Uso de treprostinil sistémico en una paciente con hipertensión pulmonar grave, sin respuesta a la máxima terapia disponible / Use of treprostinil in a patient with a severe pulmonary arterial hypertension no responding to the maximal therapy available

En los pacientes con Hipertensión Arterial Pulmonar (HAP) de alto riesgo, en clase funcional (CF)IV, la terapia específica debe ser combinada y debe incluir una prostaciclina (PGI2) de uso sistémico en espera de trasplante bipulmonar (TBP). En el sistema público la única PGI2 disponible para asociar a Sildenafil y algún inhibidor de endotelina (Ambrisentan o Bosentan) es Iloprost nebulizado, que si bien es efectiva, no logra estabilizar los casos graves con severa disfunción del ventrículo derecho (VD). Se presenta el primer caso en el Instituto del Tórax, centro de referencia nacional de HAP, del uso de treprostinil en una paciente de 24 años con HAP grave e indicación de TBP. Treprostinil es un análogo sintético de PGI2 de uso subcutáneo en dosis desde 1 a 40 ng/kg/min. La paciente presentaba una situación de extrema gravedad: CF IV, distancia recorrida en el test de caminata de 6 min (DRTC 6 min) < 300 m,derrame pericárdico y severa disfunción del VD con TAPSE (índice de disfunción del VD) de 13 cm/s asociado a ProBNP >2.500 pg/ml. Luego de 6 meses de hospitalización en intermedio, terapia triple (Sildenafil, Ambrisentan e Iloprost nebulizado) asociado a O2,diuréticos y milrinona, logró ser dada de alta a las 3 semanas del inicio de treprostinil, regresando al trabajo a los 2 meses y estabilizando su condición en CF III, con DRTC 6 min > 440 m, mejoría de la función del VD(TAPSE 19). El ProBNP persistió elevado, 1.491 pg/ml, indicando que su enfermedad es grave y progresiva; sin embargo, ha logrado un nivel de estabilidad clínica que le permite una adecuada vida de relación familiar y laboral.

In high risk Pulmonary Arterial Hypertension (PAH) patients with functional class (FC) IV, specific therapy must be combined and must include systemic prostacyclin (PGI2), meanwhile they are enlisted for double lung transplant (DLT). In Chilean Public Health System, nebulized Iloprost is the only PGI2 available to combine with Sildenafil and either Ambrisentan or Bosentan as endothelin receptor antagonist. This association is not enough for severe cases with right ventricular (RV) dysfunction. The first case from the National Institute of Thorax as a referral center is presented now in a 24 years-old lady treated with treprostinil. She has severe PAH with DLT indication. Treprostinil is a PGI2 analog, for subcutaneous use in a dose from 1 to 40 ng/kg/min. She was extremely sick, with FC IV, she walked < 300 m at 6 min walking test (6 MWT), presented pericardial effusion and severe RV dysfunction, with TAPSE (echocardiography index for RV dysfunction)=13 cm/s, ProBNP > 2,500 pg/ml. Six months after being at intensive care unit with triple therapy (Sildenafil, ambrisentan and nebulized Iloprost) plus oxygen, diuretics and milrinone, she was finally discharged after receiving a 3 weeks treprostinil course. She came back to work two months later and her condition was more stable: FC III, she walked > 440 m at 6MWT, with a significant improvement in RV function with TAPSE = 19. Although ProBNP decreased to 1,491pg/ml, it was still high, pointing out the progressive nature of her disease. However, she met a better clinical condition which allows her to reach a much better quality of life from a personal, familial and social point of view.

Levosimendan as a treatment for acute renal failure associated with cardiogenic shock after hip fracture / Levosimendana como tratamento para insuficiência renal aguda associada a choque cardiogênico após fratura de quadril

Abstract Inotropic drugs are part of the treatment of heart failure; however, inotropic treatment has been largely debated due to the increased incidence of adverse effects and increased mortality. Recently levosimendan, an inotropic positive agent, has been proved to be effective in acute heart failure, reducing the mortality and improving cardiac and renal performance. We report the case of a 75-year-old woman with history of heart and renal failure and hip fracture. Levosimendan was used in preoperative preparation as an adjuvant therapy, to improve cardiac and renal function and to allow surgery.

Resumo Fármacos inotrópicos fazem parte do tratamento de insuficiência cardíaca; no entanto, o tratamento com inotrópicos tem sido amplamente debatido devido ao aumento da incidência de efeitos adversos e da mortalidade. Recentemente, levosimendana, um agente inotrópico positivo, provou ser eficaz na insuficiência cardíaca aguda, reduz a mortalidade e melhora o desempenho cardíaco e renal. Relatamos o caso de uma paciente de 75 anos, com história de insuficiência cardíaca e renal e fratura de quadril. Levosimendana foi usada na preparação do pré-operatório como terapia adjuvante para melhorar a função cardíaca e renal e permitir a cirurgia.

Beyond ten cycles of cabazitaxel for castrate-resistant prostate cancer.

Background: There are limited data regarding cabazitaxel use beyond 10 cycles. Patients and Methods: Retrospective analysis of prospectively collected data of patients with metastatic castrate-resistant prostate cancer who received over 10 cycles of cabazitaxel after docetaxel failure. Results: Four patients received between 14 and 27 cycles. Reasons for stopping cabazitaxel were toxicity (2), progression (1) and logistics (1). Two of the three patients with measurable disease attained a partial remission (PR). Three patients continued to have a PSA response after 10 cycles; PSA nadir occurred between 17 and 23 cycles. Other than peripheral neuropathy (PN), all the cabazitaxel-related toxicities occurred after the initial cycles and did not increase cumulatively. Clinically significant neuropathy occurred after 15-17 cycles. The cabazitaxel-induced PN was partially reversible, with improvement from grade 3 to grade 2 after a 3-5-month long drug holiday. Conclusion: Cautiously continuing cabazitaxel until progression or intolerable toxicity may maximize efficacy.

Efeitos do levosimendan sobre TNF-alfa, PNB e MMP-1 em pacientes com insuficiência cardíaca com anemia / Effects of levosimendan on TNF-alpha, BNP and MMP-1 in patients with heart failure with anemia

FUNDAMENTO: O levosimendan é conhecido pelo seu efeito bilateral de fortalecimento contração das miofibrilas sem aumentar a demanda de oxigênio no miocárdio. A anemia é uma deterioração que causa aumento da dosagem de fármacos em pacientes com insuficiência cardíaca. OBJETIVO: No presente estudo comparamos a eficácia do tratamento com levosimendan em pacientes com insuficiência cardíaca descompensada com ou sem anemia. MÉTODOS: Foram incluídos no estudo 23 pacientes anêmicos com insuficiência cardíaca classe 3 ou 4, segundo a New York Heart Association (NYHA) e fração de ejeção abaixo de 35%. Outros 23 pacientes com o mesmo diagnóstico cardíaco, mas sem anemia, serviu como grupo controle. Ao tratamento da insuficiência cardíaca tradicional desses pacientes foi acrescido um tratamento de 24 horas de levosimendan. Amostras foram tomadas para dosar os níveis séricos do fator de necrose tumoral alfa sérico (TNF-alfa), peptídeo natriurético cerebral aminoterminal (NT-proPNB) e metaloproteinase da matriz 1 (MMP-1), antes e após a administração. RESULTADOS: Não houve diferença significativa entre os níveis séricos de TNF-alfa e MMP-1, antes e depois do tratamento (p > 0,05). Embora o nível de NT-proBNP tenha diminuído em ambos os grupos após o tratamento, não foi estatisticamente significativo (p = 0,531 e p = 0,913 para os grupos de anemia e de controle, respectivamente). Uma restauração significativa da capacidade funcional foi observada em ambos os grupos avaliados, de acordo com a NYHA (p < 0,001 e p = 0,001 para os grupos de anemia e controle, respectivamente). CONCLUSÃO: O tratamento com levosimendan apresenta efeitos semelhantes em pacientes com insuficiência cardíaca, com anemia e sem anemia. No entanto, o efeito precoce desse tratamento sobre os níveis de TNF-alfa, NT-proPNB e MMP-1 não é evidente. Ele oferece uma melhora significativa na capacidade funcional, sem a influência da anemia.

BACKGROUND: Levosimendan is known with its two-sided effects of strengthening myofibril contraction without increasing myocardial oxygen demand. Anemia is a deteriorating situation that causes increase of drug dosing in patients with heart failure. OBJECTIVES: In this study, we compared the effectiveness of levosimendan treatment in decompensated heart failure patients with or without anemia. METHODS: Twenty-three anemic patients having class 3 or 4 heart failure according to New York Heart Association (NYHA) and an ejection fraction of below 35% were included to the study. Another 23 patients with the same cardiac diagnosis but without anemia served as control group. Twenty-four hours levosimendan treatment was added to the traditional heart failure treatment of these patients. Samples were taken to measure serum tumor necrotizing factor alpha (TNF-alpha), aminoterminal pro-brain natriuretic peptide (NT-proBNP) and matrix metalloproteinase-1 (MMP-1) levels before and after the administration. RESULTS: There was no significant difference between serum TNF-alpha and MMP-1 levels before and after the treatment (p>0.05). Although NT-proBNP level decreased in both groups after the treatment this was not statistically significant (p=0.531 and p=0.913 for anemia and control groups respectively). Significant restoration of functional capacity was seen in both groups assessed according to NYHA (p<0.001 and p=0.001 for anemia and control groups respectively). CONCLUSION: Levosimendan treatment shows similar effects in heart failure patients with anemia to that of patients without anemia. However, the early effect of this treatment on TNF-alpha, NT-proBNP and MMP-1 levels is not evident. It provides significant improvement in functional capacity without influence from anemia.

Efeito do levosimendan em pacientes com insuficiência cardíaca sistólica severa e agravamento da função renal / Effect of levosimendan in patients with severe systolic heart failure and worsening renal function

FUNDAMENTO: O levosimendan, um sensibilizador de cálcio, aumenta a sensibilidade do coração para o cálcio, aumentando assim a contratilidade miocárdica, sem aumento do cálcio intracelular. Recentemente foi demonstrado que o levosimendan era benéfico na melhoria da função renal. No entanto, fica por determinar que o efeito benéfico esteja relacionado em forma diferencial ao status renal durante o evento-índice. OBJETIVO: O objetivo do presente estudo foi determinar se o levosimendan pode melhorar o resultado renal em pacientes com insuficiência cardíaca aguda descompensada com e sem agravamento da função renal. MÉTODOS: Quarenta e cinco pacientes consecutivos que tiveram uma taxa de filtração glomerular reduzida e pelo menos dois dados consecutivos quanto à função renal, antes da administração de levosimendan, foram incluídos no estudo. Os pacientes foram classificados em dois grupos, com e sem agravamento da função renal com base no aumento da creatinina sérica > 0,3 mg/dL. RESULTADOS: Uma melhoria significativa foi observada na função renal em pacientes com agravamento da função renal (creatinina sérica de 1,4 ± 0,16 a 1,21 ± 0,23 mg/dL, p = 0,001 e taxa de filtração glomerular de 48,9 ± 15 a 59,3 ± 21,8 mL/min/m², p = 0,011), apesar de que não houve melhoria significativa em aqueles sem agravamento da função renal (creatinina sérica de 1,29 ± 0,33 a 1,37 ± 0,66 mg/dL, p = 0,240 e taxa de filtração glomerular de 53,7 ± 17,6 a 52,9 ± 21,4 mL/min/m², p = 0,850). CONCLUSÃO: O levosimendan parece proporcionar um efeito de realce renal em pacientes com severa insuficiência cardíaca sistólica descompensada aguda e agravamento da função renal. Considerar esse efeito diferencial poderia contribuir a obter resultados renais benéficos. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0).

BACKGROUND: Levosimendan, a calcium sensitizer, increases the sensitivity of the heart to calcium, thus increasing myocardial contractility without a rise in intracellular calcium. It was recently shown that levosimendan is beneficial in improving renal function. However, it remains to be established that the beneficial effect is differentially related to renal status during index event. OBJECTIVE: The purpose of the current study was to determine whether levosimendan could improve renal outcome in acute decompensated heart failure patients with and without worsening renal function. METHODS: Forty-five consecutive patients who had a reduced glomerular filtration rate and had at least two consecutive data regarding renal function prior to administration of levosimendan were enrolled in the study. Patients were classified into two groups as those with and without worsening renal function based on an increase in serum creatinine >0.3 mg/dL. RESULTS: A significant improvement was noted in renal function in patients with worsening renal function (serum creatinine from 1.4±0.16 to 1.21±0.23 mg/dL, p=0.001 and glomerular filtration rate level from 48.9±15 to 59.3±21.8 mL/min/m², p=0.011), while there was no significant improvement in those without worsening renal function (serum creatinine from 1.29±0.33 to 1.37±0.66 mg/dL, p=0.240 and glomerular filtration rate level from 53.7±17.6 to 52.9±21.4 mL/min/m², p=0.850). CONCLUSION: Levosimendan appears to provide a renal-enhancing effect in patients with severe, acute decompensated systolic heart failure and worsening renal function. Consideration of this differential effect might help obtain beneficial renal outcomes. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0).

Levosimendan na insuficiência cardíaca descompensada: revisão sistemática e metanálise / Levosimendan in acute decompensated heart failure: systematic review and meta-analysis

FUNDAMENTO: A insuficiência cardíaca descompensada (ICD) é uma condição bastante prevalente e com alta mortalidade. O levosimendan está entre as novas drogas que têm sido testadas para o seu manejo. OBJETIVO: Realizar uma revisão sistemática da literatura e uma metanálise da redução de morbimortalidade associada ao levosimendan no tratamento da ICD. MÉTODOS: Foi feita uma pesquisa bibliográfica no Medline buscando todos os ensaios clínicos randomizados (ECRs) que avaliassem o uso do levosimendan na ICD. Os desfechos de interesse foram: morte por todas as causas, tempo de internação hospitalar e reinternação hospitalar por ICD. Todos os ECRs com desfechos de interesse foram incluídos. Critérios de qualidade metodológica, como cegamento e sigilo da lista de alocação, foram avaliados em análise de sensibilidade. O cálculo principal foi feito com efeitos randômicos. RESULTADOS: Dos 179 artigos identificados, 48 eram ECRs, sendo 19 com desfechos clínicos de interesse. Na comparação com placebo (7 ensaios clínicos, 1.652 pacientes), o risco relativo (RR) para morte total foi de 0,87 (intervalo de confiança [IC] 95 por cento: 0,65 - 1,18). Na comparação com dobutamina (10 ensaios clínicos, 2.067 pacientes), o RR foi de 0,87 (IC 95 por cento: 0,75 - 1,02). Três estudos tinham dados sobre tempo de internação, onde o levosimendan mostrou diminuição de 2,27 e 2,30 dias em relação ao placebo e a dobutamina, respectivamente (p < 0,05 para ambos). Nenhum artigo apresentou isoladamente dados sobre reinternação. CONCLUSÃO: As evidências disponíveis até o momento não mostram benefício em termos de mortalidade associada ao levosimendan, que apresentou benefício de pequena magnitude apenas no tempo de internação.

BACKGROUND: Congestive heart failure (CHF) is a rather prevalent condition with a high mortality rate. Levosimendan is one among the new drugs that have been tested for its management. OBJECTIVE: To undertake a systematic review and meta-analysis of the morbidity and mortality reduction associated with levosimendan in the treatment of CHF. METHODS: A bibliographic search was conducted in the Medline database for all randomized controlled trials (RCTs) that assessed the use of levosimendan in CHF. The outcomes were death from all causes, length of hospital stay, and hospital readmission for CHF. All RCTs with outcomes of interest were included. Methodological quality criteria, such as blinding and confidentiality of the list of allocation, were evaluated in sensitivity analysis. The main calculation was done with random effects. RESULTS: Of the 179 articles identified, 48 were RCTs, 19 of them with outcomes of interest. In the comparison with placebo (7 trials, 1,652 patients), the relative risk (RR) for overall death was 0.87 (95 percent confidence interval [CI]: 0.65 to 1.18). In comparison with dobutamine (10 trials, 2,067 patients), the RR was 0.87 (95 percent CI: 0.75-1.02). Three studies had data on length of stay, in which levosimendan showed a decrease of 2.27 and 2.30 days compared to placebo and dobutamine, respectively (p < 0.05 for both). No article presented data on readmission alone. CONCLUSION: The evidence available so far has shown no benefit in terms of mortality in association with the use of levosimendan, which only showed a small benefit in the time of hospitalization.

Miocardiopatía por hipocalcemia / Hypocalcemic cardiomyopathy

Se presenta el caso de un varón de 56 años, portador de Miocardiopatía dilatada, considerada, en algún momento, como terminal. Se comprobó que presentaba de base una hipocalcemia crónica secundaria a hipoparatiroidismo. Se discute su notable respuesta a administración de calcio e infusión de levosimendan IV fármaco inotropo positivo que actúa sensibilizando al calcio.

Pulmonary arterial hypertension in children: a medical update.

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by a progressive pulmonary vasculopathy with ensuing right heart failure if left untreated. In the 1980's, prior to the current treatment era, idiopathic pulmonary arterial hypertension (IPAH) carried a poor prognosis with a 10 month median survival for children after diagnosis. However, in 1995 continuous intravenous epoprostenol was approved for the treatment of severe PAH, improving hemodynamics, quality of life, exercise capacity, functional class and survival. In the past decade there have been further advances in the treatment of PAH; however, there is still no cure. While much of the groundbreaking clinical research has been performed in adults, children have also seen the benefits of PAH novel therapies. The target population among pediatric patients is expanding with the recent recognition of pulmonary hypertension as a risk factor for sickle cell disease patients. With rapid advances, navigating the literature becomes challenging. A comprehensive review of the most recent literature over the past year on available and emerging novel therapies as well as an approach to target pediatric populations provides insights into the management of pediatric PAH patients.

Uso de levosimendana em diversos quadros de insuficiência cardíaca aguda: [revisão] / Levosimendan use in several scenarios of acute heart failure: [review]

Nos países em que é comercializada, a administração precoce de levosimendana deve ser considerada em pacientes que permanecem sintomáticos e com dispnéia em repouso apesar da terapia inicial, principalmente aqueles com história de insuficiência cardíaca crônica ou em tratamento prolongado com betabloqueadores. Pacientes hipotensos ou com isquemia ativa não são os melhores candidatos para receber infusão de levosimendana e precisam, primeiro, ter esses problemas tratados.

In countries where it is available, early levosimendan infusion can be considered for patients who remain symptomatic with dyspnea at rest despite initial therapy, particularly those with a history of chronic heart failure or chronically treated with beta-blockers. Hypotensive patients or patients with active ischemia are not the best candidates for levosimendan administration and should have these problems addressed first.

Levosimendan: Nueva estrategia en el manejo de la falla cardíaca / Levosimendan: A new strategy in the treatment of heart failure

La insuficiencia cardíaca congestiva se ha considerado como un grave problema de salud. De manera tradicional, la insuficiencia cardíaca ha sido manejada con diferentes fármacos, como son los diuréticos, digital, inotrópicos del tipo de las catecolaminas y no catecolaminas; sin embargo, el manejo de los mismos, también tienen efectos secundarios en donde se incluyen la génesis de las arritmias e incluso la muerte. Un nuevo grupo de drogas recientemente ha impactado en el manejo de los pacientes con insuficiencia cardíaca aguda y crónica, estos son los sensibilizadores de calcio, que actúan incrementando la contractilidad miocárdica, sin aumentar la liberación del calcio citosólico. El levosimendan, es un sensibilizador de calcio que además de aumentar la contractilidad, posee efecto vasodilatador por activación de los canales de K(ATP), siendo ambos mecanismos los que ofrecen una opción terapéutica en la falla cardíaca. Varios estudios han comprobado la eficacia y seguridad de la droga en diferentes estadios y poblaciones, por lo que se considera en la actualidad que el uso del levosimendan es una alternativa real y segura de tratamiento en aquellos pacientes con falla ventricular aguda o crónica que necesiten soporte farmacológico endovenoso.

Congestive heart failure is a long standing health issue. Traditionally, heart failure has been treated with a wide array of drugs such as diuretics, digitalis, catecholamine and non catecholamine inotropics, although treatment with these drugs bears adverse effects, such as the generation of arrhythmia and even death. A new class of drugs has recently exerted a positive impact on the treatment of patients with heart failure; these are the calcium sensitizers that enhance myocardial contractility without increasing cytosolic calcium. Levosimendan is a calcium sensitizer that, besides increasing contractility, has a vasodilating effect due to the activation of K(ATP) channels, being both mechanisms responsible for an advantageous therapeutic option. Different studies have proven the efficiency and safety profile of the drug on various scenarios and populations; thereby considering levosimendan a real and safe alternative treatment for patients with acute or chronic ventricular failure that need intravenous pharmacological support.

Uso de levosimendan en enfermos con falla cardíaca aguda / Levosimendan in patients with acute cardiac failure

Objetivo: Valorar el uso de levosimendan en el contexto de la falla cardíaca aguda. Material y métodos: Se incluyeron 25 pacientes que ingresaron o desarrollaron insuficiencia cardíaca aguda, con respuesta parcial al manejo habitual definida como la presencia de bajo gasto cardíaco a pesar de tratamiento inotrópico. Se inició levosimendan administrando una dosis de carga y se continuó con una infusión durante 24 horas, monitorizándose a los pacientes con un catéter de flotación pulmonar y registrándose los parámetros hemodinámicos, así como las variables clínicas de frecuencia cardíaca (FC) y presión arterial media (PAM). Resultados: Observamos mejoría clínica en todos los pacientes. Hemodinámicamente se documentó disminución de la presión capilar pulmonar (PCP) de 18 cmH2O (11-30 cmH2O) a 14 cmH2O (8-15 cmH2O) (p = 0.3) para las 12 horas de haberse iniciado la infusión y al final de 13 cmH2O (8-12 cmH2O) (p = 0.2.) Igualmente se observó mejoría en cuanto al índice cardíaco (IC) 2.1 L/min/m² (1.8-3.5 L/min/m²), a 2.86 L/min/m² (2-4.3 L/min/m²) (p = 0.03) a las 12 h de la infusión y manteniéndose de 3.08 L/min/m² (2.4-3.9 L/min/m²) al término de la infusión (p = 0.02.). Sólo 6 pacientes mostraron como complicación taquicardia con FC mayor de 120 x min, que fue transitoria y que no requirió manejo adicional. En ningún caso requirió iniciar infusión de algún vasopresor. La mortalidad hasta el momento es de 8 pacientes. Conclusión: El uso de levosimendan en pacientes con falla cardíaca aguda mejora las variables hemodinámicas y clínicas con pocos efectos adversos en esta población de estudio.

Objective: To assess levosimendan efficacy in acute cardiac failure. Methods: We included 25 patients with acute cardiac failure and partial conventional therapy response defined as persistence of low cardiac output with inotropic support. We started levosimendan at loading dose and continuous infusion for 24 hours, recording hemodynamic data, as well as clinical variables. Results: All patients showed clinical and hemodynamic improvement. Pulmonary wedge capillary pressure (PWCP) decreased from 18 cmH2O (11 -30 cmH2O) to 14 cmH2O (8-15 cmH2O) at 12 hours (p = 0.3) and to 13 cmH2O (8-12 cmH2O) at the end of the infusion period (p = 0.2). Cardiac index increased from 2.1 L/min/m² (1.8-3.5 L/ min/m²) to 2.86 L/min/m² (2-4.3 L/min/m²) at 12 hours (p = 0.03) and to 3.08 L/min/m² at the end of the infusion period (p = 0.02). Tachycardia higherthan 120 bpm was present in six patients. No major hypotensive events were present. Mortality to the present is of eight patients. Conclusion: Levosimendan infusion improved hemodynamics and clinical variables in acute cardiac failure with few side effects in this small series of patients.

Análise de custos do tratamento de episódios de descompensacão aguda de insuficiência cardíaca: levosimendan versus dobutamina / Cost analysis of the treatment of acute decompensated heart failure: levosimendan versus dobutamine

OBJETIVO: Verificar se o tratamento com levosimendan seria mais dispendioso que o usual com dobutamina, uma vez que o preco dos medicamentos não representa a maior despesa no tratamento da descompensacão cardíaca. MÉTODOS: Comparou-se o custo do tratamento de 18 pacientes hospitalizados devido a descompensacão cardíaca, 9 tratados com dobutamina (grupo dobuta) e 9 com levosimendan (grupo levo). Os grupos foram semelhantes quanto à idade, sexo, classe funcional e funcão cardíaca. RESULTADOS: O custo do tratamento foi semelhante para os dois grupos. No grupo levo as despesas com medicamentos foram maiores, mas as relativas ao período de terapia intensiva e do material empregado foram menores. Levo - medicamentos: R$ 5.414,00; materiais: R$ 399,90; diárias hospitalares: R$ 5.061,20; servicos profissionais: R$ 3.241,80; final: R$ 14.117,00. Dobuta - medicamentos: R$ 2.320,10; materiais: R$ 1.665,70; diárias hospitalares: R$ 6.261,90; servicos profissionais: R$ 3.894,30; final: R$ 14.142,00. CONCLUSAO: Apesar do preco mais elevado da droga, o custo global do tratamento foi semelhante para os pacientes tratados com dobutamina ou levosimendan. O paciente tratado com levosimendan permaneceu menos tempo em terapia intensiva.

Effects of azelastine on allergen- and exercise-induced asthma.

The effects of the new anti-allergic drug, azelastine, on allergen- and exercise-induced asthma were studied. In six allergen inhalation tests for five asymptomatic asthmatic patients, the maximum percentage fall in FEV1.0 immediately after inhalation of allergen extract was 37.2 +/- 6.4 per cent (mean +/- SEM). As compared with a placebo, the maximum percentage fall in FEV1.0 with azelastine after inhalation of allergen extract in the same manner as with the placebo was 17.3 +/- 6.9 per cent. The difference was statistically significant (p less than 0.05). The percentage fall in FEV1.0 with placebo and azelastine in late asthmatic response (n = 4) was 36.0 +/- 5.3 per cent and 10.0 +/- 5.2 per cent, respectively. The difference was also statistically significant (p less than 0.01). An exercise test was carried out on seven asymptomatic asthmatic patients using an inclined treadmill. The maximum percentage fall in FEV1.0 without drugs, with diphenhydramine and azelastine was 38.9 +/- 5.0 per cent, 20.1 +/- 3.8 per cent and 11.3 +/- 3.1 per cent, respectively. Significant differences were found among each group (p less than 0.05). Azelastine was regarded as having sufficient potency to inhibit exercise-induced asthma; however, placebo effects cannot be ruled out with regard to the effects of diphenhydramine. These results suggests that chemical mediator release is involved not only in allergen-induced asthma but also in exercise-induced asthma, suggesting the clinical utility of azelastine.