Fig. 15.1
Simplified treatment algorithm for chronic venous disease (CVD)
Clinical Exam and Imaging
A proper history should always include a review of previous ulcers, vein surgeries (for harvest or otherwise), treatments, profession, pregnancy, hypercoagulability, trauma, family history, arteriovenous fistulas, lymphedema and risk factors for atherosclerosis. Physical exam should include inspection, palpation, auscultation, and mobility. Inspection should include the presence of any telangiectatic/reticular disease/corona phlebectactica, varicose veins, swelling, skin changes, healed ulcers, or active ulcers. Palpation is used to note any varicose dilatations, palpable cords, tenderness, thrills, or pitting edema. It is important to differentiate a venous ulcer from an arterial ulcer, and pulses should always be assessed. Maneuvers such as the Trendelenburg test to evaluate perforator and in-line valve insufficiency have been described but are rarely used now. Auscultation is particularly useful for identifying any bruits for arteriovenous malformations or fistulas. Decreased ankle mobility may represent more advanced CVD [8]. It is key to differentiate between primary and secondary venous insufficiency. Primary venous insufficiency occurs when a weakness of the vein wall results in valve incompetence. Secondary or acquired venous insufficiency from trauma or deep vein thrombosis can cause valvular disruption [12].
Signs and symptoms of CVD may include the five HASTI symptoms (heaviness, achiness, swelling, throbbing, itching) and pain relieved with activity or leg elevation, edema, skin changes, and ulcers [13]. Signs indicating skin damage include hyperpigmentation, stasis dermatitis, lipodermatosclerosis or subcutaneous fibrosis, atrophie blanche or hypopigmented scarring of previous ulcer sites, corona phlebectatica or visible ankle blood vessels, skin thickening, and induration.
Ultrasound
The AVF recommends a venous duplex to evaluate reflux disease and to assess for any outflow pathology [8]. Duplex ultrasound offers a high diagnostic accuracy and is safe, noninvasive, and a cost-effective tool for both diagnosis and treatment [14]. The technique for proper ultrasonography has been described by multiple authors [15–20]. Evaluation should be performed with the patient in the standing position with the leg rotated outward, the heel on the ground, and weight shifted toward the opposite limb [21]. If done in the supine position, false positive and false negatives have been reported [17]. Four components should be included in the study: (1) visibility, (2) compressibility, (3) venous flow including the presence of duration of reflux, and (4) augmentation [21]. Reflux can be elicited by either having the patient perform a Valsalva maneuver (particularly for evaluation of the saphenofemoral junction) or by manual compression and release of the limb just distal to the point of study [17]. The AVF recommends that reflux times of greater than 0.5 s be used as the cutoff for CVD of the saphenous, tibial, deep femoral, and perforator veins and 1 s be used for the femoral and popliteal veins [8].
Plethysmography
Air and strain-gauge plethysmography (APG and SPG, respectively) have also been used as a noninvasive evaluation of calf-muscle pump function, venous reflux, and outflow obstruction [19, 22, 23]. In particular, plethysmography is most useful in CVD when outflow obstruction is suspected and/or duplex scanning does not show evidence of reflux disease but patient symptoms and characteristics are suspicious for CVD. Therefore, they are recommended as complementary studies to duplex scanning. Air plethysmography in particular can reliably quantify reflux and is recommended for patients with CEAP C3–C6 disease that have not been definitively diagnosed by ultrasound [23, 24].
Venography
Contrast venography is primarily used in patients with more advanced CVD and in patients with suspected outflow obstruction such as in post-thrombotic syndrome or May–Thurner syndrome [8]. CT and MR venography are less commonly used due to risks of contrast when compared to ultrasonography and are most suitable for more proximal pathology such as pelvic or iliac pathology. They may also be useful for evaluation of malformations such as Klippel–Trenaunay syndrome (KTS). For obstructive disease, intravascular ultrasound (IVUS) is crucial for diagnosis and treatment and is typically used in conjunction with contrast venography.
Classification Systems
The classification systems most widely used in practice today are the CEAP (Clinical, Etiological, Anatomical, and Pathophysiological) classification system and the VCSS (Venous Clinical Severity Score ). The CEAP was first introduced in 1994 and then revised in 2004 by the AVF and provides a basic classification of the venous insufficiency using the described components [24, 25]. The revised VCSS provides additional information from the CEAP that allows for monitoring improvement in patients within CEAP C classes. For example, C6 patients may heal their ulcer and improve to a C5 class, but they can never improve their CEAP class beyond that in spite of improved symptoms. Likewise, a C2 patient with small asymptomatic varicose veins cannot be differentiated from a C2 patient with large painful varicose veins using solely the CEAP system. Linking the VCSS to the clinical CEAP class enhances communication by adding information such as ulcer size and severity of symptoms [26]. Furthermore, the VCSS can be used to assess the broader spectrum of chronic venous disease as well as to compare patients with post-thrombotic syndrome and those subjected to different treatment modalities of saphenous venous ablation, stenting for venous obstruction, pharmacomechanical thrombolysis, and other venous interventions.
Nonoperative Management
The use of compression stockings for venous disease dates back to Ambroise Paré in the 1500s; now there are various compression therapies available including elastic wraps/bandages, Unna’s boot, and pneumatic compression devices [27]. More recently, phlebotonic or vasoactive drugs have been developed but are less commonly used in practice. Table 15.1 summarizes the believed benefits and pharmacokinetics of currently used phlebotonic drugs. Among the most studied is escin, which can be found in horse chestnut seed extract (HCSE) [31–33]. A Cochrane Review of HCSE in 2012 reviewed 17 randomized clinical trials (RCTs) that compared HCSE to placebo and found a significant improvement in leg pain and reduction in leg volume. However, a comparison of HCSE with rutosides, pycnogenol, and compression stockings found no statistically significant difference between groups. Pentoxifylline used in conjunction with compression therapy may increase the likelihood of venous ulcer healing. Flavonoids such as hesperidin (found in citrus plants and peppermint) and diosmin (found in the plant Teucrium gnaphalodes) are used in micronized purified flavonoid fraction (MPFF) [31, 32]. Despite the development of phlebotonic drugs , the data has failed to show much benefit, and the mainstay of nonoperative management remains compression stockings (15–30 mmHg), but lifestyle modifications including weight loss, exercise, and leg elevation should also be advised.
Table 15.1
Phlebotonic or venoactive drugs
Drug class | Drug examples | Found naturally | Effects | Mechanism of action | Pharmacokinetics |
|---|---|---|---|---|---|
γ-Benzopyrone (flavonoids) | – MPFFa [38] – Hesperidin [30] | Citrus spp., peppermint; Rutaceae aurantiae | – Antioxidant – Anti-inflammatory – Reduces vascular permeability – Antitumor effects – Increases venous tone – Reduces edema and lymphedema – Inhibits bone resorption – Mildly lowers blood pressure | – Reduces vascular permeability – Increases venous tone by prolonged vasoconstrictive effects of norepinephrine and decreases venous capacitance, distensibility and stasis – Improves lymphatic drainage by increased intensity and frequency of lymphatic contractions | – Poor bioavailability – t 1/2: Hesperidin, 5–8 h Diosmin, 26–43 h – Hesperidin is absorbed in the colon – Diosmin augments bioavailability of p-glycoprotein substrates – Metabolized by intestinal flora and liver – Mostly cleared by urine |
α-Benzopyrone | Numerous plant spp., including Dipteryx odorata (tonka bean); Melilotus officinalis (yellow sweet clover); Hierochloe odorata (sweet grass) | – Reduces edema and lymphedema – Relieves asthma – Improved CVD symptoms and subjective quality of life – Anticoagulation effects (i.e., Coumadin) | – Amplifies proteolysis by tissue macrophages improving lymph flow and reducing edema. – Cytotoxic – Pro-apoptotic – Tumor-destroying and antifungal effects | – Hepatic metabolism, substantial first pass effect – Cleared by urine – t 1/2: ~1.5 h | |
Saponosides | Horse chestnut (Aesculus hippocastanum); Butcher’s broom (Ruscus aculeatus) | – Antioxidant – Anti-inflammatory – Antithrombin – Reduces edema and lymphedema | – Prolongs vasoconstrictive effects of norepinephrine increasing venous tone and decreasing venous capacitance, distensibility, and stasis – Augments lymphatic drainage by increased intensity and frequency of lymphatic contractions – Decreases lymphatic pressure – Reduces capillary hyperpermeability and increases capillary resistance – Reduces expression of endothelial adhesion molecules and inhibits adhesion, migration, and activation of leukocytes at the capillary level | – Half-life is approximately 10–20 h – Peak plasma levels are 2–3 h after ingestion – Not well absorbed orally – Degraded by the liver, undergoes first pass effect | |
Other plant extracts | – Bilberry (Vaccinium myrtillus) – Ginkgo biloba | – Antioxidant – Reduces edema – Accelerates healing of venous ulcers | – Regulates mucopolysaccharide metabolism in variceal walls – Reduces leukocyte adhesion to endothelial cells – Reduces circulating endothelial cell count | – Variable | |
Synthetics | Synthetic | – Antioxidant – Anti-inflammatory – Reduces leg edema – Reduces blood viscosity – Augments lymphatic flow and reduces lymphedema – Improved QoL when combined with oxerutin | – Inhibits capillary permeability by serotonin, histamine, and bradykinin pathways – Inhibits synthesis of prostaglandins and thromboxanes which reduces platelet and erythrocyte aggregation as well as blood viscosity – Increases venous tone by reduced angiogenesis and VEGF expression – Regulates apoptosis and inhibits inflammatory response | – t 1/2: 2.5–15 h – Primarily cleared by urine – May cause hepatitis and agranulocytosis | |
Synthetic | – Healing of venous ulcers (with compression hosiery) – Decreased platelet aggregation | – Nonselective phosphodiesterase inhibitor – Inhibits platelet aggregation and leukocyte activation – Inhibits synthesis of TNF-α | – Metabolized by erythrocytes and the liver – t 1/2: 0.4–0.8 h – Primarily cleared by urine |
In patients with simple varicose veins (C2 CEAP classification), Michaels et al. compared the cost-effectiveness of compression to sclerotherapy and to open high ligation and stripping (HL/S) in the REACTIV trial. They found that HL/S was significantly more cost-effective than both sclerotherapy and nonoperative management and that sclerotherapy was still significantly more cost-effective than nonoperative management alone [28]. Franks et al. [29] showed that some patient populations (particularly the obese and elderly) are unable to routinely apply the compression hosiery and that delaying surgical care costs patients in quality of life adjusted years (QALY). Additionally, Perälä et al. [30] compared perioperative and total societal costs of RFA versus HL/S and found that while RFA had higher perioperative costs, it had significantly lower total societal costs by nearly 25%. Because of the increased cost and potential delays in care, the AVF recommends that for patients with C2 disease that are candidates for operative management, compression therapy should not be the primary treatment of symptomatic varices (Table 15.2) [8].
Table 15.2
American Venous Forum recommendations for nonoperative management
Recommendation | Level of evidencea |
|---|---|
We suggest venoactive drugs (diosmin, hesperidin, rutosides, sulodexide, micronized purified flavonoid fraction, or horse chestnut seed extract [escin]) in addition to compression for patients with pain and swelling due to chronic venous disease, in countries where these drugs are available | 2B |
We suggest using pentoxifylline or micronized purified flavonoid fraction, if available, in combination with compression, to accelerate healing of venous ulcers | 2B |
We suggest compression therapy using moderate pressure (20–30 mmHg) for patients with symptomatic varicose veins | 2C |
We recommend against compression therapy as the primary treatment of symptomatic varicose veins in patients who are candidates for saphenous vein ablation | 1B |
We recommend compression as the primary therapeutic modality for healing venous ulcers | 1B |
We recommend compression as an adjuvant treatment to superficial vein ablation for the prevention of ulcer recurrence | 1A |
Operative Management
Operative management for CVD has been present for over a century [10, 11]. Table 15.3 provides a general overview of the various techniques used today and their relative drawbacks and benefits. Generally, endothermal ablation has become the standard first-line procedure, but many countries outside the United States and Europe still perform open procedures as the standard of care. There are no additional absolute contraindications to operative repair; however, relative contraindications may include patients who have arterial disease, deep vein insufficiency, known coagulopathy or hepatic disease, active thrombophlebitis, pregnancy, and are breastfeeding or patients that are immobile. A summary of the AVF operative guideline recommendations is available in Table 15.4 [8].
Table 15.3
Summary comparison of operative procedures
Procedure | Type | Complications/drawbacks | Benefits |
|---|---|---|---|
High ligation/stripping [8] | Open | – Increased perioperative disability period compared to newer techniques (7–22-day average) – Increased rate of adverse events (acute DVT ~0.5–5%; PE ~0.16%) – Significant perioperative pain (17–22%), ecchymosis (19%), hemorrhage (33%), and wound infection (3–10%) – Increased paresthesia/neuralgia (2–7%, if done up to the knee, and up to 39% if done to the ankle) – Recurrence (6.6–37%) | – Improved QoL over nonoperative management – Low cost |
Powered phlebectomy [8] | Open | – Increased rate of ecchymosis (4.9–95%) – High number of paresthesia/neuralgias (9.5–39%) – Increased skin complications including perforation (1.2–5%), wound infection (2.4–13%), hyperpigmentation (1.2–3.3%), and edema (5–17.5%) – Recurrence (9.1–21.2%) – Acute DVT reported in <1% | – Quicker compared to stab phlebectomy (mean operative time <20 min) – Fewer incisions compared to stab phlebectomy |
Open | – Divides GSV – Ecchymosis present in ~19.7% – Not well studied | – Maintains truncal drainage despite GSV division – Low cost, no special equipment necessary | |
Open | – Requires detailed superficial and deep vein mapping with individualized preoperative planning – Recurrence (~11.5%) – Variable results depending on operative team and mapping | – Preserves truncal vein | |
Open | – Requires detailed superficial and deep vein mapping with individualized preoperative planning – Recurrence in GSV or new incompetent perforators/tributaries (Hunterian or Dodd’s) – Non-truncal recurrence (~9%) – Variable results depending on operative team and mapping | – Preserves truncal vein | |
Sclerotherapy [8] | Endovenous | – Often requires multiple sessions – Lower success rates with larger veins – Multiple puncture sites – Documented air emboli – Higher rates of skin changes and necrosis, especially with extravasation of sclerosant | – Quick – Reduced perioperative disability – Excellent for telangiectatic and reticular vessels that are too small for catheter placement |
RFA [8] | Endovenous | – Increased perioperative pain/tightness (~31%) – Recurrence (~26%) – Expensive RF equipment and ultrasound needed | Overall societal costs reduced with decreased disability time (2–8-day average) Faster than open surgery Less pain and bruising compared to EVLA |
EVLA [8] | Endovenous | Perioperative pain/tightness (31%) Postoperative disability period (2–8-day average) Recurrence (26%) Expensive laser equipment and ultrasound needed | Quicker recovery period than open surgery (2–8-day average) Less wound infections Comparable closure rates without incision Less hemorrhage and ecchymoses |
Mechanochemical [8] | Endovenous | – Not well studied | – Does not require local tumescent anesthesia, reducing perioperative pain |
Endovenous glue [8] | Endovenous | – Not well studied | – High closure rates (95–99%) – Does not require tumescent anesthesia – Reduced perioperative ecchymoses |
Steam ablation [8] | Endovenous | – Not well studied – Still requires thermal ablation but with less fluid administration | – Less perivenous tissue damage resulting in less postoperative pain |
Table 15.4
American Venous Forum recommendations for surgical interventions
Recommendation | Level of evidencea |
|---|---|
For treatment of the incompetent great saphenous vein, we suggest high ligation and inversion stripping of the saphenous vein to the level of the knee | 2B |
To reduce hematoma formation, pain, and swelling, we recommend postoperative compression. The recommended period of compression in C2 patients is 1 week | 1B |
For treatment of small saphenous vein incompetence, we recommend high ligation of the vein at the knee crease, about 3–5 cm distal to the saphenopopliteal junction, with selective invagination stripping of the incompetent portion of the vein | 1B |
To decrease recurrence of venous ulcers, we recommend ablation of the incompetent superficial veins in addition to compression therapy | 1A |
We suggest preservation of the saphenous vein using the ambulatory conservative hemodynamic treatment of varicose vein (CHIVA) technique only selectively in patients with varicose veins, when performed by trained venous interventionists | 2B |
We suggest preservation of the saphenous vein using the ambulatory selective varicose vein ablation under local anesthesia (ASVAL) procedure only selectively in patients with varicose veins | 2C |
We recommend ambulatory phlebectomy for treatment of varicose veins, performed with saphenous vein ablation, either during the same procedure or at a later stage. If general anesthesia is required for phlebectomy, we suggest concomitant saphenous ablation | 1B |
We suggest transilluminated powered phlebectomy using lower oscillation speeds and extended tumescence as an alternative to traditional phlebectomy for extensive varicose veins | 2C |
For treatment of recurrent varicose veins, we suggest ligation of the saphenous stump, ambulatory phlebectomy, sclerotherapy, or endovenous thermal ablation, depending on the etiology, source, location, and extent of varicosity | 2C |
Endovenous thermal ablations (laser and radiofrequency ablations) are safe and effective, and we recommend them for treatment of saphenous incompetence | 1B |
Because of reduced convalescence and less pain and morbidity, we recommend endovenous thermal ablation of the incompetent saphenous vein over open surgery | 1B |
We recommend liquid or foam sclerotherapy for telangiectasia, reticular veins, and varicose veins | 1B |
For treatment of the incompetent saphenous vein, we recommend endovenous thermal ablation over chemical ablation with foam | 1B |
We recommend against selective treatment of incompetent perforating veins in patients with simple varicose veins (CEAP class C2) | 1B |
We suggest treatment of “pathologic” perforating veins that includes those with an outward flow duration of ≥500 ms, with a diameter of ≥3.5 mm, located beneath a healed or open venous ulcer (CEAP classes C5–C6) | 2B |
For treatment of “pathologic” perforating veins, we suggest subfascial endoscopic perforating vein surgery, ultrasonographically guided sclerotherapy, or thermal ablations | 2C |
High Ligation and Stripping (HL/S)
The technique of HL/S can be dated back to 1884 by Madelung and has undergone multiple modifications throughout the 1900s, most notably the development of the extraluminal straight stripper by Mayo in 1906 and the flexible stripper by Myers in 1943 [11]. Classic open complete HL/S is generally only offered where endovenous methods are not available. To perform HL/S, a 3–4 cm incision in the groin is made and, once the SFJ is safely dissected out, stripped down to the level of the knee. For invagination stripping, a flexible plastic Codman stripper and a metallic Oesch perforate-invaginate (PIN) stripper are used to invaginate the vein into the lumen and remove toward the knee. Alternatively, cryostripping may be performed which entails inserting a cryoprobe into the GSV and freezing for 2 s followed by invaginating the GSV toward the groin [35]. Stripping of the GSV should be taken down only to the level of the knee due to the increased incidence of saphenous nerve injury. Similarly, complete HL/S of the small saphenous vein (SSV) may cause sural nerve injury and is generally avoided [36].
Partial stripping, however, is still commonly used as in the hybrid procedure—laser-assisted distal saphenectomy (LADS) [9]. A superficial accessory saphenous vein (SASV) often acts as a reflux escape tributary as it exits the saphenous canal at mid-thigh, and treatment with thermal ablation is generally avoided as it may cause skin necrosis and eschar formation and leave a palpable cord. The LADS procedure involves performing endovenous thermal ablation of the proximal GSV (thereby avoiding a groin incision and associated complications) along with performing a partial stripping of the distal SASV using the sheath as the stripping tool (Fig. 15.2a, b).
Fig. 15.2
(a) LADS Part 1—the laser tip is positioned at the SFJ and withdrawn to mid-thigh where the reflux escapes the GSV in the saphenous canal into the subcutaneous space as the SASV. (b) LADS Part 2—the SASV is exteriorized at mid-thigh and divided. The distal vein is sutured to endovenous sheath and invagination stripping performed
Divided Saphenectomy (DS)
Divided saphenectomy (DS) is another open approach geared toward ligating the saphenous vein at multiple sites and ligating all tributaries and perforators, competent or not [37]. This is performed under local anesthesia, and the procedure entails preserving the GSV (albeit in ligated segments), ligating all perforators in the thigh, and preserving a route of venous drainage but by reducing symptoms of hemorrhage and bruising by ligating all tributaries using standard surgical equipment and small 1cm incisions as opposed to the larger 3–4 cm incision for HL/S.
ASVAL
The ASVAL (ambulatory selective varicose vein ablation under local anesthesia) operation is a minimally invasive technique that aims to remove varicose tributaries while preserving the saphenous trunk and reducing the GSV diameter. The combination of hemodynamic and anatomical modifications leads to a reduction in reflux volume [38].
CHIVA
First presented by Franceschi et al. in 1988, the CHIVA (ambulatory conservative hemodynamic treatment of varicose vein) procedure is targeted at maintaining the truncal venous system while promoting more efficient drainage into the deep venous system, i.e., a saphenous-sparing procedure [39]. The goal is to fragment the venous column of blood causing a redistribution of flow toward a competent deep venous system and decreasing the venous pressure. A Cochrane Review published in 2013 identified three RCTs comparing CHIVA vs saphenous stripping and one RCT comparing CHIVA vs compression. The results showed that CHIVA had reduced recurrence rates, reduced side effect profile compared to open surgery and compression, and improved QoL [40]. However, results vary tremendously depending on the user with recurrence rates (defined as reflux present in the GSV) ranging from 91% at 3 years to 18% at 10 years and are therefore not recommended for most practitioners [8].
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