M) (0.037; 0.031-0.037 mg/kg), ketamine (K) (0.553; 0.536-1.071 mg/kg), and thiafentanil (T) (0.0045; 0.0040-0.0046 mg/kg) was administered in a padded stall. One dart containing all drugs was used for the first two anesthesias. Subsequently, BM was administered 10 min prior to KT using two darts. Time (median; range) from initial injection to first effects (6; 3-7 min) and recumbency (14; 4-20 min) were recorded. Induction quality with the one-dart protocol was poor or fair and was good or excellent with the two-dart protocol. Following recumbency, the okapi was intubated and ventilated, and physiological parameters were recorded. Anesthesia was consistently achieved with BMKT, but induction was smoother with the staged two-dart approach. Neither resedation nor renarcotization was observed post-reversal.


Assuntos
Antílopes/fisiologia , Butorfanol/farmacologia , Fentanila/análogos & derivados , Ketamina/farmacologia , Medetomidina/farmacologia , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Anestesia/veterinária , Animais , Butorfanol/administração & dosagem , Esquema de Medicação , Espécies em Perigo de Extinção , Feminino , Fentanila/administração & dosagem , Fentanila/farmacologia , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Ketamina/administração & dosagem , Medetomidina/administração & dosagem
4.
Life Sci ; 241: 117143, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31811855

RESUMO

AIM: To investigate the effect of propofol on the migration and invasion of oral squamous cell carcinoma (OSCC) cells and explore the underlying mechanism. MAIN METHODS: Cal-27 and SCC-25 cells treated with or without propofol, then the cells metastasis were determined. The levels of SNAI1 mRNA and protein were detected by real-time PCR and western blot. Cell migration ability was evaluated by wound healing assay, and the invasion of cells was measured using transwell assay. KEY FINDINGS: Propofol treatment significantly promoted cell migration and invasion of OSCC. Further mechanistic studies of the stimulating effects of propofol on OSCC cell metastasis revealed that propofol treatment dose-dependently upregulated the expression of SNAI1, a member of the Snail superfamily of zinc-finger transcription factors. Additionally, the inhibition of endogenous SNAI1 expression reversed the effect of propofol on cell migration and invasion in Cal-27 and SCC-25 cells. SIGNIFICANCE: Our results demonstrate that propofol at clinically relevant concentrations facilitates cell migration and invasion through up-regulation of SNAI1 in OSCC cells, and suggest propofol may not be suitable for anesthesia management in OSCC patients.


Assuntos
Carcinoma de Células Escamosas/patologia , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Neoplasias Bucais/patologia , Propofol/farmacologia , Fatores de Transcrição da Família Snail/metabolismo , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Invasividade Neoplásica , Fatores de Transcrição da Família Snail/genética , Células Tumorais Cultivadas
5.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3830-3836, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602960

RESUMO

The peeled root,stem or twig of Syringa pinnatifolia is a representative Mongolian folk medicine with the effects of antidepression and pain relief. It has been used for the treatments of heart tingling,heart palpitations,upset,insomnia and other symptoms. Inspired by Mongolian medical theory and clinical practices,this study evaluated the analgesic effect of S. pinnatifolia ethanol extract( T) through three analgesic models including acetic acid writhing test,formalin test,and hot plate test,and the sedative effect of T was evaluated by locomotor activity and synergistic sleeping experiments,and furthermore the effects of T on the GABAergic nervous system were investigated by ELISA,immunohistochemistry,Western blot,and PCR methods. The results showed that T can significantly reduce the number of writhing,the time of paw licking and extend the thermal threshold of mice,suggesting the analgesic effect of T.T also can indicate its sedative effect by reducing the number of activities,decreasing latency of sleeping and extending sleeping time of mice. ELISA results showed that T can increase the content of GABA/Glu in rat cortex,hippocampus,and hypothalamus,and the most significant increase in hypothalamus. The immunohistochemistry and Western blot results showed that T can up-regulate the expression of GAD67 protein in hypothalamus,and the PCR results showed that T can up-regulate the expression of GABAA Rα1,α2,α3,α5,ß1-3,γ1-3 genes,suggesting a sedative effect through the GABAergic nervous system. In conclusion,this study shed insight into the theoretical basis and clinical application of S. pinnatifolia,and also provides inspiration for subsequent development and application.


Assuntos
Analgésicos/farmacologia , Hipnóticos e Sedativos/farmacologia , Extratos Vegetais/farmacologia , Syringa/química , Animais , Medicina Tradicional da Mongólia , Camundongos , Dor , Ratos
6.
J Vet Sci ; 20(5): e55, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31565898

RESUMO

This study examined the sedative, analgesic, behavioral, and clinical effects of a combination of xylazine (XY) and nalbuphine-xylazine (NA-XY) in camels. A total of five adult camels were used in a prospective randomized cross-over design with a wash out period of two weeks. Camels were allocated randomly to two treatment groups: the XY group (xylazine, 1.1mL/100 kg IV) and the NA-XY group (xylazine, 1.1mL/100 kg IV and nalbuphine, 1 mg/kg IV). The sedative, analgesic, behavioral, and clinical effects of XY and NA-XY combination were evaluated prior to administration (baseline) and at 5, 15, 30, 45, 60, 75, 90, and 120 minutes post-administration. The results showed that the NA-XY combination accelerates the onset of sedation and analgesia and prolongs the durations of both sedation (p < 0.001) and analgesia (p < 0.01). The behavioral parameters showed higher scores with a NA-XY combination than xylazine alone. Although a XY injection resulted in a significant decline in the heart and respiratory rate, the NA-XY combination group revealed a non-significant change in both clinical parameters compared to the baseline. In conclusion, the use of a NA-XY combination in camels improved the sedative and analgesic onset and duration with an improved outcome in the behavioral scores, as well as in both the heart and respiratory rates compared to XY alone.


Assuntos
Analgésicos/farmacologia , Camelus , Hipnóticos e Sedativos/farmacologia , Nalbufina/farmacologia , Xilazina/farmacologia , Administração Intravenosa/veterinária , Animais , Combinação de Medicamentos , Feminino , Masculino , Estudos Prospectivos
7.
Am J Vet Res ; 80(10): 912-922, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31556714

RESUMO

OBJECTIVE: To investigate the cardiovascular and sedation reversal effects of IM administration of atipamezole (AA) in dogs treated with medetomidine hydrochloride (MED) or MED and vatinoxan (MK-467). ANIMALS: 8 purpose-bred, 2-year-old Beagles. PROCEDURES: A randomized, blinded, crossover study was performed in which each dog received 2 IM treatments at a ≥ 2-week interval as follows: injection of MED (20 µg/kg) or MED mixed with 400 µg of vatinoxan/kg (MEDVAT) 30 minutes before AA (100 µg/kg). Sedation score, heart rate, mean arterial and central venous blood pressures, and cardiac output were recorded before and at various time points (up to 90 minutes) after AA. Cardiac and systemic vascular resistance indices were calculated. Venous blood samples were collected at intervals until 210 minutes after AA for drug concentration analysis. RESULTS: Heart rate following MED administration was lower, compared with findings after MEDVAT administration, prior to and at ≥ 10 minutes after AA. Mean arterial blood pressure was lower with MEDVAT than with MED at 5 minutes after AA, when its nadir was detected. Overall, cardiac index was higher and systemic vascular resistance index lower, indicating better cardiovascular function, in MEDVAT-atipamezole-treated dogs. Plasma dexmedetomidine concentrations were lower and recoveries from sedation were faster and more complete after MEDVAT treatment with AA than after MED treatment with AA. CONCLUSIONS AND CLINICAL RELEVANCE: Atipamezole failed to restore heart rate and cardiac index in medetomidine-sedated dogs, and relapses into sedation were observed. Coadministration of vatinoxan with MED helped to maintain hemodynamic function and hastened the recovery from sedation after AA in dogs.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Cães , Hipnóticos e Sedativos/farmacologia , Imidazóis/farmacologia , Medetomidina/farmacologia , Quinolizinas/farmacologia , Anestesia/veterinária , Animais , Débito Cardíaco/efeitos dos fármacos , Estudos Cross-Over , Dexmedetomidina/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Injeções Intramusculares/veterinária , Masculino , Medetomidina/administração & dosagem , Medetomidina/antagonistas & inibidores , Quinolizinas/antagonistas & inibidores , Distribuição Aleatória , Método Simples-Cego
8.
Pharmacol Rev ; 71(4): 450-466, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31471460

RESUMO

Despite continuous clinical use for more than 170 years, the mechanism of general anesthetics has not been completely characterized. In this review, we focus on the role of voltage-gated sodium channels in the sedative-hypnotic actions of halogenated ethers, describing the history of anesthetic mechanisms research, the basic neurobiology and pharmacology of voltage-gated sodium channels, and the evidence for a mechanistic interaction between halogenated ethers and sodium channels in the induction of unconsciousness. We conclude with a more integrative perspective of how voltage-gated sodium channels might provide a critical link between molecular actions of the halogenated ethers and the more distributed network-level effects associated with the anesthetized state across species.


Assuntos
Éteres/farmacologia , Inconsciência/induzido quimicamente , Inconsciência/metabolismo , Canais de Sódio Disparados por Voltagem/metabolismo , Animais , Éteres/química , Humanos , Hidrocarbonetos Halogenados/química , Hidrocarbonetos Halogenados/farmacologia , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/farmacologia
9.
Vet J ; 251: 105345, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31492389

RESUMO

A constant rate infusion (CRI) of medetomidine is used to balance equine inhalation anesthesia, but its cardiovascular side effects are a concern. This experimental crossover study aimed to evaluate the effects of vatinoxan (a peripheral α2-adrenoceptor antagonist) on cardiorespiratory and gastrointestinal function in anesthetized healthy horses. Six horses received medetomidine hydrochloride 7µg/kg IV alone (MED) or with vatinoxan hydrochloride 140µg/kg IV (MED+V). Anesthesia was induced with midazolam and ketamine and maintained with isoflurane and medetomidine CRI for 60min. Heart rate, carotid and pulmonary arterial pressures, central venous pressure, cardiac output and arterial and mixed venous blood gases were measured. Selected cardiopulmonary parameters were calculated. Plasma drug concentrations were determined. Fecal output was measured over 24h. For statistical comparisons, repeated measures analysis of covariance and paired t-tests were applied. Heart rate decreased slightly from baseline in the MED group. Arterial blood pressures decreased with both treatments, but significantly more dobutamine was needed to maintain normotension with MED+V (P=0.018). Cardiac index (CI) and oxygen delivery index (DO2I) decreased significantly more with MED, with the largest difference observed at 20min: CI was 39±2 and 73±18 (P=0.009) and DO2I 7.4±1.2 and 15.3±4.8 (P=0.014)mL/min/kg with MED and MED+V, respectively. Fecal output or plasma concentrations of dexmedetomidine did not differ between the treatments. In conclusion, premedication with vatinoxan induced hypotension, thus its use in anesthetized horses warrants further studies. Even though heart rate and arterial blood pressures remained clinically acceptable with MED, cardiac performance and oxygen delivery were lower than with MED+V.


Assuntos
Motilidade Gastrointestinal/efeitos dos fármacos , Isoflurano/farmacologia , Medetomidina/farmacologia , Quinolizinas/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 2 , Anestesia por Inalação/veterinária , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Estudos Cross-Over , Feminino , Frequência Cardíaca/efeitos dos fármacos , Cavalos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Isoflurano/administração & dosagem , Masculino , Medetomidina/administração & dosagem , Quinolizinas/sangue , Quinolizinas/farmacocinética
10.
Vet J ; 251: 105352, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31492391

RESUMO

Pneumonia is one of the potential complications of general anaesthesia in horses. Anaesthesia is known to increase neutrophils in bronchoalveolar lavage fluid (BALF) of horses after lateral recumbency, but studies after dorsal recumbency are lacking. Our primary aim was to determine when lung inflammation reaches its maximum and how rapidly BALF cytology returns to baseline after anaesthesia in dorsal recumbency. A secondary aim was to investigate the possible effect of vatinoxan, a novel drug, on the BALF cytology results. Six healthy experimental horses were enrolled in this observational crossover study. The horses were subject to repeated BALF and blood sampling for 7 days after general anaesthesia with two treatment protocols, and without anaesthesia (control). During the two treatments, the horses received either medetomidine-vatinoxan or medetomidine-placebo as premedication, and anaesthesia was induced with ketamine-midazolam and maintained with isoflurane for 1h in dorsal recumbency. The differences in BALF and blood variables between the two anaesthesia protocols and control were analysed with repeated measures analysis of variance models. In this study, anaesthesia in dorsal recumbency resulted in no clinically relevant changes in airway cytology that could be differentiated from the effect of repeated BALF sampling. No differences in BALF matrix metalloproteinase gelatinolytic activity could be detected between the two treatments or the control series. Marked increase in serum amyloid A was detected in some animals. Vatinoxan as premedication did not consistently affect lung cytology or blood inflammatory markers after anaesthesia.


Assuntos
Anestesia Geral/veterinária , Líquido da Lavagem Broncoalveolar/citologia , Cavalos/fisiologia , Quinolizinas/farmacologia , Anestesia Geral/efeitos adversos , Anestésicos Inalatórios/farmacologia , Animais , Líquido da Lavagem Broncoalveolar/química , Estudos Cross-Over , Hipnóticos e Sedativos/farmacologia , Inflamação , Isoflurano/farmacologia , Medetomidina/farmacologia , Postura/fisiologia , Proteína Amiloide A Sérica
11.
Pediatr Cardiol ; 40(7): 1536-1542, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31414158

RESUMO

This study aimed to evaluate the effects of propofol in diluted and undiluted formulations on cardiac function in infants. Infants > 30 days received propofol sedation for central line insertion. Cases were divided into two groups: those who received undiluted 1% propofol (P1%); and those who received a diluted formulation (Pd) of equal volumes propofol 1% and 0.9% NaCl. Echocardiograms were performed pre (t0)-, immediately post (t1)-, and 1-h post (t2) propofol administration. Myocardial deformation was assessed with tissue Doppler imaging (TDI) analysis and peak longitudinal strain (LS). 18 cases were included: nine (50%) P1% and nine (50%) Pd. In the P1% group, TDI velocities and LS were significantly reduced at t1 and t2. In the Pd Group, only TDI velocities in the left ventricle were reduced at t1, but not at t2. Dilution of propofol may minimize myocardial dysfunction while maintaining adequate sedation in infants. Further comparative studies are needed to investigate the safety and efficacy of this approach.


Assuntos
Hipnóticos e Sedativos/administração & dosagem , Contração Miocárdica/efeitos dos fármacos , Propofol/administração & dosagem , Feminino , Ventrículos do Coração/efeitos dos fármacos , Humanos , Hipnóticos e Sedativos/farmacologia , Recém-Nascido , Masculino , Propofol/farmacocinética
12.
Paediatr Drugs ; 21(5): 379-387, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31418168

RESUMO

BACKGROUND: Digestive endoscopies must be performed within a safe and comfortable environment. We have previously shown that the quality of intravenous sedation is influenced by preoperative stress. AIM: Our primary objective was to compare the effects of oral lorazepam and placebo on the salivary cortisol response of children undergoing a digestive endoscopy. Secondary objectives were the assessment of procedural pain and comfort as well as the occurrence of adverse events. METHODS: Participants were randomized and received either lorazepam, placebo, or no premedication. Saliva was collected upon arrival at the hospital and 1 h following randomization. The sedation protocol included midazolam and fentanyl ± ketamine. Procedural pain was evaluated with the Nurse Assessed Patient Comfort Score (NAPCOMS). Patients completed a postoperative questionnaire. The primary outcome was defined as the proportion of children having a cortisol decrease ≥ 15 nmol/L. RESULTS: 101 participants (54 females) were included. The rate of children having a cortisol decrease ≥ 15 nmol/L was 27.3%, 35.3%, and 19.4% for lorazepam, placebo, and no premedication, respectively (p = 0.356). The median (IQR) NAPCOMS pain score was 3.0 (0-6) for lorazepam, 4.4 (0-6) for placebo, and 3.4 (3-4) for no premedication (p = 0.428). With lorazepam, 75.9% of children reported experiencing a comfortable procedure, compared with 41.9% taking placebo and 34.5% with no premedication (p = 0.013). Transient tachycardia was the most frequent intraoperative adverse event, particularly with lorazepam (62.5%, p = 0.029). CONCLUSIONS: Oral lorazepam had no effect on patients' preoperative stress, as measured by salivary cortisol, but was associated with a higher rate of comfortable procedures. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, Identifier NCT03180632.


Assuntos
Endoscopia/métodos , Hipnóticos e Sedativos/uso terapêutico , Lorazepam/uso terapêutico , Adolescente , Criança , Método Duplo-Cego , Feminino , Humanos , Hipnóticos e Sedativos/farmacologia , Lorazepam/farmacologia , Masculino
13.
Nature ; 571(7764): 198-204, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31292557

RESUMO

Slow-wave sleep and rapid eye movement (or paradoxical) sleep have been found in mammals, birds and lizards, but it is unclear whether these neuronal signatures are found in non-amniotic vertebrates. Here we develop non-invasive fluorescence-based polysomnography for zebrafish, and show-using unbiased, brain-wide activity recording coupled with assessment of eye movement, muscle dynamics and heart rate-that there are at least two major sleep signatures in zebrafish. These signatures, which we term slow bursting sleep and propagating wave sleep, share commonalities with those of slow-wave sleep and paradoxical or rapid eye movement sleep, respectively. Further, we find that melanin-concentrating hormone signalling (which is involved in mammalian sleep) also regulates propagating wave sleep signatures and the overall amount of sleep in zebrafish, probably via activation of ependymal cells. These observations suggest that common neural signatures of sleep may have emerged in the vertebrate brain over 450 million years ago.


Assuntos
Neurônios/fisiologia , Sono/fisiologia , Peixe-Zebra/fisiologia , Animais , Evolução Biológica , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Epêndima/citologia , Movimentos Oculares , Fluorescência , Frequência Cardíaca , Hipnóticos e Sedativos/farmacologia , Hormônios Hipotalâmicos/metabolismo , Melaninas/metabolismo , Neurônios/efeitos dos fármacos , Pigmentação/fisiologia , Hormônios Hipofisários/metabolismo , Polissonografia/métodos , Sono/efeitos dos fármacos , Privação do Sono/fisiopatologia , Sono REM/efeitos dos fármacos , Sono REM/fisiologia , Sono de Ondas Lentas/efeitos dos fármacos , Sono de Ondas Lentas/fisiologia
14.
Paediatr Drugs ; 21(5): 371-378, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31292919

RESUMO

AIM: Triclofos sodium (TFS) has been used for many years in children as a sedative for painless medical procedures. It is physiologically and pharmacologically similar to chloral hydrate, which has been censured for use in children with neurocognitive disorders. The aim of this study was to investigate the safety and efficacy of TFS sedation in a pediatric population with a high rate of neurocognitive disability. METHODS: The database of the neurodiagnostic institute of a tertiary academic pediatric medical center was retrospectively reviewed for all children who underwent sedation with TFS in 2014. Data were collected on demographics, comorbidities, neurologic symptoms, sedation-related variables, and outcome. RESULTS: The study population consisted of 869 children (58.2% male) of median age 25 months (range 5-200 months); 364 (41.2%) had neurocognitive diagnoses, mainly seizures/epilepsy, hypotonia, or developmental delay. TFS was used for routine electroencephalography in 486 (53.8%) patients and audiometry in 401 (46.2%). Mean (± SD) dose of TFS was 50.2 ± 4.9 mg/kg. Median time to sedation was 45 min (range 5-245), and median duration of sedation was 35 min (range 5-190). Adequate sedation depth was achieved in 769 cases (88.5%). Rates of sedation-related adverse events were low: apnea, 0; desaturation ≤ 90%, 0.2% (two patients); and emesis, 0.35% (three patients). None of the children had hemodynamic instability or signs of poor perfusion. There was no association between desaturations and the presence of hypotonia or developmental delay. CONCLUSION: TFS, when administered in a controlled and monitored environment, may be safe for use in children, including those with underlying neurocognitive disorders.


Assuntos
Hipnóticos e Sedativos/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Organofosfatos/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Hipnóticos e Sedativos/farmacologia , Lactente , Masculino , Organofosfatos/farmacologia
15.
Anesthesiology ; 131(2): 254-265, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31314747

RESUMO

BACKGROUND: Elucidating networks underlying conscious perception is important to understanding the mechanisms of anesthesia and consciousness. Previous studies have observed changes associated with loss of consciousness primarily using resting paradigms. The authors focused on the effects of sedation on specific cognitive systems using task-based functional magnetic resonance imaging. The authors hypothesized deepening sedation would degrade semantic more than perceptual discrimination. METHODS: Discrimination of pure tones and familiar names were studied in 13 volunteers during wakefulness and propofol sedation targeted to light and deep sedation. Contrasts highlighted specific cognitive systems: auditory/motor (tones vs. fixation), phonology (unfamiliar names vs. tones), and semantics (familiar vs. unfamiliar names), and were performed across sedation conditions, followed by region of interest analysis on representative regions. RESULTS: During light sedation, the spatial extent of auditory/motor activation was similar, becoming restricted to the superior temporal gyrus during deep sedation. Region of interest analysis revealed significant activation in the superior temporal gyrus during light (t [17] = 9.71, P < 0.001) and deep sedation (t [19] = 3.73, P = 0.001). Spatial extent of the phonologic contrast decreased progressively with sedation, with significant activation in the inferior frontal gyrus maintained during light sedation (t [35] = 5.17, P < 0.001), which didn't meet criteria for significance in deep sedation (t [38] = 2.57, P = 0.014). The semantic contrast showed a similar pattern, with activation in the angular gyrus during light sedation (t [16] = 4.76, P = 0.002), which disappeared in deep sedation (t [18] = 0.35, P = 0.731). CONCLUSIONS: Results illustrate broad impairment in cognitive cortex during sedation, with activation in primary sensory cortex beyond loss of consciousness. These results agree with clinical experience: a dose-dependent reduction of higher cognitive functions during light sedation, despite partial preservation of sensory processes through deep sedation.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Cognição/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Imagem por Ressonância Magnética/métodos , Propofol/farmacologia , Adulto , Feminino , Humanos , Masculino , Valores de Referência , Adulto Jovem
16.
Br J Anaesth ; 123(3): 298-308, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31277837

RESUMO

BACKGROUND: Emergence from sedation entails rapid increase in the levels of both awareness and wakefulness, the two axes of consciousness. Functional MRI (fMRI) studies of emergence from sedation often focus on the recovery period, with no description of the moment of emergence. We hypothesised that by focusing on the moment of emergence, novel insights, primarily about subcortical activity and increased wakefulness, will be gained. METHODS: We conducted a resting state fMRI analysis of 17 male subjects (20-40 yr old) gradually entering into and emerging from deep sedation (average computed propofol concentrations of 2.41 and 1.11 µg ml-1, respectively), using target-controlled infusion of propofol. RESULTS: Functional connectivity analysis revealed a robust spatiotemporal signature of return of consciousness, in which subcortical seeds showed transient positive correlations that rapidly turned negative shortly after emergence. Elements of this signature included four components of the ascending reticular activating system: the ventral tegmentum area, the locus coeruleus, median raphe, and the mammillary body. The involvement of the rostral dorsolateral pontine tegmentum, which is specifically impaired in comatose patients with pontine lesions, in emergence was previously unknown. CONCLUSIONS: Emergence from propofol sedation is characterised, and possibly driven, by a transient activation of brainstem loci. Some of these loci are known components of the ascending reticular activating system, whereas an additional locus was found that is also impaired in comatose patients.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Sedação Profunda/métodos , Hipnóticos e Sedativos/farmacologia , Propofol/farmacologia , Adulto , Período de Recuperação da Anestesia , Mapeamento Encefálico/métodos , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/fisiologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiologia , Estado de Consciência/efeitos dos fármacos , Esquema de Medicação , Humanos , Hipnóticos e Sedativos/administração & dosagem , Imagem por Ressonância Magnética , Masculino , Rede Nervosa/efeitos dos fármacos , Propofol/administração & dosagem , Adulto Jovem
17.
J Zoo Wildl Med ; 50(2): 457-460, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260214

RESUMO

Two anesthetic protocols in adult giraffe were compared by retrospective study. Thirteen anesthesia records for medetomidine-ketamine (MK) and seven for medetomidine-ketamine with a potent opioid (MKO) were evaluated for differences in demographic, behavioral, drug, and respiratory parameters. Giraffe stood significantly more quickly with MKO vs MK though MK animals were physically restrained to preclude premature standing as part of normal recovery practices (5.5 min vs 21.4 min, P = 0.01). Regurgitation was recorded in 5/13 and resedation in 4/13 MK animals. The range of values for blood lactate was higher in MKO (5.18-11.25 mM/L) than in MK giraffe (0.78-6.08 mM/L). Despite limitations of a retrospective study, both MK and MKO giraffe anesthesia protocols exhibit benefits and side effects. Awareness and management of these factors will improve outcomes until standardized, prospective studies of giraffe immobilization offer more comprehensive guidance on protocol selection.


Assuntos
Analgésicos Opioides/farmacologia , Anestesia/veterinária , Girafas , Ketamina/farmacologia , Medetomidina/farmacologia , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anestésicos Dissociativos/administração & dosagem , Anestésicos Dissociativos/efeitos adversos , Anestésicos Dissociativos/farmacologia , Animais , Feminino , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/farmacologia , Injeções Intramusculares , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Masculino , Medetomidina/administração & dosagem , Medetomidina/efeitos adversos , Estudos Retrospectivos
18.
Artigo em Chinês | MEDLINE | ID: mdl-31262103

RESUMO

Objective: To compare the parameters of polysomnography (PSG) in sleep structure and respiratory events between dexmedetomidine-induced sleep and natural sleep. Methods: From April 2016 to September 2018, a total of 44 patients with obstructive sleep apnea (OSA) and 3 patients with simple snoring completed PSG monitor both in natural sleep and dexmedetomidine-induced sleep in Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tsinghua Changgung Hospital. The PSG parameters were statistically analysed with SPSS 22.0 software. Results: The average dose of dexmedetomidine was (104.60±27.93) µg, and there was no significant difference between the induced-sleep efficiency and the natural sleep efficiency (82.14%±16.66% vs. 86.50%±9.18%, t=-1.559, P>0.05). There was no rapid eye movement(REM) stages in all 47 subjects and only 1 case of them had non-rapid eye movement(NREM) stage 3 in induced sleep. The percentage of NREM1 in total sleep time was statistically different between the two groups (42.10%±26.71% vs. 17.47%±11.68%, t=5.997, P<0.001),but there was no significant difference in the percentage of NREM2 in total sleep time between the two groups (56.96%±26.0% vs. 62.95%±9.03%, t=-1.521, P=0.135). About respiratory events, there were significant differences in apnea hypopnea index ((46.29±20.23)/h vs. (39.67±25.41)/h), obstructive apnea index (25.20[10.50,45.40]/h vs. 16.20[3.30,35.20]/h) between induced-sleep and natural sleep (t=2.297, Z=-3.008, all P<0.05), these difference were more significant in mild-to-moderate OSA. There were no statistically significant differences in central apnea index (0.00[0.00,2.80]/h vs. 0.40[0.10,1.20]/h), mixed apnea index (0.00[0.00,6.20]/h vs. 0.00[0.00,3.40]/h, hypopnea index (4.20[0.00,3.30]/h vs. 12.00[5.20,17.40]/h), Z=-0.110,-0.508,-1.544, all P>0.05). There were statistical differences in the lowest oxygen saturation (84.77%±7. 59% vs. 80.21%±11.62%, t=2.558, P=0.014). Conclusions: There is no significant difference in sleep efficiency and NREM2 between dexmedetomidine induced sleep and natural sleep.NREM3 sleep is rare induced, but REM sleep is none of all. And dexmedetomidine induced sleep may aggravate obstructive sleep apnea, but not central apnea.


Assuntos
Dexmedetomidina/farmacologia , Hipnóticos e Sedativos/farmacologia , Polissonografia , Apneia Obstrutiva do Sono/fisiopatologia , Sono , Ronco/fisiopatologia , Humanos , Respiração/efeitos dos fármacos , Sono/efeitos dos fármacos , Sono/fisiologia
19.
Crit Care ; 23(1): 245, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277722

RESUMO

BACKGROUND: In critically ill patients, poor patient-ventilator interaction may worsen outcomes. Although sedatives are often administered to improve comfort and facilitate ventilation, they can be deleterious. Whether opioids improve asynchronies with fewer negative effects is unknown. We hypothesized that opioids alone would improve asynchronies and result in more wakeful patients than sedatives alone or sedatives-plus-opioids. METHODS: This prospective multicenter observational trial enrolled critically ill adults mechanically ventilated (MV) > 24 h. We compared asynchronies and sedation depth in patients receiving sedatives, opioids, or both. We recorded sedation level and doses of sedatives and opioids. BetterCare™ software continuously registered ineffective inspiratory efforts during expiration (IEE), double cycling (DC), and asynchrony index (AI) as well as MV modes. All variables were averaged per day. We used linear mixed-effects models to analyze the relationships between asynchronies, sedation level, and sedative and opioid doses. RESULTS: In 79 patients, 14,166,469 breaths were recorded during 579 days of MV. Overall asynchronies were not significantly different in days classified as sedatives-only, opioids-only, and sedatives-plus-opioids and were more prevalent in days classified as no-drugs than in those classified as sedatives-plus-opioids, irrespective of the ventilatory mode. Sedative doses were associated with sedation level and with reduced DC (p < 0.0001) in sedatives-only days. However, on days classified as sedatives-plus-opioids, higher sedative doses and deeper sedation had more IEE (p < 0.0001) and higher AI (p = 0.0004). Opioid dosing was inversely associated with overall asynchronies (p < 0.001) without worsening sedation levels into morbid ranges. CONCLUSIONS: Sedatives, whether alone or combined with opioids, do not result in better patient-ventilator interaction than opioids alone, in any ventilatory mode. Higher opioid dose (alone or with sedatives) was associated with lower AI without depressing consciousness. Higher sedative doses administered alone were associated only with less DC. TRIAL REGISTRATION: ClinicalTrial.gov, NCT03451461.


Assuntos
Analgésicos Opioides/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Respiração Artificial/métodos , Mecânica Respiratória/efeitos dos fármacos , Idoso , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/farmacologia , Estado Terminal/terapia , Feminino , Humanos , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/farmacologia , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração Artificial/efeitos adversos , Respiração Artificial/instrumentação , Espanha
20.
Artigo em Inglês | MEDLINE | ID: mdl-31280242

RESUMO

Background The aim of this experiment was to evaluate the cytotoxic, thrombolytic, analgesic, sedative-hypnotic and anxiolytic activities of the methanolic extract of Ficus cunia leaves. Methods Primary phytochemical screening was accomplished by using established methods. Cytotoxicity was studied by brine shrimp lethality test, and the thrombolytic assay was conducted through clot lysis method with human blood. The in vivo action was done using mice of both sexes. The analgesic activity was evaluated by acetic acid-induced writhing test and formalin-induced paw licking test. Open field, hole cross and thiopental Na-induced sleeping time test were used to examine the sedative-hypnotic activity, and elevated plus maze (EPM) and hole board test were used to identify the anxiolytic activity. Results The results elicited that the extract contained several phytochemicals such as alkaloid, flavonoid, and tannin. The extract was found to have a median lethal concentration (LC50) value of 55.48 µg/mL in the brine shrimp lethality bioassay. It was also assessed for antithrombotic activity when compared with streptokinase; it has significant (p < 0.001) thrombolytic effect (34.72 ± 1.74%) contrasted with standard streptokinase (67 ± 1.56%). The extract at doses of 200 and 400 mg/kg produced inhibition of 32.58% and 46.63% in acetic acid-induced pain and 45.88 and 61.18% in formalin-induced pain. The sedative and hypnotic activities on the central nervous system of the methanol extract of F. cunia (MEFC) leaves were evaluated. The extract delivered critical sedative impact at the doses of 200 and 400 mg/kg (by oral route) treated with reference to the substance diazepam, and the hypnotic impact was also observed in the case of mice. MEFC at its maximum dose (400 mg/kg) significantly (p < 0.01) increased the time spent in the open arms of the EPM. In the hole board test, there was a dose-dependent (at 200 and 400 mg/kg) and a significant (p < 0.05 and p < 0.01) increase in the number of head pokes in comparison to control. Conclusions The results of the present study gave a helpful baseline in progression for the possible use of MEFC as a cytotoxic, thrombolytic, analgesic, sedative-hypnotic and anxiolytic drug.


Assuntos
Analgésicos/farmacologia , Fibrinolíticos/farmacologia , Ficus/química , Metanol/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Artemia/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Feminino , Humanos , Hipnóticos e Sedativos/farmacologia , Camundongos , Dor/tratamento farmacológico , Fitoterapia/métodos
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