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Out of Hours Investigation of Venous Thromboembolism
Clinical Radiology (2001) 56, 1±3 doi:10.1053/crad.2000.0633, available online at http://www.idealibrary.com on
Commentary Out of Hours Investigation of Venous Thromboembolism JOHN H. REID Radiology Department, Borders General Hospital, Melrose, Scotland Received: 21 February 2000
Revised: 5 June 2000
Why do requests for investigation of a condition which is generally accepted as common, life-threatening and dif®cult to diagnose clinically, arouse such antipathy in radiologists? The reasons are probably quite straightforward. Firstly, we are acutely aware that the de®nitive exclusion of venous thromboembolic disease (VTE) is often problematic, particularly in the all too frequent context of coexisting cardiopulmonary disease. Consequently we have the impression that the question is raised too often, too casually and with too little regard to the effort involved. Secondly, radiologists inherently dislike using techniques that have a low speci®city and so we are often frustrated by the de®ciencies of the imaging techniques available to us. Experience tells us that the advent of newer techniques such as helical computed tomography (CT) have not completely resolved the issue of non-diagnostic studies. Having said this, the positive yield for deep venous thrombosis (DVT) or pulmonary embolism (PE) stands at approximately 25±30% of all investigations, which is substantially higher than the ®gure for radiological investigation of breast or colon cancer [1±3]. It is therefore salutary to remember one is playing a central role in the management of a prevalent and lethal condition when yet another request causes irritation. The situation is probably even more irksome when requests are presented out of hours. It is then that the pressures and de®ciencies in medical units and radiology departments are accentuated. As one might expect, many of the drivers for out of hours investigation of VTE are common to other areas within acute healthcare. The push for the 24-h hospital, reduced length of stay, falling bed numbers and shrinking budgets are wider medical, political and economic issues which are beyond the in¯uence of most radiologists. These topics belong in an open debate on how medical manpower is structured. There are, however, drivers speci®c to VTE often used by clinical colleagues to justify out of hours requests. The two most frequently cited are the consequences of failure to immediately diagnose and treat thromboembolic disease and the dangers of anticoagulant therapy. These assertions require scrutiny and comment, however, since they may, if unchallenged, lead to all cases of thromboembolic disease being lumped together into an amorphous condition which requires 24-h investigation. Consultant radiologists in district general hospitals and specialist registrars in teaching hospitals often 0009-9260/01/0560001+03 $35.00/0
Accepted: 9 June 2000
shoulder the responsibility for physically providing the out of hours service. Consequently they feel the greatest effect of the proliferation of unrealistic guidelines disseminated by clinical groups who insist on immediate investigation of venous thromboembolism. IS IMMEDIATE DIAGNOSIS ALWAYS REQUIRED?
Pulmonary Embolism The severity strati®cation of PE is often overlooked by clinicians who may inappropriately prioritize the urgency for imaging. The individual physical signs of PE, although shared by many other conditions, have recognizable clinical categories within which symptoms and signs tend to cluster [4]. The main groupings are summarized in Table 1. A patient presenting with sudden and unexplained dyspnoea, particularly in the presence of shock, syncope and a normal chest radiograph merits immediate investigation. The principal cause of death in this category is acute right ventricular failure and thrombolysis may be life-saving. This has been recognized in the recently published British Thoracic Society guideline which recommends the use of urgent cardiac ultrasound in cases of suspected massive PE [5]. Conversely, it can be seen that pleuritic chest pain often represents a peripheral infarct. If this symptom is unaccompanied by haemodynamic upset, and interim heparinization is commenced, the patient is unlikely to suffer as a result of a delay of 24 or even 48 h in de®nitive diagnosis. From the point of view of missing a window of diagnostic opportunity, only the tiniest of peripheral emboli is likely to disappear without trace within a 48 h period. The conventional initial treatment for non-massive PE will be iv heparin and it is generally accepted that these patients have a good prognosis once anticoagulation is commenced [6]. One group which require special mention are those with poor cardiovascular reserve due to severe concomitant cardiorespiratory disease. These patients necessitate prompt treatment since they may succumb to smaller emboli.
Deep Vein Thrombosis In the absence of chest symptoms there is little, if any, evidence to suggest that delay in diagnosis of DVT of 1 or 2 q 2001 The Royal College of Radiologists
2
CLINICAL RADIOLOGY
Table 1 ± Clinical categories of pulmonary embolism Clinical category
Clinical presentation
Radiological ®ndings
Massive PE
Dyspnoea, syncope, pre-syncope, cyanosis, tachycardia, hypotension and marked hypoxia (in the absence of any other cause)
Perfusion scintigram usually indicates >50% vascular bed occluded. Emboli are often bilateral and central on CT. Right ventricular (RV) dysfunction is usually evident on echocardiography. CT may show RV dilatation. Chest X-ray may be normal.
Moderate PE
Dyspnoea, occasional haemoptysis and chest pain. Normal systemic blood pressure, may have mild tachycardia.
Pulmonary vascular bed obstructed by 30±50%. Often have lobar/segmental abnormalities on scintigraphy or CT. Frequently demonstrate mild RV dysfunction.
Minor PE
Pleuritic chest pain, haemoptysis, and pleural rub are associated with smaller peripheral emboli which cause infarction. May have dyspnoea due to pain but tachypnoea is uncommon. Normal BP. Occasional fever and leucocytosis.
Scintigraphy shows segmental/subsegmental abnormalities. CT may fail to directly visualize subsegmental emboli but signs of infarction are often seen in the lung parenchyma on CXR and CT related to site of pleuritic pain. RV function is usually normal.
days has any effect on the clinical course of the disease process or the likelihood of subsequent PE. In an increasing number of out-patient centres, patients with suspected DVT are commenced on interim low molecular weight heparin (LMWH) and investigated by ultrasound or venography on the next working day [7]. A further development has been the initial utilization of non-imaging tests to exclude the presence of thrombus. D-dimer assay and impedance plethysmography (IPG) when used together have a negative predictive value of 98% [8]. The positive predictive value for these tests is signi®cantly poorer and so patients who have one or both tests positive should have interim anticoagulation and return for de®nitive radiological diagnosis on the next available session. The role of D-dimer in PE is not yet clearly de®ned, although there is increasing evidence to suggest that a negative D-dimer may add further weight to avoiding unnecessary thoracic imaging [9]. INTERIM ANTICOAGULATION
The perceived dangers of anticoagulant therapy are often given as a reason to push ahead with emergency radiology. There is little to support this contention with respect to interim treatment, particularly if a patient is not in a high-risk group. A study which documented the daily incidence of haemorrhage showed no signi®cant episodes within three days of commencing treatment unless the patient had an underlying bleeding tendency [10]. It is true that the incidence of complications related to conventional heparin therapy rises with time but most published data are derived from studies which look at a period of 5 days therapy or more and often overlap with concurrent administration of warfarin. Suf®ce it to say there is no evidence that 24 or 48 h heparin therapy in those who have no contraindications to anticoagulation places patients at unacceptable risk. Claims that LMWH causes fewer bleeding complications than unfractionated heparin have still to be proven conclusively but it is intuitive that in the real world outside clinical trials the predictable bio-availability of this agent lends itself to even safer interim anticoagulation [11].
In conclusion, it is mandatory that the radiologist be supplied with suf®cient information from an experienced clinical colleague to allow sensible assessment of the degree of diagnostic urgency. The clinical presentation of massive PE merits urgent out of hours investigation, particularly if thrombolysis is an option. Investigation in this clinical setting may be by scintigraphy, CT or echocardiography. A recent survey published in this journal demonstrated that scintigraphy remains by far the most widely available and most frequently used investigation [12]. Despite this, a previous review showed that only one third of nuclear medicine departments provide a 24-h service [13]. Those which do not offer an out of hours service (although it may be technically possible to do so) should perhaps review their policy for emergency imaging. Helical CT should not be seen as an easy option. Where clinical strati®cation of suspected PE suggests a lesser event it would seem reasonable to heparinize and investigate on the next available list. In larger institutions where activity levels are high it may be desirable to cost a regular weekend imaging session to avoid Monday morning log-jams. Out of hours radiological investigation of DVT in those without contraindications to anticoagulation cannot be supported on the basis of available evidence. Radiologists should agree pragmatic protocols with their clinical colleagues based on available manpower and expertise. Clinicians reluctant to participate in this debate should be strongly encouraged to utilize bedside tests and LMWH to assuage their angst. Radiologists should not feel subject to unreasonable guideline waving, particularly if these are not evidence-based and simply mask clinical impatience. REFERENCES 1 Wells PS, Hirsh J, Anderson DR, et al. Accuracy of clinical assessment of deep-vein thrombosis. Lancet 1995;345:1326±1330. 2 Hyers TM. Diagnosis of pulmonary embolism. Thorax 1995;50:930± 932. 3 The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. J Am Med Assoc 1990;263:2753±2759. 4 Goldhaber SZ. Pulmonary embolism. In: Braunwald E (ed). Heart Disease. A Textbook of Cardiovascular Medicine. Pennsylvania: WB Saunders, 1996;1582±1600.
COMMENTARY
5 Corris P, Ellis D, Foley N, Miller A (British Thoracic Society, Standards of Care Committee). Suspected acute pulmonary embolism: a practical approach. Thorax 1997;S4:52. 6 Hirsh J, Bates SM. Prognosis in acute pulmonary embolism. Lancet 1999;353:1375±1376. 7 Koopman MMW, Prandoni P, Piovella F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med 1996;334:682±687. 8 Ginsberg JS, Kearon C, Douketis J, et al. The use of D-dimer testing and impedance plethysmographic examination in patients with clinical indications of deep vein thrombosis. Arch Int Med 1997;157:1077± 1081. 9 Ginsberg JS, Wells PS, Kearon C, et al. Sensitivity and speci®city of a
10 11 12
13
3
rapid whole-blood assay for D-dimer in the diagnosis of pulmonary embolism. Ann Int Med 1998;129:1006±1011. Hull RD, Raskob GE, Pineo GF, et al. Subcutaneous low-molecularweight heparin compared with continuous heparin in the treatment of proximal vein thrombosis. N Engl J Med 1992;326:975±982. Lensing AWA, Prins MH, Davidson BL, Hirsh J. Treatment of deep venous thrombosis with low-molecular-weight heparins. Arch Int Med 1995;155:601±607. Burkill GJC, Bell JRG, Padley SPG. Survey on the use of pulmonary scintigraphy, spiral CT and conventional pulmonary angiography for suspected pulmonary embolism in the British Isles. Clin Radiol 1999;54:807±810. Bury RF, Smith AH. Out of hours scintigraphy: A survey of current practice. Nucl Med Comm 1993;14:126±129.
Commentary Out of Hours Investigation of Venous Thromboembolism JOHN H. REID Radiology Department, Borders General Hospital, Melrose, Scotland Received: 21 February 2000
Revised: 5 June 2000
Why do requests for investigation of a condition which is generally accepted as common, life-threatening and dif®cult to diagnose clinically, arouse such antipathy in radiologists? The reasons are probably quite straightforward. Firstly, we are acutely aware that the de®nitive exclusion of venous thromboembolic disease (VTE) is often problematic, particularly in the all too frequent context of coexisting cardiopulmonary disease. Consequently we have the impression that the question is raised too often, too casually and with too little regard to the effort involved. Secondly, radiologists inherently dislike using techniques that have a low speci®city and so we are often frustrated by the de®ciencies of the imaging techniques available to us. Experience tells us that the advent of newer techniques such as helical computed tomography (CT) have not completely resolved the issue of non-diagnostic studies. Having said this, the positive yield for deep venous thrombosis (DVT) or pulmonary embolism (PE) stands at approximately 25±30% of all investigations, which is substantially higher than the ®gure for radiological investigation of breast or colon cancer [1±3]. It is therefore salutary to remember one is playing a central role in the management of a prevalent and lethal condition when yet another request causes irritation. The situation is probably even more irksome when requests are presented out of hours. It is then that the pressures and de®ciencies in medical units and radiology departments are accentuated. As one might expect, many of the drivers for out of hours investigation of VTE are common to other areas within acute healthcare. The push for the 24-h hospital, reduced length of stay, falling bed numbers and shrinking budgets are wider medical, political and economic issues which are beyond the in¯uence of most radiologists. These topics belong in an open debate on how medical manpower is structured. There are, however, drivers speci®c to VTE often used by clinical colleagues to justify out of hours requests. The two most frequently cited are the consequences of failure to immediately diagnose and treat thromboembolic disease and the dangers of anticoagulant therapy. These assertions require scrutiny and comment, however, since they may, if unchallenged, lead to all cases of thromboembolic disease being lumped together into an amorphous condition which requires 24-h investigation. Consultant radiologists in district general hospitals and specialist registrars in teaching hospitals often 0009-9260/01/0560001+03 $35.00/0
Accepted: 9 June 2000
shoulder the responsibility for physically providing the out of hours service. Consequently they feel the greatest effect of the proliferation of unrealistic guidelines disseminated by clinical groups who insist on immediate investigation of venous thromboembolism. IS IMMEDIATE DIAGNOSIS ALWAYS REQUIRED?
Pulmonary Embolism The severity strati®cation of PE is often overlooked by clinicians who may inappropriately prioritize the urgency for imaging. The individual physical signs of PE, although shared by many other conditions, have recognizable clinical categories within which symptoms and signs tend to cluster [4]. The main groupings are summarized in Table 1. A patient presenting with sudden and unexplained dyspnoea, particularly in the presence of shock, syncope and a normal chest radiograph merits immediate investigation. The principal cause of death in this category is acute right ventricular failure and thrombolysis may be life-saving. This has been recognized in the recently published British Thoracic Society guideline which recommends the use of urgent cardiac ultrasound in cases of suspected massive PE [5]. Conversely, it can be seen that pleuritic chest pain often represents a peripheral infarct. If this symptom is unaccompanied by haemodynamic upset, and interim heparinization is commenced, the patient is unlikely to suffer as a result of a delay of 24 or even 48 h in de®nitive diagnosis. From the point of view of missing a window of diagnostic opportunity, only the tiniest of peripheral emboli is likely to disappear without trace within a 48 h period. The conventional initial treatment for non-massive PE will be iv heparin and it is generally accepted that these patients have a good prognosis once anticoagulation is commenced [6]. One group which require special mention are those with poor cardiovascular reserve due to severe concomitant cardiorespiratory disease. These patients necessitate prompt treatment since they may succumb to smaller emboli.
Deep Vein Thrombosis In the absence of chest symptoms there is little, if any, evidence to suggest that delay in diagnosis of DVT of 1 or 2 q 2001 The Royal College of Radiologists
2
CLINICAL RADIOLOGY
Table 1 ± Clinical categories of pulmonary embolism Clinical category
Clinical presentation
Radiological ®ndings
Massive PE
Dyspnoea, syncope, pre-syncope, cyanosis, tachycardia, hypotension and marked hypoxia (in the absence of any other cause)
Perfusion scintigram usually indicates >50% vascular bed occluded. Emboli are often bilateral and central on CT. Right ventricular (RV) dysfunction is usually evident on echocardiography. CT may show RV dilatation. Chest X-ray may be normal.
Moderate PE
Dyspnoea, occasional haemoptysis and chest pain. Normal systemic blood pressure, may have mild tachycardia.
Pulmonary vascular bed obstructed by 30±50%. Often have lobar/segmental abnormalities on scintigraphy or CT. Frequently demonstrate mild RV dysfunction.
Minor PE
Pleuritic chest pain, haemoptysis, and pleural rub are associated with smaller peripheral emboli which cause infarction. May have dyspnoea due to pain but tachypnoea is uncommon. Normal BP. Occasional fever and leucocytosis.
Scintigraphy shows segmental/subsegmental abnormalities. CT may fail to directly visualize subsegmental emboli but signs of infarction are often seen in the lung parenchyma on CXR and CT related to site of pleuritic pain. RV function is usually normal.
days has any effect on the clinical course of the disease process or the likelihood of subsequent PE. In an increasing number of out-patient centres, patients with suspected DVT are commenced on interim low molecular weight heparin (LMWH) and investigated by ultrasound or venography on the next working day [7]. A further development has been the initial utilization of non-imaging tests to exclude the presence of thrombus. D-dimer assay and impedance plethysmography (IPG) when used together have a negative predictive value of 98% [8]. The positive predictive value for these tests is signi®cantly poorer and so patients who have one or both tests positive should have interim anticoagulation and return for de®nitive radiological diagnosis on the next available session. The role of D-dimer in PE is not yet clearly de®ned, although there is increasing evidence to suggest that a negative D-dimer may add further weight to avoiding unnecessary thoracic imaging [9]. INTERIM ANTICOAGULATION
The perceived dangers of anticoagulant therapy are often given as a reason to push ahead with emergency radiology. There is little to support this contention with respect to interim treatment, particularly if a patient is not in a high-risk group. A study which documented the daily incidence of haemorrhage showed no signi®cant episodes within three days of commencing treatment unless the patient had an underlying bleeding tendency [10]. It is true that the incidence of complications related to conventional heparin therapy rises with time but most published data are derived from studies which look at a period of 5 days therapy or more and often overlap with concurrent administration of warfarin. Suf®ce it to say there is no evidence that 24 or 48 h heparin therapy in those who have no contraindications to anticoagulation places patients at unacceptable risk. Claims that LMWH causes fewer bleeding complications than unfractionated heparin have still to be proven conclusively but it is intuitive that in the real world outside clinical trials the predictable bio-availability of this agent lends itself to even safer interim anticoagulation [11].
In conclusion, it is mandatory that the radiologist be supplied with suf®cient information from an experienced clinical colleague to allow sensible assessment of the degree of diagnostic urgency. The clinical presentation of massive PE merits urgent out of hours investigation, particularly if thrombolysis is an option. Investigation in this clinical setting may be by scintigraphy, CT or echocardiography. A recent survey published in this journal demonstrated that scintigraphy remains by far the most widely available and most frequently used investigation [12]. Despite this, a previous review showed that only one third of nuclear medicine departments provide a 24-h service [13]. Those which do not offer an out of hours service (although it may be technically possible to do so) should perhaps review their policy for emergency imaging. Helical CT should not be seen as an easy option. Where clinical strati®cation of suspected PE suggests a lesser event it would seem reasonable to heparinize and investigate on the next available list. In larger institutions where activity levels are high it may be desirable to cost a regular weekend imaging session to avoid Monday morning log-jams. Out of hours radiological investigation of DVT in those without contraindications to anticoagulation cannot be supported on the basis of available evidence. Radiologists should agree pragmatic protocols with their clinical colleagues based on available manpower and expertise. Clinicians reluctant to participate in this debate should be strongly encouraged to utilize bedside tests and LMWH to assuage their angst. Radiologists should not feel subject to unreasonable guideline waving, particularly if these are not evidence-based and simply mask clinical impatience. REFERENCES 1 Wells PS, Hirsh J, Anderson DR, et al. Accuracy of clinical assessment of deep-vein thrombosis. Lancet 1995;345:1326±1330. 2 Hyers TM. Diagnosis of pulmonary embolism. Thorax 1995;50:930± 932. 3 The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. J Am Med Assoc 1990;263:2753±2759. 4 Goldhaber SZ. Pulmonary embolism. In: Braunwald E (ed). Heart Disease. A Textbook of Cardiovascular Medicine. Pennsylvania: WB Saunders, 1996;1582±1600.
COMMENTARY
5 Corris P, Ellis D, Foley N, Miller A (British Thoracic Society, Standards of Care Committee). Suspected acute pulmonary embolism: a practical approach. Thorax 1997;S4:52. 6 Hirsh J, Bates SM. Prognosis in acute pulmonary embolism. Lancet 1999;353:1375±1376. 7 Koopman MMW, Prandoni P, Piovella F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med 1996;334:682±687. 8 Ginsberg JS, Kearon C, Douketis J, et al. The use of D-dimer testing and impedance plethysmographic examination in patients with clinical indications of deep vein thrombosis. Arch Int Med 1997;157:1077± 1081. 9 Ginsberg JS, Wells PS, Kearon C, et al. Sensitivity and speci®city of a
10 11 12
13
3
rapid whole-blood assay for D-dimer in the diagnosis of pulmonary embolism. Ann Int Med 1998;129:1006±1011. Hull RD, Raskob GE, Pineo GF, et al. Subcutaneous low-molecularweight heparin compared with continuous heparin in the treatment of proximal vein thrombosis. N Engl J Med 1992;326:975±982. Lensing AWA, Prins MH, Davidson BL, Hirsh J. Treatment of deep venous thrombosis with low-molecular-weight heparins. Arch Int Med 1995;155:601±607. Burkill GJC, Bell JRG, Padley SPG. Survey on the use of pulmonary scintigraphy, spiral CT and conventional pulmonary angiography for suspected pulmonary embolism in the British Isles. Clin Radiol 1999;54:807±810. Bury RF, Smith AH. Out of hours scintigraphy: A survey of current practice. Nucl Med Comm 1993;14:126±129.