Comment to: Significant endothelin release in patients treated with foam sclerotherapy by Frullini A, Barsotti MC, Santoni T, Duranti E, Burchielli S, Di Stefano R. Dermatol Surg 2012;38:741–7.

Abstract

A greater incidence of cough, transient visual and neurological disturbances have been reported with foam rather than with liquid sclerosant. These complications have often been associated with migraine and patent foramen ovale (PFO), a common condition affecting approximately 25% of the whole adult population. Foam bubbles may pass through a PFO to the left heart chambers, with consequent paradoxical systemic embolization. Visual and neurological disturbances have often been reported also with liquid sclerosants which conflicts with the bubble theory. In a recent study, the same Authors1 demonstrated that POL foam is capable of significantly elevating endothelin 1 (ET-1) in an animal model. It is feasible that the release of ET-1 is a source of neurological and visual disturbances after sclerotherapy. In the first part of this study, the Authors tested ET-1 release in 11 rats treated with STS 1% (Fibro-vein). Five were treated with liquid STS and 6 with STS foam. A significant difference was found between ET level at 1 min and at 5 min with foam STS (P<0 .01). In the second part of the study, 11 human subjects, mean age 52.0±15.3; CEAP distribution C1 (n=3) and C2 (n=8), with chronic varicose veins were treated with foam and studied for ET-1 release. Polidocanol (Aethoxysklerol) concentration ranged from 0.5% to 3%. Mean volume per session was 3.86 mL. Patients were kept immobile and supine during the study. They were studied at T0 with a systemic blood withdrawal (arm vein) for ET-1 assay and then underwent foam sclerotherapy. One milliliter of blood was aspirated from the arm vein 3 min (T1) after treatment. To compare systemic ET-1 with local ET-1 levels, 1 mL of blood was collected from a proximal vein draining from the target area at the same time as T1. A significant increase in systemic ET-1 values was observed within 3 min after treatment using foamed sclerosant Furthermore, ET-1 values from the draining vein closely correlated with systemic ET-1 values at T1. The Authors demonstrated significant systemic production of ET after foam injection in patients with chronic venous disorders as early as 3 min after treatment; the sclerosant is capable of inducing ET-1 release from the vein wall. Vasospasm could be the key to understanding this complex physiopathology; vasospasm has been found to be related to migraine, chest tightness, retinal transient ischemia, and neurological ischemia. A clear relationship between endothelial damage and migraine attacks has been demonstrated in patients with migraine. The role of ET-1 in the first vasospastic phase has also been clarified. In 2009, Gillet suggested that visual disturbances correlate with episodes of cortical spreading depression induced by ET, as episodes of migraine with aura and not as transient cerebral ischemic attacks. To summarize, it can be postulated that ET-1 is released after sclerotherapy from the treated vein. During its transit in the pulmonary circulation, ET-1 is linked to receptors, and for the short half-life, lower ET levels are usually present in the systemic circulation. When a PFO is present (or similar right-to-left shunt), ET-1-rich blood is shunted to the left heart and in the systemic circulation, provoking side effects.