Chronic Venous Edema Research Articles

The role of the anatomical structure of the lymphatic system of lower limbs in the development of chronic venous edema in varicose veins disease

Introduction. Varicose veins disease of the lower extremities is often accompanied by edema, which persists even after the elimination of the causes of venous insufficiency. Clinically, the etiopathogenesis of edema in such patients is not always possible to differentiate. Objective. To determine the role of the lower limb lymphatic vasculature stucture variants in the development of chronic venous edema in patients with varicose veins disease. Materials and methods. A retrospective analysis of the results of X-ray contrast lymphography and radionuclide lymphoscintigraphy of 257 patients with different stages of chronic venous insufficiency (CVI). Results. Pathognomonic patterns of the lymphatic vasculature structure at various stages of lymphedema in patients with C3-C5 CVI were discovered. We found that the increasing number of cases of persistent oedema could be associated with the lower limb lymphatic vasculature hypoplasia and higher classes of CVI: 43.95 % among the patients with C4 CVI and 88 % with C5 CVI. The majority (94,1 %) of patients with C3 CVI with a normal-like lymphatic system presented with transitory oedema. With CVI C5, the capacity of the groin lymph nodes was impaired in 64 %. In C4 CVI, weak contrasting was observed in 45.1 %. With C3 – in 35.1 % of cases. Conclusions. The progressing degree of chronic venous oedema could be associated with the lymphatic vasculature hypoplasia and the malfunction of the groin lymph nodes.

Current indications for phlebotropic therapy and its duration

Phlebotropic therapy is an important component of the pathogenetic treatment of chronic venous insufficiency (CVI) of the lower extremities. Venoactive drugs, which have proven their effectiveness and safety in a variety of studies, are widely represented in international and Russian clinical guidelines and standards. However, there is no consensus on the regulation of phlebotropic therapy and, above all, its duration in different clinical classes of CVI. In addition, there are no clear indications on the methods of treatment efficacy monitoring, which can be used in real clinical practice. The presented systematized review of the literature data on micronized purified flavonoid fraction not only reveals the possibilities of phlebotropic therapy of different clinical classes and forms of CVI, but also suggests effective regulations for the use of this drug in specific situations. The data concerning the efficacy of phlebotropic therapy in real clinical practice at the initial stages of CVI (C0s-C1s), in the treatment of C2s (varicose superficial veins with venospecific symptoms), C3 (chronic venous edema), C4 (trophic skin disorders), as well as in stages C5-C6 and C6r (venous trophic ulcers) are presented in details. In addition, the results of studies on the use of micronized purified flavonoid fraction in phlebosclerosing treatment are presented. The duration of phlebotropic therapy is in direct relation to the severity of the disease and the response to the ongoing treatment. The important role is played not only by personalization of treatment according to specific symptoms and syndromes, but also, if possible, by objective control of their dynamics.

Comparative efficacy of various methods of treatment of chronic venous oedema in real clinical practice

The study was aimed at assessing efficacy and safety of micronized purified flavonoid fraction (MPFF, Detralex) in comprehensive treatment of chronic venous oedema induced by lower limb varicose veins. We performed a post hoc analysis of the results of treatment of 708 patients included into the observational programme VAP-PRO-C3 (ClinicalTrials.gov. NCT03722836). These patients, depending on the type of treatment, were divided into 8 subgroups: MPFF (n=32); MPFF + compression (n=145); MPFF + compression + topical treatment (n=158); MPFF + compression + topical treatment + endovasal laser coagulation (n=197); MPFF + endovasal laser coagulation (n=3); MPFF + compression + endovasal laser coagulation (n=152), patients not receiving MPFF (n=16); MPFF + topical treatment (n=2). Due to paucity of the participants, from the subsequent analysis we excluded the groups MPFF + endovasal laser coagulation, patients not receiving MPFF (n=16) and MPFF + topical treatment. All further statistical data are shown for the remaining 687 patients. Comparing the groups of patients undergoing conservative treatment alone and those subjected to surgical intervention demonstrated no statistically significant differences in dynamics of crural oedema. In both groups at every subsequent visit there was a statistically significant decrease in the ankle volume (p<0.001). During the whole period of follow up the crural volume in patients from the group of conservative treatment totally decreased by 0.201±0.158 L and in the operated patients by 0.236±0.189 L (p=0.021). The QOL assessed by the CIVIQ-14 global index score statistically significantly improved in the unoperated patients from 31.5±19.2 to 12.0±10.1 (p<0.001). In the operated patients, the baseline and final values of the QOL of the global index score amounted to 33.4±17.8 and 7.7±9.2, respectively (p<0.001). In the groups with and without topical treatment, the baseline values of the QOL assessed by CIVIQ-14 global index score amounted to 28.5±17.4 and 36.2±18.6, respectively. During the follow-up period, we observed statistically significant positive dynamics of all parameters of quality of life. The final visit demonstrated improvement of the CIVIQ-14 global index score to 9.4±9.2 in patients without topical treatment and 10.1±10.4 in those receiving topical treatment (p=0.367), with the mean value of this parameter during treatment in both groups decreased significantly (p<0.001). A statistically significant decrease in the ankle volume in both groups was registered at every visit, finally amounting to 0.223±0.166 L and 0.248±0.174 L (p=0.118) for patients not receiving and receiving topical treatment, respectively. In groups of patients not receiving and those receiving compression therapy, the baseline values of the QOL assessed by CIVIQ-14 global index score amounted to 21.4±14.2 and 33.1±18.5 (p<0.001), respectively. At the final visit, these indices statistically significantly (p<0.001) decreased to 7.3±9.1 and 9.9±9.9 (p=0.106). Compared with the baseline values, the ankle volume at the final visit in groups of patients with and without compression therapy statistically significantly decreased by 0.187±0.14 L and 0.238±0.17 L respectively (p=0.204). During the study, there were no adverse events related to the administration of MPFF and use of Detragel. MPFF and Detragel appear to be effective and safe components of comprehensive conservative therapy of chronic oedema induced by primary varicose veins of lower extremities.

A dual compression system: preliminary clinical insights from the US.

There is growing evidence on an interconnection between the venous and lymphatic systems in venous leg ulceration, and the possible effects of prolonged oedema and lymphatic impairment in delayed wound healing. Compression therapy is a widely accepted treatment for venous and lymphatic disorders, as it decreases recurrence rates and prolongs the interval between recurrences. Compression bandages improve venous return, increase the volume and rate of venous flow, reduce oedema and stimulate anti-inflammatory processes. The pressure at the interface (IP) of the bandage and the skin is related to the elastic recoil of the product used and its resistance to expansion. The pressure difference between the IP in the supine and standing positions is called the static stiffness index (SSI). Elastic materials provide little resistance to muscle expansion during physical activity, resulting in small pressure differences between resting and activity, with an SSI <10mmHg. Stiff, inelastic materials with a stretch of <100% resist the increase of muscle volume during physical activity, producing higher peak pressures, an SSI of >10mmHg and a greater haemodynamic benefit than elastic systems. UrgoK2 is a novel dual-layer high-compression system consisting of an inelastic (short stretch) and elastic (long stretch) bandage, resulting in sustained tolerable resting pressure and elevated working pressures over extended wear times. It is indicated for the treatment of active venous leg ulcers and the reduction of chronic venous oedema. Each bandage layer has a visual aid to enable application at the correct pressure level. Published European studies have assessed this compression system, exploring its consistency of application, tolerability and efficacy. This article presents the first reports of health professionals' clinical experience of using the compression system in the US, where it has been recently launched. Initial feedback is promising.

Efficacy of micronized purified flavonoid fraction in treatment of chronic venous oedema

The purpose of the study was to assess efficacy and safety of using in real clinical practice micronized purified flavonoid fraction (Detralex) in patients with chronic venous oedema. The study enrolled a total of 708 patients presenting with chronic venous disease, belonging to C3EpAsPr according to the CEAP classification (chronic venous oedema), who. depending on the accepted clinical practice by expert physicians were prescribed compression and phlebotropic therapy, as well as undergoing surgical interventions. The main criteria for efficacy of the micronized purified flavonoid fraction included the dynamics of chronic venous oedema, vein-specific symptoms, as well as the main parameters of quality of life. Assessment was made using visual analogue scales, the vein-specific questionnaire CIVIQ-14, and the method of discs for measuring the volume of the crus. The obtained findings demonstrated significant positive dynamics of the main vein-specific symptoms assessed by a visual analogue scale. When comparing between the visits of recruitment into the study and its termination the feeling of heaviness in calves decreased form 5.38±2.19 cm to 1.56±1.56 cm (p<0.001), pain in the calf diminished from 4.24±3.39 cm to 1.12±1.37 cm (p<0.001), feeling of oedema dropped from 5.68±2.44 cm to 1.38±1.59 cm (p<0.001), severity of nocturnal cramps fell from 2.46±2.30 cm to 0.43±1.01 cm (p<0.001), and intensity of skin inching from 1.46±2.06 cm to 0.43±1.01 cm (p<0.001). Positive dynamics of venous-specific symptoms appeared to be accompanied by significant improvement of all dimensions of quality of life according to the CIVIQ-14 scale: by the pain scale from 41.0±19.1% to 12.8±11.6% (p<0.001), by the physical condition scale - from 31.6±23.8% to 11.1±15.4% (p<0.001), by the psychological state scale - from 24.5±21.1% to 5.7±9.0% (p<0.001). The global index of quality of life also improved significantly from 32.4±18.5% to 9.9±9.9% (p<0.001). The results of the intervention along all the examined parameters (external appearance, possibility of wearing various clothes and increasing the quality of the self-performed work, to improve both interactions with surrounding people and the social activity and rest) turned out better than expectations form an intervention. The volume of the crus as the main criterion over the period of follow up averagely by the group decreased from 3.07±0.84 to 2.78±0.80 litres (p<0.001). A significant decrease in the calf volume from 3.03±0.87 to 2.77±0.85 litres was observed in 288 patients who during the follow up period were not subjected to surgical interventions, with no significant differences in the dynamics of chronic venous oedema revealed between the operated patients and those having received conservative treatment alone. According to a meta-analysis, the micronized purified flavonoid fraction (Detralex) turned out to possess better parameters in relation to therapy of chronic venous oedema as compared with other phlebotropic agents. Therefore, it appears absolutely logical to predominantly use the micronized purified flavonoid fraction in real clinical practice in patients with the CEAP C3 clinical class, which was registered in our study. An important result was also the fact that within the specified terms of follow up surgical intervention demonstrated no significant advantage over conservative therapy alone in treatment of chronic venous oedema. Moreover, conservative treatment in the form of a combination of compression and phlebotropic therapy demonstrated a dynamic decrease in the volume of the affected extremity with a probable transition of the CEAP C3 clinical class to C2. The micronized purified flavonoid fraction (Detralex) at a standard daily dose of 1000 mg in a combination with compression therapy irrespective of the surgical intervention performed resulted in a significant dynamic decrease in the volume of the calf in patients with chronic diseases of lower limb veins (C3EpAsPr according to the CEAP classification). An anti-oedematous effect of the micronized purified flavonoid fraction (Detralex) in a combination with compression manifests itself during the entire period of treatment.

Aescusan: pharmacology, pharmacokinetics and therapeutic characteristics

The article is devoted to Aescusan, a well-studied preparation that is traditionally used in clinical practice for the treatment of chronic diseases of veins, hemorrhoids, postoperative and post-traumatic edema. The main active substance is aescin that is contained in horse chestnut seed extract - Aesculus hippocastanum. The paper presents data of a randomized controlled study demonstrating the efficacy of Aescusan in the treatment of chronic venous diseases and chronic venous edema along with the compression therapy. A number of in vitro and in vivo experimental studies provided convincing proof of efficacy of Aescusan. In particular, they proved the anti-edema, anti-inflammatory and venotonic effect of the preparation. Aescusan improves calcium ions entry into the smooth muscle cell channels in the vascular wall, which increases the venous vascular tone. The anti-inflammatory effect of Aescusan is associated with blockade of prostaglandin F2 (PGF2) release from the venous wall, 5-hydroxytryptamine (5-HT) and histamine antagonism, decreased catabolism of tissue mucopolysaccharides. Conclusion: Aescusan has a pluripotent effect on various pathogenetic mechanisms of chronic venous diseases. It is known for its good tolerability and ease of use, which makes it possible to use the preparation in patients with chronic venous diseases, hemorrhoids, and peripheral post-traumatic edema.

Adjustable Velcro® Compression Devices are More Effective than Inelastic Bandages in Reducing Venous Edema in the Initial Treatment Phase: A Randomized Controlled Trial

The objective of this study was to compare the efficacy and comfort of inelastic bandages (IBs) and adjustable Velcro® compression devices (AVCDs) in reducing venous leg edema in the initial treatment phase. Forty legs from 36 patients with untreated venous edema (C3EpsAsdPr) were randomized to two groups. Patients in the first group received IBs (n = 20) and those in the second AVCDs (n = 20). Both compression devices were left on the leg day and night, and were renewed after 1 day. Patients in the AVCD group were asked to re-adjust the device as needed when it felt loose. Leg volume was calculated using the truncated cone formula at baseline (T0), after 1 day (T1) and after 7 days (T7). The interface pressure of the two compression devices was measured by an air filled probe, and the static stiffness index calculated after applying compression at T0 and T1, and just before removal of compression on T1 and T7. Patient comfort with regard to the two compression systems was assessed by grading signs and symptoms using a visual analog scale. At T1, the median percent volume reduction was 13% for the IB group vs 19% for the AVCD group; at T7 it was 19% vs 26%, respectively (P < .001). The pressure of the IBs was significantly higher compared with the AVCDs at T0 (63 vs 43 mmHg) but dropped by >50% over time, while it remained unchanged with AVCDs owing to the periodic readjustment by the patient. Comfort was reported to be similar with the two compression devices. Re-adjustable AVCDs with a resting pressure of around 40 mmHg are more effective in reducing chronic venous edema than IBs with a resting pressure of around 60 mmHg. AVCDs are effective and well tolerated, not only during maintenance therapy, but also in the initial decongestive treatment phase of patients with venous leg edema.

Adjustable Velcro® Compression Devices are More Effective than Inelastic Bandages in Reducing Venous Edema in the Initial Treatment Phase: A Randomized Controlled Trial

The objective of this study was to compare the efficacy and comfort of inelastic bandages (IBs) and adjustable Velcro compression devices (AVCDs) in reducing venous leg edema in the initial treatment phase. Forty legs from 36 patients with untreated venous edema (C3EpsAsdPr) were randomized to two groups. Patients in the first group received IBs (n = 20) and those in the second AVCDs (n = 20). Both compression devices were left on the leg day and night, and were renewed after 1 day. Patients in the AVCD group were asked to re-adjust the device as needed when it felt loose. Leg volume was calculated using the truncated cone formula at baseline (T0), after 1 day (T1) and after 7 days (T7). The interface pressure of the two compression devices was measured by an air filled probe, and the static stiffness index calculated after applying compression at T0 and T1, and just before removal of compression on T1 and T7. Patient comfort with regard to the two compression systems was assessed by grading signs and symptoms using a visual analog scale. At T1, the median percent volume reduction was 13% for the IB group versus 19% for the AVCD group; at T7 it was 19% versus 26%, respectively (p < .001). The pressure of the IBs was significantly higher compared with the AVCDs at T0 (63 vs. 43 mmHg) but dropped by > 50% over time, while it remained unchanged with AVCDs owing to the periodic readjustment by the patient. Comfort was reported to be similar with the two compression devices. Re-adjustable AVCDs with a resting pressure of around 40 mmHg are more effective in reducing chronic venous edema than IBs with a resting pressure of around 60 mmHg. AVCDs are effective and well tolerated, not only during maintenance therapy, but also in the initial decongestive treatment phase of patients with venous leg edema.

Bandages or Double Stockings for the Initial Therapy of Venous Oedema? A Randomized, Controlled Pilot Study

Treatment for leg oedema conventionally starts with compression bandaging followed by elastic stockings once swelling is reduced. The aim was to investigate if a kit consisting of a liner and outer stocking, each exerting 20 mmHg of pressure, would be equally effective in achieving and maintaining volume reduction compared with short-stretch bandaging (2 weeks) followed by a class II (23-33 mmHg) stocking (2 weeks). Forty legs (28 patients) with chronic venous oedema were randomised to either short-stretch bandages applied weekly for 2 weeks, followed by an elastic stocking for 2 weeks (group A) or a light stocking ("liner") for 1 week followed by superimposing a second stocking for 3 weeks (group B). Interface pressures and leg volumes were measured weekly. Despite differences in the pressure (median ± interquartile range) applied (bandage: 67 mmHg [55.7-73.0] vs. liner 24.5 mmHg [21.2-26.5]) volume reduction after 1 week was equal (12.8% [8.7-16.5] and 13.0% [10.4-20.6]). After 2 weeks (group A: 17.8% [10.6-20.0] vs. group B 16.2% [13.0-25.4]) and 4 weeks (group A: 17.3% [9.6-22.8] vs. group B: 17.0% [13.1-24.1]) volume reductions remained identical. The initial improvement in leg volume (1 week) was independent of the pressure applied and the reduction was maintained by superimposing a second stocking. This offers a simple alternative for managing leg oedema with reduced staffing costs.

Dose-response of compression therapy for chronic venous edema—higher pressures are associated with greater volume reduction: Two randomized clinical studies

Two phase II clinical studies used an experimental, multi-chambered compression device with different cuff pressure combinations in subjects with leg edema and chronic venous insufficiency. The objective of each study was to evaluate the safety and the relative effects of different cuff pressure combinations to determine if edema reduction was dose-dependent. Each study enrolled adults with chronic (>or=6 weeks) venous edema corresponding to CEAP C(3)-C(5). The test device could apply different pressures at the foot, gaiter, mid-calf, and upper-calf. In the first study, the following six sustained pneumatic compression (SPC) profiles were applied for six hours each: 20, 30, and 40-mm Hg at the gaiter with graduated SPC (ie, lower pressures at the calf); and 20, 30, and 40-mm Hg at the gaiter with nongraduated SPC (ie, the same pressures at the calf). In the second study, the following three intermittent pneumatic compression (IPC) profiles were applied for two hours each: 40, 50, and 60-mm Hg at the gaiter with graduated IPC (ie, lower pressures at the calf). Each study included a baseline profile with no compression and two-day intervals between profiles. Leg volume was measured before and after compression using the water-displacement method. A dose-response relationship was observed between increased SPC/IPC pressures and reduced limb edema. Limb volume was reduced most effectively with the highest pressures of 40-mm Hg nongraduated SPC and 60-mm Hg graduated IPC (136 mL and 87 mL, respectively); however, some subjects reported discomfort with these profiles. Limb volume was reduced by more than 100 mL with 30 to 40-mm Hg graduated SPC and by 69 mL with 50-mm Hg graduated IPC, and subjects rated these profiles as comfortable or very comfortable. Of the 28 study participants (12 SPC, 16 IPC), two subjects reported pain with 60-mm Hg IPC; no other adverse events were reported with SPC or IPC. Pneumatic compression was safe and well-tolerated, with a dose-response relationship between increased SPC/IPC pressures and reduced leg edema. To our knowledge, this is the first study to demonstrate a dose-relationship in compression therapy: higher pressures are associated with greater volume reduction in subjects with chronic venous edema.