Treatment of chronic venous ulcers with topical sevoflurane: a retrospective clinical study

Abstract

Editor—Chronic venous ulcers are a common problem with a significant repercussion on quality of life.1Valencia IC Falabella A Kirsner RS et al.Chronic venous insufficiency and venous leg ulceration.J Am Acad Dermatol. 2001; 44: 401-421Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar Eighty-five per cent of venous or mixed aetiology chronic ulcers are painful, with one group reporting a mean pain visual analogue scale (VAS) of 4.6.2Nemeth KA Harrison MB Graham ID et al.Pain in pure and mixed aetiology venous leg ulcers: a three-phase point prevalence study.J Wound Care. 2003; 12: 336-340Crossref PubMed Scopus (48) Google Scholar Chronic pain usually reduces adherence to treatment and impairs healing.3Guarnera G Tinelli G Abeni D et al.Pain and quality of life in patients with vascular leg ulcers: an Italian multicentre study.J Wound Care. 2007; 16: 347-351Crossref PubMed Scopus (65) Google Scholar Pain increases with cleaning and dressing changes. The most commonly used therapeutic drugs are oral analgesics (non-steroidal anti-inflammatory drugs, acetaminophen, metamizole, tramadol and opioids) and topical anaesthetic creams, such as lidocaine or prilocaine.1Valencia IC Falabella A Kirsner RS et al.Chronic venous insufficiency and venous leg ulceration.J Am Acad Dermatol. 2001; 44: 401-421Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar 3Guarnera G Tinelli G Abeni D et al.Pain and quality of life in patients with vascular leg ulcers: an Italian multicentre study.J Wound Care. 2007; 16: 347-351Crossref PubMed Scopus (65) Google Scholar Sevoflurane is an inhaled halogenated anaesthetic agent. Its efficacy by topical use has been reported in a few case reports as a topical anaesthetic in leg ulcers.4Gerónimo-Pardo M Martínez-Monsalve A Martínez-Serrano M Analgesic effect of topical sevoflurane on venous ulcer intractable pain.Phlebologie. 2011; 40: 95-97Crossref Scopus (33) Google Scholar, 5Martinez Monsalve A Gerónimo Pardo M Sevoflurano como anestésico local en herida isquémica de paciente cardiópata con insuficiencia respiratoria secundaria a morfina.Heridas y cicatrización. 2011; 6: 46-49Google Scholar, 6Rueda-Martínez JL Gerónimo-Pardo M Martínez-Monsalve A et al.Topical sevoflurane and healing of a post-operative surgical site superinfected by multi-drug-resistant Pseudomonas aeruginosa and susceptible Staphylococcus aureus in an immunocompromised patient.Surg Infect (Larchmt). 2014; 15: 843-846Crossref PubMed Scopus (26) Google Scholar, 7Imbernón A Blázquez C Puebla A et al.Chronic venous ulcer treatment with topical sevoflurane.Int Wound J. 2016; 13: 1060-1062Crossref PubMed Scopus (23) Google Scholar, 8Fernández FD Cortiñas M Fernández C et al.Sevoflurano tópico: una nueva opción terapéutica paliativa en las úlceras cutáneas.Med Paliativa. 2015; 180: 5Google Scholar We have used it in our clinical practice, from which we have retrospectively reviewed 30 cases. All patients were over 65 yr old, with a pain VAS score ≥4. Written consents were obtained from patients for off-label use of topical sevoflurane. The drug and the study protocols were approved by a Pharmacy Committee and our Hospital Ethics Committee, respectively. We excluded hospitalized patients, ulceration of any other cause, generalized arteriosclerosis, cognitive impairment or pain from another cause. Quality of life has been measured by the Charing Cross Venous Leg Ulcer Questionnaire.9González-Consuegra RV Verdú J Quality of life in people with venous leg ulcers: an integrative review.J Adv Nurs. 2011; 67: 926-944Crossref PubMed Scopus (135) Google Scholar Functional capacity was measured by the Barthel Index.10Loewen SC Anderson BA Reliability of the modified motor assessment scale and the barthel index.Phys Ther. 1988; 68: 1077-1081Crossref PubMed Scopus (182) Google Scholar Cleaning with sevoflurane every 2 days for a period of 1 month was scheduled. Treatment consisted of cleaning initially with a saline solution and irrigating the ulcer with 1 ml of liquid sevoflurane for every 1 cm2 wound size without exceeding the edges of healthy skin. We compared the results of wound cleaning without sevoflurane and subsequent treatments with sevoflurane. Mean (SD) VAS pain score during cleaning was 8.8 (1.3) in the previous cleaning without sevoflurane. Pain decreased with subsequent cleanings with sevoflurane with VAS decreasing to 0.8 (1) by the 12th cleaning (Fig. 1). A variable latency time was found between 2 and 7 min [mean 3.9 (1.5) min]. The duration of analgesia ranged between 8 and 18 h [mean 12 (2.9) h]. Each patient showed no variation in duration of analgesia throughout all cleanings with sevoflurane. Most of the patients showed low satisfaction with cleaning. After initial cleaning with sevoflurane, satisfaction increased. From the second cleaning with sevoflurane, all the patients scored satisfaction as good or very good. Following use of sevoflurane there was a progressive improvement in quality of life [83 (14) points before treatment and 50 (14) after sevoflurane] and Barthel Index [82 (13.3) before treatment and 91 (11.6) points after sevoflurane]. Wound size decreased progressively in all patients after two weeks of sevoflurane treatment. The main local adverse effects were mild and transient, including hot sensation, pruritus and erythema. No systemic adverse effects were detected. Topical sevoflurane may be an effective and safe therapeutic alternative in painful chronic venous ulcer with an intense, fast and long-lasting analgesic effect during the cleaning. Systemic absorption from a venous ulcer appears to be slow and incomplete. Topical sevoflurane may decrease or avoid use of other conventional analgesic drugs, improving the experience of wound cleaning without adversely affecting wound healing. Although the sample size was small, initial indications are that topical sevoflurane has a favourable safety profile. The mechanism of action is unknown but vasodilator, anti-inflammatory and analgesic effects are suggested.4Gerónimo-Pardo M Martínez-Monsalve A Martínez-Serrano M Analgesic effect of topical sevoflurane on venous ulcer intractable pain.Phlebologie. 2011; 40: 95-97Crossref Scopus (33) Google Scholar, 5Martinez Monsalve A Gerónimo Pardo M Sevoflurano como anestésico local en herida isquémica de paciente cardiópata con insuficiencia respiratoria secundaria a morfina.Heridas y cicatrización. 2011; 6: 46-49Google Scholar, 6Rueda-Martínez JL Gerónimo-Pardo M Martínez-Monsalve A et al.Topical sevoflurane and healing of a post-operative surgical site superinfected by multi-drug-resistant Pseudomonas aeruginosa and susceptible Staphylococcus aureus in an immunocompromised patient.Surg Infect (Larchmt). 2014; 15: 843-846Crossref PubMed Scopus (26) Google Scholar, 7Imbernón A Blázquez C Puebla A et al.Chronic venous ulcer treatment with topical sevoflurane.Int Wound J. 2016; 13: 1060-1062Crossref PubMed Scopus (23) Google Scholar, 8Fernández FD Cortiñas M Fernández C et al.Sevoflurano tópico: una nueva opción terapéutica paliativa en las úlceras cutáneas.Med Paliativa. 2015; 180: 5Google Scholar These initial promising results would support further study of the analgesic use of topical sevoflurane. All authors participated in drafting the article or revising it critically for important intellectual content and all authors approved the final version. Antonio Aguilar and Miguel Ángel Gallego for their help with the study. All authors have declared no conflicts of interest.