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2.
Minerva Med ; 111(2): 115-119, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32166934

RESUMO

BACKGROUND: Tachycardia prior to endoscopic procedures is commonly encountered which reflect patient anxiety status. Despite this frequent occurrence, it is unclear if in a patient with tachycardia sedation dose should be modified. The aim of our study was to assess the effect of pre-endoscopic tachycardia on sedation dose. METHODS: A retrospective analysis of all patients who underwent upper endoscopy and colonoscopy at EMMS Nazareth hospital were performed. We excluded patients with diseases and medications affecting the heart rate. RESULTS: A total of 2855 patients were included in the study. Two-hundred and thirty-seven patients had tachycardia before endoscopy (8.3%, group A) as compared to 2618 (group B) patients who had heart rate ≤100 beats per minute. The mean dosage of propofol in group A was significantly higher (62.6±33.2 mg vs. 57.4±29.9 mg) than in group B (P=0.01). There was no difference in the cecal intubation rate among the two groups (P=0.9). Notably, the adenoma detection rate was significantly lower among group A patients as compared to group B (13.6% vs. 22.8%, P=0.02) patients. There were no sedation related complications. CONCLUSIONS: Tachycardia prior to endoscopic procedures was associated with higher sedative dosage and lower adenoma detection rate, however no major complications were recorded. These data should be taken into consideration to optimize procedure quality.


Assuntos
Adenoma/diagnóstico por imagem , Endoscopia Gastrointestinal/psicologia , Neoplasias Gastrointestinais/diagnóstico por imagem , Hipnóticos e Sedativos/administração & dosagem , Taquicardia/psicologia , Adulto , Idoso , Ansiedade/tratamento farmacológico , Ansiedade/psicologia , Estudos de Casos e Controles , Colonoscopia/psicologia , Feminino , Fentanila/administração & dosagem , Gastroscopia/psicologia , Frequência Cardíaca , Humanos , Masculino , Midazolam/administração & dosagem , Pessoa de Meia-Idade , Período Pré-Operatório , Propofol/administração & dosagem , Estudos Retrospectivos , Taquicardia/epidemiologia
3.
N Engl J Med ; 382(12): 1103-1111, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32068366

RESUMO

BACKGROUND: In critically ill, mechanically ventilated patients, daily interruption of sedation has been shown to reduce the time on ventilation and the length of stay in the intensive care unit (ICU). Data on whether a plan of no sedation, as compared with a plan of light sedation, has an effect on mortality are lacking. METHODS: In a multicenter, randomized, controlled trial, we assigned, in a 1:1 ratio, mechanically ventilated ICU patients to a plan of no sedation (nonsedation group) or to a plan of light sedation (i.e., to a level at which the patient was arousable, defined as a score of -2 to -3 on the Richmond Agitation and Sedation Scale [RASS], on which scores range from -5 [unresponsive] to +4 [combative]) (sedation group) with daily interruption. The primary outcome was mortality at 90 days. Secondary outcomes were the number of major thromboembolic events, the number of days free from coma or delirium, acute kidney injury according to severity, the number of ICU-free days, and the number of ventilator-free days. Between-group differences were calculated as the value in the nonsedation group minus the value in the sedation group. RESULTS: A total of 710 patients underwent randomization, and 700 were included in the modified intention-to-treat analysis. The characteristics of the patients at baseline were similar in the two trial groups, except for the score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, which was 1 point higher in the nonsedation group than in the sedation group, indicating a greater chance of in-hospital death. The mean RASS score in the nonsedation group increased from -1.3 on day 1 to -0.8 on day 7 and, in the sedation group, from -2.3 on day 1 to -1.8 on day 7. Mortality at 90 days was 42.4% in the nonsedation group and 37.0% in the sedated group (difference, 5.4 percentage points; 95% confidence interval [CI], -2.2 to 12.2; P = 0.65). The number of ICU-free days and of ventilator-free days did not differ significantly between the trial groups. The patients in the nonsedation group had a median of 27 days free from coma or delirium, and those in the sedation group had a median of 26 days free from coma or delirium. A major thromboembolic event occurred in 1 patient (0.3%) in the nonsedation group and in 10 patients (2.8%) in the sedation group (difference, -2.5 percentage points; 95% CI, -4.8 to -0.7 [unadjusted for multiple comparisons]). CONCLUSIONS: Among mechanically ventilated ICU patients, mortality at 90 days did not differ significantly between those assigned to a plan of no sedation and those assigned to a plan of light sedation with daily interruption. (Funded by the Danish Medical Research Council and others; NONSEDA ClinicalTrials.gov number, NCT01967680.).


Assuntos
Sedação Consciente , Estado Terminal/terapia , Hipnóticos e Sedativos/administração & dosagem , Respiração Artificial , Idoso , Idoso de 80 Anos ou mais , Coma/complicações , Sedação Consciente/métodos , Estado Terminal/mortalidade , Delírio/complicações , Feminino , Humanos , Infusões Intravenosas , Unidades de Terapia Intensiva , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Tempo de Internação , Masculino , Midazolam/administração & dosagem , Pessoa de Meia-Idade , Propofol/administração & dosagem , Respiração Artificial/efeitos adversos , Tromboembolia/etiologia
4.
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
5.
PLoS One ; 15(1): e0227499, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31923236

RESUMO

BACKGROUND: Pain management and sedation are important aspects in the treatment of hospitalized patients, especially those mechanically ventilated. In many hospitals, such patients are treated not only in intensive care units, but also in other wards. In the nineteen eighties, numerous studies demonstrated a wide array of misconceptions and inadequate knowledge related to commonly used sedative, analgesics and muscle relaxants which may prevent appropriate treatment. Since these publications, multiple studies have shown that appropriate sedation and analgesia are associated with improved clinical outcomes, educational programs were developed and guidelines published. Whether the personnel's knowledge kept up with these changes is unknown. The aim of this study was to determine the current rate of misconceptions and knowledge gaps regarding commonly used sedative, analgesic and neuromuscular drugs. METHODS: In this prospective, observational, cross-sectional survey, a questionnaire was e-mailed to physicians and nurses routinely treating mechanically ventilated patients in Rambam Health Care Campus (Haifa, Israel). RESULTS: 355 questionnaires were returned. 82.54% knew that midazolam has no analgesic effect. 71-72% were familiar with the sedative effect of opiates. 27% believed that propofol has analgesic properties and 30.52% thought that rocuronium has a sedative effect. CONCLUSION: Our findings demonstrate that although a lot has been done during the last decades in order to improve the treatment of critically ill patients, the rate of misconceptions regarding pharmacological characteristics of commonly used drugs is unacceptably high. We call for performance of similar surveys in other institutes and for immediate action to improve patients' care.


Assuntos
Analgésicos/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Enfermeiras e Enfermeiros/psicologia , Médicos/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Midazolam/administração & dosagem , Pessoa de Meia-Idade , Propofol/administração & dosagem , Estudos Prospectivos , Respiração Artificial , Rocurônio/administração & dosagem , Inquéritos e Questionários , Resultado do Tratamento
6.
Am J Vet Res ; 81(1): 65-76, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31887090

RESUMO

OBJECTIVE: To evaluate the sedative and cardiorespiratory effects of IM administration of alfaxalone and butorphanol combined with acepromazine, midazolam, or dexmedetomidine in dogs. ANIMALS: 6 young healthy mixed-breed hounds. PROCEDURES: Dogs received each of 3 treatments (alfaxalone [2 mg/kg] and butorphanol [0.4 mg/kg] combined with acepromazine [0.02 mg/kg; AB-ace], midazolam [0.2 mg/kg; AB-mid], or dexmedetomidine [0.005 mg/kg; AB-dex], IM) in a blinded, randomized crossover-design study with a 1-week washout period between treatments. Sedation scores and cardiorespiratory variables were recorded at predetermined time points. Data were analyzed by use of mixed-model ANOVA and linear generalized estimating equations with post hoc adjustments. RESULTS: All treatments resulted in moderate to deep sedation (median score, ≥ 15/21) ≤ 5 minutes after injection. Sedation scores did not differ among treatments until the 40-minute time point, when the score was higher for AB-dex than for other treatments. Administration of AB-dex resulted in median scores reflecting deep sedation until 130 minutes, versus 80 and 60 minutes for AB-ace and AB-mid, respectively, after injection. Heart rate, cardiac output, and oxygen delivery decreased significantly after AB-dex, but not AB-ace or AB-mid administration. Respiratory variables remained within clinically acceptable ranges after all treatments. Undesirable recovery characteristics were observed in 4 dogs after AB-mid treatment. Four dogs required atipamezole administration 180 minutes after AB-dex injection. CONCLUSIONS AND CLINICAL RELEVANCE: All protocols produced reliable sedation. The results indicated that in young, healthy dogs, AB-mid may produce undesirable recovery characteristics; AB-dex treatment caused cardiovascular depression and should be used with caution.


Assuntos
Anestesia/veterinária , Anestésicos/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Sedação Profunda/veterinária , Injeções Intramusculares/veterinária , Acepromazina/administração & dosagem , Anestesia/efeitos adversos , Anestesia/normas , Anestésicos/administração & dosagem , Animais , Butorfanol/administração & dosagem , Estudos Cross-Over , Dexmedetomidina/administração & dosagem , Cães , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/farmacologia , Masculino , Midazolam/administração & dosagem , Pregnanodionas/administração & dosagem
7.
Eur J Pharm Sci ; 141: 105095, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31626965

RESUMO

PURPOSE: The aim of the present study was to develop a population pharmacokinetic model of midazolam, and to evaluate the influence of maturation process and other variability factors in critically ill children with severe acute bronchiolitis, who received a long-term intravenous infusion of midazolam. METHODS: In the study were included 49 critically ill children of both genders (from 0 to 130 weeks of age) with severe acute bronchiolitis hospitalised in intensive care units. Nonlinear mixed effects modelling approach was applied for data analyses and simulations. RESULTS: The final model is a two-compartment model that includes the effects of body weight using allometric scaling with fixed exponents and maturation of clearance. For a typical subject, scaled to the adult body weight of 70 kg, population pharmacokinetic values were estimated at 8.52 L/h for clearance (when maturation function was 1), 25.5 L/h for intercompartmental clearance, and 5.71 L and 39.8 L for the volume of the central and peripheral compartment, respectively. Based on the final model, maturation reaches 50% of the adult clearance in 45.9 weeks of postmenstrual age. The influence of gender, ABCB1 genotype and biochemical parameters on midazolam clearance was not detected. Results of simulations indicate the need for reduced dosing in certain groups of patients in order to maintain plasma concentrations of midazolam within recommended values. CONCLUSIONS: The developed population pharmacokinetic model can contribute to the dosing optimisation of midazolam, especially in critically ill children as it includes the influence of size and maturation of clearance, which are important parameters for achieving the desired plasma concentrations of midazolam.


Assuntos
Hipnóticos e Sedativos/farmacocinética , Midazolam/farmacocinética , Modelos Biológicos , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Bronquiolite/genética , Bronquiolite/metabolismo , Bronquiolite/terapia , Estado Terminal , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/sangue , Lactente , Recém-Nascido , Infusões Intravenosas , Masculino , Midazolam/administração & dosagem , Midazolam/sangue , Polimorfismo de Nucleotídeo Único , Respiração Artificial
8.
Pediatrics ; 145(1)2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31862730

RESUMO

CONTEXT: Intranasal dexmedetomidine (IND) is an emerging agent for procedural distress in children. OBJECTIVE: To explore the effectiveness of IND for procedural distress in children. DATA SOURCES: We performed electronic searches of Medline (1946-2019), Embase (1980-2019), Google Scholar (2019), Cumulative Index to Nursing and Allied Health Literature (1981-2019), and Cochrane Central Register. STUDY SELECTION: We included randomized trials of IND for procedures in children. DATA EXTRACTION: Methodologic quality of evidence was evaluated by using the Cochrane Collaboration's risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system, respectively. The primary outcome was the proportion of participants with adequate sedation. RESULTS: Among 19 trials (N = 2137), IND was superior to oral chloral hydrate (3 trials), oral midazolam (1 trial), intranasal midazolam (1 trial), and oral dexmedetomidine (1 trial). IND was equivalent to oral chloral hydrate (2 trials), intranasal midazolam (2 trials), and intranasal ketamine (3 trials). IND was inferior to oral ketamine and a combination of IND plus oral ketamine (1 trial). Higher doses of IND were superior to lower doses (4 trials). Adverse effects were reported in 67 of 727 (9.2%) participants in the IND versus 98 of 591 (16.6%) in the comparator group. There were no reports of adverse events requiring resuscitative measures. LIMITATIONS: The adequacy of sedation was subjective, which possibly led to biased outcome reporting. CONCLUSIONS: Given the methodologic limitations of included trials, IND is likely more effective at sedating children compared to oral chloral hydrate and oral midazolam. However, this must be weighed against the potential for adverse cardiovascular effects.


Assuntos
Sedação Consciente/métodos , Dexmedetomidina/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Administração Intranasal , Administração Oral , Criança , Hidrato de Cloral/administração & dosagem , Técnicas e Procedimentos Diagnósticos , Humanos , Midazolam/administração & dosagem
9.
Isr Med Assoc J ; 21(11): 743-746, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31713363

RESUMO

BACKGROUND: The use of oral midazolam as premedication to induce anxiolysis before surgical procedures under local anesthesia is widely accepted in plastic surgery. Rhinoplasty performed under local anesthesia is known to generate high levels of perioperative anxiety, thus the use of appropriate premedication is important. Oral midazolam has been shown to be safe in various procedures. However, the safety of oral midazolam before rhinoplasty has not been evaluated. OBJECTIVES: To evaluate the safety of premedication with oral midazolam prior to rhinoplasty by analyzing the intraoperative blood oxygen saturation levels as predictors of adverse respiratory events. METHODS: We retrospectively reviewed the anesthesia records of 62 patients who underwent rhinoplasty under local anesthesia and received premedication with oral midazolam for anxiolysis between March 2017 and December 2017. The median age of the patients was 25.4 years, and they were all classified as American Society of Anesthesiologists class 1. The patients received 10 mg midazolam hydrochloride orally 1 hour prior to the procedure. Oxygen blood saturation was monitored using a pulse oximeter and recorded every 15 minutes. RESULTS: All the patients maintained blood oxygen saturation levels above 95% (median peripheral capillary oxygen saturation 99%) on room air, and they did not require supplemental intraoperative oxygen. There were no transient hypoxemic events during and following the procedure. CONCLUSIONS: Our study confirmed the safety of oral midazolam premedication to reduce perioperative anxiety when performing rhinoplasty under local anesthesia.


Assuntos
Hipnóticos e Sedativos/administração & dosagem , Midazolam/administração & dosagem , Oxigênio/sangue , Rinoplastia , Administração Oral , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oximetria , Pré-Medicação , Estudos Retrospectivos
10.
Plast Reconstr Surg ; 144(5): 836e-840e, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31688759

RESUMO

BACKGROUND: Many ambulatory surgery centers use body mass index as a screening tool to make admissions decisions because of complication risks associated with high-body mass index patients. The objective of this investigation was to evaluate perioperative complications in a cohort of high-body mass index patients undergoing hand and elbow surgery at an ambulatory surgery center. The authors' hypothesis was that anesthesia-related complications for this cohort would be similar to those of a normal-body mass index group. METHODS: The authors retrospectively reviewed data from all hand and elbow procedures performed on patients with a high body mass index (>40 kg/m). One hundred eighty-nine high-body mass index patients and 189 normal-body mass index patients were included in the analysis. RESULTS: The average weight-based dosage of propofol was similar in both groups but was lower in the high-body mass index group for midazolam and fentanyl. Two high-body mass index patients had oxygen desaturations in the postanesthesia care unit. No patients developed complications related to anesthesia. In the high-body mass index group, one patient developed hypotension in the postanesthesia care unit, was admitted to the emergency room for monitoring, but was discharged the following morning. CONCLUSIONS: Outpatient hand surgical care of high-body mass index patients can be performed safely. Body mass index alone should not be considered as an absolute contraindication for surgery. Careful patient selection, evaluation of comorbidities, and close involvement of the anesthesia and medical teams are critical. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.


Assuntos
Procedimentos Cirúrgicos Ambulatórios/métodos , Índice de Massa Corporal , Articulação do Cotovelo/cirurgia , Mãos/cirurgia , Satisfação do Paciente/estatística & dados numéricos , Adulto , Procedimentos Cirúrgicos Ambulatórios/efeitos adversos , Anestésicos Intravenosos/administração & dosagem , Estudos de Coortes , Bases de Dados Factuais , Articulação do Cotovelo/fisiopatologia , Fentanila/administração & dosagem , Mãos/fisiopatologia , Humanos , Masculino , Midazolam/administração & dosagem , Pessoa de Meia-Idade , Assistência Perioperatória/métodos , Valores de Referência , Estudos Retrospectivos , Medição de Risco
12.
Arq. bras. med. vet. zootec. (Online) ; 71(5): 1558-1564, set.-out. 2019. tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1038680

RESUMO

The aim of this study was to assess the effects of chemical restraint, general anesthesia and opioid treatment on hematological components in Cuniculus paca. Eight healthy, adult, captivity female animals , underwent three laparoscopic procedures with a 15-day interval were evaluated. After physical restraint, an association of ketamine (25mg/kg) and midazolam (0.5mg/kg) was administered intramuscularly for chemical restraint. Posteriorly, anesthesia was induced and maintained with isoflurane; and randomly administered methadone (0.5mg/kg), tramadol (5mg/kg) or saline-placebo (0,1mL/kg) intramuscularly. After pharmacological restraint and in the final laparoscopy stage, venous blood samples were obtained for complete blood count, total plasma protein (TP), creatinine, alanine aminotransferase (ALT), sodium, potassium, chloride and ionized calcium analysis. During general anesthesia, hemoglobin, TP concentration and lymphocytes decreased (P=0.029; <0.001; 0.022 respectively), whereas the potassium levels increased (P=0.034). In conclusion, chemical restraint with ketamine/midazolam association causes a slight decrease in blood cellular components. Isoflurane anesthesia for laparoscopic procedure lead to decrease in hemoglobin, lymphocytes and protein concentrations, while potassium increased, without any influence from the tramadol or methadone treatment. However, these alterations were transient, and its hematologic values can collaborate in carrying out epidemiological, pathophysiological or case studies in the Cuniculus paca.(AU)


O objetivo do presente estudo foi avaliar os efeitos de contenção química, anestesia geral e tratamento com opiáceos nos parâmetros hematológicos em Cuniculus paca. Foram avaliados oito animais saudáveis, fêmeas, adultas, de cativeiro, que foram submetidas a três procedimentos laparoscópicos, com intervalo de 15 dias. Após a contenção física, uma associação de cetamina (25mg/kg) e midazolam (0,5mg/kg) foi administrada por via intramuscular para contenção química. Posteriormente, a anestesia foi induzida e mantida com isoflurano, e administrou-se aleatoriamente metadona (0,5mg/kg), tramadol (5mg/kg) ou placebo salina por via intramuscular. Após a contenção farmacológica e em estágio final da laparoscopia, foram obtidas amostras de sangue venoso para contagem sanguínea completa, proteína de plasma total (TP), creatinina, alanina aminotransferase (ALT), cálcio, sódio, potássio e cloreto ionizado. Durante a anestesia geral, a concentração de hemoglobina, TP e linfócitos diminuiu (P= 0,029;< 0,001; 0,022, respectivamente), enquanto os níveis de potássio aumentaram (P= 0,034). Em conclusão, a contenção química com associação de cetamina/midazolam promove uma ligeira diminuição dos componentes celulares do sangue. A anestesia com isoflavano para o procedimento laparoscópico levou a uma diminuição das concentrações de hemoglobina, linfócitos e proteínas, enquanto o potássio aumentou, sem qualquer influência do tratamento com tramadol ou metadona. No entanto, essas alterações foram transitórias, e os seus valores hematológicos obtidos podem colaborar na realização de estudos epidemiológicos, fisiopatológicos ou casuísticas para Cuniculus paca.(AU)


Assuntos
Animais , Feminino , Cuniculidae/cirurgia , Cuniculidae/sangue , Anestesia/veterinária , Anestésicos/sangue , Tramadol/administração & dosagem , Midazolam/administração & dosagem , Isoflurano/administração & dosagem , Ketamina/administração & dosagem , Metadona/administração & dosagem
13.
Biol Pharm Bull ; 42(9): 1590-1595, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474719

RESUMO

There are large inter- and intra-individual variations in CYP3A4 activity. Midazolam, which is predominantly metabolized to 1'-hydroxymidazolam and 4-hydroxymidazolam by CYP3A4, is considered an effective probe for CYP3A4. To determine the area under the curve (AUC) of midazolam or midazolam clearance for CYP3A4 activity, multiple plasma samples of midazolam are required. This study aimed to evaluate whether measurement of a single plasma concentration or urinary excretion of midazolam could be used to predict the AUC of midazolam in healthy volunteers. We conducted a retrospective analysis of two pharmacokinetic studies. Nineteen volunteers received intravenous (5, 15, and 30 µg/kg) and oral (15, 50, and 100 µg/kg) administration of midazolam on sequential days. The midazolam concentration in plasma and urine was determined by LC-MS/MS. Plasma midazolam concentrations showed a good correlation with the AUC at all blood sampling points after the administrations. The coefficient of determination was highest at 1-2 and 2-4 h after intravenous (>0.96) and oral administration (>0.94), respectively, among all the sampling times. The errors for bias and accuracy of prediction were the lowest at 1.5 and 4 h after intravenous and oral administration, respectively. In case of urinary excretion, a significant positive correlation between midazolam and the AUC was observed only after oral administration. Thus, the AUC of midazolam can be evaluated by blood sampling at 1.5 h after intravenous administration and at 4 h after oral administration.


Assuntos
Citocromo P-450 CYP3A/metabolismo , Voluntários Saudáveis , Midazolam/administração & dosagem , Midazolam/sangue , Midazolam/urina , Administração Oral , Área Sob a Curva , Estudos Cross-Over , Relação Dose-Resposta a Droga , Humanos , Injeções Intravenosas , Taxa de Depuração Metabólica , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Tempo
14.
Nat Commun ; 10(1): 4373, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31558719

RESUMO

MR-guided focused ultrasound (MRgFUS) is an emerging technology that can accurately and transiently permeabilize the blood-brain barrier (BBB) for targeted drug delivery to the central nervous system. We conducted a single-arm, first-in-human trial to investigate the safety and feasibility of MRgFUS-induced BBB opening in eloquent primary motor cortex in four volunteers with amyotrophic lateral sclerosis (ALS). Here, we show successful BBB opening using MRgFUS as demonstrated by gadolinium leakage at the target site immediately after sonication in all subjects, which normalized 24 hours later. The procedure was well-tolerated with no serious clinical, radiologic or electroencephalographic adverse events. This study demonstrates that non-invasive BBB permeabilization over the motor cortex using MRgFUS is safe, feasible, and reversible in ALS subjects. In future, MRgFUS can be coupled with promising therapeutics providing a targeted delivery platform in ALS.


Assuntos
Esclerose Amiotrófica Lateral/diagnóstico por imagem , Barreira Hematoencefálica/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Ultrassonografia/métodos , Idoso , Esclerose Amiotrófica Lateral/tratamento farmacológico , Anestésicos Intravenosos/administração & dosagem , Barreira Hematoencefálica/fisiologia , Sistemas de Liberação de Medicamentos/métodos , Estudos de Viabilidade , Feminino , Fentanila/administração & dosagem , Humanos , Masculino , Midazolam/administração & dosagem , Pessoa de Meia-Idade , Estudos Prospectivos
15.
Vet Anaesth Analg ; 46(5): 587-596, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31395483

RESUMO

OBJECTIVE: To determine whether the use of a single dose of midazolam affects quality and duration of the recovery period in healthy dogs undergoing elective castration or ovariohysterectomy. STUDY DESIGN: Prospective, randomized, placebo-controlled, masked clinical trial. ANIMAL POPULATION: Seventy-four client-owned dogs undergoing neutering. METHODS: Following cage demeanour scoring using a simple descriptive scale (SDS), dogs were premedicated with acepromazine (0.03 mg kg-1) and pethidine (3 mg kg-1) intramuscularly (quadriceps muscle). Twenty minutes later sedation was scored with an SDS. Male dogs were induced with midazolam (0.25 mg kg-1) (group M) or an equivalent amount of Hartmann's solution (group P) and propofol intravenously (IV). Female dogs were induced with propofol alone and were administered midazolam (group M) or Hartmann's solution (group P) 5 minutes before intraoperative manipulation of the first ovary. Anaesthesia was maintained with isoflurane in oxygen. Intraoperative analgesia was provided with morphine (0.3 mg kg-1 IV) prior to the start of surgery. Male dogs were administered intratesticular lidocaine (1 mg kg-1). All dogs were administered meloxicam (0.2 mg kg-1 IV) at the end of the procedure, and recovery was scored with an SDS following extubation and 30 minutes later. Time to extubation, head lift, sternal position and standing and complications during recovery were recorded. Data are presented as median (range). RESULTS: Time to standing was significantly longer in animals in group M [56 (13-179) minutes] than in group P [44 (4-137) minutes], and the early recovery score in group M [3 (2-6)] was overall worse than in group P [3 (1-5)]. Significantly more dogs in group M (n = 30) than in group P (n = 22) displayed hypotension. CONCLUSIONS AND CLINICAL RELEVANCE: The administration of midazolam prolonged time to standing and had a mild negative effect on the quality of recovery in a pooled population of healthy male and female dogs undergoing neutering.


Assuntos
Anestesia Geral/veterinária , Anestésicos Intravenosos/uso terapêutico , Cães/cirurgia , Midazolam/uso terapêutico , Período de Recuperação da Anestesia , Anestésicos Intravenosos/administração & dosagem , Animais , Cães/fisiologia , Feminino , Masculino , Midazolam/administração & dosagem , Orquiectomia/veterinária , Ovariectomia/veterinária , Estudos Prospectivos
16.
Am J Vet Res ; 80(9): 819-824, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31449447

RESUMO

OBJECTIVE: To compare IV doses of alfaxalone and ketamine needed to facilitate orotracheal intubation and assess effects of each treatment on selected physiologic variables in goats undergoing orthopedic surgery with isoflurane anesthesia. ANIMALS: 18 healthy adult goats. PROCEDURES: Behavior was assessed before and after sedation with midazolam (0.1 mg/kg, IV) for IV catheter placement. Anesthesia was induced with additional midazolam (0.1 mg/kg, IV) and alfaxalone (n = 9) or ketamine (9) at 2 mg/kg, IV, over 30 seconds. An additional dose of alfaxalone or ketamine (1 mg/kg) was given IV if needed for intubation; anesthesia was maintained with isoflurane in oxygen and IV fluids with ketamine (0.5 to 1 mg/kg/h). Direct systolic (SAP), diastolic (DAP), and mean (MAP) arterial blood pressures; heart rate; and respiratory rate were recorded before induction, immediately after intubation, and during surgery. Qualitative anesthetic induction and recovery characteristics were assessed. Variables were compared within and between groups by statistical methods. RESULTS: No preinduction variables differed significantly between groups. Postintubation and 30-minute intraoperative SAP, DAP, and MAP were higher for the ketamine group than for the alfaxalone group; within the alfaxalone group, postintubation SAP, MAP, and respiratory rate prior to mechanical ventilation were lower than respective preinduction values. All alfaxalone-group goats were intubated after 1 dose of the induction agent; 5 of 9 ketamine-group goats required an additional (1-mg/kg) dose. Postoperative recovery was good to excellent for all animals. CONCLUSIONS AND CLINICAL RELEVANCE: Both drugs were suitable for induction of anesthesia after sedation with midazolam, but most goats required higher doses of ketamine to allow intubation. For situations in which alfaxalone administration is appropriate, the potential for decreased arterial blood pressures and respiratory rate should be considered.


Assuntos
Anestesia Intravenosa/veterinária , Anestesia/veterinária , Anestésicos Intravenosos/administração & dosagem , Cabras/cirurgia , Isoflurano/administração & dosagem , Ketamina/administração & dosagem , Pregnanodionas/administração & dosagem , Animais , Feminino , Frequência Cardíaca/efeitos dos fármacos , Midazolam/administração & dosagem , Estudos Prospectivos , Distribuição Aleatória , Taxa Respiratória/efeitos dos fármacos , Método Simples-Cego
17.
Cardiol Young ; 29(9): 1189-1195, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31451130

RESUMO

OBJECTIVE: There are several agents used for conscious sedation by various routes in children. The aim of this prospective randomised study is to compare the effectiveness of three commonly used sedatives: intranasal ketamine, intranasal midazolam, and oral chloral hydrate for children undergoing transthoracic echocardiography. METHODS: Children who were referred to paediatric cardiology due to a heart murmur for transthoracic echocardiography were prospectively randomised into three groups. Seventy-three children received intranasal midazolam (0.2 mg/kg), 72 children received intranasal ketamine (4 mg/kg), and 72 children received oral chloral hydrate (50 mg/kg) for conscious sedation. The effects of three agents were evaluated in terms of intensity, onset, and duration of sedation. Obtaining high-quality transthoracic echocardiography images (i.e. absence of artefacts) were regarded as successful sedation. Side effects due to medications were also noted. RESULTS: There was no statistical difference in terms of sedation success rates between three groups (95.9, 95.9, and 94.5%, respectively). The median onset of sedation in the midazolam, ketamine, and chloral hydrate was 14 minutes (range 7-65), 34 minutes (range 12-56), and 40 minutes (range 25-57), respectively (p < 0.001 for all). However, the median duration of sedation in study groups was 68 minutes (range 20-75), 55 minutes (range 25-75), and 61 minutes (range 34-78), respectively (p = 0.023, 0.712, and 0.045). Gastrointestinal side effects such as nausea and vomiting were significantly higher in the chloral hydrate group (11.7 versus 0% for midazolam and 2.8% for ketamine, respectively, p = 0.002). CONCLUSION: Results of our prospectively randomised study indicate that all three agents provide adequate sedation for successful transthoracic echocardiography. When compared the three sedatives, intranasal midazolam has a more rapid onset of sedation while intranasal ketamine has a shorter duration of sedation. Intranasal ketamine can be used safely with fewer side effects in children undergoing transthoracic echocardiography.


Assuntos
Hidrato de Cloral/administração & dosagem , Sedação Consciente/métodos , Ecocardiografia/métodos , Ketamina/administração & dosagem , Midazolam/administração & dosagem , Administração Intranasal , Administração Oral , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Lactente , Masculino , Estudos Prospectivos
18.
Vet Anaesth Analg ; 46(5): 662-666, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31371196

RESUMO

OBJECTIVE: To establish and compare the effectiveness of two medetomidine-based immobilization protocols in Persian fallow deer (Dama dama mesopotamica). STUDY DESIGN: Prospective, randomized, blinded clinical study. ANIMALS: A group of 31 captive Persian fallow deer. METHODS: Deer scheduled for translocation were immobilized with a combination of medetomidine (76 ± 11 µg kg-1) and ketamine (1.0 ± 0.2 mg kg-1) (MK; n = 15) or medetomidine (77 ± 11 µg kg-1) and midazolam (0.10 ± 0.01 mg kg-1) (MM; n = 16) administered intramuscularly. An observer unaware of group assignments recorded times to immobilization and recovery, monitored physiologic variables and scored the quality of induction, immobilization and recovery (scale 1-5: 1, poor; 5, excellent). Atipamezole was administered for reversal. Data analysis was performed using the t test, the Mann-Whitney U test, the chi-square test and the Fisher's exact test. Significance was set at p < 0.05. RESULTS: Data are presented as mean ± standard deviation or median (range). Time to induce immobilization was 9 ± 4 and 10 ± 4 minutes in the MK and MM groups, respectively. Immobilization quality score was 5 (1-5) following both combinations. Hemoglobin oxygen saturation (SpO2) was significantly lower in the MK (80 ± 8%) than in the MM group (87 ± 8%) although respiratory frequency did not differ between MK and MM (11 ± 5 and 10 ± 2 breaths minute-1, respectively). Recovery times were 13 ± 6 (MK) and 14 ± 7 minutes (MM) and did not differ between groups. No morbidities or mortalities were recorded during 1 month after immobilization. CONCLUSIONS AND CLINICAL RELEVANCE: The MK and MM combinations produced sufficient immobilization in captive Persian fallow deer for short nonpainful procedures. Based on the SpO2 values, the MM combination may be associated with less respiratory depression; nevertheless, both combinations may result in a decrease in SpO2.


Assuntos
Anestésicos Dissociativos/farmacologia , Cervos/fisiologia , Imobilização/veterinária , Ketamina/farmacologia , Medetomidina/farmacologia , Midazolam/farmacologia , Anestésicos Dissociativos/administração & dosagem , Animais , Animais Selvagens , Comportamento Animal/efeitos dos fármacos , Método Duplo-Cego , Quimioterapia Combinada/veterinária , Feminino , Ketamina/administração & dosagem , Masculino , Medetomidina/administração & dosagem , Midazolam/administração & dosagem , Estudos Prospectivos
19.
Trials ; 20(1): 430, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307505

RESUMO

INTRODUCTION: Premedication of surgical patients with benzodiazepines has become questionable regarding risk-benefit ratio and lack of evidence. Though preoperative benzodiazepines might alleviate preoperative anxiety, a higher risk for adverse events is described, particularly for elderly patients (≥ 65 years). Several German hospitals already withhold benzodiazepine premedication from elderly patients, though evidence for this approach is lacking. The patient-centred outcome known as global postoperative patient satisfaction is recognised as a substantial quality indicator of anaesthesia care incorporated by the American Society of Anesthesiologists. Therefore, we aim to assess whether the postoperative patient satisfaction after premedication with placebo compared to the preoperative administration of 3.75 mg midazolam in elderly patients differs. METHODS: This study is a multicentre, randomised, placebo-controlled, double-blinded, two-arm parallel, interventional trial, conducted in nine German hospitals. In total 614 patients (≥ 65-80 years of age) undergoing elective surgery with general anaesthesia will be randomised to receive either 3.75 mg midazolam or placebo. The primary outcome (global patient satisfaction) will be assessed with the validated EVAN-G questionnaire on the first postoperative day. Secondary outcomes will be assessed until the first postoperative day and then 30 days after surgery. They comprise among other things: functional and cognitive recovery, postoperative delirium, health-related quality of life assessment, and mortality or new onset of serious cardiac or pulmonary complications, acute stroke, or acute kidney injury. Analysis will adhere to the intention-to-treat principle. The primary outcome will be analysed with the use of mixed linear models including treatment effect and study centre as factors and random effects for blocks. Exploratory adjusted and subgroup analyses of the primary and secondary outcomes with regard to gender effects, frailty, pre-operative anxiety level, patient demographics, and surgery experience will also be performed. DISCUSSION: This is, to the best of our knowledge, the first study analysing patient satisfaction after premedication with midazolam in elderly patients. In conclusion, this study will provide high-quality data for the decision-making process regarding premedication in elderly surgical patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03052660 . Registered on 14 February 2017. EudraCT 2016-004555-79 .


Assuntos
Hipnóticos e Sedativos/administração & dosagem , Midazolam/administração & dosagem , Satisfação do Paciente , Pré-Medicação/métodos , Cuidados Pré-Operatórios/métodos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisão Clínica , Método Duplo-Cego , Esquema de Medicação , Feminino , Alemanha , Humanos , Hipnóticos e Sedativos/efeitos adversos , Masculino , Midazolam/efeitos adversos , Estudos Multicêntricos como Assunto , Pré-Medicação/efeitos adversos , Cuidados Pré-Operatórios/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento
20.
Anesth Analg ; 129(4): 1118-1123, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31295177

RESUMO

BACKGROUND: Unconscious racial bias in anesthesia care has been shown to exist. We hypothesized that black children may undergo inhalation induction less often, receive less support from child life, have fewer opportunities to have a family member present for induction, and receive premedication with oral midazolam less often. METHODS: We retrospectively collected data on those <18 years of age from January 1, 2012 to January 1, 2018 including age, sex, race, height, weight, American Society of Anesthesiologists (ASA) physical status, surgical service, and deidentified anesthesiology attending physician. Outcome data included mask versus intravenous induction, midazolam premedication, child life consultation, and family member presence. Racial differences between all outcomes were assessed in the cohort using a multivariable logistic regression model. RESULTS: A total of 33,717 Caucasian and 3901 black children were eligible for the study. For the primary outcome, black children 10-14 years were 1.3 times more likely than Caucasian children to receive mask induction (adjusted odds ratio [AOR], 1.3; 95% confidence interval [CI], 1.1-1.6; P = .001). Child life consultation was poorly documented (<0.5%) and not analyzed. Black children <15 years of age were at least 31% less likely than Caucasians to have a family member present for induction (AOR range, 0.4-0.6; 95% CI range, 0.31-0.84; P < .010). Black children <5 years of age were 13% less likely than Caucasians to have midazolam given preoperatively (AOR, 0.9; 95% CI, 0.8-0.9; P = .012). CONCLUSIONS: This study suggests that disparities in strategies for mitigating anxiety in the peri-induction period exist and adultification may be 1 cause for this bias. Black children 10 to 14 years of age are 1.3 times as likely as their Caucasian peers to be offered inhalation induction to reduce anxiety. However, black children are less likely to receive premedication with midazolam in the perioperative period or to have family members present at induction. The cause of this difference is unclear, and further prospective studies are needed to fully understand this difference.


Assuntos
Afro-Americanos , Anestesia Geral , Ansiedade/prevenção & controle , Grupo com Ancestrais do Continente Europeu , Disparidades em Assistência à Saúde/etnologia , Procedimentos Cirúrgicos Operatórios , Administração Oral , Adolescente , Comportamento do Adolescente/etnologia , Fatores Etários , Anestesia Geral/efeitos adversos , Anestesia Geral/psicologia , Ansiolíticos/administração & dosagem , Ansiedade/etnologia , Ansiedade/psicologia , Criança , Comportamento Infantil/etnologia , Feminino , Humanos , Masculino , Midazolam/administração & dosagem , Pré-Medicação , Estudos Retrospectivos , Fatores de Risco , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Procedimentos Cirúrgicos Operatórios/psicologia
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