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Vol. 72. Issue 6.
Pages 500-502 (June 2019)
Scientific letter
DOI: 10.1016/j.rec.2018.06.012
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Subcutaneous Furosemide in Patients With Refractory Heart Failure
Furosemida subcutánea como tratamiento para pacientes con insuficiencia cardiaca refractaria
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Ainara Lozano Bahamonde
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, Vanessa Escolar Pérez, Amaia Echebarria Chousa, Alberto Azcona Lucio, Silvia Alfambra Vicente, Begoña Rodríguez Rodríguez
Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitario Basurto, Organización Sanitaria Integrada Bilbao Basurto, Vizcaya, Spain
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Table. Characteristics of Patients and Subcutaneous Furosemide Treatment
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To the Editor,

Reports of subcutaneous (SC) furosemide used to treat heart failure (HF) are scarce and mainly involve small case series in which this administration route was used for decompensation with congestive symptoms during relatively short periods.1–3 A recently published phase-II clinical trial4 compared the efficacy of intravenous furosemide vs a new SC furosemide formulation for treating decompensated HF, and concluded that the new formulation is similar to the intravenous drug in terms of efficacy and safety. These results suggest that the new formulation may also be effective as long-term treatment for patients with chronic resistance to oral diuretics, who have few therapeutic options.

The main aim of this study was to determine the mid- and long-term effectiveness of HF treatment using SC furosemide infusion with elastomeric pumps, by comparing the hospitalization rates for HF during the year prior to inclusion and during follow-up. The secondary aims were to evaluate the weight reduction in patients with congestive symptoms, assess dry weight maintenance in euvolemic patients starting this therapy, and determine the safety of the intervention. Between December 2014 and March 2018, we recruited 16 consecutive patients with decompensated HF refractory to oral diuretic control and with at least 2 hospitalizations in the previous 6 months or requiring repeat intravenous administration. Severe adverse events were defined as infusion-related infections, local skin lesions leading to treatment discontinuation, and deterioration of renal function or hyperpotassemia requiring treatment. Local skin lesions not requiring specific treatment were considered mild adverse events.

Patient characteristics are shown in Table 1. In the year prior to starting SC furosemide, patients had a mean of a 3.2 ± 2.5 hospitalizations for HF, yielding a rate of 0.26 hospitalizations for decompensated HF/patient/mo of follow-up. All patients had been receiving high doses of oral furosemide (mean dose, 138.7 ± 41.1mg/d; 9 patients [56.3%] took potassium-sparing diuretics and 7 [50.0%] thiazides). Treatment was started during a decompensation or while congestive symptoms persisted in 12 patients. Four patients started treatment while they were euvolemic, after achieving clinical stability with intravenous diuretics.

Table.

Characteristics of Patients and Subcutaneous Furosemide Treatment

Patient  Age/sex  Heart disease  LVEF  PASA > 55 mmHg  GF (mL/min)  Hospitalization for HF in the 12 previous mo  Emergency room stay for HF in the 12 previous mo  Status at the start of subcutaneous treatment  Days on treatment with subcutaneous furosemide  Initial dose*  Maintenance dose*  Initial NYHA  NYHA at 2 weeks  Reason for end of follow-up  Decompensations during follow-up  Vital status  Cause of death 
91/M  Valvular  50  Yes  20  Congestive  56  250  50  IV  II  Death  Dead  Aspiration pneumonia 
61/M  Ischemic  20  Yes  60  Congestive  19  350  250  IV  III  Death  Dead  Sudden cardiac death 
71/M  Ischemic  25  Yes  20  Congestive  273  180  70  IV  III  Death  Dead  Sudden cardiac death 
84/M  Ischemic  38  Yes  60  Congestive  177  250  180  III  II  Death  Dead  Respiratory sepsis 
90/M  Ischemic  42  Yes  24  Congestive  77  250  60  III  II  Switch to oral  Dead  Sudden cardiac death 
84/M  Ischemic  30  No  21  Congestive  82  215  110  III  II  Death  Dead  Overall deterioration 
88/M  Ischemic  45  No  25  Congestive  658  215  110  III  II  Continuing  Alive   
68/M  Valvular  35  Yes  45  Congestive  35  360  140  IV  III  Death  Dead  Refractory HF 
81/M  Ischemic  50  Yes  25  Euvolemic  114  110  110  III  II  Death  Dead  Renal sepsis 
10  71/W  Idiopathic  20  Yes  25  Euvolemic  500  150  110  III  II  Continuing  Alive   
11  67/M  Ischemic  35  No  10  Congestive  124  250  200  IV  III  Death  Dead  Urinary sepsis 
12  91/W  Valvular  55  Yes  11  Congestive  26  200  200  III  II  Local complications  Dead  Refractory HF 
13  82/W  Idiopathic  28  Yes  35  Euvolemic  280  130  80  III  II  Continuing  Alive   
14  85/M  Valvular  34  Yes  24  Congestive  86  130  65  IV  II  Death  Dead  Refractory HF 
15  55/W  Valvular  55  Yes  90  Euvolemic  15  100  65  III  III  Death  Dead  Sudden cardiac death 
16  78/M  Idiopathic  25  Yes  63  Congestive  39  160  65  IV  II  Switch to oral  Alive   

GF, glomerular filtration; HF, heart failure; LVEF, left ventricular ejection fraction; M, man; NYHA, New York Heart Association functional class; PASP, pulmonary artery systolic pressure; W, woman

Two patients did not have hospital admissions, but they experienced decompensation that required intravenous furosemide administration.

*

Initial and maintenance doses of subcutaneous furosemide (mg/d).

The mean duration of therapy with SC furosemide infusion was 159.6 ± 185.1 days. The initial furosemide dose was 234.2 ± 68.4mg/d in congestive patients and 122.5 ± 15.0mg/d in euvolemic patients. During follow-up, only 2 patients experienced a decompensation, with a predominance of signs of low cardiac output; both died during hospital admission. This implied a rate of 0.02 admissions/patient/mo of follow-up. In the remaining patients, there were no decompensations requiring intravenous diuretic administration or hospital admission.

Patients starting SC furosemide therapy with symptoms of congestion experienced weight loss of 2.6 ± 1.0kg in the first 3 days and 0.4 ± 0.3kg in the following days; this loss persisted at 30 days (Figure 1). Those starting SC furosemide after the congestive symptoms had been controlled showed only a slight weight loss.

Figure.

Mean weigh loss at 3 and 7 days and at 1 month after starting subcutaneous furosemide therapy in patients with congestive and euvolemic status, respectively. 95% CI, 95% confidence interval.

(0.08MB).

In 2 patients, SC therapy could be discontinued at 39 and 77 days after initiation, with patients continuing on oral diuretics.

With regard to safety, 2 patients developed local complications (skin erosion without infection) that required treatment discontinuation, permanently in 1 patient and temporarily in the other. There were only 2 infectious complications, which resolved with antibiotics and did not require treatment withdrawal. No significant deterioration of renal function occurred, although there were some mild, transient creatinine increases.

In the group studied (patients attended in a heart failure unit with persistent decompensation attributed to ineffective oral diuretic therapy and requiring intermittent intravenous therapy), SC furosemide administration using elastomeric pumps was useful for decreasing the number of hospitalizations, improving the congestive symptoms, achieving weight reductions in congestive patients, and maintaining the dry weight in euvolemic patients. Adverse events were local and were related to lengthy periods of administration.

Although the number of patients studied is limited, we believe that these promising observations open a new line of investigation for the treatment of patients with refractory HF.

References
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H. Zacharias, J. Raw, A. Nunn, S. Parsons, M. Johnson.
Is there a role for subcutaneous furosemide in the community and hospice management of end-stage heart failure?.
Palliat Med., 25 (2011), pp. 658-663
[2]
J.M. Beattie, M.J. Johnson.
Subcutaneous furosemide in advanced heart failure: has clinical practice run ahead of the evidence base?.
BMJ Support Palliat Care., 2 (2012), pp. 5-6
[3]
E. Zatarain-Nicolás, J. López-Díaz, L. de la Fuente-Galán, H. García-Pardo, A. Recio-Platero, J.A. San Román-Calvar.
Subcutaneous infusion of furosemide administered by elastomeric pumps for decompensated heart failure treatment: initial experience.
Rev Esp Cardiol., 66 (2013), pp. 1002-1004
[4]
N.A. Gilotra, O. Princewill, B. Marino, et al.
Efficacy of intravenous furosemide versus a novel, pH-neutral furosemide formulation administered subcutaneously in outpatients with worsening heart failure.
JACC Hear Fail., 6 (2018), pp. 65-70
Copyright © 2018. Sociedad Española de Cardiología
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