GENERAL ORTHOPAEDICS
The rate of symptomatic venous thromboembolism in patients undergoing elective Ilizarov surgery and the cost of chemical prophylaxis J. Y. Ferguson, M. Sutherland, H. G. Pandit, M. McNally From Oxford University Hospitals NHS Trust, Oxford, United Kingdom
J. Y. Ferguson, MB ChB (Hons) MRCS (Ed.), Specialty Trainee in Orthopaedics M. Sutherland, RGN, DON, BSc, INP, Ilizarov Clinical Nurse Specialist H. G. Pandit, FRCS (Orth), DPhil, Honorary Senior Clinical Lecturer M. McNally, MD, FRCS Ed, FRCS (Orth), Consultant in Limb Reconstruction Surgery and Honorary Senior Lecturer in Orthopaedic Surgery Oxford University Hospitals NHS Trust, The Limb Reconstruction Unit, Nuffield Orthopaedic Centre, Windmill Road, Headington, Oxford, OX3 7LD, UK. Correspondence should be sent to Mr J. Y. Ferguson; e-mail: jamiefergusonresearch@gmail. com ©2014 The British Editorial Society of Bone & Joint Surgery doi:10.1302/0301-620X.96B3. 32939 $2.00 Bone Joint J 2014;96-B:426–30. Received 2 August 2013; Accepted after revision 6 December 2013
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Recent recommendations by the National Institute for Health and Care Excellence (NICE) suggest that all patients undergoing elective orthopaedic surgery should be assessed for the risk of venous thromboembolism (VTE). Little is known about the incidence of symptomatic VTE after elective external fixation. We studied a consecutive series of adult patients who had undergone elective Ilizarov surgery without routine pharmacological prophylaxis to establish the incidence of symptomatic VTE. A review of a prospectively maintained database of consecutive patients who were treated between October 1998 and February 2011 identified 457 frames in 442 adults whose mean age was 42.6 years (16.0 to 84.6). There were 425 lower limb and 32 upper limb frames. The mean duration of treatment was 25.7 weeks (1.6 to 85.3). According to NICE guidelines all the patients had at least one risk factor for VTE, 246 had two, 172 had three and 31 had four or more. One patient (0.23%) developed a pulmonary embolus after surgery and was later found to have an inherited thrombophilia. There were 27 deaths, all unrelated to VTE. The cost of providing VTE prophylaxis according to NICE guidelines in this group of patients would be £89 493.40 (£195.80 per patient) even if the cheapest recommended medication was used. The rate of symptomatic VTE after Ilizarov surgery was low despite using no pharmacological prophylaxis. This study leads us to question whether NICE guidelines are applicable to these patients. Cite this article: Bone Joint J 2014;96-B:426–30.
There has been a move towards the use of chemical thromboprophylaxis in orthopaedic surgery in an attempt to prevent post-operative deep vein thrombosis (DVT) and pulmonary embolism (PE). The National Institute for Health and Care Excellence (NICE) provides treatment recommendations for the National Health Service (NHS) in England and Wales. It released revised guidelines on venous thromboembolism (VTE) prophylaxis in 2010, which recommended an individual patient risk assessment.1 The decision on whether to administer prophylaxis to an individual should be based on the presence of certain risk factors, which NICE has defined (Table I). Most orthopaedic patients qualify for chemical VTE prophylaxis based on these risk factors. Several studies have shown a reduction in the incidence of asymptomatic DVT and PE with the use of chemical prophylaxis.2-4 However, concerns about the risks of bleeding, heparininduced thrombocytopenia and prolonged wound ooze have fuelled debate as to whether
the NICE guidelines need to be applied to all forms of orthopaedic surgery. There is also continuing debate about the link between asymptomatic VTE and fatal PE. Unlike trauma surgery, in which the risk of VTE is relatively high,5 the true incidence of PE and DVT after the elective application of an external fixator is unknown. Although the use of thromboprophylaxis after elective total hip and knee replacement (THR and TKR) has been clearly defined by NICE, the same guidance has not been given for other forms of orthopaedic surgery involving the lower limbs. The recommendations state that each individual should be assessed for the general risk of developing VTE and that pharmacological prophylaxis should be continued until the patient is mobile. This statement is ambiguous as it is difficult to determine the period of reduced mobility that may cause VTE. The mobility of a patient after Ilizarov surgery is often affected to a varying degree for some time. Without establishing the incidence of THE BONE & JOINT JOURNAL
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Table I. Risk factors for the development of venous thromboembolism (VTE) according to NICE guidelines Surgical patients and patients with trauma If total anaesthetic + surgical time > 90 minutes or If surgery involves pelvis or lower limb and total anaesthetic + surgical time > 60 minutes or If acute surgical admission with inflammatory or intra-abdominal condition or If expected to have significant reduction in mobility or If any VTE risk factor present. VTE risk factors Active cancer or cancer treatment Age over 60 years Critical care admission Dehydration Known thrombophilias Obesity (body mass index [BMI] over 30 kg/m2) One or more significant medical comorbidities (for example: heart disease; metabolic, endocrine or respiratory pathologies; acute infectious diseases; inflammatory conditions) Personal history or first-degree relative with a history of VTE Use of hormone replacement therapy Use of oestrogen-containing contraceptive therapy Varicose veins with phlebitis
VTE in this group it is difficult to balance the benefits and risks of pharmacological prophylaxis. We, therefore, retrospectively investigated the incidence of clinical VTE in a group of patients who had undergone elective external fixator surgery using the Ilizarov method without the use of pharmacological VTE prophylaxis. We also considered the cost implications of chemoprophylaxis.
Patients and Methods The study had ethical approval. We identified a consecutive series of patients who had undergone elective surgery using the Ilizarov method from a prospectively compiled database. Children aged < 16 years at the time of the index procedure were excluded. All operations were undertaken by a single surgeon (MM). Between October 1998 and February 2011, 442 patients underwent 457 elective applications of an external fixator. Information about risk factors for VTE as outlined by NICE was collected for each patient including the length of surgery and type of anaesthesia; age; body mass index; significant comorbidities; and a personal or family history of VTE. Unless contraindicated, each patient wore a below-knee thromboembolic deterrent (TED) stocking on the opposite leg: this was applied pre-operatively. All were encouraged to bear as much weight as possible on the first post-operative day. No patient received any pharmacological VTE prophylaxis except for 14 operated on after 2009. These 14 patients needed a free muscle flap at the same time as their Ilizarov reconstruction and the plastic surgeons requested that they receive a once daily subcutaneous injection of 5000 units of the low molecular-weight heparin (LMWH), dalteparin, during their inpatient stay. They received no further pharmacological cover after discharge. All patients were regularly reviewed post-operatively and were followed-up for at least three months after the frame had been removed. Consequently, we were aware of any patient who developed VTE, or was investigated for VTE while the frame was applied. We also established, from our VOL. 96-B, No. 3, MARCH 2014
regional thrombosis centre, whether any of these patients had subsequently been seen for investigation or treatment of VTE. The Personal Demographics Service, the national patient database for the NHS, was used to establish if any patients had died after their surgery. The General Practice for these patients was then contacted to establish the cause of death. Statistical analysis. All information was collected using Microsoft Excel (Microsoft, Redmond, Washington). Mean values and a range were calculated in each category. Fisher’s exact test was used to compare groups. A cost analysis was performed based on the mean duration of management with a frame and using costs available to our hospital for chemoprophylaxis.
Results We identified 457 elective operations involving the application of a frame in 442 adults. The mean age of the patients was 42.6 years (16.0 to 84.6). There were 306 men and 136 women, and 425 lower limb and 32 upper limb frames were used. Six patients had bilateral lower limb frames applied simultaneously (five tibial and one femoral). An Ilizarov frame (Smith & Nephew, Huntingdon, UK) was used 413 times and a monolateral frame (Monotube, Stryker Osteosynthesis, Newbury, UK) in 44 cases. In total, 185 cases were performed to treat osteomyelitis and 62 involved the addition of a local or free microvascular muscle flap. Patients were given either a general anaesthetic or regional or spinal anaesthesia with sedation. The mean duration of treatment in the frame was 25.7 weeks (1.6 to 85.3). Table II illustrates the method used in each case and shows the anatomical location of the frames. Only one patient (0.23%; confidence interval 0.04 to 1.27) developed a symptomatic VTE. This was a 17-year old girl who had a tibial Ilizarov frame for correction of a valgus deformity of the distal tibia caused by hereditary multiple exostoses. Her surgery was uneventful and she mobilised rapidly. Six weeks after application of the frame,
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J. Y. FERGUSON, M. SUTHERLAND, H. G. PANDIT, M. MCNALLY
Table II. The Ilizarov method used and the location of the frame in each case
300 250
Method used Compression/ distraction Deformity correction Combined techniques Stabilisation Lengthening Fusion Bone transport
134 112 56 48 39 37 31
Number of cases
Number of patients
200 150 100 50 0
Location Tibia Femur Ankle Humerus Forearm Foot Knee Femur and tibia Hip
1 258 105 30 19 14 13 11 6 1
she developed pleuritic chest pain and a CT Pulmonary Angiogram (CTPA) revealed a pulmonary embolus (PE). She was treated with warfarin for six months. Following haematological investigation she was found to be heterozygous for both factor V Leiden and the Prothrombin mutation G20210A. The presence of both these genetic prothrombotic risk factors is thought to increase the risk of developing VTE by a factor of about 20.6,7 A year later she returned for correction of the contralateral distal tibia. Following discussion with the haematologists it was advised that she should be given prophylactic dalteparin (5000 units) daily for a period of six weeks following surgery. Despite this she suffered a further PE 30 days postoperatively while still receiving dalteparin. She was again treated with warfarin. Interestingly, her sister also suffered a PE at this time without undergoing surgery. She was also shown to be thrombophilic. A second patient developed a DVT five years after removal of his frame, immediately after a femoral-popliteal bypass graft. We did not consider this to be related to the Ilizarov management. During the follow-up period three further patients were investigated for VTE; two with a swollen leg had a negative CT venogram and one, who had an episode of breathlessness, had a negative CTPA. There were 27 deaths in the follow-up period at a mean of 5.56 years (0.5 to 10.8) post-operatively, but none were related to VTE. Each patient in this series had at least one of the risk factors for VTE as described in the NICE guidelines (Table I). Eight patients had one risk factor, 246 had two, 172 had three and 31 had four or more (Fig. 1). Thus, according to NICE guidance, every patient should have been treated with LMWH.
2
3
≥4
Number of risk factors Fig. 1 Bar graph showing the number of NICE risk factors identified in each patient.
If pharmacological prophylaxis (dalteparin) had been continued for the whole time the frame was applied, the cost would have been £195.82 per patient or £89 493.40 for the whole group. These are real-world costs for dalteparin as they have been calculated based on the reduced cost of this drug from bulk buying. They would be higher if based on the British National Formulary stock price.8
Discussion Pharmacological thromboprophylaxis remains a contentious issue. With the advent of national guidelines for thromboprophylaxis in orthopaedic surgery, the debate about their applicability to various subspecialties has become more intense. NICE gives specific guidance on areas of orthopaedic surgery for which published data are available and groups the rest into a single entity that it regards as always being associated with a high risk of VTE. Although there have been no published studies on the incidence of VTE in elective Ilizarov surgery without pharmacological thromboprophylaxis, NICE continues to recommend its use by extrapolation of risk data from joint replacement and or fracture surgery. Our study found that the rate of symptomatic VTE in a group undergoing elective frame surgery without chemoprophylaxis was very low (0.23%; C.I. 0.04 to 1.27) and, possibly more significantly, there were no deaths related to VTE. We did not find assessment of general risk factors, as recommended by NICE, useful in these patients. Although they all had at least one risk factor, and many had more, this did not correlate with a high rate of VTE. What constitutes a significant reduction in mobility also remains controversial. We encourage early mobilisation in all our patients but most have relatively limited mobility while in a frame compared with their pre-operative state. It is not clear whether NICE recommends thromboprophylaxis until the frame is removed and full mobility has been restored. It is unlikely that strict application of the NICE guidelines would have prevented any episode of VTE in this THE BONE & JOINT JOURNAL
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group given that the only case of VTE was in a patient with an unrecognised thrombophilia who subsequently developed a further PE despite being given prophylaxis. In this series, 14 patients were given chemoprophylaxis because of concern about their immobility in the 10 to 14 days after a free muscle flap transfer. This change in practice was triggered by the publication of the modified NICE Guidance in 2010. In the whole series, 62 patients had free muscle flaps. No VTE was recorded in either the 48 patients without chemoprophylaxis or the 14 who were treated with dalteparin. We have shown that patients undergoing elective Ilizarov surgery under spinal or regional anaesthesia with mechanical thromboprophylaxis and early mobilisation have a very low risk of VTE. It has been reported that the rates of VTE in foot and ankle surgery9,10 and outpatient arthroscopic procedures11 are extremely low. Certain groups of patients have a low risk of developing VTE. The rate of DVT in a group of Japanese patients undergoing THR, for instance, has been reported to be low with no difference between those treated with pharmacological agents and those receiving mechanical prophylaxis alone.12 This further suggests that NICE guidance will need to be more specific and evidence-based, if it is to be of clinical use. A recent study showed that the incidence of VTE after elective frame surgery using pharmacological thromboprophylaxis was 0.9 % (two of 214 cases).13 This is similar to our rate of 0.23% without the use of thromboprophylaxis, which suggests that there is no clear benefit from their use in elective Ilizarov surgery. Furthermore, in a study of the general Danish population, the annual incidence of VTE without surgery in 257,895 people was 0.17%, again similar to the rate in our series.14 The risks associated with the use of drugs to prevent VTE are significant. The incidence of major bleeding complications in a study of 715 patients who underwent lower limb arthroplasty and were treated with LMWH was 2.8%.15 Other studies have shown similar rates for haematoma formation, ranging from 3.7% to 6.2%.16,17 In patients with an external fixator, bleeding from the pin sites has been seen after anticoagulation and may increase the risk of pin site infection. This is the largest series to date that has studied symptomatic VTE in patients who have undergone elective Ilizarov surgery. Although the final analysis was retrospective, complications were recorded prospectively and all patients were followed-up until at least three months after their frame had been removed. We are confident that we have captured all patients with suspected or confirmed symptomatic VTE and all deaths. It is possible that some of these patients may have developed a VTE at a later stage, but this is unlikely to have been related to the surgery and would not have been prevented by peri-operative chemoprophylaxis. All patients were given a below-knee anti-embolism stocking on discharge for the opposite leg or bilateral antiembolism stockings if in an upper limb frame. However, we VOL. 96-B, No. 3, MARCH 2014
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have no information about how many patients actually used them and for how long. Finally, our calculation of cost for pharmacological prophylaxis does not take into account any of the ancillary costs associated with the administration of LMWH. These could include the issuing and disposal of sharps containers and the provision of a district nurse to give injections to those unable to do so themselves. We believe that the benefit and cost effectiveness of pharmacological thromboprophylaxis in this group of patients is doubtful. Our study has shown a very low rate of symptomatic VTE in patients undergoing elective Ilizarov surgery without anticoagulation. Risk assessment, as outlined by NICE guidelines, was not helpful in identifying or managing the single patient who did develop VTE. Supplementary material Radiographs detailing a patient with a symptomatic pulmonary embolism are available with the electronic version of this article on our website www.bjj.boneandjoint.org.uk We are most grateful for the assistance of J. Brown and C. Medom Madsen for their help with the database analysis of the patients in this study. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. This article was primary edited by A. Ross and first-proof edited by J. Scott.
References 1. No authors listed. National Institute for Health and Care Excellence. Venous thromboembolism: reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital, 2010. http://guidance.nice.org.uk/CG92 (date last accessed 16 January 2014). 2. Knudson MM, Morabito D, Paiement GD, Shackleford S. Use of low molecular weight heparin in preventing thromboembolism in trauma patients. J Trauma 1996;41:446–459. 3. Bergqvist D, Benoni G, Björgell O, et al. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996;335:696–700. 4. Fitzgerald RH Jr, Spiro TE, Trowbridge AA, et al. Prevention of venous thromboembolic disease following primary total knee arthroplasty: a randomized, multicenter, open-label, parallel-group comparison of enoxaparin and warfarin. J Bone Joint Surg [Am] 2001;83-A:900–906. 5. Geerts WH, Code KI, Jay RM, Chen E, Szalai JP. A prospective study of venous thromboembolism after major trauma. N Engl J Med 1994;331:1601–1606. 6. Emmerich J, Rosendaal FR, Cattaneo M, et al. Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism: pooled analysis of 8 case-control studies including 2310 cases and 3204 controls. Study Group for Pooled-Analysis in Venous Thromboembolism. Thromb Haemost 2001;86:809–816. 7. Rosendaal FR, Reitsma PH. Genetics of venous thrombosis. J Thromb Haemost 2009;7(Suppl):301–304. 8. No authors listed. British National Formulary (BNF) 66. London: Royal Pharmaceutical Society; 2013. 9. Jameson SS, Augustine A, James P, et al. Venous thromboembolic events following foot and ankle surgery in the English National Health Service. J Bone Joint Surg [Br] 2011;93-B:490–497. 10. Griffiths JT, Matthews L, Pearce CJ, Calder JD. Incidence of venous thromboembolism in elective foot and ankle surgery with and without aspirin prophylaxis. J Bone Joint Surg [Br] 2012;94-B:210–214. 11. Hetsroni I, Lyman S, Do H, Mann G, Marx RG. Symptomatic pulmonary embolism after outpatient arthroscopic procedures of the knee; the incidence and risk factors in 418,323 arthroscopies: J Bone Joint Surg [Br] 2011;93-B:47–51.
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12. Yokote R, Matsubara M, Hirasawa N, et al. Is routine chemical thromboprophylaxis after total hip replacement really necessary in a Japanese population? J Bone Joint Surg [Br] 2011;93-B:251–256.
15. Hull R, Raskob G, Pineo G, et al. A comparison of subcutaneous low-molecularweight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation. N Engl J Med 1993;329:1370–1376.
13. Roberts D, Panagiotidou A, Calder P. The incidence of deep vein thrombosis with external fixators: are current thromboprophylaxis guidelines appropriate? Bone Joint J 2013;95-B(Supp 1):222. 14. Pedersen AB, Johnsen SP, Sørensen HT. Increased one-year risk of symptomatic venous thromboembolism following total hip replacement: a nationwide cohort study. J Bone Joint Surg [Br] 2012;94-B:1598–1603.
16. Eikelboom JW, Quinlan DJ, Douketis JD. Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomised trials. Lancet 2001;358:9–15. 17. Hoek JA, Nurmohamed MT, Hamelynck KJ, et al. Prevention of deep vein thrombosis following total hip replacement by low molecular weight heparinoid. Thromb Haemost 1992;67:28–32.
THE BONE & JOINT JOURNAL
The rate of symptomatic venous thromboembolism in patients undergoing elective Ilizarov surgery and the cost of chemical prophylaxis J. Y. Ferguson, M. Sutherland, H. G. Pandit, M. McNally From Oxford University Hospitals NHS Trust, Oxford, United Kingdom
J. Y. Ferguson, MB ChB (Hons) MRCS (Ed.), Specialty Trainee in Orthopaedics M. Sutherland, RGN, DON, BSc, INP, Ilizarov Clinical Nurse Specialist H. G. Pandit, FRCS (Orth), DPhil, Honorary Senior Clinical Lecturer M. McNally, MD, FRCS Ed, FRCS (Orth), Consultant in Limb Reconstruction Surgery and Honorary Senior Lecturer in Orthopaedic Surgery Oxford University Hospitals NHS Trust, The Limb Reconstruction Unit, Nuffield Orthopaedic Centre, Windmill Road, Headington, Oxford, OX3 7LD, UK. Correspondence should be sent to Mr J. Y. Ferguson; e-mail: jamiefergusonresearch@gmail. com ©2014 The British Editorial Society of Bone & Joint Surgery doi:10.1302/0301-620X.96B3. 32939 $2.00 Bone Joint J 2014;96-B:426–30. Received 2 August 2013; Accepted after revision 6 December 2013
426
Recent recommendations by the National Institute for Health and Care Excellence (NICE) suggest that all patients undergoing elective orthopaedic surgery should be assessed for the risk of venous thromboembolism (VTE). Little is known about the incidence of symptomatic VTE after elective external fixation. We studied a consecutive series of adult patients who had undergone elective Ilizarov surgery without routine pharmacological prophylaxis to establish the incidence of symptomatic VTE. A review of a prospectively maintained database of consecutive patients who were treated between October 1998 and February 2011 identified 457 frames in 442 adults whose mean age was 42.6 years (16.0 to 84.6). There were 425 lower limb and 32 upper limb frames. The mean duration of treatment was 25.7 weeks (1.6 to 85.3). According to NICE guidelines all the patients had at least one risk factor for VTE, 246 had two, 172 had three and 31 had four or more. One patient (0.23%) developed a pulmonary embolus after surgery and was later found to have an inherited thrombophilia. There were 27 deaths, all unrelated to VTE. The cost of providing VTE prophylaxis according to NICE guidelines in this group of patients would be £89 493.40 (£195.80 per patient) even if the cheapest recommended medication was used. The rate of symptomatic VTE after Ilizarov surgery was low despite using no pharmacological prophylaxis. This study leads us to question whether NICE guidelines are applicable to these patients. Cite this article: Bone Joint J 2014;96-B:426–30.
There has been a move towards the use of chemical thromboprophylaxis in orthopaedic surgery in an attempt to prevent post-operative deep vein thrombosis (DVT) and pulmonary embolism (PE). The National Institute for Health and Care Excellence (NICE) provides treatment recommendations for the National Health Service (NHS) in England and Wales. It released revised guidelines on venous thromboembolism (VTE) prophylaxis in 2010, which recommended an individual patient risk assessment.1 The decision on whether to administer prophylaxis to an individual should be based on the presence of certain risk factors, which NICE has defined (Table I). Most orthopaedic patients qualify for chemical VTE prophylaxis based on these risk factors. Several studies have shown a reduction in the incidence of asymptomatic DVT and PE with the use of chemical prophylaxis.2-4 However, concerns about the risks of bleeding, heparininduced thrombocytopenia and prolonged wound ooze have fuelled debate as to whether
the NICE guidelines need to be applied to all forms of orthopaedic surgery. There is also continuing debate about the link between asymptomatic VTE and fatal PE. Unlike trauma surgery, in which the risk of VTE is relatively high,5 the true incidence of PE and DVT after the elective application of an external fixator is unknown. Although the use of thromboprophylaxis after elective total hip and knee replacement (THR and TKR) has been clearly defined by NICE, the same guidance has not been given for other forms of orthopaedic surgery involving the lower limbs. The recommendations state that each individual should be assessed for the general risk of developing VTE and that pharmacological prophylaxis should be continued until the patient is mobile. This statement is ambiguous as it is difficult to determine the period of reduced mobility that may cause VTE. The mobility of a patient after Ilizarov surgery is often affected to a varying degree for some time. Without establishing the incidence of THE BONE & JOINT JOURNAL
THE RATE OF SYMPTOMATIC VTE IN PATIENTS UNDERGOING ELECTIVE ILIZAROV SURGERY AND THE COST OF CHEMICAL PROPHYLAXIS
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Table I. Risk factors for the development of venous thromboembolism (VTE) according to NICE guidelines Surgical patients and patients with trauma If total anaesthetic + surgical time > 90 minutes or If surgery involves pelvis or lower limb and total anaesthetic + surgical time > 60 minutes or If acute surgical admission with inflammatory or intra-abdominal condition or If expected to have significant reduction in mobility or If any VTE risk factor present. VTE risk factors Active cancer or cancer treatment Age over 60 years Critical care admission Dehydration Known thrombophilias Obesity (body mass index [BMI] over 30 kg/m2) One or more significant medical comorbidities (for example: heart disease; metabolic, endocrine or respiratory pathologies; acute infectious diseases; inflammatory conditions) Personal history or first-degree relative with a history of VTE Use of hormone replacement therapy Use of oestrogen-containing contraceptive therapy Varicose veins with phlebitis
VTE in this group it is difficult to balance the benefits and risks of pharmacological prophylaxis. We, therefore, retrospectively investigated the incidence of clinical VTE in a group of patients who had undergone elective external fixator surgery using the Ilizarov method without the use of pharmacological VTE prophylaxis. We also considered the cost implications of chemoprophylaxis.
Patients and Methods The study had ethical approval. We identified a consecutive series of patients who had undergone elective surgery using the Ilizarov method from a prospectively compiled database. Children aged < 16 years at the time of the index procedure were excluded. All operations were undertaken by a single surgeon (MM). Between October 1998 and February 2011, 442 patients underwent 457 elective applications of an external fixator. Information about risk factors for VTE as outlined by NICE was collected for each patient including the length of surgery and type of anaesthesia; age; body mass index; significant comorbidities; and a personal or family history of VTE. Unless contraindicated, each patient wore a below-knee thromboembolic deterrent (TED) stocking on the opposite leg: this was applied pre-operatively. All were encouraged to bear as much weight as possible on the first post-operative day. No patient received any pharmacological VTE prophylaxis except for 14 operated on after 2009. These 14 patients needed a free muscle flap at the same time as their Ilizarov reconstruction and the plastic surgeons requested that they receive a once daily subcutaneous injection of 5000 units of the low molecular-weight heparin (LMWH), dalteparin, during their inpatient stay. They received no further pharmacological cover after discharge. All patients were regularly reviewed post-operatively and were followed-up for at least three months after the frame had been removed. Consequently, we were aware of any patient who developed VTE, or was investigated for VTE while the frame was applied. We also established, from our VOL. 96-B, No. 3, MARCH 2014
regional thrombosis centre, whether any of these patients had subsequently been seen for investigation or treatment of VTE. The Personal Demographics Service, the national patient database for the NHS, was used to establish if any patients had died after their surgery. The General Practice for these patients was then contacted to establish the cause of death. Statistical analysis. All information was collected using Microsoft Excel (Microsoft, Redmond, Washington). Mean values and a range were calculated in each category. Fisher’s exact test was used to compare groups. A cost analysis was performed based on the mean duration of management with a frame and using costs available to our hospital for chemoprophylaxis.
Results We identified 457 elective operations involving the application of a frame in 442 adults. The mean age of the patients was 42.6 years (16.0 to 84.6). There were 306 men and 136 women, and 425 lower limb and 32 upper limb frames were used. Six patients had bilateral lower limb frames applied simultaneously (five tibial and one femoral). An Ilizarov frame (Smith & Nephew, Huntingdon, UK) was used 413 times and a monolateral frame (Monotube, Stryker Osteosynthesis, Newbury, UK) in 44 cases. In total, 185 cases were performed to treat osteomyelitis and 62 involved the addition of a local or free microvascular muscle flap. Patients were given either a general anaesthetic or regional or spinal anaesthesia with sedation. The mean duration of treatment in the frame was 25.7 weeks (1.6 to 85.3). Table II illustrates the method used in each case and shows the anatomical location of the frames. Only one patient (0.23%; confidence interval 0.04 to 1.27) developed a symptomatic VTE. This was a 17-year old girl who had a tibial Ilizarov frame for correction of a valgus deformity of the distal tibia caused by hereditary multiple exostoses. Her surgery was uneventful and she mobilised rapidly. Six weeks after application of the frame,
428
J. Y. FERGUSON, M. SUTHERLAND, H. G. PANDIT, M. MCNALLY
Table II. The Ilizarov method used and the location of the frame in each case
300 250
Method used Compression/ distraction Deformity correction Combined techniques Stabilisation Lengthening Fusion Bone transport
134 112 56 48 39 37 31
Number of cases
Number of patients
200 150 100 50 0
Location Tibia Femur Ankle Humerus Forearm Foot Knee Femur and tibia Hip
1 258 105 30 19 14 13 11 6 1
she developed pleuritic chest pain and a CT Pulmonary Angiogram (CTPA) revealed a pulmonary embolus (PE). She was treated with warfarin for six months. Following haematological investigation she was found to be heterozygous for both factor V Leiden and the Prothrombin mutation G20210A. The presence of both these genetic prothrombotic risk factors is thought to increase the risk of developing VTE by a factor of about 20.6,7 A year later she returned for correction of the contralateral distal tibia. Following discussion with the haematologists it was advised that she should be given prophylactic dalteparin (5000 units) daily for a period of six weeks following surgery. Despite this she suffered a further PE 30 days postoperatively while still receiving dalteparin. She was again treated with warfarin. Interestingly, her sister also suffered a PE at this time without undergoing surgery. She was also shown to be thrombophilic. A second patient developed a DVT five years after removal of his frame, immediately after a femoral-popliteal bypass graft. We did not consider this to be related to the Ilizarov management. During the follow-up period three further patients were investigated for VTE; two with a swollen leg had a negative CT venogram and one, who had an episode of breathlessness, had a negative CTPA. There were 27 deaths in the follow-up period at a mean of 5.56 years (0.5 to 10.8) post-operatively, but none were related to VTE. Each patient in this series had at least one of the risk factors for VTE as described in the NICE guidelines (Table I). Eight patients had one risk factor, 246 had two, 172 had three and 31 had four or more (Fig. 1). Thus, according to NICE guidance, every patient should have been treated with LMWH.
2
3
≥4
Number of risk factors Fig. 1 Bar graph showing the number of NICE risk factors identified in each patient.
If pharmacological prophylaxis (dalteparin) had been continued for the whole time the frame was applied, the cost would have been £195.82 per patient or £89 493.40 for the whole group. These are real-world costs for dalteparin as they have been calculated based on the reduced cost of this drug from bulk buying. They would be higher if based on the British National Formulary stock price.8
Discussion Pharmacological thromboprophylaxis remains a contentious issue. With the advent of national guidelines for thromboprophylaxis in orthopaedic surgery, the debate about their applicability to various subspecialties has become more intense. NICE gives specific guidance on areas of orthopaedic surgery for which published data are available and groups the rest into a single entity that it regards as always being associated with a high risk of VTE. Although there have been no published studies on the incidence of VTE in elective Ilizarov surgery without pharmacological thromboprophylaxis, NICE continues to recommend its use by extrapolation of risk data from joint replacement and or fracture surgery. Our study found that the rate of symptomatic VTE in a group undergoing elective frame surgery without chemoprophylaxis was very low (0.23%; C.I. 0.04 to 1.27) and, possibly more significantly, there were no deaths related to VTE. We did not find assessment of general risk factors, as recommended by NICE, useful in these patients. Although they all had at least one risk factor, and many had more, this did not correlate with a high rate of VTE. What constitutes a significant reduction in mobility also remains controversial. We encourage early mobilisation in all our patients but most have relatively limited mobility while in a frame compared with their pre-operative state. It is not clear whether NICE recommends thromboprophylaxis until the frame is removed and full mobility has been restored. It is unlikely that strict application of the NICE guidelines would have prevented any episode of VTE in this THE BONE & JOINT JOURNAL
THE RATE OF SYMPTOMATIC VTE IN PATIENTS UNDERGOING ELECTIVE ILIZAROV SURGERY AND THE COST OF CHEMICAL PROPHYLAXIS
group given that the only case of VTE was in a patient with an unrecognised thrombophilia who subsequently developed a further PE despite being given prophylaxis. In this series, 14 patients were given chemoprophylaxis because of concern about their immobility in the 10 to 14 days after a free muscle flap transfer. This change in practice was triggered by the publication of the modified NICE Guidance in 2010. In the whole series, 62 patients had free muscle flaps. No VTE was recorded in either the 48 patients without chemoprophylaxis or the 14 who were treated with dalteparin. We have shown that patients undergoing elective Ilizarov surgery under spinal or regional anaesthesia with mechanical thromboprophylaxis and early mobilisation have a very low risk of VTE. It has been reported that the rates of VTE in foot and ankle surgery9,10 and outpatient arthroscopic procedures11 are extremely low. Certain groups of patients have a low risk of developing VTE. The rate of DVT in a group of Japanese patients undergoing THR, for instance, has been reported to be low with no difference between those treated with pharmacological agents and those receiving mechanical prophylaxis alone.12 This further suggests that NICE guidance will need to be more specific and evidence-based, if it is to be of clinical use. A recent study showed that the incidence of VTE after elective frame surgery using pharmacological thromboprophylaxis was 0.9 % (two of 214 cases).13 This is similar to our rate of 0.23% without the use of thromboprophylaxis, which suggests that there is no clear benefit from their use in elective Ilizarov surgery. Furthermore, in a study of the general Danish population, the annual incidence of VTE without surgery in 257,895 people was 0.17%, again similar to the rate in our series.14 The risks associated with the use of drugs to prevent VTE are significant. The incidence of major bleeding complications in a study of 715 patients who underwent lower limb arthroplasty and were treated with LMWH was 2.8%.15 Other studies have shown similar rates for haematoma formation, ranging from 3.7% to 6.2%.16,17 In patients with an external fixator, bleeding from the pin sites has been seen after anticoagulation and may increase the risk of pin site infection. This is the largest series to date that has studied symptomatic VTE in patients who have undergone elective Ilizarov surgery. Although the final analysis was retrospective, complications were recorded prospectively and all patients were followed-up until at least three months after their frame had been removed. We are confident that we have captured all patients with suspected or confirmed symptomatic VTE and all deaths. It is possible that some of these patients may have developed a VTE at a later stage, but this is unlikely to have been related to the surgery and would not have been prevented by peri-operative chemoprophylaxis. All patients were given a below-knee anti-embolism stocking on discharge for the opposite leg or bilateral antiembolism stockings if in an upper limb frame. However, we VOL. 96-B, No. 3, MARCH 2014
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have no information about how many patients actually used them and for how long. Finally, our calculation of cost for pharmacological prophylaxis does not take into account any of the ancillary costs associated with the administration of LMWH. These could include the issuing and disposal of sharps containers and the provision of a district nurse to give injections to those unable to do so themselves. We believe that the benefit and cost effectiveness of pharmacological thromboprophylaxis in this group of patients is doubtful. Our study has shown a very low rate of symptomatic VTE in patients undergoing elective Ilizarov surgery without anticoagulation. Risk assessment, as outlined by NICE guidelines, was not helpful in identifying or managing the single patient who did develop VTE. Supplementary material Radiographs detailing a patient with a symptomatic pulmonary embolism are available with the electronic version of this article on our website www.bjj.boneandjoint.org.uk We are most grateful for the assistance of J. Brown and C. Medom Madsen for their help with the database analysis of the patients in this study. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. This article was primary edited by A. Ross and first-proof edited by J. Scott.
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