Catheter-directed thrombolysis for iliofemoral deep vein thrombosis

Transcription

1 Original article Catheter-directed thrombolysis for iliofemoral deep vein thrombosis J. H. Saunders, P. H. Arya, S. Abisi, Y. P. Yong, S. MacSweeney, B. Braithwaite and N. Altaf Department of Vascular and Endovascular Surgery, Queen s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK Correspondence to :MrJ.H.Saunders( jhsaunders@doctors.org.uk) Background: Recent international guidance recommends the use of catheter-directed thrombolysis (CDT) in selected patients with symptomatic iliofemoral deep vein thrombosis (DVT). The aim of this study was to estimate the potential increase in workload as a result of this recommendation. Methods: Using the radiology database, a review was performed of all DVTs diagnosed between August 2010 and February 2012 at a large tertiary referral hospital. The National Institute for Health and Clinical Excellence and American College of Chest Physicians guidance was applied retrospectively to this cohort, using case-note review by two independent clinicians to determine which patients would have been suitable for CDT. Results: Some 563 patients had DVT confirmed radiologically over the 18-month interval. Fifty-three of the 128 patients with iliofemoral DVT would have been eligible for intervention with CDT, equivalent to 4 4 patients per per year. Only eight (15 per cent) of the 53 were actually referred to vascular services for treatment. All eight patients had successful CDT, which involved a stay in critical care for monitoring (median 2 (range 1 3) sessions). Conclusion: Vascular units should be prepared for a major increase in the requirement for CDT for iliofemoral DVT. This increase will affect inpatient beds, the interventional radiology suite, critical care and interhospital referrals. Presented to the Annual Meeting of the Vascular Society of Great Britain and Ireland, Manchester, UK, November 2012; published in abstract form as Br J Surg 2013; 100(Suppl 2): 1 Paper accepted 28 March 2013 Published online in Wiley Online Library ( DOI: /bjs.9158 Introduction Acute deep vein thrombosis (DVT) of the iliofemoral vein is a significant cause of morbidity. Standard anticoagulation decreases pulmonary embolism and thrombus propagation, but does not treat the occlusion itself. Up to half of all patients with an iliofemoral DVT treated by anticoagulation alone subsequently develop post-thrombotic syndrome (PTS) 1 3. PTS is associated with significant morbidity (leg swelling, pain, ulceration), resulting in poor quality of life, and lifelong socioeconomic implications 4. Catheter-directed thrombolysis (CDT) aims to remove the obstructing thrombus and restore flow in the iliofemoral veins, thereby reducing the risk and severity of PTS in these patients. A Cochrane review suggested a significant reduction in PTS from 65 to 48 per cent with any thrombolysis 5, and more recent systematic review reported PTS with systemic thrombolysis in 57 per cent reduced to 27 per cent with CDT 6. The recently published Norwegian CaVenT trial 7 provided good-quality evidence to support the American College of Chest Physicians (ACCP) guidelines 8 as well as the recent UK National Institute for Health and Clinical Excellence (NICE) guidance 9, which recommend a change in practice to the use of CDT in selected patients with symptomatic iliofemoral DVT 10. The aim of this study was to assess the potential increase in workload from the implementation of these recommendations, and its effect on service provision. Methods This was a review of all DVTs diagnosed between August 2010 and February 2012 (18 months) at Nottingham University Hospitals NHS Trust (NUH). NUH provides 2013 British Journal of Surgery Society Ltd British Journal of Surgery 2013; 100:

2 1026 J. H. Saunders, P. H. Arya, S. Abisi, Y. P. Yong, S. MacSweeney, B. Braithwaite and N. Altaf services to a population of across Nottinghamshire, with 1663 inpatient beds. The majority of patients referred to NUH with suspected DVT are assessed in the nurse-led DVT clinic, which is supported by physicians in the medical assessment unit. Onward referrals to vascular services are then made according to individual clinical judgement. The hospital radiology computer database was used to identify all patients with a radiologically confirmed leg DVT. Radiology reports were then examined independently by two investigators to determine the extent of the radiological thrombus. For a proximal thrombus to be considered for CDT, the entire deep venous outflow of the leg should be occluded (thrombus occluding both the common femoral and profunda veins, with or without suprainguinal extension into the iliac veins), as this group has the greatest risk of PTS 1 3, The ACCP/NICE guidance was then applied retrospectively to this cohort, using case-note review by the two independent clinicians to determine which patients were potentially suitable for CDT. Any discrepancies were referred to a third clinician for adjudication. The outcomes, patient demographics, mode of presentation and exclusion criteria were all recorded. The ACCP/NICE guidance for inclusion criteria is clear, but not comprehensive, and leaves room for individual judgement around issues such as concomitant cancer. It suggests the following indications for CDT of symptomatic iliofemoral DVT: symptoms for fewer than 14 days, good functional status, life expectancy of 1 year or more, and low risk of bleeding. There is a 5 11 per cent risk of bleeding complications 6, so careful patient selection is important to ensure that only patients with a high risk of PTS and a low risk of bleeding complications are offered intervention. To maintain this favourable risk benefit ratio for CDT intervention, the literature upon which the ACCP/NICE guidance is based was examined, and the inclusion criteria for the three major international randomized clinical trials CaVenT, CAtheter Versus Anticoagulation (CAVA) and ATTRACT 7,16,17 were noted in order to create an evidence-based series of unambiguous selection criteria (Appendix S1, supporting information). These were applied to the cohort of patients, which also helped avoid the risk of interobserver bias. All patients treated with CDT in the series had intervention using a pharmacomechanical thrombectomy (PhMT) technique, by means of the AngioJet system (Possis, Medical, Minneapolis, Minnesota, USA) 18. If thrombus clearance was not achieved in the first session then a slow catheter-directed infusion of tissue plasminogen activator was commenced with concurrent heparinization. This was continued overnight, followed by further venography and repeat PhMT the following day, until thrombus clearance had been achieved. Results A total of 563 patients with a radiologically confirmed DVT were identified over the 18-month interval; 301 had a proximal (above-knee) DVT that could potentially have been referred to vascular services for further assessment (Table 1). Review of the radiological reports showed that 128 DVTs were extensive enough to be suitable for consideration for CDT. Of this group of 128 patients, 63 3 per cent were diagnosed and managed as an outpatient, 25 0 per cent were diagnosed as an outpatient but required admission for treatment, and 11 7 per cent were already in hospital when diagnosed. Their mean age was 64 (range ) years and 50 8 per cent were men. The thrombus extended above the groin in 41 4 per cent. The suspected cause of thrombosis is outlined in Table 2. Examination of patient records revealed that, with application of the detailed selection criteria, 53 of the 128 patients would have been eligible for intervention with CDT of their iliofemoral DVT (Fig. 1). The reasons for exclusion are summarized in Table 3. The demographics of the patients considered suitable for intervention were similar to those of patients treated in other studies from Table 1 Anatomical location of the above-knee deep vein thrombosis Proximal extent of thrombus Deep venous outflow obstruction No. of patients (n = 301) Inferior vena cava Yes 3 (1 0) Iliac veins Yes 50 (16 6) Common femoral and Yes 75 (24 9) profunda vein Superficial femoral vein No 114 (37 9) Popliteal vein No 59 (19 6) Table 2 Suspected cause of deep vein thrombosis No. of patients (n = 128) Spontaneous 68 (53 1) Immobility 21 (16 4) Hypercoagulability 5 (3 9) Cancer 21 (16 4) Intravenous drug use 9 (7 0) After surgery 3 (2 3) Pregnancy 1 (0 8)

3 Catheter-directed thrombolysis for iliofemoral deep vein thrombosis 1027 All deep vein thromboses n = 563 Above-knee n = 301 Complete deep venous outflow obstruction n = 128 Patient clinically suitable for CDT n = 53 Below-knee n = 262 Not obstructing deep venous outflow n = 173 Patient not clinically suitable for CDT n = 75 per population per year, and an estimated 29 per cent increase in the number of patients admitted to hospital for treatment of iliofemoral DVT. In the 18-month study interval, only eight of the 53 potentially suitable patients were actually referred to vascular services; all eight subsequently underwent CDT. Seven patients needed multiple sessions of PhMT to achieve complete thrombus clearance. Between these sessions thrombolysis was maintained overnight with a slow catheter-directed infusion. Four patients required two sessions and three patients required three sessions of PhMT; patients were all treated and monitored in the critical care unit. Three patients had May Thurner syndrome and underwent venous stenting to prevent recurrence at the time of the second session of PhMT. Only one patient had a caval filter inserted before CDT, due to thrombus extending into the inferior vena cava. Routine caval filter insertion was not done There was a single complication from CDT: one episode of non-severe, self-limiting, gastrointestinal bleeding. Fig. 1 Patient selection for possible catheter-directed thrombolysis (CDT) for iliofemoral deep vein thrombosis Table 3 Reasons why catheter-directed thrombolysis not indicated No. of patients (n = 75) Disseminated malignancy 19 (25) Age > 80 years 32 (43) Intravenous drug use 9 (12) Poor functional status and immobility 7 (9) Chronicity (>14 days) 4 (5) After surgery 1 (1) Pregnancy 1 (1) Renal transplant 1 (1) Large abdominal aortic aneurysm 1 (1) the UK 19,20 and USA 21 : mean age was 56 (range 16 80) years and 52 per cent were men. The thrombus extended above the groin in 43 per cent. The majority of the 53 patients (70 per cent) presented as an outpatient, 17 per cent as outpatients who needed admission, and 13 per cent were inpatients. The lower proportion of potential CDT patients in the group outpatients requiring admission was due to exclusion of elderly patients who were unable to cope at home but too old for CDT. These numbers represent 17 potential patients per month with an above-knee DVT who might have been referred to vascular services and an estimated three per month requiring CDT. This is equivalent to 4 4 patients Discussion Implementation of international guidelines for the management of iliofemoral DVT with CDT could have a significant service impact. This additional cohort of patients will require new pathways for referral and management, and careful planning for increased inpatient care, interventional treatment as well as critical care support. The development of a clear and well publicized strategy is required to ensure a smooth adoption of the new treatment pathway, and also to deal with potential barriers to CDT. Current nurse-led DVT assessment units identify iliofemoral DVT in 7 9 per cent of patients undergoing duplex ultrasound assessment 20,21. These outpatient units clearly provide an efficient service for assessment and referral of patients who potentially require intervention. In the present study only eight (15 per cent) of 53 patients with iliofemoral DVT suitable for CDT were actually referred to vascular services. Vascular units should form links with DVT assessment services to support their practice and introduce new referral pathways. Education of medical colleagues is also important to ensure timely referral of hospital inpatients. Where expertise and facilities are not available, referral to larger centres will be required 9. The current policy at this institution is for all patients undergoing infusion thrombolysis to be monitored in critical care. The impact of the extra workload might be reduced by centralizing these patients on an experienced specialist vascular ward. Single-session CDT (initial full

4 1028 J. H. Saunders, P. H. Arya, S. Abisi, Y. P. Yong, S. MacSweeney, B. Braithwaite and N. Altaf thrombus clearance without requirement for overnight lysis with critical care support) has been described 26 28, particularly with the Trellis system (Trellis -8 infusion system; Bacchus Vascular, Santa Clara, California, USA). Although one study demonstrated that caval filters placed before PhMT for iliofemoral DVT had evidence of thrombus in 2 of 7 patients 29, concurrent symptomatic pulmonary embolism is rare in those undergoing CDT or PhMT without caval filter placement and reported in fewer than 1 per cent of patients Pragmatic indications for caval filter insertion include iliofemoral DVT while anticoagulated or proximal thrombus extension into the inferior vena cava. Routine (temporary) filter insertion carries its own potential complications, such as thrombosis, migration and perforation. It also requires a second procedure for filter removal 25. Percutaneous mechanical thrombectomy alone does not remove sufficient thrombus, and so is best used in conjunction with CDT to provide PhMT 25. PhMT has been used successfully in the treatment of peripheral arterial occlusions and recently a number of studies have reported that it improves the effectiveness of proximal DVT clearance This study was retrospective and therefore limited by the assumption that the outcomes from CDT are widely reproducible. Ongoing prospective controlled studies will provide more information about cost-effectiveness. The implementation of CDT guidelines for iliofemoral DVT will involve education of other medical disciplines, reorganization and expansion of services, with a significant increase in workload and bed occupancy. It is expected, however, to result in both long-term cost reduction and improved outcomes for patients with iliofemoral DVT. 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