Description of the condition
Heart failure is a common and frequently life-limiting illness with increasing prevalence, particularly among the ageing population. During the 1980s the age-adjusted prevalence of overt heart failure in the United States was 24/1000 in men and 25/1000 in women (Kalon 1993). Over the 40 years of observation in the Framingham study, despite improvements in the treatment of ischaemic heart disease and hypertension, the age-adjusted incidence of heart failure has declined by only 11% per calendar decade in men and by 17% per calendar decade in women (Kalon 1993). The incidence rate increases with age, with a European incidence of 1.4 per 1000 person-years in the 55 to 59 age band, rising to 47.4 per 1000 person-years in the over-90s. Heart failure remains a highly lethal condition, with a five-year survival rate of 25% in men and 38% in women (Bleumink 2004).
The term heart failure covers a complex clinical syndrome that can result from a number of underlying disorders that impair the ability of the heart to respond to physiological demands for increased cardiac output (McMurray 2012). It encompasses a large spectrum of disease, from people with mild heart failure and minimal symptoms to those who have severe disease with symptoms at rest.
Chronic heart failure is characterised by symptoms that include exertional breathlessness (dyspnoea), fatigue, lower limb swelling, dyspnoea on lying flat or abrupt onset dyspnoea, which wakens patients from sleep (McMurray 2012).
Heart failure is often a progressive condition, beginning with predisposing factors and leading to the development and worsening of clinical illness. There are several stages in the evolution of heart failure, as outlined by an American College of Cardiology/American Heart Association (ACC/AHA) task force (Hunt 2006).
Stage A: high risk for heart failure, without structural heart disease or symptoms
Stage B: heart disease with asymptomatic left ventricular dysfunction
Stage C: prior or current symptoms of heart failure
Stage D: refractory end-stage heart failure
People with end-stage heart failure have marked symptoms of dyspnoea, fatigue and other symptoms at rest or with minimal exertion. Identifying those likely to die soon from heart failure is challenging and the course to death varies with illness severity and adherence to treatment. Management of symptoms such as dyspnoea is essential to provide an acceptable quality of life for people with heart failure as their disease progresses (Zambroski 2008).
Description of the intervention
The terms 'opiates' and 'opioids' are sometimes used interchangeably. An opiate, strictly speaking, is one of a group of drugs derived from the opium poppy that have narcotic and sedative effects. Opioids are synthetic compounds that resemble opiates in terms of their clinical effects (Martin 2002). The term opioid is used throughout this review to encompass all compounds meeting either of these definitions. Opioids can be given by any route (oral, subcutaneous or intravenous).
The most common forms used in heart failure are morphine sulphate oral solution (Oramorph), morphine sulphate long-acting oral tablets (MST Continus), oxycodone hydrochloride modified-release oral (OxyContin) and diamorphine hydrochloride subcutaneous injection or infusion. The dose range is very wide as tolerance occurs during chronic therapy (starting at 5 mg with no real upper limit). Adverse effects are respiratory depression and constipation. Parenteral doses last four hours whereas long-acting oral preparations need to be repeated 12-hourly. The main interactions are with other opioids, pethidine and monoamine oxidase inhibitors (BNF 2013).
How the intervention might work
Opioids have several actions other than analgesia and it is these secondary actions that may help reduce the sensation of dyspnoea (Hallenbeck 2012), which many people with end-stage heart failure describe.
Opioids exert their effect through at least three groups of receptors which are distributed throughout the body, accounting for the global and varied effects of these drugs. The primary receptors opioids work on are mu receptors. Within the central nervous system, mu receptors are found in large numbers in the mid-brain, periaqueductal grey matter and dorsal horn of the spinal cord. At these sites they induce intense analgesia and also a number of other effects, including bradycardia, sedation, euphoria and respiratory depression (Rosenquist 2013). Another mechanism of action suggested is that opioids may ameliorate the sensation of dyspnoea by reducing hypercapnic chemosensitivity (Chua 1997). Indeed, opioids are widely used in people with cancer to treat the symptom of dyspnoea.
Opioids are available in a variety of oral and intravenous preparations; additional options are transdermal patches and transmucosal or intraspinal preparations. In addition, long-acting forms of the drug are available, with a variety of methods of delivery.
Alternative medications often used to alleviate the anxiety associated with dyspnoea are benzodiazepines such as lorazepam (Dudgeon 2013).
Why it is important to do this review
Knowledge about symptom management in heart failure lags behind knowledge about how to improve other outcomes. The lack of clearly identified interventions for palliative care in heart failure presents significant challenges to ensuring these people are provided with optimal care.
The use of opioids for the treatment of dyspnoea in cancer is well established within palliative care. However, as opioids are extensively used for pain management in cancer, it is difficult to separate out the effects on dyspnoea. Although the majority of people with advanced chronic heart failure suffer pain (O'Leary 2009), it is rare for this to be treated with opioids.
Other reviews have combined heart failure patients with other conditions (Oxberry 2008), particularly chronic obstructive pulmonary disease (COPD). Published data for cancer and COPD patients cover different opioids at a range of doses (Jennings 2001), making it difficult to identify suitable dose regimes for dyspnoea in heart failure. Reviews that focus on heart failure are either based on a limited literature review (Hochgerner 2009) or on uncontrolled trials or studies (Lowey 2013).
Opioids are commonly used in palliative care to relieve dyspnoea. Existing heart failure guidelines either do not discuss dyspnoea (McKelvie 2013; McMurray 2012; NICE 2010), or are limited to a good practice point due to a lack of robust evidence (SIGN 2007). A review that either provides evidence on the effectiveness of this treatment in the context of chronic heart failure, or confirms the lack of clear evidence, would be of benefit to both front-line clinicians and researchers with an interest in this area.