Pharmacological management

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Oxygen

Oxygen is often the first treatment to be thought of by both patients and staff when faced with breathlessness and is well-established in the management of acute left heart failure in addition to diuretics and opioids. There is the assumption that it is also beneficial in chronic heart failure, but this does not fit with the evidence that, if anything, oxygen blood levels are increased in patients with chronic heart failure, and oxygen desaturation during exercise is not typical in compensated patients. There have been no studies specifically looking at the benefits of oxygen on the sensation of breathlessness in severe heart failure, although a few have commented on it as a secondary end-point. The studies are small, and only one randomized and controlled. Moore et al. looked at the benefits of 30 per cent and 50 per cent inspired oxygen in exercising 12 patients with heart failure and found that during exercise with oxygen-enriched air there was a significant increase in arterial oxygen saturation, total exercise duration was prolonged, carbon dioxide production was reduced and subjective dyspnoea scores rated lower on a visual analogue

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scale. However this finding has not been confirmed. ' Restrick, in a similar study, found that although 2 and 4l/min ambulatory oxygen increased resting arterial oxygen saturation compared with air, there was no significant difference in distance walked or perceived breathlessness.38 Both of these studies were uncontrolled. In a randomized placebo controlled cross-over study of 16 patients, Russell et al. compared 21 per cent and 60 per cent inspired oxygen.39 There was no reduction in minute ventilation or functional benefit with higher oxygen concentrations. The study did not look at the subjective assessment of breathlessness but did comment on the number of patients stopping because of breathlessness; all patients had the same reason for stopping during both exercise tests.39

Patients included in these studies had stable mild to moderate heart failure (NYHAII-III) and patients with unstable heart failure, concurrent respiratory disease or FEV1 < 70 per cent were excluded. Thus it is difficult to extrapolate these results to patients with severe (NYHA IV) chronic heart failure, or those with unstable disease. Comorbidity with concurrent lung disease is common in many patients with heart failure and there may be some benefit to individual patients of oxygen therapy to symptomatically improve breathlessness. The practicalities of providing ambulatory oxygen should also be remembered in considering cost-benefit balance. Current recommendations therefore do not routinely include oxygen therapy, and decisions need to be made on an individual patient basis.

Opioids

Although morphine has been used for many years to relieve symptoms in acute left ventricular failure or myocardial ischaemia, there is still concern about its use in chronic heart failure by many because of the potential for respiratory depression - although paradoxically this does not appear to be a cause for concern in acute situations sufficient to prevent its use in these circumstances. There is also relatively little published literature supporting its use in chronic disease, and thus opioids tend to be reserved for use in advanced heart failure and may not be considered early in their illness where it could be a useful tool in the management ofbreathlessness. In chronic stable heart failure, there is only one report of two cases describing the use of nebulized morphine, a study on the effect of a single dose of dihydrocodeine on chemosensitivity and exercise tolerance, a study with the use of diamor-phine prior to exercise, and more recently a pilot study using oral morphine for the relief of breathlessness in patients with heart failure.40-43 This dearth of information about a potential useful palliative therapy has been recognized.44 The beneficial effect is thought to be mediated through modulating the sensitivity of chemoceptors, rather than to the known minimal haemodynamic effects, or to respiratory depression.

The two single dose studies of diamorphine and dihydrocodeine respectively in patients with chronic heart failure suggest improvement in abnormal ventilatory patterns. The pilot study was a randomized placebo controlled cross-over study of 10 patients with NYHA III/IV symptoms.43 Patients were recruited from a heart failure clinic and randomized to receive oral morphine or placebo. Patients were given 5mg of morphine four times a day in the active arm, or dose reduced to 2.5mg four times a day if the serum creatinine was greater than 200mcmol/l. Patients with a peak flow less than 150l/min or a serum creatinine greater than 300mcmol/l were excluded. On morphine, median breathlessness score (Visual Analogue Score 0 - 100mm) fell by 23mm (p = 0.022) by day 2, and this improvement was maintained. Sedation scores increased until day 3, reducing on day 4. Four patients reported constipation on morphine compared with one on placebo, but there were no other differences between the two arms in nausea, blood pressure, pulse or respiratory rate. The study concluded that oral morphine gave clinically significant improvement in breathlessness with few side-effects and good tolerability of chronic dosing. However questions remain regarding which patients will benefit, which is the best opioid (morphine is not the best opioid to use in renal failure) and the best regimen. Patients sometimes have fears relating to morphine and good communication skills are required to introduce opioids as a therapeutic option.

Beta-2 agonists

Many patients with heart failure will also have lung disease (asthma or chronic obstructive disease) and may take an inhaled beta-2 agonist. It has been suggested that such therapy might benefit patients with heart failure in the absence of significant lung disease because of the demonstrable increased airways resistance. Witte et al. have shown some benefit in breathlessness in 12 patients treated with inhaled salbutamol and the anticholinergic ipratropium (compared with 10 controls).45 Breathlessness and airways resistance improved as did lung reactance and peak tidal volume during exercise although exercise capacity did not improve. The role of beta-2 agonists remains unclear; the benefits of beta blockade are now well established and should always be used in the absence of contraindications.

Benzodiazepines

The use of anxiolytic drugs, such as benzodiazepines, is another issue that causes concern to some clinicians. This is again due to fears of causing respiratory depression and oxygen desaturation as well as issues around addiction and tolerance. There are also more general concerns regarding the risks of giving sedative drugs to often frail and elderly patients with comorbidities.

Indeed the known increased risk of falling has to be considered. However, there appears little evidence to support the concerns regarding respiratory depression if used with care, and benzodiazepines such as lorazepam (which is also usefully absorbed sublingually for quicker onset of action) may be very useful in counteracting the panic and fear associated with acute episodes of severe breathlessness. It must be remembered that the respiratory depressive effects of opioids and benzodiazepines may be additive. In the light of a poor prognosis the issue of dependence and tolerance is less of an issue than in other patients with chronic anxiety. Depression is under-recognized and treated; careful choice of antidepressant is required due to the potential cardiac toxicity of these drugs. Tricyclics should be avoided and venlafaxine is relatively contra-indicated although selective serotonin reuptake inhibitors such as citalopram appear to be safe and well-tolerated.

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