P. D. Coleridge Smith

European guidelines for sclerotherapy in chronic venous disorders

Aim Sclerotherapy is the targeted chemical ablation of varicose veins by intravenous injection of a liquid or foamed sclerosing drug. The treated veins may be intradermal, subcutaneous, and/or transfascial as well as superficial and deep in venous malformations. The aim of this guideline is to give evidence-based recommendations for liquid and foam sclerotherapy. Methods This guideline was drafted on behalf of 23 European Phlebological Societies during a Guideline Conference on 7–10 May 2012 in Mainz. The conference was organized by the German Society of Phlebology. These guidelines review the present state of knowledge as reflected in published medical literature. The regulatory situation of sclerosant drugs differs from country to country but this has not been considered in this document. The recommendations of this guideline are graded according to the American College of Chest Physicians Task Force recommendations on Grading Strength of Recommendations and Quality of Evidence in Clinical Guidelines. Results This guideline focuses on the two sclerosing drugs which are licensed in the majority of the European countries, polidocanol and sodium tetradecyl sulphate. Other sclerosants are not discussed in detail. The guideline gives recommendations concerning indications, contraindications, side-effects, concentrations, volumes, technique and efficacy of liquid and foam sclerotherapy of varicose veins and venous malformations.

Endothelial Activation in Patients With Chronic Venous Disease

OBJECTIVES Leukocyte trapping due to leukocyte-endothelial activation has been implicated as the cause of lipodermatosclerosis and ulceration in patients with chronic venous disease. We investigated endothelial activity in normal controls and patients subjected to short-term venous hypertension. METHODS Twenty-five normal volunteers and 30 patients with chronic venous disease divided into two groups: varicose veins with skin changes (LDS, n = 15); and varicose veins without skin changes (VVs, n = 15) were studied. Blood samples were taken from a foot vein before and after experimental venous hypertension. Plasma levels of ELAM-1 (endothelial leukocyte adhesion molecule-1), ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), and von Willebrand factor (vWf) was measured by an ELISA. RESULTS There was a significant rise in the plasma concentration of ELAM-1, ICAM-1 and VCAM-1 in patients and normal controls in response to venous hypertension. Basal levels of plasma VCAM-1 and vWf were higher in patients with LDS compared to patients with VVs. The magnitude of rise of VCAM-1 was greater in patients with LDS compared to patients with VVs (p = 0.01, Mann-Whitney U-test). There was no difference in the basal levels or in the magnitude of change in plasma ICAM-1 and ELAM-1 between the two patient groups. CONCLUSION Venous hypertension results in endothelial activation which may aid endothelial-leukocyte adhesion. Patients with LDS exhibit increased VCAM-1, which is a counterligand for receptors expressed by monocytes and lymphocytes signifying that these cells may be more important in the development of skin changes.

Consensus Paper on Venous Leg Ulcers

No justification is needed for a group of specialists trying to summarize current knowledge about the pathophysiology. investigation and management of venous leg ulcers. It is a very common and still largely neglected condition where ignorance is sometimes matched by dogmatic opinions. This paper is the outcome of the deliberations of 20 specialists in various aspects of venous ulcer disease from the United States and several European countries. The Alexander House Group met initially in May 1990 and again in October 1991 to identify those aspects of venous ulceration where consensus exists between leading experts from Europe and the United States. The participants in these meetings have tried to confine their statements to those areas where there is widespread agreement but, at the same time. they have sought to identify areas where much further research is required. Statements made in this document are supported by an extensive bibliography.

Sclerotherapy and foam sclerotherapy for varicose veins

OBJECTIVES To review published evidence concerning treatment of varicose veins using ultrasound-guided foam sclerotherapy (UGFS) to assess the safety and efficacy of this treatment. METHODS Medical literature databases including MedLine, Embase and DH-DATA were searched for recent literature concerning UGFS. Papers describing the early results and later outcome have been assessed and their main findings were included in this summary. RESULTS Few randomized studies have been published in this field and much of the available data come from clinical series reported by individual clinicians. It is clear that foam sclerotherapy is far more effective than liquid sclerotherapy and that ultrasound imaging allows the treatment to be delivered accurately to affected veins. There is evidence that 3% polidocanol foam is no more effective than 1% polidocanol foam. The optimum ratio of gas to liquid is 4:1, although a range of ratios is reported in the published work. There is a wide variation in the volume used as well as the method by which it is injected. The use of carbon dioxide foam reduces the systemic complications, particularly visual disturbance, as compared with air foams. Very few serious adverse events have been reported in the literature despite the widespread use of this method. Rates of recanalization of saphenous trunks following UGFS are similar to those observed after endovenous laser and endovenous RF ablation of veins, as well as the residual incompetence after surgical treatment. CONCLUSION UGFS is a safe and effective method of treating varicose veins. The relative advantages or disadvantages of this treatment in the longer term have yet to be published.

Foam and liquid sclerotherapy for varicose veins

Objective The objective of this study is to review the methods and outcome of ultrasound-guided foam sclerotherapy (UGFS) for the treatment of superficial venous incompetence. Method Medical literature databases including Medline were searched for recent literature concerning UGFS. Papers describing methods and outcome have been assessed and their main findings included in this summary. A detailed description of the methods used by the author has been included as an example of how successful the treatment may be achieved. Results A diverse range of practice is described in published literature in this field. Each group of authors used their own variation of the methods, described in the published literature, with good results. It is clear that foam sclerotherapy is far more effective than liquid sclerotherapy and that ultrasound imaging allows the treatment to be delivered accurately to affected veins. There is evidence that 3% policocanol foam is no more effective than 1% polidocanol foam. The optimum ratio of gas to liquid is 4:1, although a range of ratios is reported in published work. There is a wide variation in the volume used as well as the method by which it is injected. The use of carbon dioxide foam reduces the systemic complications, particularly visual disturbance, when compared with air foams. Very few serious adverse events have been reported in the literature despite the widespread use of this method. Rates of recanalization of saphenous trunks following UGFS are similar to those observed after endovenous laser and endovenous radiofrequency ablation of veins, as well as the residual incompetence after surgical treatment. Conclusions UGFS is a safe and effective method of treating varicose veins. The relative advantages or disadvantages of this treatment in the longer term are yet to be published.OBJECTIVE The objective of this study is to review the methods and outcome of ultrasound-guided foam sclerotherapy (UGFS) for the treatment of superficial venous incompetence. METHOD Medical literature databases including Medline were searched for recent literature concerning UGFS. Papers describing methods and outcome have been assessed and their main findings included in this summary. A detailed description of the methods used by the author has been included as an example of how successful the treatment may be achieved. RESULTS A diverse range of practice is described in published literature in this field. Each group of authors used their own variation of the methods, described in the published literature, with good results. It is clear that foam sclerotherapy is far more effective than liquid sclerotherapy and that ultrasound imaging allows the treatment to be delivered accurately to affected veins. There is evidence that 3% policocanol foam is no more effective than 1% polidocanol foam. The optimum ratio of gas to liquid is 4:1, although a range of ratios is reported in published work. There is a wide variation in the volume used as well as the method by which it is injected. The use of carbon dioxide foam reduces the systemic complications, particularly visual disturbance, when compared with air foams. Very few serious adverse events have been reported in the literature despite the widespread use of this method. Rates of recanalization of saphenous trunks following UGFS are similar to those observed after endovenous laser and endovenous radiofrequency ablation of veins, as well as the residual incompetence after surgical treatment. CONCLUSIONS UGFS is a safe and effective method of treating varicose veins. The relative advantages or disadvantages of this treatment in the longer term are yet to be published.

Plasma Lactoferrin as a Marker of White Cell Degranulation in Venous Disease

Objective: To measure plasma lactoferrin as a marker of neutrophil degranulation in groups of patients with varying severity of venous disease and compare with age- and sex-matched control subjects. Design: Prospective study of patients with varicose veins compared with a group of control subjects with no history or clinical findings of varicose veins. Setting: The Middlesex Hospital Vascular Laboratory, Mortimer Street, London WIN 8AA, UK. Patients: Patients referred to the Middlesex Hospital Vascular Laboratory for investigation of venous disease. Control subjects were obtained from within the laboratory and hospital staff, and from a group of Patients attending the London Foot Hospital for routine chiropody. Neither group had arterial disease nor any other illness or medication known to alter white cell activity. Interventions: 10 ml of blood taken from an arm vein into EDTA for a neutrophil count and measurement of Plasma lactoferrin using an ELISA. Results: Significantly raised plasma lactoferrin was found in all four groups of patients compared with their controls (p = 0.0156 for uncomplicated varicose veins, P = 0.01 for lipodermatosclerosis, p = 0.0413 for active venous ulceration, and p = 0.0005 for healed ulcers, Mann-Whitney U-test). Differences between medians (95% confidence interval) for the four groups were 269 (62–603), 199 (60–314), 133 (44–218) and 215 (98–349) ng/ml respectively. There was no difference in the neutrophil count between the patient and control groups, and correcting plasma lactoferrin for the neutrophil count did not remove significance in any group. Conclusions: This study shows evidence of increased neutrophil activation as shown by increased degranulation in patients with venous disease.

Effects of compression and type of bed surface on the microcirculation of the heel

OBJECTIVE To assess the effects of compression on the skin microcirculation of the heel using laser Doppler fluxmetry. DESIGN Parallel groups comparing patients with control groups. SETTING Department of Surgery, University College London Medical School, London. SUBJECTS AND MATERIALS Ten patients at risk of developing pressure ulceration, 10 age- and sex-matched healthy subjects and 10 young, healthy volunteers. An acrylic indenter with a slot to accommodate a laser Doppler probe was used to apply compression to the heel region. A pressure sensor was used to measure the applied compression. OUTCOME MEASURES The resting laser Doppler flux was measured with the subject lying supine. Compression forces were then applied in increments from 50 g to 1500 g and the corresponding interface pressure (IP) and laser Doppler flux (LDF) recorded. The IP and LDF were also measured from the heel while the subject was lying on a low air-loss system and then on an NHS conventional hospital bed. RESULTS The resting LDF is lower in the patient group compared to the control groups (p < 0.05). Compression of the heel caused a progressive decrease in LDF in all groups. Compression greater than 50 mmHg as well as lying on an NHS bed reduced the LDF signal to a minimal value (biological zero). On the low air-loss system, the median LDF was 17% of the resting value in the age-matched control group and 32% in the patient group. CONCLUSIONS The results indicate that the heel microcirculation is vulnerable to compression. The low air-loss system maintained the IP sufficiently low to prevent complete cessation of the heel microcirculation.

A Study of Tourniquets in the Investigation of Venous Insufficiency

Tourniquets are used extensively in the assessment of the venous system. They are employed not only for clinical tourniquet tests but are also used during examinations by Doppler ultrasound, plethysmography and venography, and during ambulatory venous pressure measurements. Surgical management is based on conclusions reached by the use of tourniquets. This study was undertaken to evaluate the pressure required to prevent reflux in the incompetent long saphenous vein. A total of 44 limbs with sapheno–femoral incompetence were studied. Duplex doppler ultrasound was used to detect retrograde flow within the long saphenous vein during inflation of a 2.5 cm wide pneumatic tourniquet applied around the thigh. The pressure required to prevent reflux, the diameter of the imaged vein and the circumference of the thigh were measured. The pressure required to prevent reflux varied from 40 mmHg to 300 mmHg. There was a correlation between this pressure and the circumference of the thigh (r = 0.62 P < 0.001). There was no correlation with the diameter of the vein. In conclusion, tourniquets introduce a source of error into evaluation of venous disease.

Neutrophil Activation in Experimental Venous Hypertension

Objective: To investigate the white cell trapping hypothesis of venous ulceration by measuring plasma lactoferrin as a marker of neutrophil degranulation in normal volunteers in two experimental models of venous hypertension. Design: A prospective study of volunteers with no history or clinical evidence of venous disease. Setting: The Middlesex Hospital Vascular Laboratory, Mortimer Street, London WIN 8AA, UK. Patients: Volunteers within the Middlesex Hospital Vascular Laboratory with no history or clinical findings of venous or arterial disease, no other systemic disease, on no medication known to alter white cell activity, and with no recent infection. Interventions: Venous blood was taken from cannulae in both feet and the right arm for a neutrophil count and Plasma lactoferrin, measured using an ELISA, during application of a tourniquet to 80 mmHG for 30 min to the right leg while supine, 5 min after release of tourniquet, and then during a 30 min period of standing. Results: During application of a tourniquet to the right leg there was a significant rise in plasma lactoferrin and in lactoferrin corrected for the neutrophil count (p < 0.05, Wilcoxon). In the unoccluded leg, although Plasma lactoferrin rose, this was not significant when corrected for the rise in neutrophil count. After standing for 30 min, the lactoferrin and neutrophil count increased in all three limbs; corrected lactoferrin showed a significant increase in the legs (p < 0.02), though not in the arm. Conclusion: Increased neutrolphil degranulation occurs during periods of short-term venous hypertension in normal volunteers, in keeping with the white cell trapping hypothesis.

Three Tests of Microcirculatory Function in the Evaluation of Treatment for Chronic Venous Insufficiency

No investigation exists which has been shown to detect accurately microcirculatory improvement following treatment for chronic venous insufficiency. This study examines three possible techniques for doing so. Fourteen patients with chronic venous insufficiency and fourteen controls underwent measurement of transcutaneous PO2, 133xenon clearance from the skin and subcutaneous tissues and laser–Doppler flowmetry in the gaiter region. Patients with venous disease then followed a regime of intermittent pneumatic compression for 4 h each day for 4 weeks. The same measurements were then repeated. Xenon clearance from subcutaneous fat and the time taken to reach maximal laser–Doppler flow after release of a tourniquet showed a significant improvement after compression treatment. These tests may be useful as parameters in the objective monitoring of response to treatment in patients with liposclerotic skin.