Prevention of venous thromboembolism in the critically ill patient

Venous thromboembolism (VTE) contributes significantly to morbidity and mortality. The VITAE (VTE Impact Assessment Group in Europe) study estimated that each year in Europe almost 460,000 people develop deep vein thrombosis (DVT), including 300,000 cases of pulmonary embolism (PE). ¹ In the USA, annual incidence is reported as 150 per 100,000 of the population. ² The US Agency for Healthcare Quality and Research ranked appropriate use of venous thromboprophylaxis in patients at risk top of their list for widespread implications to patient safety. In 2005, the House of Commons Health Committee reported that an estimated 25,000 people in the UK die from preventable hospital-acquired VTE every year. This includes patients admitted to hospital for medical and surgical care.

Amongst hospitalised patients, critical care admission is the strongest risk factor for VTE. This is a function of both the patient’s underlying disease process and acquired risk factors during an intensive care unit (ICU) stay including prolonged immobility, use of neuromuscular blockade and vasopressors, central venous catheter insertion and sepsis. ³ VTE in this population can be expensive to diagnose and challenging to manage with a huge impact on morbidity and mortality. Up to 14% of post mortems in ICU patients demonstrate massive or submassive PE. ⁴ Furthermore, hospital data show that improving VTE prophylaxis as part of compliance with a ventilator ‘bundle’ would contribute to reduced length of stay and free up a significant number of ICU bed days per annum. ⁵

We can appreciate the disease burden of venous thromboembolic disease on a global scale and have witnessed a national drive forward in assessing the VTE risk for patients on admission to hospital. After implementing VTE Commissioning for Quality and Innovation (CQUIN) targets in the UK, risk assessment has risen to over 94%. ⁶ NHS England reports that 3.4 million patients admitted to NHS acute care were risk assessed for VTE in the last quarter of 2013–2014.

Greater focus on admission risk assessment has been shown to potentially reduce preventable VTE however, risk assessment must be followed by the appropriate intervention. ⁷ The multinational cross sectional survey (ENDORSE) ⁸ examined compliance rates to the American College of Chest Physicians (ACCP) guidelines for DVT prophylaxis and showed that in the UK, 50% of those assessed are at risk of VTE and only approximately 60% at risk are receiving recommended levels of prophylaxis.

What are the current guidelines?

The UK National Institute for Clinical Excellence (NICE) recommend VTE risk assessment for all patients on admission to the critical care unit, and offering pharmacological prophylaxis after taking into account the risk of bleeding, current anti-coagulation and comorbidities. If the risk of bleeding outweighs the thrombosis risk, mechanical VTE prophylaxis should be considered. Regular VTE re-assessment is required and more frequently if the clinical condition is changing rapidly. ⁹

With this standard outlined why are we not achieving the recommended levels of prophylaxis in critical care patients?

Ensuring critical care patients receive appropriate VTE thromboprophylaxis remains challenging. This population includes patients with complex medical co-morbidities, post-operative general surgical patients, poly-trauma, neuro-intensive care and bariatric patients coupled with risk factors acquired during their ICU stay. Irrespective of causality, severe physiological upset stimulates the inflammatory response increasing the thromboembolic risk. This must be balanced against the bleeding risk, hence timing and mode of prophylaxis must be considered carefully.

A recent multi-centred survey amongst experienced health professionals in North America examined some of the common barriers to prescribing low-molecular-weight heparin (LMWH) prophylaxis in the critical care population. These included lack of education, bleeding risk, planned interventional procedures or surgery and concern over bioaccumulation in renal failure. Conversely, prescription order sets for critical care admission containing appropriate VTE prophylaxis, educational programmes reinforced on a regular basis through audit and local quality improvement committees all facilitated VTE prophylaxis compliance. ¹⁰

How do we move forward with VTE prophylaxis in critical care?

In 2010, NHS England produced ‘Venous Thromboembolism(VTE) Risk Assessment in England’, a national program to increase screening on hospital admission. Targeted questions around mobility, thrombosis and bleeding risk help to identify potential patients at risk of thromboembolic disease. The Department of Health (DOH) and NICE have published guidelines outlining best practice for VTE prevention.^5,9 Both national standards suggest that the critical care population is a complex subgroup of patients; hence, the emphasis should be on staff evaluating VTE risk frequently on an individual basis.

Mechanical prophylaxis

The randomised controlled trials (RCTs) to date examining the use of mechanical prophylaxis, graduated elastic compression stockings (GEC) or intermittent pneumatic compression devices (IPC) suggest that there is a small or insignificant reduction in VTE. ¹¹ However, a recent critical care study published in Chest suggests that IPCs independently lower the incidence of VTE. ¹² As the NICE guidelines recommend in patients where anticoagulant therapy is contraindicated, there is a role for this mode of prophylaxis.

Pharmacological prophylaxis

RCTs conducted on LMWH or unfractionated heparin (UFH) versus placebo have shown significant reductions in DVT and pulmonary emboli detection. ¹³ Furthermore, both the control and intervention groups have comparable rates of major bleeding. Nonetheless, it is important to select our patients carefully to avoid their use with concurrent therapeutic anticoagulation, thrombocytopenia (platelets <50 × 10⁹/L), underlying inherited or acquired coagulopathy, active haemorrhage, uncontrolled systolic hypertension, lumbar puncture, spinal or epidural anaesthesia within 12 h and new ischaemic or haemorrhagic cerebrovascular accidents. We know that a substantial proportion of critical care patients may have one or more of these features and hence are relatively or absolutely contraindicated to further anticoagulant therapy.

Looking more closely at the choice of heparin anticoagulation, LMWH offers a lower incidence of heparin-induced thrombocytopenia (HIT) but needs to be monitored in patients with renal impairment due to the risk of bioaccumulation. The Protec T study randomised 3764 patients to dalteparin 5000 IU versus UFH twice daily. ¹⁴ The authors conclude that the rate of pulmonary emboli was reduced significantly in the LMWH cohort. No difference was observed in the rate of DVTs. ¹⁴ Furthermore, McGarry et al. ¹⁵ examined the cost effectiveness of LMWH versus UFH using a mathematical model of a cohort of 10,000 acutely ill medical patients. The outcome rates of DVT, PE and death over 30 days showed that LMWH was more efficacious and cost effective.

Whilst the literature currently implies that LMWH is the preferred mode of pharmacological prophylaxis, clinicians need to consider dosing based on ideal body weight, appreciate that subcutaneous absorption may be variable in multi-organ dysfunction and exercise caution in patients with renal impairment.

When should we consider using inferior vena cava filters and novel devices?

Retrievable inferior vena cava (IVC) filters were designed for prevention of pulmonary emboli in patients with known VTE in whom anticoagulant therapy is contraindicated. Despite being in use for several decades, there is little data on their efficacy. An RCT published in 1998 suggests some short-term additive benefit in reducing the incidence of pulmonary emboli. ¹⁶ Numerous serious complications have been documented with these filters, the most notable being difficulty in IVC filter retrieval; therefore, the Medicines and Healthcare Products Regulatory Agency (MHRA) has issued warnings on their use. ¹⁷

The Angel® catheter (BIO2 Medical Ltd, Cullompton, Devon, UK) has been developed with this cohort in mind, combining a central venous catheter (CVC) with IVC filter that can be inserted at the bedside. Studies examining the efficacy of this new catheter are awaited. IVC filters and Angel catheters should be viewed as a temporising measure for VTE prophylaxis until anticoagulant therapy can be safely resumed. ¹⁸

A novel neuromuscular electro stimulation device, Geko™ (Firstkind Ltd, High Wycombe, UK), has recently undergone technology assessment by NICE. This non-invasive device can be attached below the knee bilaterally to stimulate the common peroneal nerve. This causes muscular contractions to drive the venous muscle pump of the lower leg. Whilst there is limited direct clinical evidence to date, this device may be considered for high-risk patients in whom mechanical and pharmacological prophylaxis are contraindicated. ¹⁹

Critical care rehabilitation and ventilator care bundles

The Protec T study showed that over one-third of pulmonary emboli diagnosed in clinical practice are occurring in patients admitted to the ICU without known VTE and that most of these happen during the initial days of hospitalisation. ¹⁴ Implementation of ventilator care bundles on admission including VTE anticoagulant prophylaxis reminders and the use of optimal sedation required to facilitate physical and occupational therapy are globally beneficial measures that may protect against VTE and allow early rehabilitation during a critical care stay. Early rehabilitation prevents prolonged immobility which itself is a risk factor for VTE and has been shown to result in better functional outcomes at hospital discharge and more ventilator free days.^20,21 The NICE recommendations are that all critically ill patients are assessed and appropriately provided with early rehabilitation. ²⁰

Conclusions

VTE in the critically ill patient is a significant problem and remains a challenge as this population has the highest risk of both bleeding and thromboembolism. Assessing VTE risk on admission has improved but this needs to translate into delivering the optimal mode of prophylaxis on an individual basis. Focusing on continued VTE education of allied healthcare professionals, the bedside implementation of the NICE guidelines, improving critical care rehabilitation and the use of pharmacological and non-pharmacological devices will all drive the reduction in ICU mortality and morbidity from VTE. In addition, working collaboratively with our neighbouring medical and surgical specialities will minimise VTE risk prior to and following admission to critical care.