Hey, I don't argue with the apparent logic of giving Lasix to someone in heart failure. My brain says it makes sense that diuresing the volume overloaded CHFer is a good idea. However, everything I am reading from the "smart guys" is telling me that the physiology isn't that simple.
I think lasix makes the most sense in the gradual onset, mildly hypertensive, visibly edematous patient. The one that had 3 servings of ham and forget their lasix for 3 days and is a bit winded.
Alternatively, I think Nitrates and BiPAP (maybe ACE-I?) makes more sense in (i) patients with extremely high SBP and sudden onset symptoms and also in (ii) patients with CP that sounds like ACS.
Patients with pulmonary edema and hypotension d/t acute cardiogenic shock are a mess, but I would argue lasix isn't good for these people either.
Anyway, in the majority of heart failure patients I see, I end up giving both medications (lasix and nitrates).
And since you want references:
(1) Cotter G, Metzkor E, Kaluski E et al. Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema. Lancet 1998; 351:389-93.
"high-dose isosorbide dinitrate, given as repeated intravenous boluses after low-dose intravenous furosemide, is safe and effective in controlling severe pulmonary oedema. This treatment regimen is more effective than high-dose furosemide with low-dose isosorbide nitrate in terms of need for mechanical ventilation and frequency of myocardial infarction."
And excuse the extensive cut-and-past here
(2)Am J Med. 2006 Dec;119(12 Suppl 1):S26-36.
Practical applications of intravenous diuretic therapy in decompensated heart failure.
Cleland JG, Coletta A, Witte K.
"RANDOMIZED CONTROLLED TRIALS OF DIURETICS
Two prospective, randomized trials, both conducted nearly 20 years ago, have evaluated the immediate hemodynamic effects of IV diuretics in patients with heart failure (HF) secondary to myocardial infarction.9, 10 In the first trial, Verma and associates[10] compared the effects of an IV diuretic (furosemide, 1 mg/kg), a venodilator (isosorbide dinitrate, 50 to 200 μg/kg per hr), an arteriolar dilator (hydralazine, 0.15 mg/kg), and a positive inotropic agent (prenalterol, 50 to 200 μg/kg per hr) as first-line therapy in 48 male subjects with left ventricular dysfunction after acute myocardial infarction. Both furosemide and isosorbide dinitrate reduced left ventricular filling pressure (furosemide by −4 mm Hg, isosorbide dinitrate by −6 mm Hg; both P <0.01) without affecting cardiac output or heart rate. In contrast, both hydralazine and prenalterol increased cardiac output and heart rate but had less effect on left ventricular filling pressure (–2 mm Hg for both drugs; P <0.05). In the second trial, Hutton and colleagues[9] compared the effects of IV furosemide (0.5 mg/kg) and isosorbide 5-mononitrate (15 mg) at the time of routine cardiac catheterization in an unspecified number of patients with left ventricular dysfunction secondary to myocardial infarction. Unlike the first trial, in this trial furosemide induced acute vasoconstriction (PCWP, +6 mm Hg; systolic blood pressure, +20 mm Hg) with a reduction in cardiac output (−0.3 L/min). In contrast, isosorbide 5-mononitrate maintained cardiac output (+0.3 L/min) while reducing both PCWP (−22 mm Hg) and systolic blood pressure (−14 mm Hg). Of note, these trials were too small to assess morbidity or mortality.
Cotter and coworkers[11] assessed the effects of diuretics and nitrates in 104 patients presenting to mobile emergency units with pulmonary edema and signs of DHF. Patients were randomly assigned to treatment with either a low-dose diuretic (furosemide, 40 mg) plus a high-dose nitrate (isosorbide dinitrate, 3-mg bolus every 5 minutes) or a high-dose diuretic (furosemide, 40 mg followed by 80-mg bolus every 15 minutes) plus a low-dose nitrate (isosorbide dinitrate, 1 mg/hr and increased by 1 mg/hr every 10 minutes), and therapy was continued until arterial oxygen saturation was >96% or mean arterial blood pressure had decreased by >30% or was <90 mm Hg. In this trial, the use of high-dose diuretics plus low-dose nitrates was associated with a trend toward increased mortality (6% vs. 2%; P = 0.61) and significant increases in the development of myocardial infarction (37% vs. 17%; P = 0.047), the need for mechanical ventilation (40% vs. 13%; P = 0.004), and the combined end point of death, myocardial infarction, or mechanical ventilation (46% vs. 25%; P = 0.041) compared with the use of low-dose diuretics plus high-dose nitrates. However, these data are inconsistent with the experience of others in the general population with acute HF and may reflect only the experience in a small group of exceptionally sick patients. Mechanical ventilation is used for only a small minority of patients with pulmonary edema in most clinical practice, and it is not the experience of others that myocardial infarction develops as a consequence, as opposed to a cause, of DHF.
Although minimal and contradictory evidence exists, IV diuretic therapy is generally accepted for the treatment of patients with DHF; future assessment of this therapy in large-scale, randomized, controlled clinical trials will be difficult.[4] This article reviews what is currently known about the use of diuretics in patients with DHF and makes suggestions regarding the management of patients with diuretic resistance."
and
"POTENTIAL DELETERIOUS EFFECTS OF INTRAVENOUS DIURETICS
Diuretics, and especially their overuse, produce several deleterious effects that can influence clinical outcomes. A frequent consequence of diuretic therapy is electrolyte disturbances. 4, 6, 13, 20, 22 Loop diuretics increase urinary excretion of potassium, magnesium, and calcium, reducing total body stores of these essential cations, causing secondary hyperparathyroidism, and potentially increasing the risk of arrhythmic mortality.20, 22, 33, 34 Patients with advanced HF and long-term furosemide usage have elevated parathyroid hormone levels and associated moderate-to-marked reductions in bone mineral density.[34] In addition, reduction in cytosolic free magnesium increases intracellular calcium loading, and reduction of magnesium in circulating mononuclear cells produces a proinflammatory phenotype.[34]
Diuretics can cause intravascular volume depletion, leading to hypotension, diminished cardiac output, reduced glomerular filtration rate (GFR), and renal dysfunction.4, 13, 22, 26, 35, 36, 37, 38 In a prospective, randomized evaluation of 33 patients in the intensive care unit who had pulmonary edema or fluid overload, aggressive diureses with either bolus or continuous-infusion furosemide therapy produced a significant reduction in mean arterial pressure (bolus, −13 mm Hg; 95% confidence interval [CI], −5 to −21 mm Hg; and continuous infusion: −16 mm Hg; 95% CI, −9 to −24 mm Hg) and an increase in mean serum creatinine levels (bolus, +0.23 mg/dL; 95% CI, +0.01 to +0.45 mg/dL; and continuous infusion, +0.14 mg/dL; 95% CI, −0.03 to +0.31 mg/dL [1 mg/dL = 88.4 μmol/L]).[38] In 20 patients with severe HF, a continuous infusion of furosemide (mean daily dose, 690 mg) produced a 5% increase in mean serum creatinine level (P <0.01).[36] In 20 subjects with refractory HF, use of medium-dose (5 mg/kg per day) and high-dose (10 mg/kg per day) IV furosemide was associated with 14% ± 8% and 15% ± 6% reductions in mean arterial pressure and 41% ± 23% and 42% ± 23% reductions in creatinine clearance, respectively, with the reduction in creatinine clearance correlated directly with the reduction in blood pressure (r = 0.7; P = 0.007).[26] In a randomized, double-blind evaluation of patients with symptomatic HF, IV administration of 80 mg furosemide produced a 7.4-mm Hg decline in systolic blood pressure and a 17.3% decline in GFR, compared with a 1.4-mm Hg increase in systolic blood pressure and a 2.5% increase in GFR following IV placebo administration.[37] Finally, in a nested case-control study of 382 subjects hospitalized for HF, use of loop diuretics was associated with a significant increase in the risk of worsening renal function (odds ratio [OR], 1.04 per 20-mg furosemide equivalent received during the preceding day; 95% CI, 1.004 to 1.076; P = 0.03).[35]
Diuretics cause adverse neurohormonal activation.39, 40, 41, 42, 43, 44 In 10 patients with HF, mean plasma renin, aldosterone, and angiotensin II activity increased within 30 minutes following a 1-mg/kg bolus of IV furosemide (although only the change in angiotensin II activity was statistically significant), and these elevations persisted in 4 patients receiving chronic furosemide administration.[42] In 15 patients with chronic HF, furosemide produced acute vasoconstriction with significant increases in plasma renin and norepinephrine levels within 10 minutes of IV administration (Figure 3).[44] Similarly, in 8 patients with NYHA class II to III HF, plasma renin activity increased 170%, aldosterone activity increased 40%, and norepinephrine activity increased 40% (all P <0.01) in the 2-hour period immediately following IV administration of furosemide (mean dose, 248 mg).[39] These hormone levels remained elevated for the next 4 days and were associated with fluid retention, leading to the return of elevated filling pressures, and reoccurrence of pulmonary congestion.[45] "
Or we could just agree with the Best Bets review (
http://www.bestbets.org/bets/bet.php?id=937) which concludes: "Nitrates and diuretics both have beneficial effects in acute heart failure. Nitrates have been shown to have more benefit than diuretics, but a combination of the two drugs is ideal. "
