RESUMO
BACKGROUND: Limited evidence exists regarding efficacy and safety of diuretic regimens in ambulatory, congestion-refractory, chronic heart failure (CHF) patients. OBJECTIVES: The authors sought to compare the potency and safety of commonly used diuretic regimens in CHF patients. METHODS: A prospective, randomized, open-label, crossover study conducted in NYHA functional class II to IV CHF patients, treated in an ambulatory day-care unit. Each patient received 3 different diuretic regimens: intravenous (IV) furosemide 250 mg; IV furosemide 250 mg plus oral metolazone 5 mg; and IV furosemide 250 mg plus IV acetazolamide 500 mg. Treatments were administered once a week, in 1 of 6 randomized sequences. The primary endpoint was total sodium excretion, and the secondary was total urinary volume excreted, both measured for 6 hours post-treatment initiation. RESULTS: A total of 42 patients were recruited. Administration of furosemide plus metolazone resulted in the highest weight of sodium excreted, 4,691 mg (95% CI: 4,153-5,229 mg) compared with furosemide alone, 3,835 mg (95% CI: 3,279-4,392 mg; P = 0.015) and to furosemide plus acetazolamide 3,584 mg (95% CI: 3,020-4,148 mg; P = 0.001). Furosemide plus metolazone resulted in 1.84 L of urine (95% CI: 1.63-2.05 L), compared with 1.58 L (95% CI: 1.37-1.8); P = 0.039 collected following administration of furosemide plus acetazolamide and 1.71 L (95% CI: 1.49-1.93 L) following furosemide alone. The incidence of worsening renal function was significantly higher when adding metolazone (39%) to furosemide compared with furosemide alone (16%) and to furosemide plus acetazolamide (2.6%) (P < 0.001). CONCLUSIONS: In ambulatory CHF patients, furosemide plus metolazone resulted in a significantly higher natriuresis compared with IV furosemide alone or furosemide plus acetazolamide.
Assuntos
Acetazolamida , Estudos Cross-Over , Diuréticos , Furosemida , Insuficiência Cardíaca , Metolazona , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Furosemida/administração & dosagem , Furosemida/uso terapêutico , Masculino , Feminino , Diuréticos/administração & dosagem , Diuréticos/uso terapêutico , Acetazolamida/administração & dosagem , Acetazolamida/uso terapêutico , Metolazona/administração & dosagem , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Quimioterapia Combinada , Diurese/efeitos dos fármacos , Resultado do TratamentoRESUMO
BACKGROUND: Current treatment of fluid retention in heart failure relies primarily on diuretics. However, adequate decongestion is not achieved in many patients. We aimed to study the feasibility and short-term performance of a novel approach to remove fluids and sodium directly from the interstitial compartment by enhancing sweat rate. METHODS: We used a device designed to enhance fluid and salt loss via the eccrine sweat glands. Skin temperature in the lower body was increased from 35 °C to 38 °C, where the slope of the relationship between temperature and sweat production is linear. The sweat evaporates instantaneously, thus avoiding the awareness of perspiration. The primary efficacy endpoint was the ability to increase skin temperature to the desired range. A secondary efficacy endpoint was a clinically meaningful hourly sweat output, defined as ≥150 mL/h. The primary safety endpoint was any procedure-related adverse events. RESULTS: We studied 6 normal subjects and 18 patients with congestion. Participants underwent 3 treatment sessions of up to 4 hours. Skin temperature increased to a median of 37.5 °C (interquartile range, 37.1-37.9 °C) with the median core temperature increasing by 0.2 °C (interquartile range, 0.1-0.3 °C). The median hourly weight loss during treatment was 215 g/h (interquartile range, 165-285; range, 100-344 g/h). In 80% of treatment procedures, the average sweat rate was ≥150 mL/h. There were no significant changes in hemodynamic variables or renal function and no procedure-related adverse events. CONCLUSIONS: Enhancing sweat rate was safe and resulted in a clinically meaningful fluid removal and weight loss. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04578353.