Fentanil peridural versus venoso na analgesia pós-operatória de cirurgia ortopédica: ensaio clínico aleatório

CONTEXT AND OBJECTIVE: Controversy exists regarding the site of action of fentanyl after epidural injection. The objective of this investigation was to compare the efficacy of epidural and intravenous fentanyl for orthopedic surgery. DESIGN AND SETTING: A randomized double-blind study was performed in Hospital São Paulo. METHODS: During the postoperative period, in the presence of pain, 29 patients were divided into two groups: group 1 (n = 14) received 100 µg of fentanyl epidurally and 2 ml of saline intravenously; group 2 (n = 15) received 5 ml of saline epidurally and 100 µg of fentanyl intravenously. The analgesic supplementation consisted of 40 mg of tenoxicam intravenously and, if necessary, 5 ml of 0.25% bupivacaine epidurally. Pain intensity was evaluated on a numerical scale and plasma concentrations of fentanyl were measured simultaneously. RESULTS: The percentage of patients who required supplementary analgesia with tenoxicam was lower in group 1 (71.4%) than in group 2 (100%): 95% confidence interval (CI) = 0.001-0.4360 (P = 0.001, Fisher's exact test; relative risk, RR = 0.07). Epidural bupivacaine supplementation was also lower in group 1 (14.3%) than in group 2 (53.3%): 95% CI = 0.06-1.05 (P = 0.03, Fisher's exact test; RR = 0.26). There was no difference in pain intensity on the numerical scale. Mean fentanyl plasma concentrations were similar in the two groups. CONCLUSION: Intravenous and epidural fentanyl appear to have similar efficacy for reducing pain according to the numerical scale, but supplementary analgesia was needed less frequently when epidural fentanyl was used. CLINICAL TRIAL REGISTRATION NUMBER: NCT00635986CONTEXTO E OBJETIVO: Existem controvérsias sobre o local de ação do fentanil injetado por via peridural. O objetivo foi comparar a eficácia do fentanil peridural e do venoso em cirurgias ortopédicas. TIPO DE ESTUDO E LOCAL: Estudo aleatório, duplo-cego, realizado no Hospital São Paulo. MÉTODO: No pós-operatório, na presença de dor, 29 pacientes foram divididos em dois grupos: grupo 1 (n = 14) recebeu solução de 100 mcg de fentanil por via peridural e 2 ml de solução salina venosa; grupo 2 (n = 15), 5 ml de solução salina peridural e 100 µg de fentanil venoso. A complementação analgésica foi com 40 mg de tenoxicam venoso e, se necessário, 5 ml de bupivacaína 0.25%. A intensidade da dor foi avaliada pela escala numérica e a concentração plasmática do fentanil foi medida simultaneamente. RESULTADOS: A percentagem de pacientes que necessitaram de complementação analgésica com tenoxicam foi menor no grupo 1 (71.4% versus 100.0% grupo 2): intervalo de confiança, IC 95% = 0.001-0.4360 (P = 0.001, teste exato de Fisher; risco relativo, RR = 0.07). A complementação com bupivacaína peridural também foi menor no grupo 1 (14.3% versus 53.3% grupo 2): IC 95% = 0.06-1.05 (P = 0.03, teste exato de Fisher; RR = 0.26). Não houve diferença na intensidade da dor avaliada pela escala numérica. As concentrações plasmáticas do fentanil foram semelhantes nos dois grupos. CONCLUSÃO: A eficácia do fentanil venoso e peridural parece ser semelhante na redução da dor de acordo com a escala numérica, porém a frequência de analgesia suplementar foi menor com o uso do fentanil peridural. REGISTRO DE ENSAIO CLÍNICO: NCT0063598

Efecto de la lidocaína venosa intraoperatoria sobre el dolor e interleucina-6 plasmática en pacientes sometidas a histerectomía

ResumenJustificación y objetivosLa interleucina-6 (IL-6) es predictora de intensidad en el trauma. El objetivo de este estudio fue evaluar el efecto de la lidocaína por vía venosa sobre la intensidad del dolor e IL-6 después de la histerectomía.MétodoEl estudio fue prospectivo, aleatorizado, comparativo y doble ciego en 40 pacientes, entre 18 y 60 años. Fue administrada lidocaína (2mg/kg–1.h–1) en el G1 o solución salina al 0,9% en el G2 durante la operación. La anestesia fue con O2/isoflurano. Se calculó la intensidad del dolor (T0: despertar y 6, 12, 18 y 24h), la primera solicitud de analgésico, y la dosis de morfina en las primeras 24h. La IL-6 se midió antes del inicio de la operación (T0), después de 5h del inicio (T5) y 24h después de finalizada (T24).ResultadosNo hubo diferencia en la intensidad del dolor entre los grupos. Hubo disminución de la intensidad del dolor entre T0 y los otros momentos evaluados en el G1. El tiempo para la primera complementación fue mayor en el G2 (76±104,4min) que en el G1 (26,7±23,3min). No hubo diferencia en las dosis de morfina complementaria entre G1 (23,5±12,6mg) y G2 (18,7±11,3mg). Hubo aumento en las concentraciones de IL-6 en los 2 grupos de T0 para T5 y T24. No hubo diferencia en la dosificación de IL-6 entre los grupos. La concentración de lidocaína fue 856,5±364,1ng/ml–1 en T5 y 30,1±14,2ng/ml–1 en T24.ConclusiónLa lidocaína (2mg/kg–1 /h–1) por vía venosa no generó reducción de la intensidad del dolor y de los niveles plasmáticos de IL-6 en pacientes sometidas a histerectomía abdominal.AbstractBackground and objectivesInterleukin-6 (IL-6) is a predictor of trauma severity. The purpose of this study was to evaluate the effect of intravenous lidocaine on pain severity and plasma IL-6 after hysterectomy.MethodA prospective, randomized, comparative, double-blind study with 40 patients, aged 18-60 years. G1 received lidocaine (2mg.kg−1.h−1) or G2 received 0.9% saline solution during the operation. Anesthesia was induced with O2/isoflurane. Pain severity (T0: awake and 6, 12, 18 and 24hours), first analgesic request, and dose of morphine in 24hours were evaluated. IL-6 was measured before starting surgery (T0), 5hours after the start (T5), and 24hours after the end of surgery (T24).ResultsThere was no difference in pain severity between groups. There was a decrease in pain severity between T0 and other measurement times in G1. Time to first supplementation was greater in G2 (76.0±104.4min) than in G1 (26.7±23.3min). There was no difference in supplemental dose of morphine between G1 (23.5±12.6mg) and G2 (18.7±11.3mg). There were increased concentrations of IL-6 in both groups from T0 to T5 and T24. There was no difference in IL-6 dosage between groups. Lidocaine concentration was 856.5±364.1ng.ml−1 in T5 and 30.1±14.2ng.ml−1 in T24.ConclusionIntravenous lidocaine (2mg.kg−1.h−1) did not reduce pain severity and plasma levels of IL-6 in patients undergoing abdominal hysterectomy

Efeito da lidocaína venosa intraoperatória sobre dor e interleucina‐6 plasmática em pacientes submetidas a histerectomia

ResumoJustificativa e objetivosA interleucina‐6 (IL‐6) é preditora de intensidade no trauma. O objetivo deste estudo foi avaliar o efeito da lidocaína por via venosa sobre a intensidade da dor e IL‐6 após histerectomia.MétodoO estudo foi prospectivo, randomizado, comparativo e duplo‐encoberto em 40 pacientes, entre 18 e 60 anos. Foi administrada lidocaína (2mg.kg–1.h–1) no G1 ou solução salina a 0,9% no G2 durante a operação. A anestesia foi com O2/isoflurano. Foi avaliada a intensidade da dor (T0: despertar e seis, 12, 18 e 24 horas), a primeira solicitação de analgésico, a dose de morfina nas 24 horas. A IL‐6 foi medida antes do início da operação (T0), após cinco horas do início (T5) e 24 horas após o término (T24).ResultadosNão houve diferença na intensidade da dor entre os grupos. Ocorreu diminuição da intensidade da dor entre T0 e os outros momentos avaliados no G1. O tempo para primeira complementação foi maior no G2 (76,0±104,4min) do que no G1 (26,7±23,3min). Não houve diferença na dose de morfina complementar entre G1 (23,5±12,6mg) e G2 (18,7±11,3mg). Houve aumento das concentrações de IL‐6 em ambos os grupos de T0 para T5 e T24. Não houve diferença na dosagem de IL‐6 entre os grupos. A concentração de lidocaína foi 856,5±364,1 ng.mL–1 em T5 e 30,1±14,2 ng.mL–1 em T24.ConclusãoA lidocaína (2mg.kg‐1.h–1) por via venosa não promoveu redução da intensidade da dor e dos níveis plasmáticos de IL‐6 em pacientes submetidas a histerectomia abdominal.AbstractBackground and objectivesInterleukin‐6 (IL‐6) is a predictor of trauma severity. The purpose of this study was to evaluate the effect of intravenous lidocaine on pain severity and plasma IL‐6 after hysterectomy.MethodA prospective, randomized, comparative, double‐blind study with 40 patients, aged 18‐60 years. G1 received lidocaine (2mg.kg−1.h−1) or G2 received 0.9% saline solution during the operation. Anesthesia was induced with O2/isoflurane. Pain severity (T0: awake and 6, 12, 18 and 24hours), first analgesic request, and dose of morphine in 24hours were evaluated. IL‐6 was measured before starting surgery (T0), five hours after the start (T5), and 24hours after the end of surgery (T24).ResultsThere was no difference in pain severity between groups. There was a decrease in pain severity between T0 and other measurement times in G1. Time to first supplementation was greater in G2 (76.0±104.4min) than in G1 (26.7±23.3min). There was no difference in supplemental dose of morphine between G1 (23.5±12.6mg) and G2 (18.7±11.3mg). There were increased concentrations of IL‐6 in both groups from T0 to T5 and T24. There was no difference in IL‐6 dosage between groups. Lidocaine concentration was 856.5±364.1 ng.mL−1 in T5 and 30.1±14.2 ng.mL−1 in T24.ConclusionIntravenous lidocaine (2mg.kg−1.h−1) did not reduce pain severity and plasma levels of IL‐6 in patients undergoing abdominal hysterectomy

METODOLOGIA ANALÍTICA DE RESÍDUO DO HERBICIDA 2,4-D (ÁCIDO 2,4-DICLOROFENOXIACÉTICO) EM AMOSTRAS DE ÁGUA EM ÁREA DE CULTIVO DE CANA-DE-AÇÚCAR

Desenvolveu-se método de análise de resíduo do herbicida 2,4-D para amostras de água coletadas na microbacia do Córrego do Espraiado no período de 1996 a 1999. A avaliação da tendência do produto alcançar camadas mais profundas do solo foi efetuada por simulação de sistemas (CMLS-94-Chemical Movement in Layered Soils) para melhor entendimento do comportamento do herbicida. O método analítico, utilizando cromatografia a gás, permitiu correlação de 99,9% entre a área dos picos e a concentração existente, indicando alta eficiência. Não foi encontrado resíduo de 2,4-D na água coletada nos anos de 1996 a 1999, o que também reforça os dados encontrados por simulação. Esses indicaram que 60 cm foi a profundidade máxima atingida no período de três anos, tanto para o Latossolo Roxo quanto para o Latossolo Vermelho Escuro. O mesmo estudo evidenciou que a partir do segundo ano após a aplicação já não havia mais resíduos do produto em ambos os solos estudados. ANALYTICAL METHODOLOGY OF 2,4-D (2,4-DICHLOROPHENOXYACETIC ACID) HERBICIDE RESIDUES IN SAMPLES OF WATER IN A SUGAR-CANE CULTIVATION AREA IN BRAZIL Abstract A method of analysis of the herbicide 2,4-D was developed for water samples collected in the Espraiado watershed in the period of 1996 and 1999. The evaluation of the tendency of the product to reach deeper layers of the soil was made by systems simulation (CMLS-94-Chemical Movement in Layered Soils) for better understanding of the herbicide behavior. The gas chromatography analytical method resulted in a 99.9% correlation of the peaks area in the graphics and the herbicide concentration, and indicated that it was highly effective. No residue of 2,4-D was detected in water in the years of 1996 to 1999, which also reinforce the data obtained by simulation. This indicated the leaching down to 60 cm., reached in a three-year period, in both types of soils, Latossolo Roxo and Latossolo Vermelho-Escuro The same study evidenced that from the second year after application there were no more product residues in both types of the soils studied

Picloram residues and leaching in water in a sugar cane area

A região de Ribeirão Preto, SP, Brasil, é abastecida com água proveniente de mananciais subterrâneos advindos do aqüífero Guarani, importante lençol de água subterrânea da região centro-sul do país. Na microbacia do Córrego do Espraiado, localizado nesta região, encontra-se um dos pontos de recarga desse aqüífero. Nesse local, com predomínio da cultura de cana-de-açúcar e presença de solo arenoso, a água se infiltra para camadas mais profundas do solo podendo lixiviar defensivos aplicados na superfície, tornando-a vulnerável a essa exposição. O herbicida picloram é um dos produtos aplicados na cultura e para tal foi desenvolvido um método de análise de resíduo do herbicida para amostras de água coletadas na microbacia no período de 1996 a 2001. A avaliação da tendência do produto alcançar camadas mais profundas do solo foi efetuada por análise cromatográfica e também por simulação de sistemas (CMLS-94-"Chemical Movement in Layered Soils") para melhor entender o comportamento do herbicida. O método analítico utilizado em cromatografia gasosa permitiu correlação de 98,0% entre a área dos picos e a concentração existente, indicando que foi altamente eficiente. Não foi encontrado resíduo de piclorarn em água, nos anos de 1996 a 2001. Estudos com o modelo matemático indicaram as profundidades máximas finais registrados para o terceiro ano de 8,2 m para Areia Quartzosa cinza (AQ-Cin), 7,3 m para a Areia Quartzosa rosa (AQ-Ros) e 6,7 m para Areia Quartzosa amarela (AQ-Ama), seguidas pelos Latossolos Vermelho-Escuro (LE-Col, 5,7 m) e Roxo (LRCol, 5,3 m) indicando possibilidades de lixiviação do picloram.The region of Ribeirão Preto, SP, Brazil, is located on the Guarani aquifer, the most important source of ground water in the South Central region of the country. The recharge area of this aquifer is located in the Espraiado watershed. The presence of sandy soi! and a sugar cane crop treated with pesticides makes the aquifer vulnerable to groundwater contamination. The herbicide picloram was among the pesticides used. To study its behavior, a gas chromatography analytical method for residue analysis was developed and picloram was measured during the years of 1996 until 1999. The movement also was evaluated with simulation using the software CMLS-94-"Chemical Movement in Layered Soils". The gas chromatography analytical method resulted in a 98.0% correlation of the area in the graphics and the herbicide concentration, and indicated that it was highly effective. No residue of picloram was detected in water in any year from 1986 to 1989. The simulation model CMLS have indicated the leaching down to maximum depth of 8.2 m for "Areia Quartzosa cinza" (AQ-Cin) sandy soi!, 7.3 m for "Areia Quartzosa rosa" (AQ-Ros) sandy soil and 6.7m for "Areia Quartzosa amarela" (AQ-Ama) sandy soi!, followed by latossols "Latossolos Vermelho-Escuro" ( LE-Col, 5.7 m) and "Latossolos Vermelho-Roxo" (LR-Col, 5.3 m), indicating possibilities of picloram leaching

Translation, Cross-Cultural Adaptation, and Validation of the Portuguese Version of the Rotterdam Elderly Pain Observation Scale

INTRODUCTION: This study reports on the translation, cultural adaptation, and validation of a Portuguese version of the Rotterdam Elderly Pain Observation Scale (REPOS), a Dutch scale to assess pain in patients who cannot communicate, with or without dementia. METHODS: This is a multicenter study in pain and neurological units involving Brazil (clinical phase) and the Netherlands (training phase). We performed a retrospective cross-sectional, 2-staged analysis, translating and culturally adapting the REPOS to a Portuguese version (REPOS-P) and evaluating its psychometric properties. Eight health professionals were trained to observe patients with low back pain. REPOS consists of 10 behavioral items scored as present or absent after a 2-min observation. The REPOS score of ≥3 in combination with the Numerical Rating Scale (NRS) of ≥4 indicated pain. The Content Validity Index (CVI) in all items and instructions showed CVI values at their maximum. According to the higher correlation coefficient found between NRS and REPOS-P, it may be suggested that there was an adequate convergent validity. RESULTS: The REPOS-P was administered to 80 patients with a mean age of 60 years (SD 11.5). Cronbach's alpha coefficient showed a moderate internal consistency of REPOS-P (α = 0.62), which is compatible with the original study of REPOS. All health professionals reached high levels of interrater agreement within a median of 10 weeks of training, assuring reproducibility. Cohen's kappa was 0.96 (SD 0.03), and the intraclass correlation coefficient was 0.98 (SD 0.02), showing high reliability of REPOS-P scores between the trainer (researcher) and the trainees (healthcare professionals). The Pearson correlation coefficient was 0.95 (95% confidence interval 0.94–0.97), showing a significant correlation between the total scores of REPOS-P and NRS. CONCLUSION: The REPOS-P was a valuable scale for assessing elderly patients with low back pain by different healthcare professionals. Short application time, ease of use, clear instructions, and the brief training required for application were essential characteristics of REPOS-P

Determination of acetonitrile and cyanide in rat blood: Application to an experimental study

Methods were developed for the analysis of acetonitrile and its metabolite cyanide in the blood of rats exposed to acetonitrile. Acetonitrile was analyzed by the headspace technique coupled to gas chromatography with detection by flame ionization, and cyanide was analyzed by high-performance liquid chromatography with fluorescence detection (λ ex = 418 nm and λ em = 460 nm) after derivatization of the ion with naphthalene 2,3-dicarboxyaldehyde and taurine. The quantitation limits of the methods for the analysis of acetonitrile and cyanide were 4.875 μg/mL and 0.025 μg/mL, respectively. The coefficients of variation of 10% or less obtained for intra- and interassay precision indicate the precision of these analytical methods and the systematic errors, all less than 5%, indicate that the methods are quite accurate. The methods were applied to an experimental study after the animals received acetonitrile at the doses of 2 mmol/kg or 5 mmol/kg

Enantioselectivity in the Pharmacokinetic Interaction Between Fluvastatin and Lercanidipine in Healthy Volunteers

Hypertension and dyslipidemia are independent risk factors for cardiovascular mortality and are frequently present in the same patient. Fluvastatin (FV), used to reduce cholesterol levels, and lercanidipine (LER), used to control blood pressured are marketed as racemic mixtures. Therapeutic activities are 30-fold higher for (+)-3R,5S-FV and 100- to 200-fold higher for S-LER compared with their respective antipodes. The present study describes the enantioselective pharmacokinetic interaction between LER and FV in healthy volunteers. A crossover randomized study was conducted in 3 phases on 8 volunteers treated with a single oral racemic dose of LER (20 mg) or FV (40 mg) or LER plus FV. Serial blood samples were collected from 0 to 24 hours. Plasma concentrations of the LER and FV enantiomers were determined by liquid chromatography/tandem mass spectrometry, and pharmacokinetic parameters were evaluated using the WinNonlin software. The Wilcoxon and Mann-Whitney tests (P < .05) were used to analyze enantiomer ratios and the pharmacokinetic drug interaction. Data are expressed as medians. In monotherapy, the kinetic disposition of both FV and LER was enantioselective. AUC values were significantly higher for (-)-3S,5R-FV than for (+)-3R,5S-FV (358.20 vs 279.68 ng.h/mL) and for S-LER compared with R-LER (13.90 vs 11.88 ng.h/mL). The pharmacokinetic parameters of FV were not enantioselective when combined with LER (AUC: (-)-3S,5R-FV: 325.21; (+)-3R,5S-FV: 316.44 ng.h/mL). There was a significant reduction in S-LER (8.06 vs 13.90 ng.h/mL) and R-LER (6.76 vs 11.88 ng.h/mL) AUC values when FV was coadministered. In conclusion, the interaction between FV-LER might be clinically relevant because AUC values of (+)-3R,5S-FV were increased when LER was coadministered, and AUC values of the 2 LER enantiomers were reduced when FV was coadministered.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Apoio a Pesquisa and Assistencia do HCFMRP-USP (FAEPA)Conselho Nacional de Desenvolvimento Cientifico and Tecnologico (CNPq