Acute heart failure with dyspnoea: initial treatment. Furosemide and trinitrine, despite the lack of a proven survival benefit

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Prescrire International 2011, 20 (117): 156-60
For patients with acute heart failure and dyspnoea due to pulmonary congestion, the risk of death in the short term is high. To determine how best to manage these patients, we reviewed the relevant literature using the standard Prescrire methodology. There are few reliable clinical trial data. None of the available drugs has been shown to improve survival. Loop diuretics such as furosemide improve some haemodynamic parameters and dyspnoea due to congestion, i.e., water and salt retention. The dose is adjusted on the basis of clinical response, renal status and previous use of a loop diuretic, especially in chronic heart failure. The main adverse effects of loop diuretics are hypotension, hyponatraemia, hypokalaemia, renal failure and ototoxicity. Compared with repeated injections, continuous infusion seems to carry a lower risk of death and ototoxicity. High doses are associated with excess mortality. Nitrate derivatives such as trinitrine and isosorbide dinitrate are vasodilators. Only intravenous administration has been assessed in acute heart failure. These drugs improve certain haemodynamic parameters, reduce blood pressure and increase coronary flow.Their effect declines rapidly above a certain dose in about 20% of patients. They seem to improve dyspnoea and, according to a difficult-to-interpret trial of isosorbide dinitrate, may reduce the risk of myocardial infarction. There is no firm evidence that nitrate derivatives improve survival in patients with acute heart failure, but they reduce mortality in patients with myocardial infarction, a frequent cause of acute heart failure. The main adverse effect of nitrate derivatives is hypotension, meaning that these drugs should not be used when blood pressure is low and that blood pressure should be closely monitored during treatment. Randomised trials of another vasodilator, nesiritide, showed excess mortality at 30 days. There are no such trials of nitrate derivatives. In patients with cardiogenic shock, inotropes (mainly dopamine, dobutamine and milrinone) improve symptoms and haemodynamic parameters but may increase mortality.These drugs carry a risk of ventricular and supraventricular arrhythmias and tachycardia. Their use requires continuous monitoring in an intensive care unit. Cardiac glycosides, including digoxin, have been used empirically in acute heart failure. The use of digoxin is mentioned in only one clinical practice guideline, in patients with atrial fibrillation and a rapid heart rate. Its narrow therapeutic margin and its frequent interactions with other drugs make digoxin difficult to use. Oxygen is usually recommended in case of hypoxaemia but its clinical value has not been assessed comparatively in acute heart failure. In some trials, routine oxygen delivery, without taking into account the degree of hypoxia, appeared to be harmful in patients with myocardial infarction. Non-invasive ventilation has been assessed in several comparative randomised trials, in which it was found to improve some physiological parameters. In a trial in 1069 patients, it had no impact on mortality at 30 days, or on the need for endotracheal intubation. It is not appropriate for patients with respiratory distress necessitating intubation, or with altered consciousness, severe dementia, major anxiety. It is often poorly tolerated. Its main adverse effects are aggravation of right heart failure, pneumothorax, and aspiration of gastric contents. Early treatment probably improves outcome. Clinical practice guidelines recommend urgent hospitalisation of patients with acute heart failure. In summary, the choice of initial treatment for patients with acute heart failure and dyspnoea depends largely on blood pressure.Treatment is mainly based on loop diuretics, nitrate derivatives (when blood pressure is not too low) and non-invasive ventilation. It should be emphasised that these patients are highly unstable and that there is a narrow margin between beneficial and harmful effects of available treatments. Patients receiving treatment should always be closely monitored.

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