Can neuromuscular electrical stimulation help prevent venous thromboembolism?

Venous thromboembolism (VTE) is a largely preventable but serious condition encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE). ¹ DVTs occur when a blood clot forms in deep veins, usually in the legs. They are commonly caused by immobility, surgery, and disorders or health factors which can make the blood more prone to clotting. Part of these clots can break off and travel to the lungs resulting in a PE.^2,3 DVT commonly presents with symptoms of throbbing pain or swelling of the limb, and chest pain and difficulty breathing for PE. VTE has a huge impact on morbidity and mortality, affecting 1 in 1000 adults per year in the United States.^1,2

VTE prevention can take many forms, including pharmacological; low molecular weight heparins (LMWHs) such as enoxaparin, oral anticoagulants such as aspirin are commonly used in VTE prevention. ³ Pharmacological VTE prophylaxis can sometimes be contraindicated due to factors such as bleeding risk; in these cases, mechanical VTE prophylaxis is useful.^3,4

Current forms of mechanical VTE prophylaxis used include intermittent pneumatic compression (IPC) and graduated compression stockings (GCS) which apply pressure or squeeze the lower leg, promoting blood flow. ³ IPC promotes pulsatile flow in the deep veins of the legs, mimicking the skeletal muscle pump whereas GCS provide a constant pressure on the legs, increasing blood flow velocity. GCS are a continuous but passive VTE prophylaxis and IPC use inflation and deflation of a cuff to alter pressure intermittently. ³ Despite their benefits and common use, there are limitations and contraindications to their use. Problems with use can arise when the patient presents with skin problems such as ulcers, and contraindications to GCS include complex peripheral vascular disease whereby stockings can further limit blood flow and diabetic neuropathy whereby loss of sensation can result in unnoticed skin damage or poor circulation. These factors limit their use in a clinical setting. ³ The efficacy of GCS is also in question, with IPC being superior in the prevention of VTE and in terms of safety. IPC efficacy is however limited by incorrect usage and fitting of the device. ³

Neuromuscular electrical stimulation (NMES) is another mechanical method of VTE prevention; it delivers electrical impulses directly to the nerves and induces calf muscle contraction.^1,5 These contractions facilitate the movement of blood through the veins, and may be beneficial where pharmacological or other mechanical prophylaxis are not suitable or effective. ⁶ NMES can activate the muscle itself (direct), or target the nerve which supplies the muscle (indirect). ⁶ NMES is already producing promising results amongst a variety of clinical indications, including restoration of muscle mass and function in those with prolonged immobilisation and it holds the advantage over pharmacological interventions with no bleeding risk.^4,7

The literature supporting the use of NMES in VTE prophylaxis is weak. Hajibandeh et al. reviewed a total of 904 participants across 8 studies in a systematic review. Four studies compared NMES with no prophylaxis, and five studies compared NMES with alternative methods of prophylaxis. ¹ When compared to no prophylaxis, NMES significantly reduced VTE risk. ² However, NMES arms showed higher incidence of VTE compared to those who received heparin, with 23.9% NMES group developing DVT compared to 13.4% for the heparin group. ¹ Despite showing inferiority to heparin in VTE prophylaxis, NMES still maintains the advantage of circumventing the risks associated with heparin administration such as bleeding, stroke and major haemorrhage.^1,6,8

Another review analysed NMES versus basic prophylaxis, referring to early mobilisation, ankle pumping exercises and fluid balance, and NMES versus other mechanical thromboprophylaxis. It included 1686 participants across sixteen studies. ⁹ Compared with basic thromboprophylaxis and GCS, NMES significantly reduced post-operative DVT incidence with a risk ratio of 0.46. ⁹ Additionally, no NMES related adverse events were reported. In both reviews, the authors acknowledge that conclusions are low-power and more robust studies are needed to provide stronger comparisons between the groups.^1,9

Despite the promises and successes of NMES in VTE prevention, there are certain factors limiting its real-world use. Careful consideration must be made surrounding NMES in certain patient groups such as pregnant women, and those with pacemakers, where NMES has potential to cause electromagnetic interference. User compliance is a drawback, with inconsistent or incorrect usage of NMES devices having substantial impacts on the efficacy of the devices. ⁵ Improper electrode placement and device setup difficulties contribute to lower user compliance, which is correlated with outcomes. Adherence to NMES is the most important factor in its efficacy in prevention of VTE. ⁵ NMES users also report discomfort when using devices, which may deter patients from using NMES consistently.^1,5 Additionally, LMWH has been shown to reduce VTE risk more than NMES, however studies assessing their use in conjunction are limited. ⁶

It is clear that further research is required to draw strong conclusions about the efficacy of NMES devices in VTE prevention, but there is certainly promise for its application in certain patient groups such as those with limited mobility, or as an adjunct to commonly used pharmacological prophylaxis. Future research should aim to compare devices and groups with increased uniformity to provide more robust findings, for example by standardising the intensity and duration of stimulation. ⁶ NMES may be particularly useful for VTE prevention in patients with contraindications to pharmacological methods. Additionally, NMES may increase the efficacy of pharmacological methods when used in conjunction. Future research should explore combination use of NMES as adjunct to traditional methods of VTE prevention. ⁹ Finally, a robust trial to compare NMES to a sham-controlled device would be useful to highlight any device-related placebo effects, with one trial comparing NMES to a sham-controlled device stopped due to funding issues and slow patient recruitment. It did however note significant improvements in secondary outcomes such as mean walking distance and muscle strength. ¹⁰ This observation is important in showing NMES has potential to improve walking distance, but also could implicate reduced necessity of post-discharge pharmacological prophylaxis. This again highlights the promise for NMES as an effective method of VTE prevention, and it will be interesting to see what future research reveals.