Impact of natriuresis on worsening renal function during episodes of acute heart failure.

INTRODUCTION AND OBJECTIVES: Worsening renal function (WRF) is a frequent complication in acute heart failure (AHF) with a controversial prognostic value. We aimed to study the usefulness of natriuresis to evaluate WRF. METHODS: We conducted an observational, prospective, multicenter study of patients with AHF who underwent a furosemide stress test. The patients were classified according to whether WRF was present or absent and according to the median natriuretic response. The main endpoint was the combination of mortality, rehospitalization due to HF, and heart transplant at 6 months of follow-up. RESULTS: One hundred and fifty-six patients were enrolled, and WRF occurred in 60 (38.5%). The patients were divided into 4 groups: a) 47 (30.1%) no WRF/low UNa (UNa ≤ 109 mEq/L); b) 49 (31.4%) no WRF/high UNa (UNa > 109 mEq/L); c) 31 (19.9%) WRF/low UNa and d) 29 (18.6%) WRF/high UNa. The parameters of the WRF/low UNa group showed higher clinical severity and worse diuretic and decongestive response. The development of WRF was associated with a higher risk of the combined event (HR, 1.88; 95%CI, 1.01-3.50; P = .046). When stratified by natriuretic response, WRF was associated with an increased risk of adverse events in patients with low natriuresis (HR, 2.28; 95%CI, 1.15-4.53; P = .019), but not in those with high natriuresis (HR, 1.18; 95%CI, 0.26-5.29; P = .826). CONCLUSIONS: Natriuresis could be a useful biomarker for interpreting and prognosticating WRF in AHF. WRF is associated with a higher risk of adverse events only in the context of low natriuresis.

Torsemida em Comparação com Furosemida no Tratamento da Insuficiência Cardíaca: Uma Revisão Sistemática e Metanálise de Ensaios Clínicos Randomizados / Torsemide versus Furosemide in the Treatment of Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Resumo A furosemida é o diurético mais utilizado para o tratamento de sintomas de sobrecarga de volume em pacientes com insuficiência cardíaca. Dados recentes sugerem que a torsemida pode ser superior à furosemida neste contexto. No entanto, ainda não é claro se isso se traduz em melhores resultados clínicos nesta população. Avaliar se a torsemida é superior à furosemida no contexto da insuficiência cardíaca. Realizamos uma revisão sistemática e metanálise de estudos clínicos randomizados (ECRs) comparando a eficácia da torsemida em comparação com a furosemida em pacientes com insuficiência cardíaca. PubMed, Embase e Web of Science foram as bases de dados pesquisadas em busca de estudos elegíveis. Os desfechos de interesse foram internações por todas as causas, internações por insuficiência cardíaca (IIC), internações por todas as causas cardiovasculares, mortalidade por todas as causas, e melhoria de classe da NYHA. Parâmetros ecocardiográficos também foram avaliados. Foi aplicado um modelo de efeitos aleatórios para calcular as razões de risco (RR) e as diferenças médias (DM) com intervalos de confiança (IC) de 95% e nível de significância de 0,05. Foram incluídos 12 ECRs, envolvendo 4.115 pacientes. A torsemida reduziu significativamente a IIC (RR de 0,60; IC de 95%, 0,43-0,83; p=0,002; I2=0%), internação por causas cardiovasculares (RR de 0,72; IC de 95%, 0,60-0,88; p=0,0009; I2=0%), e melhora da fração de ejeção do ventrículo esquerdo (FEVE) (DM de 4,51%; IC de 95%, 2,94 a 6,07; p<0,0001; I2=0%) em comparação com a furosemida. Não houve diferença significativa no número de internações por todas as causas (RR de 0,93; IC de 95%, 0,86-1,00; p=0,04; I2=0%), mortalidade por todas as causas (RR de 0,98; IC de 95%, 0,87-1,10; p=0,73; I2=0%), melhora da classe NYHA (RR de 1,25; IC de 95%, 0,92-1,68; p=0,15; I2=0%), ou mudança de classe NYHA (DM de -0,04; IC de 95%, -0,24 a 0,16; p=0,70; I2=15%) entre os grupos. A torsemida reduziu significativamente as internações por insuficiência cardíaca e causas cardiovasculares, melhorando também a FEVE.

Abstract Furosemide is the most used diuretic for volume overload symptoms in patients with heart failure (HF). Recent data suggested that torsemide may be superior to furosemide in this setting. However, whether this translates into better clinical outcomes in this population remains unclear. To assess whether torsemide is superior to furosemide in the setting of HF. We performed a systematic review and meta-analysis of RCTs comparing the efficacy of torsemide versus furosemide in patients with HF. PubMed, Embase, and Web of Science were searched for eligible trials. Outcomes of interest were all-cause hospitalizations, hospitalizations for HF (HHF), hospitalizations for all cardiovascular causes, all-cause mortality, and NYHA class improvement. Echocardiographic parameters were also assessed. We applied a random-effects model to calculate risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) and a 0.05 level of significance. 12 RCTs were included, comprising 4,115 patients. Torsemide significantly reduced HHF (RR 0.60; 95% CI, 0.43-0.83; p=0.002; I2=0%), hospitalization for cardiovascular causes (RR 0.72; 95% CI, 0.60-0.88; p=0.0009; I2=0%), and improved LVEF (MD 4.51%; 95% CI, 2.94 to 6.07; p<0.0001; I2=0%) compared with furosemide. There was no significant difference in all-cause hospitalizations (RR 0.93; 95% CI, 0.86-1.00; p=0.04; I2=0%), all-cause mortality (RR 0.98; 95% CI, 0.87-1.10; p=0.73; I2=0%), NYHA class improvement (RR 1.25; 95% CI, 0.92-1.68; p=0.15; I2=0%), or NYHA class change (MD -0.04; 95% CI, -0.24 to 0.16; p=0.70; I2=15%) between groups. Torsemide significantly reduced hospitalizations for HF and cardiovascular causes, also improving LVEF.

Diagnóstico y manejo de la congestión en insuficiencia cardíaca aguda

La congestión en pacientes con insuficiencia cardíaca representa una manifestación de diversos procesos estructurales y funcionales cardiovasculares, asociada a alta morbimortalidad y reducción de calidad de vida, se considera la principal causa de ingreso a hospitalización y reingreso por insuficiencia cardíaca. Durante las últimas décadas, se ha logrado un mejor entendimiento de los diversos eventos fisiopatológicos desencadenantes, lo cual ha mejorado su pronóstico, diagnóstico y tratamiento. Por estos constantes avances, es necesaria su frecuente revisión y análisis. La atención del paciente con insuficiencia cardíaca y episodios de congestión es compleja y crucial. Su abordaje inicia con el reconocimiento temprano de las manifestaciones clínicas, uso de métodos no invasivos diagnósticos, delimitación del perfil de congestión; consecuentemente, es necesario brindar un manejo oportuno, intensivo y eficaz que contemple el empleo temprano de diuréticos intravenosos, la evaluación de metas de descongestión y, en casos específicos, terapia diurética combinada e incluso medicamentos vasoactivos o ultrafiltración continua.

Summary: Congestion in patients with heart failure represents a manifestation of various cardiovascular structural and functional processes, associated with high morbidity and mortality and reduced quality of life, being considered the main cause of hospitalization and readmission due to heart failure. During the last decades, a better understanding of the various triggering pathophysiological events has been achieved, modifying their prognosis, diagnosis, and treatment. Due to these constant advances, its frequent review and analysis is necessary. The care of patients with heart failure and episodes of congestion is complex and crucial. Its approach begins with early recognition of clinical manifestations, use of non-invasive diagnostic methods, delimitation of the congestion profile; followed by timely, intensive, and effective management that contemplates the early use of intravenous diuretics, evaluation of decongestion goals and, in specific cases, combined diuretic therapy, and even vasoactive medications or continuous ultrafiltration.

A congestão em pacientes com insuficiência cardíaca representa manifestação de diversos processos cardiovasculares estruturais e funcionais, associada a elevada morbidade e mortalidade e redução da qualidade de vida, é considerada a principal causa de internação e reinternação por insuficiência cardíaca. Durante as últimas décadas, conseguiu-se uma melhor compreensão dos vários eventos fisiopatológicos desencadeantes, o que melhorou o seu prognóstico, diagnóstico e tratamento. Devido a esses constantes avanços, sua revisão e análise frequente se fazem necessárias. O cuidado de pacientes com insuficiência cardíaca e episódios de congestão é complexo e crucial. Sua abordagem inicia-se com reconhecimento precoce das manifestações clínicas, utilização de métodos diagnósticos não invasivos, delimitação do perfil de congestão. Consequentemente, é necessário proporcionar manejo oportuno, intensivo e eficaz que inclua o uso precoce de diuréticos intravenosos, a avaliação das metas de descongestão e, em casos específicos, terapia diurética combinada e até mesmo medicações vasoativas ou ultrafiltração contínua.

Eficiencia diurética inicial como predictor de resistencia a diuréticos y evolución clínica en insuficiencia cardíaca aguda descompensada / Initial Diuretic Efficiency as Predictor of Diuretic Resistance and Clinical Outcome in Acute Decompensated Heart Failure

RESUMEN Introducción: En pacientes con insuficiencia cardíaca aguda descompensada (ICAD) la eficiencia diurética (ED) evaluada en forma precoz podría predecir la respuesta a diuréticos y la evolución clínica. Objetivos: Nuestro objetivo fue evaluar la asociación de la ED con la resistencia a diuréticos (RD), la mortalidad cardiovascular intrahospitalaria, y la mortalidad cardiovascular y las reinternaciones a 60 días en la ICAD. Material y métodos: Estudio prospectivo y multicéntrico que incluyó pacientes internados por ICAD. Recibieron 40 mg de furosemida dentro de las 2 horas del ingreso y 20 mg cada 8 horas en las primeras 24 horas. El escalamiento diurético posterior quedó a criterio del investigador según un protocolo preestablecido. Se definió la ED como balance hídrico/dosis de furosemida en las primeras 24 horas y la RD como el requerimiento de infusión de furosemida ≥240 mg/día en las primeras 72 horas. Se evaluaron variables clínicas y bioquímicas, y el punto final combinado (PFC) de mortalidad cardiovascular intrahospitalaria, y mortalidad cardiovascular y reinternaciones por ICAD a 60 días. Resultados: Se incluyeron 157 pacientes, mediana de edad de 74 años, 56 % hombres. La ED fue -15 mL/mg (rango intercuartílico, RIC, -20 a -11). Se evidenció la RD en el 13 % de los pacientes, el 8 % requirió bloqueo tubular y el 4 % terapia de reemplazo renal. El 22 % desarrolló empeoramiento de la función renal. La mortalidad cardiovascular intrahospitalaria fue del 5,7 % y en el seguimiento a 60 días, del 6 %. Las reinternaciones por ICAD a 60 días fueron del 12 %. Una peor ED se asoció al desarrollo de RD (p = 0,013) y los pacientes con ED superior a -11 mL/mg tuvieron mayor probabilidad de no desarrollar RD (área bajo la curva, AUC, 0,73; valor predictivo negativo, VPN, 92,5 %). Una peor ED se asoció al PFC (p = 0,025), mayor mortalidad cardiovascular intrahospitalaria (p = 0,003), persistencia de congestión a 48 horas (p = 0,007), mayor dosis de furosemida a 72 horas (p = 0,001) y empeoramiento de la ICAD en la internación (p = 0,004). Conclusión: La ED inicial baja se asoció a la RD, la dificultad en la descongestión y una mayor mortalidad cardiovascular intrahospitalaria en ICAD. Es un parámetro útil para detectar pacientes que podrían beneficiarse de un tratamiento diurético intensivo precoz.

ABSTRACT Background: In patients with acute decompensated heart failure (ADHF), early evaluation of diuretic efficiency (DE) could predict diuretic response and clinical outcome. Objectives: The aim of our study was to evaluate the association of DE with diuretic resistance (DR) in-hospital cardiovascular mortality, and readmission or cardiovascular mortality at 60 days in ADHF. Methods: We conducted a multicenter and prospective study of patients hospitalized for ADHF. All patients received 40 mg of furosemide within two hours of admission and 20 mg every 8 hours in the first 24 hours. Subsequent adjustment of diuretic dose was left to the discretion of the investigator as determined by a pre-established protocol. Diuretic efficiency was defined as the ratio of net fluid balance and cumulative amount of furosemide within the first 24 hours. Diuretic resistance was defined as requirement of furosemide infusion ≥240 mg/day during the first 72 hours. The clinical and biochemical variables were evaluated. The primary outcome was a composite of in-hospital cardiovascular mortality, and cardiovascular mortality or readmissions for ADHF at 60 days. Results: The cohort was made up of 157 patients; median age was 74 years and 56 % were men. Diuretic efficiency was -15 mL/ mg (interquartile range, IQR, -20 to -11). Diuretic resistance was evident in 13 % of patients, 8 % required sequential diuretic blockade, and 4 % required renal replacement therapy. Worsening renal function occurred in 22 % of patients. Cardiovascular mortality during hospitalization and at 60 days was 5.7 % and 6 %, respectively. Readmission rate for ADHF at 60 days was 12 %. Worse DE value was associated DR (p = 0.013), while patients in DE quartiles above -11 mL/mg were highly unlikely to develop DR (AUC 0.73, negative predictive value, NPV, 92.5 %). Worse DE value was associated with the CEP (p = 0.025), higher in-hospital cardiovascular mortality (p = 0.003), persistent congestion at 48 hours (p = 0.007), higher cumulative dose of furosemide at 72 hours (p = 0.001) worsening ADHF during hospitalization (p = 0.004). Conclusion: Low initial DE was associated with DR, persistent congestion, and higher in-hospital cardiovascular mortality in ADHF and constitutes a useful parameter to detect those patients who could benefit from early intensive diuretic treatment.

Furosemide-related thiamine deficiency in hospitalized hypervolemic patients with renal failure and heart failure / Deficiencia de tiamina relacionada con la furosemida en pacientes hipervolémicos con insuficiencia renal e insuficiencia cardíaca

Background: We aimed to describe the thiamine status in hospitalized hypervolemic heart failure (HF) and/or renal failure (RF) patients treated with furosemide and to investigate whether there was a difference in furosemide-related thiamine deficiency between patients with RF and HF. Methods: Patients who were diagnosed as hypervolemia and treated with intravenous furosemide (at least 40mg/day) were included in this prospective observational study. Whole blood thiamine concentrations were measured 3 times during hospital follow-up of patients. Results: We evaluated 61 hospitalized hypervolemic patients, of which 22 (36%) were men and 39 (64%) were women, with a mean age of 69.00±10.39 (45–90) years. The baseline and post–hospital admission days 2 and 4 mean thiamine levels were 51.71±20.66ng/ml, 47.64±15.43ng/ml and 43.78±16.20ng/ml, respectively. Thiamine levels of the hypervolemic patients decreased significantly during the hospital stay while furosemide treatment was continuing (p=0.029). There was a significant decrease in thiamine levels in patients who had HF (p=0.026) and also, thiamine was significantly lower in HF patients who had previously used oral furosemide before hospitalization. However, these findings were not present in patients with RF. (AU)

Antecedentes: Nos propusimos describir el estado de la tiamina en pacientes hospitalizados con insuficiencia cardíaca (IC) y/o insuficiencia renal (IR) hipervolémica tratados con furosemida, e investigar si había una diferencia en la deficiencia de tiamina relacionada con la furosemida entre los pacientes con IR y con IC. Métodos: En este estudio observacional prospectivo se incluyeron pacientes con diagnóstico de hipervolemia y tratados con furosemida intravenosa (al menos 40 mg/día). Se midieron las concentraciones de tiamina en sangre total 3 veces durante el seguimiento hospitalario de los pacientes. Resultados: Se evaluaron 61 pacientes hipervolémicos hospitalizados, de los cuales 22 (36%) eran hombres y 39 (64%) eran mujeres, con una edad media de 69,00±10,39 (45-90) años. Los niveles medios de tiamina en la línea de base y tras el ingreso hospitalario en los días 2 y 4 fueron de 51,71±20,66 ng/ml, 47,64±15,43 ng/ml y 43,78±16,20 ng/ml, respectivamente. Los niveles de tiamina de los pacientes hipervolémicos hipervolemia disminuyeron significativamente durante la estancia en el hospital mientras se mantenía el tratamiento con furosemida furosemida (p = 0,029). Hubo una disminución significativa de los niveles de tiamina en los pacientes que tenían IC (p = 0,026) y también, la tiamina fue significativamente menor en los pacientes con IC que habían habían utilizado previamente furosemida oral antes de la hospitalización. Sin embargo, estos hallazgos no se presentes en los pacientes con IC. (AU)

Furosemide-related thiamine deficiency in hospitalized hypervolemic patients with renal failure and heart failure.

BACKGROUND: We aimed to describe the thiamine status in hospitalized hypervolemic heart failure (HF) and/or renal failure (RF) patients treated with furosemide and to investigate whether there was a difference in furosemide-related thiamine deficiency between patients with RF and HF. METHODS: Patients who were diagnosed as hypervolemia and treated with intravenous furosemide (at least 40mg/day) were included in this prospective observational study. Whole blood thiamine concentrations were measured 3 times during hospital follow-up of patients. RESULTS: We evaluated 61 hospitalized hypervolemic patients, of which 22 (36%) were men and 39 (64%) were women, with a mean age of 69.00±10.39 (45-90) years. The baseline and post-hospital admission days 2 and 4 mean thiamine levels were 51.71±20.66ng/ml, 47.64±15.43ng/ml and 43.78±16.20ng/ml, respectively. Thiamine levels of the hypervolemic patients decreased significantly during the hospital stay while furosemide treatment was continuing (p=0.029). There was a significant decrease in thiamine levels in patients who had HF (p=0.026) and also, thiamine was significantly lower in HF patients who had previously used oral furosemide before hospitalization. However, these findings were not present in patients with RF. CONCLUSIONS: Thiamine substantially decreases in most hypervolemic patients receiving intravenous furosemide treatment during the hospital stay. Thiamine levels were significantly decreased with furosemide treatment in especially HF patients, but the decrease in thiamine levels did not detected at the same rate in RF patients. Diuretic-induced thiamine loss may be less likely in RF patients, probably due to a reduction in excretion.

Clinical significance of frusemide stress test in predicting the severity of acute kidney injury / Significância clínica do teste de estresse com furosemida na predição da gravidade da lesão renal aguda

Abstract Introduction: The outcomes of Acute Kidney Injury (AKI) remain dismal even today, owing in part due to the lack of an ideal biomarker for detecting renal damage early enough. We conducted this pilot study to determine the clinical significance of Frusemide Stress Test (FST) to predict the severity of AKI. Methods: A total of 80 patients with AKI-KDIGO (Kidney Disease: Improving Global Outcomes) stage 1 or stage 2 underwent FST by administering a bolus dose of frusemide (1mg/kg for frusemide naïve and 1.5mg/kg for prior frusemide exposure in the past week), and urine output was then measured for the next two hours with volume replacement as desirable. The progression to AKI-KDIGO stage 3 within 14 days of FST was studied as the primary outcome. The composite end point of achieving AKI-KDIGO stage 3 or death within 14 days of FST was studied as the secondary outcome. Results: Out of 80 patients, 28(35%) patients met the primary outcome, and 34(42.5%) patients met the secondary composite outcome. Except for baseline Chronic Kidney Disease (CKD) status (p=0.018), other demographic characteristics were comparable between progressors and non-progressors group. Using receiver operating characteristics (ROC) curve analysis, a cumulative 2-hour post-FST urine output of ≤300 mL predicted progression to stage 3 AKI with 82.14% sensitivity, 82.69% specificity, and AUC of 0.89±0.03 (p<0.0001). Conclusion: The FST showed promising results as a novel tubular biomarker to identify progression to severe AKI with good predictive ability.

Resumo Introdução: Os desfechos da Lesão Renal Aguda (LRA) permanecem desanimadores ainda hoje, em parte pela falta de um biomarcador ideal para detectar danos renais com a devida antecedência. Realizamos este estudo piloto para determinar a importância clínica do Teste de Estresse com Furosemida (TEF) em prever a gravidade da LRA. Métodos: Um total de 80 pacientes com LRA-KDIGO estágio 1 ou 2 foram submetidos ao TEF pela administração de uma dose em bolus de furosemida (1mg/kg para pacientes virgens de furosemida e 1,5mg/kg para exposição prévia à furosemida na semana anterior). O débito urinário foi então medido durante as duas horas seguintes com reposição de volume conforme desejável. A progressão para LRA-KDIGO estágio 3 dentro de 14 dias de TEF foi estudada como principal desfecho. O desfecho composto de atingir a LRA-KDIGO estágio 3 ou óbito em 14 dias após TEF foi estudado como desfecho secundário. Resultados: Dos 80 pacientes, 28 (35%) atingiram desfecho primário, e 34 (42,5%) pacientes atingiram o desfecho composto secundário. Exceto pelo estado basal da Doença Renal Crônica (DRC) (p=0,018), outras características demográficas foram comparáveis entre o grupo progressores e não progressores. Usando a análise da Curva Característica de Operação do Receptor (ROC), um débito urinário cumulativo de 2 horas pós-TEF de ≤300 mL previu a progressão para estágio 3 da LRA com 82,14% de sensibilidade, 82,69% de especificidade, e AUC de 0,89±0,03 (p<0,0001). Conclusão: O TEF mostrou resultados promissores como novo biomarcador tubular para identificar progressão para LRA grave com boa capacidade preditiva.

Perfusión de furosemida subcutánea como tratamiento paliativo en insuficiencia cardiaca refractaria / Subcutaneous furosemide infusion as palliative treatment in refractory end-stage heart failure

Resumen En la insuficiencia cardiaca terminal los síntomas predominantes habitualmente están relacionados con la congestión; sin embargo, la resistencia a diuréticos vía oral es frecuente y necesita tratamiento parenteral para paliar los síntomas. La administración intravenosa de furosemida requiere hospitalización o asistencia hospitalaria, lo que supone un deterioro significativo de la calidad de vida de pacientes en fases avanzadas de la enfermedad. La administración subcutánea continua de furosemida mediante infusor elastomérico es una técnica eficaz con baja tasa de complicaciones graves que permite la administración de diurético parenteral en el ámbito domiciliario, y evita la necesidad de hospitalizar. A pesar de que esta modalidad de tratamiento no está aceptada en ficha técnica y requiere más estudios que precisen su indicación, puede suponer un recurso adecuado para pacientes seleccionados. Se presenta el caso de una paciente con insuficiencia cardiaca avanzada, síntomas congestivos y ausencia de respuesta a tratamiento deplectivo vía oral, tratada con perfusión continua subcutánea domiciliaria de furosemida mediante infusor elastomérico de forma prolongada.

Abstract In end-stage heart failure the predominant symptoms are usually associated with congestion. However, the resistance to oral diuretics is common and requires parenteral treatment to alleviate the symptoms. The intravenous administration of furosemide requires hospital admission or hospital care. This leads to a significant decrease in the quality of life of patients in advance stages of the disease. The continuous subcutaneous infusion of furosemide using an elastomeric pump is an effective technique, with a low rate of serious complications that allows a parenteral diuretic to be administered in the home environment and thus avoiding the need for hospital admission. Despite this mode of treatment not being indicated in the drug data sheet, and requires more studies that specify its indication, it may be a suitable recourse for selected patients. It is presented a case of a patient with advanced heart failure, congestive symptoms, and a lack of response to oral diuretics treatment, and then treated with a continuous and prolonged subcutaneous infusion of furosemide at home using an elastomeric infusion pump.

Uso inapropiado de diuréticos: Algunas características no tan conocidas / Diuretic misuse: Some not so well known characteristics

Entre las situaciones asociadas al uso inapropiado de diuréticos se encuentran los intentos por descencer rápidamente de peso, comunes en los desordenes de la alimentación, y los intentos por enmascarar el consumo de otras sustancias, en el caso de las competencias deportivas. El uso sin indicación ni supervisión médica de estos fármacos genera un desbalance electrolítico, que puede manifestarse con hiponatremia, hipocalemia, hipocalcemia e hipomagnesemia, hipercalemia, entre otras alteraciones. El objetivo de este trabajo fue investigar las caracteríscas del uso inapropiado de diuréticos a partir de la casuística del CENATOXA. Se realizó un estudio descriptivo restrospectivo sobre los análisis ingresados al CENATOXA con solicitud de investigación cualitativa de diuréticos en orina, entre los años 2002 y 2016. En dicho período ingresaron al CENATOXA 138 casos, de los cuales el 56 % resultó positivo para algún diurético. Del total de casos con resultado positivo, el 93,5 % fueron mujeres entre 25 y 55 años de edad y predominó la etiología intencional. Los diuréticos mayoritariamente encontrados fueron hidroclorotiazida y furosemida. El perfil de diuréticos hasta el año 2008 (hidroclorotiazida = 68% de los casos positivos) se diferenció del hallado entre 2009 y 2016 (furosemida + hidroclorotiazida = 60% de los casos positivos). Se observó recurrencia en el uso inapropiado en el 8% de los casos. El uso simultáneo de más de un diurético y la recurrencia son factores que pueden contribuir a la aparición de toxicidad. Estos resultados sugieren que el uso inapropiado de diuréticos es una situación que debería ser ob­servada más atentamente para establecer mejor su alcance y sus riesgos.

Among the situations associated with diuretics misuse are the attempts to lose weight fast, frequently observed in eating disorders, and the attempts to mask the consumption of other substances, in the case of sports competitions. The use of these drugs with no medical indication or supervision generates an electrolyte imbalance, leading to hyponatremia, hypokalemia, hypocalcemia and hypomagnesemia, hyperkalemia, among other alterations. The objective of this work was to investigate the characteristics of diuretics misuse from the CENATOXA database, where the qualitative investigation of diuretics in urine is per­formed. A descriptive retrospective study was conducted on the cases admitted to the CENATOXA with a request for qualitative diuretic investigation, between 2002 and 2016. During this period, 138 urine samples were received at the CENATOXA and 56% were positive for at least one diuretic. Of all cases with positive results, 93.5% were women between 25 and 55 years of age, and intentional etiology predominated. The most detected diuretics were hydrochlorothiazide and furosemide. The diuretic misuse pattern detected up to 2008 (hydrochlorothiazide = 68% of positive cases) differed from that detected between 2009 and 2016 (furosemide + hydrochlorothiazide = 60% of positive cases). Recurrence in misuse was observed in 8% of the cases. The simul­taneous misuse of more than one diuretic and the recurrence are factors that can contribute to the onset of toxicity. These results suggest that diuretic misuse is a situation that should be observed more closely to better assess its consequences and its risks.

Furosemida en el control de la hipertensión arterial posparto en preeclámpticas severas / Furosemide in the control of postpartum hypertension in severe preeclamptic women

RESUMEN OBJETIVO: Establecer la utilidad de la furosemida en el control de la hipertensión arterial posparto en preeclámpticas severa. MÉTODOS: Se realizó un estudio de casos y controles en el Hospital Central "Dr. Urquinaona", Maracaibo, Venezuela. Se incluyeron pacientes con preeclampsia severa, las cuales durante el posparto fueron asignadas al azar para ser tratadas con furosemida, alfametildopa y cloruro de potasio oral (grupo A) o alfa-metildopa oral (grupo B) por 48 horas. Los parámetros evaluados fueron: variaciones en los valores de presión arterial y frecuencia cardiaca, persistencia de hipertensión, parámetros de laboratorio y efectos adversos. RESULTADOS: Para el análisis final estaban disponibles los datos de 198 pacientes en el grupo A y 197 pacientes en el grupo B en cada uno de los grupos. Luego de 48 horas de tratamiento se observaron disminuciones estadísticamente significativas en los valores de presión arterial sistólica y diastólica entre las pacientes tratadas con furosemida y las pacientes del grupo control (p < 0,0001). Se observó persistencia de la hipertensión en 52 pacientes (26,3 %) del grupo A y en 134 pacientes (68,0 %) del grupo B (p < 0,0001). No se encontraron diferencias entre los grupos en la frecuencia cardiaca, valores de laboratorio y efectos adversos (p = ns). CONCLUSIÓN: La furosemida produce disminuciones significativas en los valores promedios de presión arterial sistólica y diastólica, al igual que en la frecuencia de persistencia de hipertensión postparto en preeclámpticas severas.

ABSTRACT OBJECTIVE: To establish the utility of furosemide in the control of postpartum blood pressure in severe preeclamptic patients. METHODS: A case-control study was conducted at the Central Hospital "Dr. Urquinaona", Maracaibo, Venezuela. Patients diagnosed with severe preeclampsia were included, who during the postpartum period were randomized to be treated with furosemide, alpha-methyldopa and oral potassium chloride (group A) or oral alpha-methyldopa (group B) for 48 hours. The parameters evaluated were: variations in blood pressure and heart rate values, the persistence of hypertension, laboratory parameters and adverse effects related to treatment. RESULTS: Data of 198 patients in group A and 197 patients in group B in each of the groups were available for the final analysis. After 48 hours of treatment, statistical significant decreases were observed in the values of systolic and diastolic blood pressure between patients treated with furosemide and patients in the control group (p <0.0001). Persistence of hypertension was observed in 52 patients (26.3 %) of group A and in 134 patients (68.0 %) of group B (p < 0.0001). No differences were found between the groups in heart rate, laboratory values and adverse effects (p = ns). CONCLUSION: Furosemide produces significant decreases in the mean values of systolic and diastolic blood pressure, as well as in the frequency of persistence of postpartum hypertension in severe preeclamptic patients.

Furosemide-induced pseudoporphyria in a patient with chronic kidney disease: case report / Pseudoporfiria induzida por furosemida em paciente com doença renal crônica: relato de caso

ABSTRACT Introduction: Pseudoporphyria is a rare photodermatosis with characteristics similar to those of porphyria cutanea tarda, without, however, presenting abnormalities in porphyrin metabolism. Its etiology is related to chronic kidney disease, ultraviolet radiation and certain medications. The aim of the present study is to describe a case of furosemide-related pseudoporphyria in a patient with chronic kidney disease. Case description: A 76-year-old male patient with stage 4 chronic kidney disease and in continuous use of furosemide presented ulcerated lesions with peripheral erythema and central hematic crust in the legs. On a skin infection suspicion, treatment with quinolone and neomycin sulfate was initiated, without improvement. A biopsy of the lesion was performed, with histopathological examination demonstrating findings compatible with porphyria, although the patient did not present high porphyrin levels. The diagnosis of furosemide-induced pseudoporphyria was then established, with medication suspension, and there was a significant improvement of the lesions. Discussion: There are few cases of pseudoporphyria described, but it is believed that this condition is underdiagnosed, especially in patients with chronic kidney disease. Both clinical and histopathological findings closely resemble porphyria, differentiating it from normal levels of porphyrin in plasma, urine, or feces. Conclusions: Although the lesions are mostly benign, they may increase the morbidity and mortality of these patients, so a proper diagnosis and early treatment are extremely important.

RESUMO Introdução: A pseudoporfiria é uma fotodermatose rara com características semelhantes às da porfiria cutânea tardia, sem, no entanto, apresentar anormalidades no metabolismo da porfirina. Sua etiologia está relacionada a doença renal crônica, radiação ultravioleta e determinados medicamentos. O objetivo do presente trabalho é descrever um caso de pseudoporfiria relacionada a furosemida em paciente portador de doença renal crônica. Descrição do caso: Paciente masculino, 76 anos, com doença renal crônica estágio 4 e em uso contínuo de furosemida, apresentou lesões ulceradas com eritema periférico e crosta hemática central nas pernas. Por suspeita de infecção de pele, foi iniciado tratamento com quinolona e sulfato de neomicina, sem melhora. Foi realizada então biópsia da lesão, com exame histopatológico demonstrando achados compatíveis com porfiria, sem, no entanto, o paciente apresentar níveis elevados de porfirinas. Foi então estabelecido o diagnóstico de pseudoporfiria induzida por furosemida, com suspensão de medicação , e houve melhora significativa das lesões. Discussão: Há poucos casos de pseudoporfiria descritos, mas acredita-se que essa condição seja subdiagnosticada, principalmente em pacientes com doença renal crônica. Tanto achados clínicos quanto histopatológicos se assemelham muito à porfiria, diferenciando desta por níveis normais de porfirina no plasma, na urina ou nas fezes. Conclusões: Embora as lesões sejam majoritariamente benignas, podem aumentar a morbimortalidade desses pacientes, por isso um diagnóstico adequado e tratamento precoce são de extrema importância.

Prueba de estrés con furosemida para predecir el éxito o fracaso del retiro de la terapia de reemplazo renal lenta continua en lesión renal aguda / Furosemide stress test to predict success or failure to remove continuos slow renal replacement therapy in acute renal injury / Prova de estresse com furosemida para prever o êxito ou fracasso da remoção da terapia contínua de substituição renal na lesão renal aguda

Resumen: Introducción: La lesión renal aguda (LRA) es una falla orgánica frecuente en el paciente en estado de choque. La terapia de reemplazo renal lenta continua (TRRLC) es un soporte extracorpóreo que modifica el pronóstico del paciente; los criterios para su inicio así como para su retiro no están del todo generalizados. La prueba de estrés con furosemida podría ser un marcador de pronóstico en los pacientes en quienes se retira el soporte renal. Material y métodos: Estudio prospectivo, observacional, analítico y transversal. Se incluyeron pacientes con LRA que ameritaron TRRLC. Se administró 1 mg/kg de furosemida a los pacientes en quienes se decidió el retiro de la misma. Se cuantificó uresis a las dos, seis y 24 horas y se midieron variables bioquímicas de función renal. La prueba se consideró exitosa en pacientes que no ameritaron nuevamente TRRLC durante los siguientes siete días. Resultados: De 31 pacientes conectados a TRRLC dentro de la unidad de cuidados intensivos (UCI), siete fueron eliminados por fallecer dentro de su primer día de estancia en UCI. Se incluyó un total de 24 pacientes para el estudio. El retiro de la TRRLC fue exitoso en 45.8%. Para predecir el éxito del retiro de la TRRLC y la recuperación de la función renal, la uresis de 200 mL posterior a la prueba de furosemida debe tener una sensibilidad de 64% y especificidad de 100% con un área bajo la curva de 0.944. Conclusión: La presencia de uresis de 200 mL después de dos horas de la administración de furosemida es útil como predictor del éxito del retiro de la TRRLC y recuperación de la función renal.

Abstract: Introduction: Acute kidney injury (AKI) is a frequent organ failure in the patient in shock; continuous slow renal replacement therapy (CSRRT) is an extracorporeal support that modifies the patient's prognosis; the criteria for its initiation as well as for retirement are not completely generalized. The furosemide stress test may be a prognostic marker in patients in whom renal support is withdrawn. Material and methods: Prospective, observational, analytical and cross-sectional study. Patients with AKI requiring CSRRT were included; 1 mg/kg of furosemide was given to the patients in whom it was decided to withdraw, uresis was quantified at 2, 6 and 24 hours and biochemical variables of renal function were measured. Patients who did not merit CSRRT again during the next seven days were considered successful to the test. Results: Thirty-one patients connected to TRRLC within the Intensive care unit (ICU), seven were removed for dying within their first day of ICU stay, including a total of twenty four for their study. 45.8% were successful at withdrawal from CSRRT. The 200 mL uresis after the furosemide test has a sensitivity of 64%, a specificity of 100% to predict success on withdrawal and recovery of renal function, with an area under the curve of 0.944. Conclusion: The presence of 200 mL uresis at 2 hours after administration of furosemide is useful as a predictor of successful withdrawal of TRRLC and recovery of renal function.

Resumo: Introdução: A lesão renal aguda (LRA) é uma falha orgânica comum no paciente em choque; a terapia contínua de substituição renal (TCSR) é um suporte extracorpóreo que altera o prognóstico do paciente; os critérios para a sua iniciação, bem como para a sua retirada, não estão totalmente generalizados. O teste de estresse com furosemida poderia ser um marcador prognóstico nos pacientes em que o suporte renal é removido. Material e métodos: Estudo prospectivo, observacional, analítico e transversal. Foram incluídos pacientes com LRA que necessitaram TCSR; foram administrados 1 mg/kg de furosemida aos pacientes em que a retirada foi decidida, a uresis foi quantificado às 2, 6 e 24 horas e foram medidas as variáveis bioquímicas da função renal. Foram considerados bem-sucedidos os testes em que os pacientes que não necessitaram novamente TCSR nos próximos 7 dias. Resultados: 31 pacientes conectados ao TCSR na Unidade de Terapia Intensiva (UTI), sete foram eliminados por falecer no primeiro dia de estadia na UTI, incluindo um total de 24 pacientes para o estudo. 45.8% tiveram êxito na retirada do TCSR. A uresis de 200 ml após o teste de furosemida teve uma sensibilidade de 64%, especificidade de 100% para prever o sucesso na retirada e recuperação da função renal, com uma área sob a curva de 0.944. Conclusão: A presença da uresis de 200 ml às 2 horas após a administração de furosemida é útil como preditor de remoção bem-sucedida de TCSR e recuperação da função renal.

Actividad antiurolítica del extracto etanólico de propóleo ayacuchano en ratas / Antiurolithic Activity of the Ethanolic Extract of Ayacuchano Propolis in Rats

RESUMEN Objetivos Determinar la actividad antiurolítica del extracto etanólico de propóleo ayacuchano en un modelo preventivo de urolitiasis inducido en ratas. Materiales y métodos Se estudiaron 45 ratas albinas macho Sprague-Dawley. El efecto antiurolítico se analizó en cinco grupos de seis animales: blanco, control (1 mL de etilenglicol al 5% y 1 mL cloruro de amonio al 5%) y tres grupos tratados con el extracto etanólico de propóleo a dosis diaria de 250, 350 y 500 mg/Kg. Las sustancias fueron administradas mediante canulación orogástrica durante 16 días. El efecto diurético se evaluó en 15 ratas distribuidas en cinco grupos: blanco, control (furosemida 20 mg/Kg) y tres grupos tratados con extracto etanólico de propóleo a dosis de 250, 350 y 500 mg/Kg. Se midió el pH urinario, densidad urinaria y sedimentación del oxalato de calcio; la presencia de cálculos renales se evaluó mediante cortes histopatológicos por tinción con hematoxilina-eosina bajo luz polarizada. Resultados El extracto etanólico de propóleo ayacuchano produjo cambios significativos en los valores de ácido úrico, lactato deshidrogenasa sérico, pH, densidad urinaria al comparar los tres grupos dosis; en el análisis histológico observado a luz polarizada se observó menor presencia de cristales de oxalato de calcio en células tubulares del riñón en el grupo tratado a dosis de 250 mg/Kg; el efecto diurético en el grupo tratado con dosis de 250 mg/kg fue mayor en comparación con la furosemida. Conclusiones El extracto etanólico de propóleo ayacuchano presenta actividad antiurolítica en el modelo preventivo de urolitiasis en ratas albinas.

ABSTRACT Objectives To determine the antiurolytic activity of the ethanolic extract of Ayacuchan propolis in a preventive model of urolithiasis in rats. Materials and methods A total of 45 male Sprague-Dawley albino rats were studied. The antiurolithic effect was analyzed in five groups of six animals each: blank, control (treated with 1 mL of 5% ethylene glycol and 1 mL of 5% ammonium chloride), and three experimental groups (treated with the ethanol extract of propolis at a daily dose of 250, 350, and 500 mg/kg, respectively). The drugs were administered by orogastric cannulation for 16 days. The diuretic effect was evaluated in 15 rats distributed in five groups: blank, control (treated with furosemide at 20 mg/kg), and three experimental groups (treated with the ethanol extract of propolis at daily doses of 250, 350, and 500 mg/kg, respectively). Urinary pH, urinary density, and sedimentation of calcium oxalate were measured. The presence of kidney stones was evaluated by examination of hematoxylin-eosin-stained histopathological sections under polarized light. Results The ethanolic extract of Ayacuchan propolis caused significant changes in the levels of uric acid, serum lactate dehydrogenase, pH, and urinary density in the three dose groups. The results of histological analysis indicated a lower presence of calcium oxalate crystals in kidney tubular cells in the group treated with 250 mg/kg. The diuretic effect in the group treated with 250 mg/kg was higher than that in the control group. Conclusions The ethanolic extract of Ayacuchan propolis demonstrated antiurolytic activity in a preventive rat model of urolithiasis.

Efecto de la fuerza de compresión sobre los atributos críticos de calidad en tabletas de liberación inmediata de furosemida / Effect of compression force on critical quality attributes of immediate release tablets of furosemide

RESUMEN La furosemida es un fármaco poco soluble en agua (0,01825 mg/mL). Debido a su baja solubilidad y baja permeabilidad, se ubica en la clase IV del Sistema de Clasificación Biofarmacéutica (BCS, por sus siglas en inglés). Se absorbe rápida pero incompletamente en el tracto gastrointestinal (GI). Actualmente, este fármaco se comercializa en tabletas, las que para su obtención deben ser sometidas a un proceso de compresión. La fuerza aplicada en dicha compresión puede influenciar algunas de las características de calidad del producto; por ello, la presente investigación estudia el efecto de la fuerza de compresión sobre los atributos críticos de calidad en el proceso de fabricación (dureza, friabilidad y desintegración) y en el producto terminado (uniformidad de dosificación y disolución) de comprimidos de furosemida. El efecto sobre la disolución se determinó por los factores de diferencia (f 1) y de similitud (f 2) de los perfiles de disolución y los parámetros de eficiencia de la disolución (ED) y tiempo medio de disolución (TMD), los cuales se calcularon con el software académico kinetDS®. Los resultados obtenidos permitieron definir el rango de la fuerza de compresión para el cual se obtuvo una ED superior al 85% y un TMD inferior a 7,5 min.

SUMMARY Furosemide is poorly water soluble drug (0.01825 mg/mL). Due to its low solubility and low permeability, it is labeled in class IV of the Biopharmaceutical Classification System (BCS). It is rapidly but incompletely absorbed from the gastrointestinal (GI) tract. Currently, this drug is marketed as tablets, which should be subjected to a compression process. The force applied in this compression can influence some of the quality characteristics of the product. Therefore, this investigation was carried out to determine the effect of compression force on the critical quality attributes of the product in process (hardness, friability and disintegration) and of the finished product (uniformity of dosage and dissolution). The effect on the dissolution was determined by the difference factor (f 1) and similarity factor f 2 ) of the dissolution profiles, the dissolution efficiency (ED) and mean dissolution time (TMD) parameters, which were calculated by kinetDS® academic software. The results obtained allowed to define the range of compression force for which the ED was higher than 85% and the TMD lower than 7.5 min.

Uso combinado de furosemida y salbutamol inhalados, en el tratamiento de la crisis aguda de asma bronquial / Combined use of inhaled Furosemide and Salbutamol in the treatment of the acute crisis of bronchial asthma

Fundamento: en la literatura especializada se proponen diferentes alternativas en el tratamiento de pacientes con asma, tanto en el manejo ambulatorio como en las crisis.Objetivo: evaluar el efecto de la combinación furosemida/salbutamol inhalada, sobre la permeabilidad bronquial y los parámetros clínicos, en pacientes asmáticos atendidos en el cuerpo de guardia del Policlínico Universitario “Romárico Oro Peña”.Métodos: se realizó un estudio de intervención, en 41 pacientes asmáticos en crisis, atendidos en la referida institución. Los pacientes se distribuyeron en dos grupos de 18 y 23 pacientes, a través de un muestreo aleatorio, al primero se le aplicó tratamiento con furosemida/salbutamol inhalado y al segundo con salbutamol. Las mediciones del flujo pico y parámetros clínicos se realizaron al inicio y a los 60 minutos de aplicar el medicamento.Resultados: el grupo estudio incrementa el flujo pico en 13,86 L/min, sobre el control; la media de la presión sistólica, en los pacientes de este grupo, se redujo en 1,95 mm de Hg, en relación al control; la presión diastólica (estudio) se redujo en 1,66 mm de Hg, mientras en el control se incrementó 0,43 mm de Hg; ambos grupos disminuyeron la frecuencia respiratoria y cardíaca. No se reportaron efectos adversos.Conclusiones: la adición de furosemida al salbutamol nebulizado, en el tratamiento de pacientes asmáticos en crisis, no supone una ventaja para la mejoría del flujo pico; solo los parámetros clínicos, presión arterial diastólica y sistólica, mostraron superioridad en el grupo estudio (AU)

Background: in the specialized literature there are different alternatives proposed for the treatment of patients suffering from asthma, both in the outpatient management and in the emergency.Objective: to assess the effect of the combination of the inhaled furosemide and salbutamol on the bronchial permeability and clinical parameters in asthmatic patients treated at the emergency room of “Romárico Oro” Teaching Polyclinic.Methods: an intervention study was carried out in 41 asthmatic patients in crisis, who were assisted at the mentioned institution. The patients were distributed at random into two groups of 18 and 23 patients each one. The first group received a treatment with inhaled furosemide and salbutamol and the second one was administered salbutamol. The peak flow and clinical parameters were measured at the beginning and 60 minutes after applying the medicament.Results: the study group increased the peak flow in 13,86 l/min., upper than the control group; the systolic blood pressure values in the patients of the study group were reduced in 1,95 mm Hg in relation to the control group; the diastolic blood pressure values were reduced in 1,66 mm Hg in the study group, meanwhile the control group increased this value in 0,43 mm Hg; both groups decreased their respiration and heart rate.Conclusions: adding furosemide to nebulized salbutamol in the treatment of asthmatic patients in crisis does not take for granted an advantage for the improvement of the peak flow; only the clinical parameters and systolic and diastolic blood pressure showed superiority in the study group (AU)

Vasculitis leucocitoclástica cutánea por posible hipersensibilidad a medicamento de uso crónico en el marco de una infección por virus de la hepatitis C / Leukocytoclastic cutaneous vasculitis due to possible hypersensitivity to cronic drug use in connection with an infection of hepatitis C virus

INTRODUCCIÓN: La Vasculitis leucocitoclástica cutánea (VLC) es una inflamación vascular, habitualmente de vénulas post-capilares. Posee baja incidencia. El signo más frecuente es púrpura palpable (PP). Puede ser primario, o secundario a infecciones, enfermedades sistémicas o fármacos. LaVLC por fármacos es un trastorno poco definido y difícilmente demostrable, la evidencia actual sugiere como criterio principal: asociación temporal fármaco-lesión. PRESENTACIÓN DE CASO CLÍNICO: Mujer, 60 años, antecedentes de Hipertensión Arterial (HTA) en tratamiento, alérgica a Enalapril,Metamizol, y Atenolol, ex-consumidora de anfetaminas, acudió a Urgencias Hospital Las Higueras (HLH), por cuadro de una semana de evolución de lesiones purpúricas, solevantadas, no pruriginosas, ubicadas desde tercio inferior del muslo al pie en extremidades inferiores (EEII), dolorosas EVA 9/10, atenuado con el frío. Lesiones evolucionaron a necrosis durante estadía intrahospitalaria. EcoDoppler descartó trombosis venosa profunda. Función hepática normal. Serología destacó Virus Hepatitis C (VHC) positivo confirmado por Instituto de Salud pública (ISP). Biopsia confirma VLC. Nuevo antecedente reveló inicio reciente de tratamiento con Furosemida; paciente suspendió medicamento. Egresó tras 29 días hospitalizada con dolor leve y lesiones de EEII en regresión. DISCUSIÓN:VLC es una entidad clínico-patológica de difícil abordaje, muchos casos resultan de etiología desconocida aun después de una detallada historia clínica. Es discutible si este caso de VLC se desencadenó por VHC o Furosemida, muchos casos son provocados por hipersensibilidad a medicamentos sumado a infección subyacente. Si bien la Furosemida, medicamento de alta prescripción en patologías GES, ha demostrado ser seguro, es necesaria la administración cuidadosa en pacientes con antecedentes de hipersensibilidad

INTRODUCTION: Leukocytoclastic cutaneous vasculitis (LCV) is a vascular inflamation, usually of post-capillary veins. It has low incidence. The most common sign is palpable purpura. It can be primary or secondary to infections, systemic diseases or drugs. Drug-induced LCV is poorly defined and a difficult to prove disorder. Current evidence suggests as the main criteria: drug-injury temporal association. CASE-REPORT: Female, 60 years old, history of arterial hypertension (AHT) in treatment; allergic to Enalapril, (Metamizol) Dipyrone, and Atenolol; former consumer of amphetamines. Attended to Hospital Las Higueras (HLH) Emergency on 04.18.2014, due to nonpruritic up thrust purpuric lesions, painful EVA 9/10 and attenuated with cold, located from the lower third of the thigh to the foot in lower limbs, one week of evolution. Lesions evolved to necrosis during hospital stay. Doppler ultrasound ruled out deep vein thrombosis. Normal liver function. Serology shows positive HCV confirmed later by IPH. Dermatological biopsy confirms LCV. New data reveals recent onset of treatment with Furosemida; patient stopped taking medication. Patient was discharged after 29 days in hospital with mild pain and lesions in lower limbs in regression. DISCUSION: LCV is a clinicopathological entity of difficult approach. A large number of cases are of unknown etiology entity even after a detailed medical history. It is debatable whether this event was triggered by HCV or Furosemide, because many cases are caused by drug hypersensitivity coupled with an underlying infection. Though furosemide, high prescription drug in GES pathologies, has been proven safe, careful administration in patients with known hypersensitivity is necessary

Lesão renal aguda em pacientes em uso de inibidor da enzima conversora de angiotensina para tratar insuficiência cardíaca descompensada / Acute kidney injury in patients using angiotensin-converting enzyme inhibitors to treat decompensated heart failure

JUSTIFICATIVA E OBJETIVO: Esse estudo procurou descrevera incidência de lesão renal aguda (LRA) em pacientes com insuficiência cardíaca (IC) descompensada pós uso de inibidor de enzima conversora de angiotensina (IECA) e o perfil clínico-epidemiológico desses pacientes. MÉTODOS: Trata-se de um estudo de coorte prospectiva. Foram incluídos no estudo pacientes com insuficiência cardíaca classe IV segundo critérios doNew York Heart Association (NYHA) descompensada admitidos nas enfermarias de Clínica Médica do Hospital Santo Antônio no período de 01/03/2011 a 30/10/2012. Foram excluídos pacientescom doença renal crônica estágios III, IV, V e com dados incompletos. A lesão renal aguda foi definida de acordo como critério RIFLE (Risk/Injury/Failure/Loss/End-stage). Os dados foram analisados através do programa estatístico SPSS 14.0.Esse projeto foi aprovado pelo Comitê de Ética e Pesquisa do Hospital Santo Antônio. RESULTADOS: Dos 100 pacientes estudados, a maioria era do sexo masculino, de etnia afrodescendentee apresentavam como etiologia da insuficiência cardíaca amiocardiopatia chagásica crônica. O sexo feminino, a presença de hipertensão arterial prévia, maiores valores médios basais depressão arterial sistólica (PAS) e pressão arterial diastólica (PAD)e maiores valores médios de idade foram associados à ocorrência de lesão renal aguda, bem como valores médios mais elevados de creatinina sérica basal. Doses médias maiores de inibidores de enzima conversora de angiotensina e de furosemida venosadurante a primeira semana de tratamento foram associadas à ocorrência lesão renal aguda. A área sob a curva ROC (Receiver Operating Characteristic) Curve (AuROC) para uso de inibidores da enzima conversora de angiotensina foi de 0,70 com p=0,001...

BACKGROUND AND OBJECTIVE: This study sought to describe the incidence of acute kidney injury (AKI) in patients with decompensated heart failure after angiotensin converting enzyme (ACE) inhibitors and the clinical - epidemiological profile of these patients. METHODS: This is a prospective cohort study. Patients with New York Heart Association (NYHA) class IV were included in the study. They were admitted in thewards of Internal Medicine, Hospital Santo Antonio in theperiod from 01/03/2011 to 30/10/2012. Patients with chronic kidney disease stages III, IV, V, and without complete data were excluded. Acute kidney injury was defined according to the RIFLE (Risk/Injury/Failure/Loss/End-stage) criteria. Data were analyzed using SPSS 14.0 statistical program. This project was approved by the Ethics and Research Comitee of Hospital St. Anthony. RESULTS: Of the 100 patients, the majority were male, of african descente and and had Chagas´ cardiomyopathy as a cause of heart failure. Females, the presence of previous hypertension and higher baseline mean of diastolic or sistolic pressure and higher mean values of age were associated with the occurrence of acute kidney injury, as well as higher values of baseline serum creatinine. Higher doses of angiotensin converting enzyme inhibitors and furosemide were associated with the occurrence of renal injury. The area under the Receiver Operating Characteristic (ROC) Curve (AUROC) for angiotensin converting enzyme inhibitors (ACEI) was 0.70 with p-0.001. CONCLUSION: High doses of angiotensin converting enzyme inhibitors and intravenous furosemide are associated with acute kidney injury especially in the first week of introduction of angiotensin converting enzyme inhibitors...

Asma bronquial y furosemida / Bronchial asthma and furosemide

La compleja fisiopatología del asma bronquial se refleja en el manejo del paciente asmático, constituyendo un problema de salud en la medicina moderna. Se realizó una revisión bibliográfica, con el objetivo de abordar aspectos relacionados con la aplicación de la furosemida en el tratamiento de esta enfermedad, en busca de esclarecer posibles efectos beneficiosos de esta modalidad terapéutica. Se utilizaron los recursos disponibles en la red Infomed, mediante la cual se accedieron a bases de datos especializadas. De la bibliografía consultada se concluye que el efecto corrector de este fármaco sobre el asma se explica a través de mecanismos que involucran el transporte iónico a través de membranas celulares, produciendo acción directa sobre la vía aérea, efecto antitusígeno, vasodilatación pulmonar, sobre los derivados de la cicloxigenasa y antinflamatorio. Aún no se dispone de datos significativos que permitan concluir con certeza acerca de la efectividad del tratamiento, ya que existen discrepancias entre varios de los estudios realizados. Se recomienda prudencia y proceder con rigurosidad a la hora de experimentar el uso de la furosemida en el asma (AU)

The complex Bronchial asthma pathophysiology and the handling of asthmatic patients constitute difficult problems for modern medicine. This led to carry out a revision research study with the aim of dealing with some aspects related to the application of furosemide for the treatment of this disease, as well as to elucidate the possible beneficial effects of this therapeutic method. It was concluded that: the corrective effect of furosemide on asthma is explained through of mechanisms that involving transport of ions across cellular membranes, that provoke direct effect on pulmonary airway, antitussive effect, pulmonary vasodilator effect, over cycloxygenase derivatives and antiinflammatory effect. There is not significant data that could allow us to accept or deny any hypothesis, because there are important discrepancies between existing studies, so that, to the present day, is prudent fallow a rigorous procedure in experimental studies with asthmatic patient that receive treatment with inhaled furosemide (AU)

Nanocristais de furosemida: preparação, caracterização físico-química e avaliação in silico de absorção oral e pulmonar / Furosemide nanocrystals: preparation, physical-chemical characterization and in silico evaluation of oral and lung absorption

Segundo a Organização Mundial de Saúde, a hipertensão arterial é responsável por uma crise global de saúde pública, sendo as doenças cardiovasculares implicadas em aproximadamente 17 milhões de mortes/ano, das quais, 9,4 milhões ocasionadas por complicações provocadas pela hipertensão, como edema pulmonar. Quanto ao arsenal terapêutico disponível, a furosemida, potente diurético de alça, é amplamente utilizada em situações de controle e emergência relacionadas à hipertensão e ao edema pulmonar cardiogênico. Apesar do elevado índice de sua prescrição, esse fármaco pertence à classe IV do Sistema de Classificação Biofarmacêutica (SCB), apresentando absorções intestinais erráticas e variáveis. Tais características representam desafio para o desenvolvimento de formas farmacêuticas orais. Assim, adoção de tecnologias inovadoras associadas à via de administração pulmonar pode permitir abordagem terapêutica alternativa, com elevado potencial de aplicação. Entre as tecnologias inovadoras, a obtenção de nanocristais de fármacos classes II e IV tem sido promissora. Nanocristais podem exibir desempenho in vivo superior quando comparados aos seus homólogos, na forma micronizada. Portanto, estratégias que permitam o desenvolvimento de medicamentos contendo furosemida, com maior eficácia e segurança, são de fundamental importância. Nesse sentido, a aplicação de tecnologia in silico, com propriedade preditiva, contribui para a racionalização de ensaios na pesquisa e no desenvolvimento de novas formas farmacêuticas. Objetivou-se, desse modo, a preparação e a caracterização físico-química de nanocristais de furosemida e sua avaliação in silico na absorção oral e pulmonar empregando ferramenta computacional. Os nanocristais foram obtidos por moagem à alta energia, utilizando movimentos simultâneos de revolução/rotação. A determinação da distribuição do tamanho e a morfologia foram realizadas por difração de raios laser e microscopia eletrônica de varredura, respectivamente. As possíveis interações e/ou alterações do estado cristalino do fármaco foram investigadas por calorimetria exploratória diferencial, termogravimetria diferencial, difração de raio X e espectroscopia Raman de baixo deslocamento. Quanto à solubilidade do nanocristal, foram realizados ensaios para a determinação do aumento na solubilidade de equilíbrio e da velocidade dissolução, utilizando os métodos shake flask e velocidade de dissolução intrínseca (VDI), respectivamente. A moagem à alta energia permitiu a obtenção de nanocristais com tamanho médio trinta vezes menor (231nm) do que o tamanho inicial, na escala micrométrica (7,1 µm). Os nanocristais apresentaram estabilidade térmica. Não foram observadas interações entre os excipientes e os nanocristais, que, entretanto, exibiram estrutura cristalina menos definida, o que indica parcial amorfização do nanocristal. A solubilidade de saturação dos nanocristais aumentou aproximadamente três vezes; como consequência, houve aumento na VDI em 2,2 vezes, 1,8 vezes e 3,8 vezes, quando comparado à VDI da furosemida micronizada em meio SGF, tampão 4,5 e SIF, respectivamente. Quanto às avaliações in silico dos nanocristais, sua absorção oral revelou moderada alteração no perfil farmacocinético. Quando foi utilizada a via de administração pulmonar, os nanocristais apresentaram maior desempenho quando comparada a via de administração oral; destacando-se o aumento na Fa% e na Cmáx e a acentuada diminuição no Tmáx. Em conclusão, a plataforma tecnológica obtida tem potencial aplicação no desenvolvimento de formas farmacêuticas inovadoras para administração pulmonar de furosemida

According to the World Health Organization, hypertension is responsible for global public health crisis, being the cardiovascular diseases involved in approximately 17 million deaths a year, of these, 9.4 million occasioned by hypertension complications such as pulmonary edema. Regarding therapeutic arsenal available, Furosemide is a potent loop diuretic widely used in control and emergency situations related to hypertension and cardiogenic pulmonary edema. Despite the high level of prescribing, this drug belongs a class IV drug, according to Biopharmaceutics Classification System (BCS), exposing erratic and variable intestinal absorption. These characteristics represent a challenge for the development of oral dosage forms. Thus, adoption of innovative technologies associated with pulmonary route of administration may allow an alternative therapeutic approach, with high potential for application. Among the new technologies, those for obtaining nanocrystals of classes II and IV drugs have been a promising approach. Nanocrystals can exhibit in vivo higher performance when compared to their counterparts in micronized form. Therefore, strategies to develop medicines containing Furosemide, with greater efficacy and safety, are of critical importance. In this sense, the application of technology in silico, with predictive property, contributes to the rationalization of testing in research and development of new dosage forms. The objectives, as a result, were the preparation and the physicochemical characterization of Furosemide nanocrystals, and it's in silico evaluation on oral and pulmonary absorption using a computational tool. The nanocrystals were obtained using a high-energy milling technology under simultaneous revolution/rotation motion. The determination of the size distribution and morphology was performed using laser diffraction and scanning electron microscopy, respectively. Furthermore, differential scanning calorimetry, differential thermogravimetry, X-ray diffraction and Low Shift Raman spectroscopy were performed to investigate possible interactions and changes in the crystalline state of the nanocrystals. To measure the increase in the equilibrium solubility and dissolution rate, the shake flask and intrinsic dissolution rate (IDR) methods were used respectively. The nanocrystals size appeared thirty times lower (231 nm) compared to the initial size (7,1 µm). The nanocrystals were stable with concern to its thermal characteristic not showing interactions between the excipients and the nanocrystals; however, they exhibited less defined crystal structure, indicating partial amorphization. The nanocrystals saturation solubility increased approximately three times. Consequently, 2.2, 1.8 and 3.8 folds increase were observed in IDR when compared to the Furosemide raw material in SGF, buffer 4.5 and SIF, respectively. The in silico nanocrystal studies revealed moderate changes in its oral absorption and pharmacokinetic profile. When the pulmonary route of administration was used, the nanocrystals showed higher performance compared to oral route administration; highlighting the increase in Fa % and Cmax and a significant decrease in Tmax. In conclusion, the technology platform obtained has potential application in the development of innovative dosage forms for Furosemide pulmonary delivery