Description of the condition
Peripheral arterial disease (PAD) is a common disease that affects the blood supply of the limbs. It affects 3% to 10% of the population. It is more common among elderly patients and affects 15% to 20% of people over the age of 70 years (Dua 2016). PAD is caused by progressive narrowing and occlusion of the arteries due to atherosclerosis. Atherosclerosis is a progressive and chronic process whereby fat accumulates in the inner layer of blood vessel walls. This process leads to hardening of the vessel wall and eventually a significant reduction in the flow of blood to target tissues (Peach 2012).
Despite the relatively high prevalence of PAD, most patients are asymptomatic and have no major walking disability (McDermott 2001). However, as the disease burden increases, patients can present with intermittent claudication (IC), which is a cramp-like pain in a specific muscle group that is brought on by exertion (i.e. walking or exercise) and is rapidly relieved by rest. This can lead to reduced mobility, which has a direct effect on patients' quality of life (Peach 2012).
In 5% to 10% of patients, asymptomatic PAD or IC will progress to the severe presentation of critical limb ischaemia (CLI) over a five-year period. CLI, also referred to as chronic limb-threatening ischaemia (CLTI), is defined as rest pain for longer than two weeks or tissue loss attributed to arterial occlusion (Slovut 2008). The prevalence of CLI has been reported as 1% in the adult population (Norgren 2007). CLI occurs when significant arterial insufficiency impairs the nutritive requirements of tissues at rest, leading to limb loss if not urgently investigated and treated (Slovut 2008).
Critical limb ischaemia has a major impact on patients' quality of life. Rest pain affects patients' sleep rhythm and daily activities (Sprengers 2010). Furthermore, these patients are at high risk of limb loss. A recent insurance registry of 41,882 patients with PAD revealed four-year amputation rates between 35% and 67% among those with CLI and tissue loss (Reinecke 2015).
Description of the intervention
Interventions for treating CLI aim to improve circulation within the limb by means of an operation, which could take the form of a bypass or a minimally invasive balloon procedure, when patients are suitable for these procedures. The standard treatment for CLI is revascularisation by bypass surgery or angioplasty and stenting (Norgren 2007). However, revascularisation is not always a valid option, as the absence of a suitable vessel runoff makes reconstruction of blood flow impossible. Furthermore, some patients have extensive comorbidities that preclude their undergoing a revascularisation procedure (Adam 2005). These patients are usually left with no option other than medical therapy alone, or amputation when medical therapy fails. The bleak outcome of patients with CLI who are not suitable for revascularisation has led to the emergence of alternative therapies that can be used in conjunction with medical therapy.
Intermittent pneumatic compression
Intermittent pneumatic compression (IPC) is an alternative treatment for patients with CLI in the absence of reconstructable anatomy. IPC involves sequential inflation and deflation of pneumatic pressure cuffs placed on the patient's limb. An automatic air source is connected to the cuff to allow intermittent inflation of the cuffs to pressures close to systolic pressure, followed by rapid deflation (van Bemmelen 1994).
Intermittent pneumatic compression is used in combination with medical therapy, which aims to reduce cardiovascular risk on a systemic basis. Medical therapy can include any of the following: antiplatelet therapy, lipid-lowering therapy, antithrombotic therapy, antihypertensive therapy, or smoking cessation therapy, as detailed in the reporting standards of the Society for Vascular Surgery (SVS) for endovascular treatment of chronic lower extremity PAD (Stoner 2016).
How the intervention might work
Intermittent pneumatic compression works through three interconnected mechanisms (Labropoulos 2005).
Increasing the arteriovenous pressure gradient
The veno-arteriolar reflex (VAR) is related to precapillary sphincter stricture and causes an increase in venous pressure. Application of the cuffs to the calves and feet empties the venous system and reduces venous pressure. This promotes perfusion of the limbs by increasing blood flow through the capillary bed (Delis 2005).
Reversing vasomotor paralysis
Repeated compression of the sympathetic nerve receptors is an important effect of IPC, as it can influence peripheral blood flow by controlling precapillary sphincter tension (Henriksen 1974).
Enhancing the release of nitric oxide
IPC mediates release of nitric oxide (NO) from the endothelial cells. This increases the shear stress of blood in the affected vessel (Dai 2002). NO is a potent vasodilator as the primary endothelium-derived relaxing factor (EDRF). Furthermore, it inhibits platelet activation and aggregation, thus playing an important role in preventing formation of thrombosis (Dai 2002).
These three mechanisms combine to improve perfusion in ischaemic limbs. In association with appropriate risk factor modification, this can provide a feasible method of treatment not only for patients with non-reconstructable CLI, but also for those who are physiologically unfit for surgical intervention (Labropoulos 2005).
For patients with non-reconstructable CLI, IPC therapy may be associated with improved amputation-free survival, fewer minor amputations, and reduced rest pain in comparison with no use of IPC (Moran 2015; Zaki 2016).
Why it is important to do this review
CLI results in pain at rest and ischaemic leg ulcers/gangrene with substantial deterioration in quality of life (QoL) (Matsumoto 2016). Ischaemic leg pain limits activities and tends to isolate patients from social connections, with consequent stagnating effects on emotional and mental health (Sprengers 2010). Improving the QoL of patients with CLI has become as important as improving their clinical status in terms of setting a treatment goal (Norgren 2007).
Not all patients are suitable for revascularisation. As reported in the BASIL trial, 34% of patients were not offered any revascularisation, as they did not have reconstructable options, lacking proper runoff or suitable anatomy. Furthermore, 7% of the total number of patients were deemed unfit for any surgical option owing to their other comorbidities (Adam 2005).
No pharmacological therapy has proved effective as a single treatment modality (Hiatt 2001), and ultimately, amputation is often the only option left. Therefore, new therapies are urgently needed (Sprengers 2010). With the ageing population and the associated rise in prevalence of CLI, the social and economical burden continues to increase. Establishing high-quality evidence to evaluate the use of IPC in CLI treatment is imperative. This Cochrane Review will investigate available evidence to establish the effectiveness of IPC for treatment of CLI.