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(Circulation. 2000;102:e126.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Investigation of Chronic Venous Insufficiency

A Consensus Statement

A. N. Nicolaides, MS, FRCS, FRCSE¹

From Irvine Laboratory for Cardiovascular Investigation and Research, Department of Vascular Surgery, Imperial College School of Medicine (St Mary’s Campus), London W2 1NY, UK.

Correspondence to Prof A.N. Nicolaides, Irvine Laboratory for Cardiovascular Investigation and Research, Department of Vascular Surgery, Imperial College School of Medicine (St Mary’s Campus), 10th Floor, Queen Elizabeth the Queen Mother Wing, Praed Street, London W2 1NY, UK. E-mail a.nicolaides{at}ic.ac.uk

	Abstract

Top Abstract Introduction Magnitude of the Problem Pathophysiology of CVI Methods of Investigation Application of Methods in... Investigation of Congenital... Appendix 1 References

 
Abstract—This consensus document provides an up-to-date account of the various methods available for the investigation of chronic venous insufficiency of the lower limbs (CVI), with an outline of their history, usefulness, and limitations. CVI is characterized by symptoms or signs produced by venous hypertension as a result of structural or functional abnormalities of veins. The most frequent causes of CVI are primary abnormalities of the venous wall and the valves and secondary changes due to previous venous thrombosis that can lead to reflux, obstruction, or both. Because the history and clinical examination will not always indicate the nature and extent of the underlying abnormality (anatomic extent, pathology, and cause), a number of diagnostic investigations have been developed that can elucidate whether there is calf muscle pump dysfunction and determine the anatomic extent and severity of obstruction or reflux. The difficulty in deciding which investigations to use and how to interpret the results has stimulated the development of this consensus document. The aim of this document was to provide an account of these tests, with an outline of their usefulness and limitations and indications of which patients should be subjected to the tests and when and of what clinical decisions can be made. This document was written primarily for the clinician who would like to learn the latest approaches to the investigation of patients with CVI and the new applications that have emerged from recent research, as well as for the novice who is embarking on venous research. Care has been taken to indicate which methods have entered the clinical arena and which are mainly used for research. The foundation for this consensus document was laid by the faculty at a meeting held under the auspices of the American Venous Forum, the Cardiovascular Disease Educational and Research Trust, the European Society of Vascular Surgery, the International Angiology Scientific Activity Congress Organization, the International Union of Angiology, and the Union Internationale de Phlebologie at the Abbaye des Vaux de Cernay, France, on March 5 to 9, 1997. Subsequent input by co-opted faculty members and revisions in 1998 and 1999 have ensured a document that provides an up-to-date account of the various methods available for the investigation of CVI.

Key Words: veins • valves • thrombosis • chronic venous insufficiency • tests

	Introduction

Top Abstract Introduction Magnitude of the Problem Pathophysiology of CVI Methods of Investigation Application of Methods in... Investigation of Congenital... Appendix 1 References

 
Chronic venous insufficiency of the lower limbs (CVI) is characterized by symptoms or signs produced by venous hypertension as a result of structural or functional abnormalities of veins. Symptoms may include aching, heaviness, leg-tiredness, cramps, itching, sensations of burning, swelling, the restless leg syndrome, dilatation or prominence of superficial veins, and skin changes. Signs may include telangiectasia, reticular or varicose veins, edema, and skin changes such as pigmentation, lipodermatosclerosis, eczema, and ulceration.

The most frequent causes of CVI are primary abnormalities of the venous wall and the valves and secondary changes due to previous venous thrombosis that can lead to reflux, obstruction, or both. Congenital malformations are rare causes of CVI. Because the history and clinical examination will not always indicate the nature and extent of the underlying abnormality (anatomic extent, pathology, and cause), a number of diagnostic investigations have been developed that can elucidate whether there is calf muscle pump dysfunction and can determine the anatomic extent and functional severity of obstruction or reflux. The difficulty in deciding which investigations to use and how to interpret the results has stimulated the development of this consensus document. The aim of this document was to provide an account of these tests, with an outline of their usefulness and limitations and indications of which patients should be subjected to the tests and when and of what clinical decisions can be made.

The foundation for this consensus document was laid by the faculty at a meeting held under the auspices of the American Venous Forum (AVF), the Cardiovascular Disease Educational and Research Trust (CDER Trust), the European Society of Vascular Surgery (ESVS), the International Angiology Scientific Activity Congress Organization (IASACO), the International Union of Angiology (IUA), and the Union Internationale de Phlebologie (UIP) at the Abbaye des Vaux de Cernay, France, on March 5 to 9, 1997. Subsequent input by co-opted faculty members and revisions in 1998 and 1999 have ensured a document that provides an up-to-date account of the various methods available for investigating CVI.

	Magnitude of the Problem

Top Abstract Introduction Magnitude of the Problem Pathophysiology of CVI Methods of Investigation Application of Methods in... Investigation of Congenital... Appendix 1 References

 
CVI has a considerable socioeconomic impact in Western countries due to its high prevalence, cost of investigations and treatment, and loss of working days.^{1 2} Varicose veins are present in 25% to 33% of female and 10% to 20% of male adults.^{3 4 5 6 7 8 9 10 11 12 13} In the Framingham study, the incidence of varicose veins per year was 2.6% in women and 1.9% in men.¹⁴ The prevalence of edema and skin changes such as hyperpigmentation and eczema due to CVI varies between 3.0%⁵ and 11%⁷ of the population.

Venous ulcers occur in 0.3% of the adult population in Western countries.^{5 9 15 16 17 18 19 20 21 22} The prevalence of active and healed ulcers combined is 1%.^{23 24} Healing of venous ulcers may be delayed in patients of low socioeconomic class, those who are single, and especially in those who do not have central heating.²⁵ The overall prognosis of venous leg ulcers is poor: only 50% heal at 4 months,²⁶ 20% remain open at 2 years, and 8% remain open at 5 years.²⁷ The annual recurrence rate varies from 6% to 15%.^{28 29 30} In 1 study, 12.5% of patients with ulcers took early retirement because of continued disability.³¹ Data from the Brazilian Security System show that CVI is the 14th most-frequently quoted disease for temporary work absenteeism and the 32nd most frequent cause of permanent disability and public financial assistance.³²

The annual cost of venous ulcers has been estimated to be £400 to 600 million for the United Kingdom^{33 34} and >$1 billion for the United States.³⁵ The total cost of CVI to society, both direct and indirect, is estimated to be $1 billion (US dollars) in each of 3 European countries (Germany, France, and the United Kingdom).^{36 37}

	Pathophysiology of CVI

Top Abstract Introduction Magnitude of the Problem Pathophysiology of CVI Methods of Investigation Application of Methods in... Investigation of Congenital... Appendix 1 References

 
The symptoms and signs of CVI are produced by ambulatory venous hypertension, which is itself the result of obstruction, reflux, or a combination.

Changes in the Major Veins
Varicose veins are the most common manifestation of CVI. It is believed that they are usually due to abnormal distensibility of connective tissue in the vein wall. Early work has suggested that veins from patients with varicosities are more distensible than those from patients with normal veins,³⁸ indicating a probable systemic basis for the abnormality. Varicosities usually start at points where superficial veins communicate with deep veins, particularly at the saphenofemoral and saphenopopliteal junctions and in the perforating system, because of valvular incompetence. Primary varicose veins result from venous dilatation without previous thrombosis. Secondary varicose veins are caused by valvular damage after deep vein thrombosis (DVT) and recanalization that gives rise to incompetent deep and perforating veins. Sometimes, varicose veins may be associated with reflux through vulvar varices without any relation to the saphenofemoral junction or other deep-to-superficial reflux in the lower limb. Such varices also may be associated with clinical symptoms and signs suggestive of pelvic congestion, including uterine retroversion and dyspareunia. They are more common in women who have had several pregnancies and had had hemorrhoids and vulvar varicosities during and after pregnancy.^{39 40 41} Poor venous drainage and resulting venous hypertension increase transmural pressure in postcapillary vessels, producing skin capillary damage, fluid exudation, edema, and tissue malnutrition, which favors inflammation, infection, thrombosis, and tissue necrosis with lipodermatosclerosis and eventual ulceration.^{42 43 44}

Reflux in deep veins can be due to past venous thrombosis and recanalization with destruction of venous valves, but it can also be idiopathic. Descending phlebography in limbs with deep venous reflux detected with duplex scanning fails to show any evidence of a previous DVT in 30% of cases. In such limbs, reflux is the result of floppy valve cusps, valvular agenesis, or aplasia.^{45 46 47}

Outflow obstruction can result from DVT without adequate subsequent recanalization and with poor development of collaterals. Less frequently, obstruction results from extramural venous compression^{48 49} or from congenital agenesis or hypoplasia of the femoral or iliac veins.⁵⁰ Left common iliac vein compression by the right common iliac artery is the most frequent type of external obstruction seen in young subjects.^{51 52 53 54}

Nearly 30% of fractures of the lower extremities result in venous thrombosis and postthrombotic sequelae.^{55 56 57 58 59} During military conflicts, severe injuries often involve major veins of the lower extremity. The long-term sequelae of postthrombotic changes become evident only many years after such injuries.^{60 61}

Venous recanalization occurs in 50% to 80% of patients several months or even years after DVT.^{62 63 64 65 66 67 68 69} Rapid recanalization after DVT is associated with a higher incidence of valve competency.⁶⁶ The chronic sequelae of DVT are most often ascribed to reflux rather than to obstruction.^{70 71 72 73}

Several studies have investigated the relationship among acute DVT, long-term venous hemodynamic disturbances and the incidence of the postthrombotic syndrome.^{72 74 75 76 77 78 79 80 81 82 83 84 85 86} In these studies, the incidence of the postthrombotic syndrome was 35% to 69% at 3 years after DVT and 49% to 100% at 5 to 10 years, depending on the extent of the thrombosis. The incidence of the postthrombotic syndrome and the severity of the hemodynamic abnormalities increased when the popliteal or more proximal veins were involved in the original thrombotic episode. Patients with both chronic obstruction and reflux have the highest incidence of skin changes or ulceration.⁸⁶ Ulceration was more frequent in patients with recurrent DVT.⁸⁷ In recent studies in which patients with proximal thrombosis have been treated with adequate anticoagulation, early mobilization, and long-term prophylaxis with elastic compression, skin changes or ulceration were present in 4% to 8% depending on the severity of the hemodynamic changes, duration of follow-up, use of effective compression therapy, local hygiene, and the cause.^{88 89}

Microcirculation: The Final Target of Venous Hypertension
New noninvasive techniques, such as laser Doppler,^{90 91} measurements of transcutaneous PO₂⁹² and interstitial pressure,⁹³ capillaroscopy,⁹⁴ and microlymphography,⁹⁵ provide the means to study the extent of changes in the skin microcirculation of limbs with CVI.

The blood capillary circulation is often severely impaired in limbs with CVI,^{96 97} leading to skin changes, eczema, and ulceration. Changes in skin capillaries may be moderate in patients with mild venous insufficiency. The capillaries become markedly dilated, elongated, and tortuous, especially at skin sites with hyperpigmentation and lipodermatosclerosis, and in patients with insufficiency of the perforating veins or the deep venous system. These changes are associated with a high microvascular blood flow.^{98 99 100 101 102} As a late phenomenon, capillary thromboses successively lead to a reduction in nutritional skin capillaries and transcutaneous PO₂, predisposing the patient to ulceration.^{94 103}

A striking finding in the skin of patients with CVI is a "halo" formation around the dilated capillaries observed on capillaroscopy. This is associated with microedema and pericapillary fibrin,¹⁰⁴ which possibly prevent normal nutrition to the skin cells as part of the final process in the development of venous leg ulcers.^{96 97}

Microangiopathy in lymphatics plays an important role (see Capillaroscopy) in the pathophysiology of skin changes and venous leg ulcers.^{105 106} Another finding is that white cells accumulate in legs with CVI on dependency.¹⁰⁷ Indirect evidence suggests that this finding could be the result of leukocyte activation^{108 109 110} and adhesion to the endothelium.^{111 112} The implications for the development of capillary loss and venous ulceration require further evaluation.¹¹³

Associated Hematological Changes
Since the late 1970s, many studies in patients with CVI have shown progressive changes in fibrinogen and associated blood properties, and impaired fibrinolysis.

Since the original observation of pericapillary fibrin deposits,¹⁰⁴ increased plasma fibrinogen levels have frequently been observed in patients with CVI.^{114 115} Elevated fibrinogen degradation products, particularly in patients with ulcers, indicate a rapid turnover of the macromolecule.¹¹⁶ Increased fibrinogen transport due to venous hypertension, high endothelial permeability, and plasma leakage found in such patients leads to significantly higher amounts of lymph fibrinogen than those found in normal subjects.¹¹⁷ Subsequent impaired fibrinolysis leads to hyperfibrinogenemia. Finally, although hyperfibrinogenemia can be related to aging and vascular risk factors, CVI is likely to play an independent role in the enhancement of the fibrinogen level.¹¹⁵

Elevated plasma fibrinogen levels are alleged to be the cause of rheological changes in viscosity and red cell aggregation.^{114 118 119 120} Whether fibrinogen-related red cell aggregates in the microcirculation are an additional factor in the pathogenesis of CVI is not known.

Impaired fibrinolysis has been determined in several studies in all kinds of patients with varicosities^{121 122} and venous disease with and without skin lesions.^{123 124 125} The precise mechanism for the defect in fibrinolysis in the majority of patients appears to be an increase in the inhibitor plasminogen activator-1 (PAI-1) ("poor responders" type I).^{126 127 128} A defect in tissue plasminogen activator ("poor responders" type II) is infrequent.¹²⁷ PAI-1 is synthesized by the endothelium, particularly that of microvessels, and by smooth muscle cells of the microvessel walls. It is released by mechanical stress due to venous hypertension and by hypoxia. The maximum effect of this inhibitor occurs in lipodermatosclerosis, which favors the hypothesis of an important role for the affected microvessels in the skin. PAI-1 may therefore be considered a marker for damage to the skin microcirculation.^{126 127 128}

The rheological and fibrinolytic disorders are strongly correlated in CVI, particularly the PAI-1 levels and red cell aggregation. The red cell aggregation index is increased proportionally to the severity of the CVI.¹²⁷ Hyperfibrinogenemia, enhanced erythrocyte aggregation, and hypofibrinolysis may be interrelated factors, with their main effect being damage of the skin of the lower limbs. In patients with CVI, there is a risk of subsequent thrombosis in association with hypofibrinolysis when the PAI-1 levels become very high.¹²⁹

Other hematological alterations in CVI have not been fully explored. Abnormal levels of tissue factor can be detected in patients with CVI and functional tissue factor pathway inhibitor levels are decreased to create a thrombogenic state.¹³⁰ Soluble thrombomodulin levels are increased in CVI, suggesting endothelial dysfunction. The severity of CVI is also proportional to the inflammatory response.^{101 128 131 132} The tissue factor pathway inhibitor has anti-inflammatory properties. Initial investigations have shown upregulation of tissue factor, resulting in increased consumption of tissue factor pathway inhibitor.

In patients with long-term skin damage (lipodermatosclerosis), immunohistochemical studies have shown that capillaries of the papillary plexus in the skin are surrounded by an infiltrate of inflammatory cells (macrophages and T-lymphocytes), as well as the fibrin cuff.¹³³ The exact role of these cells is unclear, but they probably are important in the clinical changes seen in the skin.

Diagnostic Challenge
A careful clinical history and examination should reveal the patient’s symptoms, their severity, and whether they are due to venous disease rather than to coexisting nonvenous musculoskeletal, arterial, or neurological pathology. Subsequent noninvasive or, in some cases invasive, investigations may be required to confirm the clinical assessment.

The classic tourniquet tests provide some information about the sites of deep-to-superficial reflux, but they are difficult to interpret when varicose veins are not prominent and offer little information as to whether there is obstruction or reflux in the deep veins. They have been complemented by examination with hand-held continuous-wave Doppler; as a result, it is now realized that many "recurrent" varicose veins are the result of unsuspected incompetent perforating veins or reflux in the short saphenous vein.

Because the history and clinical examination will not always indicate the nature and extent of the underlying abnormality (anatomic extent, pathology, and cause), a number of diagnostic investigations have been developed.^{134 135 136} Provided they are performed and interpreted by physicians or technologists who have a good knowledge of venous disease, they can provide qualitative and quantitative information and offer answers to most questions posed in clinical practice. They can be used to elucidate whether there is calf muscle pump dysfunction and determine the anatomic extent and severity of obstruction or reflux. The difficulty in deciding which investigations to use and how to interpret the results has stimulated the development of this consensus document. The aim of this document was to provide an account of these tests, with an outline of their usefulness and limitations and indications of which patients should be subjected to the tests and when and of what clinical decisions can be made.

	Methods of Investigation

Top Abstract Introduction Magnitude of the Problem Pathophysiology of CVI Methods of Investigation Application of Methods in... Investigation of Congenital... Appendix 1 References

 
Tests That Provide Information on Morphology
Ascending Phlebography
Until recently, ascending phlebography has been the method of choice to demonstrate patency of the veins, define the anatomy, and help to distinguish between primary and secondary disease. A second role has been to detect incompetent perforating veins. It is still used as the "gold standard" to establish the accuracy of new investigations that determine the presence or absence of disease or its anatomic extent. However, the development of several noninvasive tests, particularly duplex scanning, now makes it unnecessary in most cases. Its current application is limited to cases in which duplex scanning is unavailable, inadequate, or equivocal.

The examination is performed by injecting contrast medium into a vein on the dorsum of the foot and directing it into the deep veins with an ankle tourniquet. The ascent of the contrast is slowed down by a second midthigh cuff or by having the patient in a semierect position with use of a tilting table. It is possible to demonstrate deep veins consistently from the muscular veins in the calf up to the inferior vena cava but not the internal iliac or profunda femoris veins.^{137 138 139 140 141} Good visualization of iliac veins and the inferior vena cava may require a percutaneous injection of contrast into the femoral vein combined with the Valsalva maneuver.

The phlebographic criterion for the diagnosis of DVT established by DeWeese and Rogoff¹⁴² is the presence of well-defined filling defects in opacified veins demonstrated on 2 radiographs. This criterion is also valid for chronic obstruction. Nonvisualization of 1 calf veins is not considered diagnostic of thrombosis because frequently not all of these veins are visualized in normal limbs. Nonvisualization of a calf vein or a more proximal vein with good opacification of its proximal and distal parts in the presence of collateral vessels is evidence of thrombotic obstruction.

Loose thrombus appears as a cylindrical filling defect surrounded by a thin white line of contrast medium. Obliteration of the white line indicates adherence to the vein wall. Use of the image intensifier to obtain several views just before and after a Valsalva maneuver helps to distinguish most artifacts from thrombosis. Fresh thrombus fills most of the venous lumen but is not adherent to the wall. Old thrombus with recanalization produces irregularity of the venous wall. Incompetent perforating veins can be identified by the flow of contrast medium from deep to superficial veins.

Although phlebography has been deemed the gold standard in the detection of the presence, site, and anatomic extent of chronic venous obstruction, it cannot provide a quantitative functional assessment of its severity or the adequacy of collateral veins.¹⁴³

Descending Phlebography
The aim of descending phlebography is to demonstrate reflux in either the superficial or deep veins and to determine the points of leakage from the pelvis to the lower limbs and from deep to superficial veins. It also is used to provide information on the anatomic localization and morphology of the venous valves, assess the extent of reflux, delineate the venous anatomy in complex cases, and differentiate primary from secondary disease. The criticism that descending phlebography is a nonphysiological test because it involves the use of contrast agents that are heavier than blood merits recognition, but this does not invalidate the observations that are gained from a careful study.

Descending phlebography can be performed by introducing a cannula through a brachial, contralateral, or ipsilateral femoral¹⁴⁴ or popliteal¹⁴⁵ vein and injecting contrast medium with the patient in the standing position with the use of a tilting table. A Valsalva maneuver is required to elicit valve closure. A popliteal injection is necessary if distal reflux is suspected in the presence of competent proximal valves. Repeated boluses of contrast medium are injected with serial or continuous recording. The competence of deep veins as well as the deep-to-superficial junctions is assessed by determining the extent and duration of distal reflux of contrast medium. Several variations in the technique of phlebography have been described.^{46 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158}

Five grades of phlebographic reflux (0 to 4) have been described as follows^{151 153 154} : grade 0 indicates no reflux below the confluence of the superficial femoral and profunda femoris veins; grade 1, reflux into the superficial femoral vein but not below the middle of the thigh; grade 2, reflux into the superficial femoral vein but not through the popliteal vein, demonstrating competent popliteal valves; grade 3, reflux to a level just below the knee, indicating incompetent popliteal valves, but competent valves in the axial calf veins; and grade 4, reflux through the axial veins (femoral, popliteal, and calf) to the level of the ankle. Pathological reflux through the popliteal vein has been shown to be associated with symptoms, but the association is not clear cut.¹⁵³

The disadvantages of descending phlebography are that it is invasive and costly and has potential complications. The development of duplex scanning that can be used to detect the presence and anatomic extent of reflux has resulted in a decrease in the number of descending phlebograms. The latter are now performed mainly when deep venous reconstruction is being considered or before redo surgery for varicose veins when duplex scanning is not conclusive.

Varicography
Varicography involves the direct injection of contrast medium through a butterfly cannula into the superficial vein under investigation. It is a simple and valuable technique that can supplement ascending phlebography. It has a particularly valuable clinical role, not so much in primary varicose veins but rather in the elucidation of the anatomic connections of recurrent varicose veins as a "road map" to guide the surgeon.¹⁵⁹ On the operating table, it facilitates the use of minimal incisions and precise surgery.^{160 161 162} It is also used to define abnormal drainage patterns in patients with venous malformations.⁵⁰

Per-uterine Phlebography
Per-uterine phlebography has been used to demonstrate veins in the broad ligaments, ovarian plexus, and ovarian veins in patients with a suspected pelvic congestion syndrome.¹⁶³ After injection directly into the fundus of the uterus, pressure over the iliac fossa shows contrast filling the contralateral ovarian vein.^{164 165 166}

Selective Ovarian and Internal Iliac Phlebography
Selective ovarian and internal iliac phlebography are used to investigate patients with leg varices that fill from vulvar veins and who are suspected to have incompetence of the ovarian veins with reflux into the vulvar veins via the internal iliac. In such patients, the finding of bilateral ovarian reflux is often associated with the pelvic congestion syndrome.¹⁶³

The ovarian veins are investigated with selective catheterization via the basilic, right femoral, or internal jugular veins.¹⁴¹ After the injection of contrast medium, reflux is demonstrated by tilting the table or by a Valsalva maneuver. Contrast from either ovarian vein fills large varices in both the broad ligaments of the uterus and then passes through the obturator and internal pudendal veins to fill varices in the thigh and even to extend down to the calf. Sometimes, injection into 1 ovarian vein can be seen to reflux down both legs. Contrast medium may be returned to the pelvic varices and ovarian vein by reversing the table tilt. During this investigation, the internal iliac veins may also be catheterized to assess this possible source of reflux.¹⁶⁷ The description of ultrasound windows to abdominal and pelvic veins has made duplex scanning an alternative investigation.¹⁶⁸

The complications of all types of phlebography are pain, contrast extravasation, deterioration of renal function, localized infection, idiosyncratic reactions, and venous thrombosis.¹⁶⁹ Pain is alleviated by administering an analgesic agent to the patient and slowly injecting the contrast medium. Minimal pain, tenderness, or swelling on the day after the phlebogram are rarely severe and clear within days. The incidence of phlebographically induced thrombosis is reduced by flushing the veins with heparinized saline at the end of the examination. Nonionic contrast media should be used to minimize these complications.¹⁷⁰

Duplex Scanning
Duplex scanning has been used since the early 1980s to diagnose DVT.^{171 172 173 174} Its use has now been extended to detect obstruction or reflux and to determine their anatomic extent in CVI.^{175 176 177} Color flow duplex imaging provides instant visualization of blood flow and its direction and has decreased examination time and improved its accuracy. It has become conventional to show cephalad flow as blue and distal flow as red.

A 4- to 7-MHz multifrequency transducer is used. The saphenofemoral junction is examined first with the patient standing, facing the examiner, and holding onto a frame, with most of the weight placed on the opposite limb. Holding onto a frame provides stability and prevents muscle contractions, which produce blood velocity artifacts.¹⁷⁷ An alternative method would be to examine the patient in the 15° reverse Trendelenburg position with the Valsalva maneuver to elicit reflux, specifically for the examination of thigh veins.¹⁷⁸ This method produces similar results to those achieved when a pneumatic cuff is placed below the level of interrogation and reflux is measured after rapid deflation with the patient in the standing position. The advantage of the Valsalva maneuver in the 15° reversed Trendelenburg position is that it provides comfort for both patient and examiner. The disadvantage is that the test is dependent on a cooperative patient who is able to perform the maneuver.

The probe is placed longitudinally over the groin so that the distended femoral vein, the long saphenous vein, and their junction can be identified. If there is any difficulty, one can start with a transverse image, identify the 2 veins, and then visualize them longitudinally.¹⁷⁷ Several features identify a normal vein; they include red cell aggregates shown as echogenic intraluminar structures that move slowly cephalad,^{179 180 181} movement of venous valve cusps phasic with respiration, smooth lining of the venous wall, and approximation of the anterior and posterior walls with compression. High echoes in the lumen, irregular walls, and failure to fully approximate the walls by compression indicate old thrombosis with or without recanalization.

Additional help in the elucidation of the anatomy and pathology is provided with color-flow duplex imaging. In normal veins, cephalad flow phasic with respiration is indicated by the blue color in the lumen. This is enhanced with distal thigh or calf compression. On release of the compression, reflux is shown as red that lasts for >0.5 second.^{182 183 184} In the absence of reflux, the lumen is black. In the presence of old thrombosis with recanalization, color-flow imaging shows blue among the luminal echoes on distal limb compression and red on release of the compression. The extent of venous changes can be determined by repeating these maneuvers throughout the length of the leg. If there is iliac occlusion, collateral circulation in the groin with suprapubic flow that crosses to the opposite groin can be visualized.

The short saphenous and popliteal veins are examined with the patient standing and facing away from the examiner and holding onto the frame. An alternative position is to sit on the edge of a couch with the foot on a chair or stool. In this position, both the popliteal and calf veins can be examined with comfort for both the patient and the examiner.¹⁷⁷ The probe is placed over the popliteal fossa longitudinally to image the popliteal artery, which lies deepest; the popliteal vein lies more superficially and parallel to it; and the short saphenous vein is the most superficial. The main gastrocnemial veins (medial and lateral) are seen in the gastrocnemius muscle between the short saphenous and popliteal veins. The sites and levels of the junctions of these veins in relation to each other and the popliteal vein are identified. If an operation is contemplated, these levels can be marked on the skin. This is very helpful in view of the variable anatomy of the popliteal fossa.^{185 186} Features of normality, chronic obstruction with or without recanalization, or reflux are identical to those mentioned earlier.

The posterior tibial and peroneal veins can also be tested for reflux with anterolateral or posteromedial views.¹⁷⁷ They are usually paired, lying on each side of the corresponding artery. Cephalad flow or reflux can be identified with compression of the foot or lower calf followed by sudden release.

Incompetent perforating veins are identified by sliding the transducer up and down the leg with dilated superficial varicose veins imaged in transverse section. A perforating vein appears as a vessel that joins the superficial vein being examined with a deep vein. At this point, the probe is held still, the color flow is switched on, and distal compression is performed. The presence of 1 color (eg, blue) on compression with a different color on release (eg, red) indicates reflux. Reflux is diagnosed by outward flow that lasts >0.5 second. Although duplex scanning can localize incompetent perforating veins, there is considerable controversy as to whether it can be used to assess their hemodynamic significance.^{187 188 189 190 191}

Duplex scanning is operator dependent, and imaging can be difficult in certain circumstances, especially when operating above the inguinal ligament, in obese patients, and in those with swollen legs, in which case phlebography may be a better choice.^{192 193 194}

Recent Applications of Duplex Scanning: New Messages That Have Emerged

Duplex Scanning in the Study of the Natural History of Thrombi. Recent studies have shown that duplex scanning is an ideal method for serial examinations to monitor the evolution of thrombi and to check for the appearance of reflux after acute DVT.^{66 67 68 69 195 196} These studies indicate that reflux develops progressively and that even a complete occlusion may alternately partially recanalize and reocclude before a final complete recanalization. However, the factors that cause reflux to develop in some patients and not in others remain unclear.

The process and rate of organization of a thrombus may have the potential to identify those patients most at risk of developing late symptoms. Analysis of echogenicity of thrombi in vivo shows that the organizational process and rate of thrombolysis differ greatly from patient to patient.^{68 69} The resolution of thrombi follows 1 of 3 distinctive sequences: (1) rapid spontaneous thrombolysis, which preserves valvular function and returns the vein to its normal appearance; (2) increasing echogenicity, indicating fibrosis of a thrombus that remains occlusive, with or without evidence of collateral veins and with no symptoms at 1 year; and (3) slow recanalization that causes the destruction of valves, resulting in reflux and early postthrombotic symptoms.

Relationship Between Anatomic Extent of Reflux and Grade of Chronic Venous Disease.
Duplex scanning is a very sensitive diagnostic method. It can show whether reflux is in the deep, superficial, or perforating veins or in any combination thereof. It can detect small amounts of reflux in isolated segments of veins often present in "normal" asymptomatic individuals. It can determine whether reflux is confined to a vein above or below the knee or whether it extends throughout the whole limb.

In the absence of deep venous obstruction, limbs with reflux confined to the proximal (above knee) veins rarely develop skin changes or ulceration.^{197 198} In contrast, even in the presence of normal deep veins, symptoms and signs of CVI are more often found when the entire length of the greater saphenous vein is involved or when reflux is present in both the long and short saphenous veins.^{197 198} Multisegmental reflux is significantly more prevalent in legs with ulcers than in nonulcerated limbs (75% versus 22%).¹⁹⁹ A pattern of reflux that involves 2 of the venous systems (superficial and deep; superficial and perforating; or superficial, perforating, and deep) is found in about two thirds of patients with skin changes or ulceration.^{198 199 200 201 202}

The available data suggest that there is a strong association between the severity of CVI and the anatomic distribution and extent of venous reflux.²⁰³ However, the information is fragmented in multiple studies that use different classifications and reporting methods. Therefore, further studies with uniform criteria that combine the anatomic information provided by duplex scanning and pressure or plethysmographic quantitative measurements are needed to establish such an association.

Significance of Gastrocnemial Reflux.
The importance of gastrocnemial reflux was recognized by Dodd^{204 205} and May and Nissl⁶⁴ but has only recently obtained general recognition as a cause of primary venous insufficiency and, more important, as a common cause of recurrence.^{206 207 208}

When gastrocnemial vein incompetence is suspected, the demonstration of reflux by duplex scanning is mandatory because reflux can be eliminated by surgical ligation.^{206 209 210 211}

Liquid Crystal Thermography
Thermography immediately after a tiptoe exercise demonstrates incompetent perforating veins as "hot spots."^{212 213 214 215} When compared with operative findings and phlebography, it has a sensitivity of 94% and 98%, respectively.^{216 217} The recent development of liquid crystal thermographic plates¹⁷⁴ has simplified the method, so it can be used as a screening test to localize incompetent perforators.²¹⁸ The liquid crystal thermographic plates are applied to the thigh and leg after 20 tiptoe movements. Incompetent perforating veins appear as clearly defined hot spots. Compared with duplex scanning, the positive predictive value of this test is 91%.²¹⁸ It appears that liquid crystal thermography is an accurate, simple, relatively inexpensive, and rapid method that allows preoperative marking of incompetent perforating veins without resorting to duplex scanning.

Tests That Provide Hemodynamic Information
Ambulatory Venous Pressure
Ambulatory venous pressure (AVP) measurements can supplement the anatomic information provided by phlebography. The test is based on the original observation made in the 1940s that the venous pressure in the foot decreases during walking²¹⁹ and gradually returns to the resting value when walking stops. It has been used extensively in Scandinavian countries to evaluate venous pathophysiology.^{220 221 222 223 224} In the 1970s and 1980s, AVP measurements became the hemodynamic gold standard used in the development of noninvasive methods for screening and diagnostic evaluation.^{225 226 227 228 229 230}

Venous pressure is measured by inserting a needle into a vein on the dorsum of the foot; the needle is then connected through a pressure transducer and an amplifier to a potentiometric pen recorder. It has been suggested that erroneous results may be obtained if there is a competent valve in the foot and that the needle may have to be replaced in the lower leg.²³¹ The patient supports himself of herself in the standing position by holding onto an orthopedic frame so the resting pressure is recorded. Holding the frame prevents contractions of the calf muscle, which may produce artifacts during the resting period before and immediately after exercise. The patient then performs a standard exercise of 10 tiptoe movements²³⁰ or knee bends²²⁷ at the rate of 1 per second, synchronous with a metronome. Walking on a treadmill is technically more difficult to perform but can be taken as a reference stress test. An alternative method with 10 manual compressions of the calf performed by the examiner has been shown to be more reproducible than the classical tiptoe method.^{178 232} At the end of the exercise, the patient remains still while recovery of the pressure to baseline level is recorded in seconds. The exercise is then repeated after either the inflation of a 2.5-cm-wide pneumatic cuff at the ankle or the use of digital compression to occlude the superficial veins. The width of the cuff is critical because wider cuffs tend to compress deep as well as superficial veins. Likely sites of deep-to-superficial reflux may be determined by repeating the exercise with the cuff positioned just below the knee and at the lower and upper thigh.²³⁰ However, the use of tourniquets to attempt to occlude the superficial veins does not reliably differentiate between deep and superficial venous reflux.²³³

AVP is the best method to assess venous hypertension. The pressure at rest (P₀), the mean AVP during the steady state toward the end of the 10 tiptoe movements (P₁₀), the calculated difference of the 2 pressures (P₀-P₁₀) (Table 1), and the RT are the most useful measurements. Because of the exponential character of the refilling curve, it is much easier and more accurate to define the 50% (t/2) or the 90% RT than the 100% RT. Considerable variation has been found within normal groups as well as overlapping values between limbs with primary varicose veins or with the postthrombotic syndrome (Table 1). P₁₀ is considered to be a measure of the severity of venous hypertension regardless of whether the latter results from obstruction or reflux in the superficial or deep venous systems or both.²³⁴ Values of P₁₀ in different pathoanatomic states are shown in Table 2, the relationship of P₁₀ with the prevalence of ulceration is shown in Table 3, and the range of values of 90% RT in limbs with different pathology identified with phlebography is shown in Table 4.

View this table: [in this window] [in a new window]   Table 1. AVP P10 and Change in Pressure After 10 Tiptoe Movements in Different Groups of Patients

View this table: [in this window] [in a new window]   Table 2. Values of AVP P10

View this table: [in this window] [in a new window]   Table 3. Prevalence of Leg Ulceration (Active or Healed) in Relation to AVP (P10) in 251 Limbs

View this table: [in this window] [in a new window]   Table 4. Values of Venous Pressure 90% Refilling Time

If there is severe outflow obstruction and extensive deep venous reflux, including reflux in the popliteal vein, P₁₀ may actually become higher than P₀ because of the increased blood flow and venous volume due to exercise hyperemia. This is characteristic of a group of patients who complain of "bursting" pain on walking (venous claudication). In another subgroup with outflow obstruction and competent popliteal valves, venous pressure in the foot may become normal during exercise because the valves protect the leg despite the proximal occlusion, although extremely high pressures may develop in the veins in the thigh.

Because AVP testing is invasive, it cannot be repeated frequently or used for screening. Noninvasive screening tests such as photoplethysmography (PPG), Doppler ultrasound, air-plethysmography, and foot volumetry are more frequently used for routine investigation. Nevertheless, AVP testing remains the gold standard for the assessment of overall hemodynamic function and for validation of noninvasive tests. As a research tool, it must be used to assess the hemodynamic effect of surgical reconstructive procedures in the deep veins to develop criteria for improved selection of patients.

An attempt was made to correlate AVP with the grades of reflux defined by descending phlebography in patients with skin changes or ulceration.²³⁵ If the popliteal valves were competent (grades 0 to 2), the range of AVP was 32 to 68 (mean 48) mm Hg, and an ankle tourniquet to eliminate superficial reflux resulted in an AVP of <45 mm Hg in all limbs. However, if the popliteal valves were incompetent (grades 3 and 4), the range of AVP was 50 to 95 (mean 72) mm Hg, and the application of an ankle tourniquet had little effect.

Femoral Vein Pressure Measurements
This method is used to determine the severity of iliocaval obstruction. A needle or catheter is inserted into the common femoral vein, and pressures are measured in the supine or semierect position at rest and after exercise. Exercise can be performed with 10 active dorsiflexions of the foot or 20 calf muscle contractions. Elevated pressures after exercise are related to the severity of venous occlusion,²³⁶ but no set standards are available for femoral vein pressure parameters.^{237 238} Early investigations suggested that a pressure difference of 2 mm Hg between the femoral vein pressure and central venous pressure at rest and an increase of >3 mm Hg after exercise were associated with a significant proximal occlusion.²³⁹ A 3-fold increase in femoral vein pressure after exercise indicated an uncompensated proximal occlusion. More recently, a pressure difference of 5 mm Hg between the femoral and central venous pressures at rest in the supine position has been considered indicative of a significant proximal venous occlusion that requires surgical reconstruction.²⁴⁰

Arm/Foot Pressure Differential
The arm/foot pressure differential (p) provides hemodynamic information on the severity of obstruction and the adequacy of recanalization or of the collateral circulation.^{241 242} Venous pressures are recorded simultaneously in a vein of the foot and a vein in the hand, with the patient supine, and then repeated during reactive hyperemia or after the injection of papaverine.^{243 244} With these measurements, limbs with venous obstruction can be classified into 1 of 4 grades (Table 5). The more proximal the obstruction, the poorer is the compensation and the higher is the grade. The technique provides a global measurement of hemodynamic obstruction due to outflow occlusion in 1 vein. Venous obstruction involves >1 anatomic segment in 75% of limbs,¹⁴⁵ and additional direct femoral pressure measurements may be necessary for a more precise assessment of functional obstruction.

View this table: [in this window] [in a new window]   Table 5. Arm/Foot Pressure Differential in Limbs With Outflow Obstruction

This method has the disadvantage of being invasive in that it require 2 venipunctures. The technique has been compared with measurements of resistance and outflow fraction, with conflicting results in 2 studies.^{245 246}

In clinical practice, the main value of the method is to help select patients for venous reconstruction. A bypass procedure is not indicated unless a high arm/foot pressure differential (grade 3 or 4 obstruction) is present.²⁴¹

PPG, Light Reflection Rheography, and Quantitative Digital PPG
PPG and light reflection rheography are noninvasive techniques that can detect local changes in the blood content of tissues. The principal application is to study blood flow and blood volume changes in the skin.^{247 248 249 250 251 252 253} A probe that consists of a light source and a light-sensitive diode is positioned on the skin. Although skin is essentially opaque to light, slight light transmission and backscattering do occur in the range of the visible and infrared light spectrum. The backscatter of light detected with the light-sensitive diode is affected by changes in the number of red blood cells in the dermis. Red blood cells absorb maximum light in the sitting or standing position when the pressure is high and the veins are full. Venous plexuses become less full and light absorption decreases as the venous pressure falls with exercise.

PPG Evaluation of Venous Reflux and Ejecting Capacity of the Calf Muscle Pump
In practice, the PPG probe can be fixed to the leg with transparent adhesive tape some centimeters proximal to the medial malleolus or to the dorsum of the foot. The PPG is set at zero once a resting baseline is achieved, and venous emptying is then produced through repeated dorsiflexion and plantar flexion of the foot. Most investigators perform this with the patient sitting on a couch with the legs vertical.^{247 254 255 256 257 258} Others prefer the standing position and tiptoeing 10 times to empty the veins.²⁵² When standing, it is essential for the patient to hold onto an orthopedic frame or table so artifacts from leg muscle contractions during the refilling period are avoided. When the test was performed in both the standing and sitting positions in the same patients, a better separation was obtained between patient groups when the patients were standing²⁵² (Figure 1).

View larger version (18K): [in this window] [in a new window]   Figure 1. PPG-RT in normal limbs, limbs with superficial venous incompetence (SVI), and limbs with deep venous incompetence (DVI) in sitting and standing position (median and 90% range). Reproduced with permission from Nicolaides and Sumner.245

In the 1980s, PPG had a limited application for quantitative measurements because of the inability to calibrate the signal and failure of the recorded signal to return to the same baseline. Only postexercise RT measurements were reproducible. A high degree of linear relationship was found for RTs measured with the simultaneous use of both PPG and venous pressure in 4 studies (r=0.93, 0.96, 0.98, and 0.88, respectively),^{247 252 259 260} but this was not reproduced in a fifth study (r=0.41).²⁶¹

In practice, PPG is performed with a diagnostic algorithm shown in Figure 2 when valvular incompetence is suspected. If the venous RT (VRT) is abnormally short (<20 seconds in the sitting position²⁴⁷ or 25 seconds^{256 257 258} or 18 seconds in the standing position²⁵² ), the test may be repeated after inflating a narrow (2.5 cm wide) cuff at the ankle or below the knee to occlude the superficial veins. Failure of the cuff to normalize the RT suggests deep venous or perforator incompetence. Normalization of the RT after occlusion of the superficial veins suggests that reflux is confined to the superficial venous system and that the deep veins have competent valves.^{245 252 258}

View larger version (21K): [in this window] [in a new window]   Figure 2. Relationship between PPG RT and mean AVP obtained in standing position (•, normal limbs; , limbs with superficial venous incompetence; , limbs with deep venous incompetence). Reproduced with permission from Nicolaides and Sumner.245

Although the PPG RT without and with occlusion of superficial veins can help to distinguish among limbs without major venous pathology, limbs with superficial venous incompetence, and limbs with deep venous incompetence, it is not considered to be a good indicator of the severity of deep venous insufficiency.^{262 263} Any AVP in the range of 45 to 100 mm Hg can be associated with a short RT of 2 to 10 seconds²⁵² (Figure 3) because RT depends on several factors, including the diameter of the vein in which the reflux occurs and the size of the reservoir to be filled. A long RT may be observed when reflux occurs in small-diameter veins despite a low volume reflux. In contrast, when reflux occurs in large-diameter veins in which the volume flow is large and the reservoir is filled rapidly, reflux can be very short. The PPG RT reflects regional rather than overall venous hemodynamics in the limb. It is related more to superficial than to deep venous insufficiency.²⁶⁴ An abnormally short RT in the absence of reflux in the main superficial trunks or deep veins on duplex examination suggests reflux through pelvic and vulvar veins.²⁶⁵ It is hardly surprising that PPG RTs correlate poorly with other methods.^{263 266}

View larger version (10K): [in this window] [in a new window]   Figure 3. Algorithm showing that RT and its changes with application of cuffs to occlude superficial veins is a practical diagnostic tool. Reproduced with permission from Nicolaides and Sumner.245

PPG can be used for screening to detect CVI or to assess the overall physiological function of the lower limb veins without resorting to more invasive or expensive tests. Suspected reflux due to a short RT should always be confirmed with continuous-wave Doppler or, preferably, duplex scanning. The test should not be relied on to identify the anatomic distribution of disease.

Quantitative digital PPG^{255 256 257 258} is a more recent descendant of PPG. It incorporates modern computer technology with self-standardization and allows measurements of amplitude- as well as time-related parameters. Recent studies have demonstrated that these measurements have a better quantitative relationship with symptoms than conventional PPG or light reflection rheography (Figure 4).²⁵⁶ Evaluations of muscle pump efficiency and venous long-term monitoring are also possible with the quantitative PPG.²⁵³

View larger version (34K): [in this window] [in a new window]   Figure 4. Mean To and Vo values in patients with CVI. Stage I indicates skin complications absent; stage II, skin complications present but no venous ulcer; and stage III, presence of history of venous ulcer. Reproduced with permission from Schultz-Ehrenburg and Blazek.256

PPG Vein Occlusion Test: Evaluation of Venous Outflow Dynamics

The vein occlusion test measures VO during muscle rest. For the first time, it has become possible to measure VO rates with an optical sensor due to the calibration of the curve amplitude with quantitative PPG. The patient lies supine, with the extremity raised. The optical PPG sensor is attached to the inner or outer aspect of the lower leg. The entire measurement process is automatically conducted with quantitative digital PPG. Venous outflow is obstructed by means of a wide cuff (15 cm, 80 mm Hg) on the thigh for 2 minutes. In addition, a narrow cuff (2.5 cm, 80 mm Hg) is placed below the knee. The occlusion maneuver changes the optical properties of the skin by increasing the blood volume in the skin vessels, reflecting the changes in the total venous pool of the extremity. Among other parameters, venous capacity in PPG% and VO in PPG%/min can be determined from the resulting PPG curve. In the venous emptying phase, the outflow kinetics are measured over 30 seconds. VO gives the change in the PPG signal between 1 and 2 seconds after release of the occlusion. This change is >30%/min in healthy subjects.²⁵³ Although PPG is related more to superficial venous insufficiency, it is possible to assess deep VO dynamics when an additional narrow cuff is used, which forces the blood to make its way through the deep venous system. In the case of hemodynamically significant DVT or external tumor compression, the outflow value is reduced.²⁶⁷

Ambulatory Strain Gauge Plethysmography
Calf volume changes during exercise can be detected with strain gauge, and comparison with AVP measurements was proposed by Holm et al in 1974.²⁶⁸ Originally, the strain gauge was applied at midcalf level, and the exercise consisted of 5 tiptoe movements; it was later changed to 10.²⁶⁹ Other researchers used walking on a treadmill²⁷⁰ or dorsiflexion of the foot in the sitting position²⁷¹ as exercise. Alteration in the mode of exercise to knee bends, the application of double strain gauges in plastic chains (Gutmann strain gauges), and recording at the supramalleolar region reduced the coefficient of variation for repeated measurements on the same day and for day-to-day variation from 40% to 12%.²⁷²

Ambulatory strain gauge plethysmography (ASGP) is used to measure calf volume changes in the upright position without the need to change position from the supine to the upright. This avoids the venoarteriolar reflex, which causes precapillary arteriolar vasoconstriction that may influence the venous return time.²⁷³ Strain gauges are applied to both ankles above the malleolus to avoid artifacts related to calf muscle contraction. Strain gauges are electrically calibrated in situ to percentage volume change (mL/100 mL). The preferred exercise is in the form of 20 kneebends (knee flexion 60°) at a rate of 30 per minute. After the exercise, the patient must stand completely still until full-volume restitution takes place, which in a normal person occurs between 1 and 2 minutes after cessation of the exercise. The plethysmographic recording allows calculation of venous refilling time (RT) and expelled volume (EV). The second part of the examination involves the application of a below knee compression cuff that is 2.5 cm wide and inflated to a pressure of 70 mm Hg. In patients with isolated superficial venous reflux, this compression will normalize the venous return time. Reference values for normal controls are RT of 42 to 96 seconds and EV of 0.7 to 3.1 mL/100 mL.

The reproducibility for ASGP was calculated with ANOVA.²⁷² For consecutive measurements, the coefficients of variation for RT were 4.7% in normal limbs and 8.8% in limbs with CVI. Corresponding values for EV were 11.3% and 13.1%. The coefficients for day-to-day variation were 7.8% for RT and 11.5% for EV. The positive predictive value for the presence of CVI was 100% for both RT and EV, and the negative predictive value for absence of chronic venous disease was 94% for RT and 75% for EV.²⁷⁴ Thus, ASGP is suitable for screening to exclude venous disease.

AVP is the gold standard to which external volumetric methods refer. The coefficient of correlation between AVP and ASGP was 0.91 (P<0.001) for RT and 0.41 for EV (P<0.05), respectively, as determined in 41 patients and 8 normal control patients.²⁷³ The poor correlation between EV and AVP may be explained by possible variations in venous and tissue compliance that determine the shape of the pressure-volume relation curve; in addition, small EV leg changes reflect a high percentage of blood volume changes.^{275 276}

ASGP is used to quantify the performance of the venous muscle pump in terms of venous reflux and expelled volume. It may differentiate superficial from deep venous insufficiency, but it cannot precisely localize the site and extent of the reflux or obstruction in either system. For this purpose, duplex scanning with color flow imaging is required.

Symptoms of CVI such as pain, itching, swollen legs, pigmentation, heavy legs, and objective changes in the skin have been shown to correlate with the ASGP-derived parameters for venous muscle pump function.²⁷⁴ The lowest values of RT and EV were recorded in patients with venous ulceration.²⁷⁴

ASGP may be used to screen for and to quantify CVI.²⁷³ It may also be used to evaluate venous claudication.²⁷⁷ It can be used to differentiate between CVI and lymphedema.²⁷⁸ Although duplex scanning is excellent for localization and diagnosis of venous reflux, ASGP provides quantitative information and is suited for the assessment of surgical outcome²⁷⁴ and that of compression therapy.²⁷⁸ In 1 study, ASGP allowed a longitudinal follow-up and could demonstrate that venous function had progressively deteriorated through pregnancy but had normalized 3 months after term.²⁷⁹

Air-Plethysmography
Venous hypertension is the result of impaired venous return. The latter is often due to the combined effects of venous reflux, obstruction, and poor calf muscle pump function. Air-plethysmography has the ability to measure each of these 3 components and, by doing so, has improved the understanding of venous pathophysiology.

The air-plethysmograph consists of a 35-cm-long polyurethane tubular air chamber that surrounds the entire leg. The air chamber is inflated with air at 6 mm Hg and connected to a pressure transducer/amplifier and a recorder or computer. A syringe connected to the air circuit is used for calibration. Changes in the volume of the leg as a result of filling or emptying of veins produce corresponding changes in the pressure of the air chamber. Thus, leg volume changes can be measured in milliliters according to the calibration.²⁸⁰

Evaluation of Venous Reflux

With the patient supine, the leg is elevated 45° with the knee slightly flexed to empty the veins. After a plateau is reached (Figure 5), the patient is asked to stand up with the knee of the examined leg slightly flexed and the weight on the opposite leg. An increase in leg volume is observed due to venous filling. The functional venous volume (VV) is 80 to 150 mL in normal limbs and up to 400 mL in limbs with CVI.^{280 281} The ratio of 90% of VV by the time taken for 90% filling (VFT90) is defined as the venous filling index (VFI=90%VV/VFT90) (Figure 5). This is a measure of the average filling rate of the veins expressed in mL/s. The VFI is <2 mL/s in normal limbs in which the veins fill slowly from the arterial side. It may increase up to 30 mL/s in limbs with severe venous reflux.²⁸⁰ A VFI of >7 mL/min has a 73% sensitivity, a 100% specificity, and a 100% positive predictive value of identifying limbs with venous ulceration.²⁸² The prevalence of sequelae from CVI in relation to VFI is shown in Table 6. The prevalence of edema, skin changes, and ulceration increases with higher VFI regardless of whether the reflux is in the superficial or deep veins. When VFI measurements were repeated after surgery²⁸³ or after reflux in the superficial veins was abolished with finger compression of the long saphenous vein at the level of the knee, VFI was reduced to <5 mL/s in limbs with primary varicose veins but not in those with reflux in the deep veins (Figure 6). Reflux through the short saphenous vein is difficult to eliminate with finger compression.

View larger version (15K): [in this window] [in a new window]   Figure 5. Diagrammatic representation of typical recording of volume changes during standard sequence of postural changes and exercise. a, Patient in supine position with leg elevated 45 degrees. b, Patient standing with weight on nonexamined leg. c, Single tiptoe movement. d, Ten tiptoe movements. e, Return to resting standing position as in b. Reproduced with permission from Nicolaides and Sumner.245

View this table: [in this window] [in a new window]   Table 6. Prevalence of the Sequelae of Venous Disease in Relation to VFI in 134 Limbs With Venous Disease Studied With Air-Plethysmography

View larger version (10K): [in this window] [in a new window]   Figure 6. VFI (median and 90% range) without and with a tourniquet (T) that occluded superficial veins at knee in normal (N) limbs, limbs with primary varicose veins without sequelae of chronic venous disease (liposclerosis and ulceration) (PVV), limbs with primary varicose veins with sequelae of chronic venous disease (PVV/S), and limbs with popliteal reflux (PR). Reproduced with permission from Nicolaides and Sumner.245

Evaluation of the Ejecting Capacity of the Calf Muscle Pump
The patient is asked to do 1 tiptoe movement with the weight on both legs and to return to the initial position (Figure 5c). The recorded decrease represents the expelled volume (EV). The ejection fraction (EF) of the calf muscle pump is derived from the formula EF=[(EV/VV)x100]. EF is >60% in limbs without venous disease, 30% to 70% in limbs with primary varicose veins, and possibly as low as 10% in limbs with deep venous disease.²⁸⁰ The ejection capacity is as important as reflux for the development of venous ulceration. A good EF (>60%) was associated with a low incidence of ulceration despite marked reflux, and a poor EF (<40%) was found with ulceration in limbs with minimal reflux.²⁸¹ The EF and VFI measurements when used in combination have a good correlation with the incidence of ulceration and offer the potential for the selection of patients most likely to benefit from deep vein reconstruction (Figure 7