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Eur J Anaesthesiol ; Publish Ahead of Print2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33399383


BACKGROUND: Nitrous oxide (N2O) has been used since the 19th century for its analgesic, antinociceptive and anxiolytic effects during surgical procedures in awake and anaesthetised patients. However, quantification of noxious stimuli that occur under general anaesthesia is a constant challenge for anaesthesiologists, and recently two new indices have been developed to assess intra-operative nociception. OBJECTIVE: The aim of this study was to quantify with new indices as well as with more classical clinical parameters the antinociceptive effect of N2O during general anaesthesia. DESIGN: Prospective, open label, patient-blinded, observational and descriptive trial. SETTING: Single-centre academic hospital. PARTICIPANTS: Forty American Society of Anesthesiologists' physical status 1 to 3 patients undergoing general anaesthesia for elective abdominal surgery via laparotomy were recruited. MAIN OUTCOMES MEASURES: Intra-operative pain was assessed using a standardised electrical stimulation of the forearm (tetanic stimulation at 70 mA, 100 Hz for 30 s), at 0, 25 and 50% inhaled N2O/O2. Heart rate (HR), mean arterial blood pressure, bispectral index, the analgesia nociception index and the nociception level (NOL) index were used to evaluate intra-operative nociception before and after each standardised tetanic stimulation. RESULTS: There was a 16% reduction of the analgesia nociception index reaction, a 31% reduction of the NOL reaction and a 51% reduction of the HR reaction to a standardised electrical tetanic nociceptive stimulation during administration of 50% N2O. Administration of 50 or 25% inhaled N2O produced the same quality of antinociception based on HR and NOL index analyses. HR and the NOL index were the best parameters to identify the antinociceptive effect of intra-operatively administered N2O. CONCLUSION: In anaesthetised patients, our study demonstrated clinically significant antinociceptive properties of N2O. Our results showed that low concentrations of N2O (25%) are as effective as higher concentrations (50%) to achieve a significant antinociceptive effect. These findings may help decrease negative effects of using higher concentrations of N2O, including its side effects and its environmental pollution. TRIAL REGISTRATION: registration identifier: NCT02701478.

PLoS One ; 14(5): e0215221, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31120888


Poor reporting quality may contribute to irreproducibility of results and failed 'bench-to-bedside' translation. Consequently, guidelines have been developed to improve the complete and transparent reporting of in vivo preclinical studies. To examine the impact of such guidelines on core methodological and analytical reporting items in the preclinical anesthesiology literature, we sampled a cohort of studies. Preclinical in vivo studies published in Anesthesiology, Anesthesia & Analgesia, Anaesthesia, and the British Journal of Anaesthesia (2008-2009, 2014-2016) were identified. Data was extracted independently and in duplicate. Reporting completeness was assessed using the National Institutes of Health Principles and Guidelines for Reporting Preclinical Research. Risk ratios were used for comparative analyses. Of 7615 screened articles, 604 met our inclusion criteria and included experiments reporting on 52 490 animals. The most common topic of investigation was pain and analgesia (30%), rodents were most frequently used (77%), and studies were most commonly conducted in the United States (36%). Use of preclinical reporting guidelines was listed in 10% of applicable articles. A minority of studies fully reported on replicates (0.3%), randomization (10%), blinding (12%), sample-size estimation (3%), and inclusion/exclusion criteria (5%). Statistics were well reported (81%). Comparative analysis demonstrated few differences in reporting rigor between journals, including those that endorsed reporting guidelines. Principal items of study design were infrequently reported, with few differences between journals. Methods to improve implementation and adherence to community-based reporting guidelines may be necessary to increase transparent and consistent reporting in the preclinical anesthesiology literature.

Avaliação Pré-Clínica de Medicamentos/normas , Relatório de Pesquisa/normas , Analgésicos/uso terapêutico , Animais , Bases de Dados Factuais , Guias como Assunto , Dor/tratamento farmacológico
Can J Anaesth ; 66(9): 1049-1061, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30997633


BACKGROUND: The Pain Monitoring Device (PMD) monitor (Medasense Biometrics Ltd., Ramat Gan, Israel) uses the Nociception Level (NOL) index, a multiple parameter-derived index that has recently shown a good sensitivity and specificity to detect noxious stimuli. The aim of this study was to assess the latest version of the device (PMD200TM) on variations of the NOL response after standardized tetanic stimuli to study the correlation between remifentanil doses and NOL. METHODS: Data from 26 patients undergoing midline laparotomy and receiving a desflurane-remifentanil-based anesthetic coupled with low thoracic epidural analgesia were analyzed. A standardized tetanic stimulus was applied to the forearm of the patients at different remifentanil infusion rates. The primary aim was to evaluate the correlation between post-tetanic stimulation NOL values from the PMD200 and remifentanil doses. The NOL index variations after experimental and clinical stimuli were also compared with heart rate (HR), mean arterial pressure (MAP), and Bispectral Index™ (BIS). RESULTS: A correlation between post-tetanic stimulation NOL values and remifentanil doses was found (r = -0.56; 95% confidence interval [CI], -0.70 to -0.44; P < 0.001). The NOL discriminated noxious from non-noxious states with the maximal Youden's index value of the NOL receiver operating characteristic (ROC) curve showing a specificity of 88% (95% CI, 69.0 to 100) and sensitivity of 79.1% (95% CI, 56.2 to 95.5). The area under the NOL ROC curve (AUC, 0.9; 95% CI, 0.84 to 0.95) was significantly different from the other variables (P < 0.001 vs HR; P < 0.001 vs MAP; P < 0.001 vs BIS). CONCLUSIONS: The NOL value after noxious stimulus decreased with incremental remifentanil doses, showing a significant inverse correlation between the NOL index and opioid doses. The sensitivity and specificity of NOL to discriminate between noxious and non-noxious stimuli suggests its interesting potential as a monitor of nociception intensity during anesthesia. TRIAL REGISTRATION: (NCT02884778); 27 July, 2016.

Analgésicos Opioides/administração & dosagem , Laparotomia/métodos , Monitorização Intraoperatória/métodos , Remifentanil/administração & dosagem , Idoso , Analgesia Epidural/métodos , Pressão Arterial/fisiologia , Desflurano/administração & dosagem , Relação Dose-Resposta a Droga , Estimulação Elétrica , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Nociceptividade/fisiologia , Sensibilidade e Especificidade
Pharmaceutics ; 9(4)2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-28954402


Various diseases such as type 2 diabetes (T2D) may alter drug clearance. The objective of this study was to evaluate the effects of T2D on CYP450 expressions and activities using high-fat diet (HFD) as a model of obesity-dependent diabetes in C57BL6 mice. The cyp450 mRNA expression levels for 15 different isoforms were determined in the liver and extra-hepatic tissues (kidneys, lungs and heart) of HFD-treated animals (n = 45). Modulation of cyp450 metabolic activities by HFD was assessed using eight known substrates for specific human ortholog CYP450 isoforms: in vitro incubations were conducted with liver and extra-hepatic microsomes. Expression levels of cyp3a11 and cyp3a25 mRNA were decreased in the liver (>2-14-fold) and kidneys (>2-fold) of HFD groups which correlated with a significant reduction in midazolam metabolism (by 21- and 5-fold in hepatic and kidney microsomes, respectively, p < 0.001). HFD was associated with decreased activities of cyp2b and cyp2c subfamilies in all organs tested except in the kidneys (for tolbutamide). Other cyp450 hepatic activities were minimally or not affected by HFD. Taken together, our data suggest that substrate-dependent and tissue-dependent modulation of cyp450 metabolic capacities by early phases of T2D are observed, which could modulate drug disposition and pharmacological effects in various tissues.