Tratamiento crónico ambulatorio con sevoflurano tópico en pacientes con úlceras vasculares / Chronic outpatient treatment with topical sevoflurane in patients with vascular ulcers

Objetivo mostrar la efectividad y seguridad del sevoflurano tópico tras la administración ambulatoria y prolongada en los pacientes con úlceras vasculares refractarias. Métodos estudio observacional retrospectivo de pacientes con úlceras vasculares dolorosas refractarias a terapias habituales y que fueron tratados con sevoflurano tópico durante al menos 36 meses. Se recogieron las variables: edad, sexo, antecedentes médicos, comorbilidad asociada, etiología de úlcera y tratamiento médico. Se analizó la mejoría clínica y la variación de la superficie de las úlceras vasculares. Para cuantificar la intensidad del dolor basal e irruptivo antes y después del tratamiento se utilizó la escala visual analógica. Resultados del total de pacientes tratados, 9 cumplían los criterios de inclusión. La edad media fue de 74,8 ± 7,5 años. Los casos 2 y 9 fallecieron durante el seguimiento. La acción analgésica del sevoflurano tópico fue rápida (3,1 ± 2,1 min), intensa (escala visual analógica: 7 ± 1,1 a 1,4 ± 1,1 puntos) y duradera (de 6 a 24 h). Salvo el caso 4, todos experimentaron una reducción de la superficie (15,1 ± 5,0 a 2,7 ± 4,2) de las úlceras vasculares y no se observó tolerancia a lo largo del tiempo. Conclusión la aplicación de sevoflurano tópico es una estrategia analgésica y reepitelizante para las úlceras vasculares que presenta un perfil correcto de seguridad (AU)

Objective To show the effectiveness and safety of topical sevoflurane after ambulatory and prolonged administration in patients with refractory vascular ulcers. Methods Retrospective observational study analyzing clinical improvement and vascular ulcers surface area variation after topical application of sevoflurane. Inclusion criteria were patients with painful vascular ulcers refractory to usual therapies and who were treated with topical sevoflurane for at least 36 months. The following variables were collected: age, sex, medical history, associated comorbidity, ulcer etiology and medical treatment. The visual analog scale was used to measure baseline and break through pain intensity before and after treatment. Results Nine patients met the inclusion criteria of the total number of patients treated whose median age was 74.8 ± 7.5 years. Cases 2 and 9 died during follow-up. In all cases, the analgesic action of topical sevoflurane was rapid (3.1 ± 2.1 minutes), intense (visual analog scale: 7 ± 1.1 to 1.4 ± 1.1 points) and long-lasting (6 to 24 h). With the exception of case 4, all patients experienced a large reduction in vascular ulcers surface area (15.1 ± 5.0 a 2.7 ± 4.2) and tolerance was not observed over time. Conclusion Topical application of sevoflurane is an analgesic and re-epithelializing strategy for vascular ulcers with a successful safety profile (AU)

Chronic outpatient treatment with topical sevoflurane in patients with vascular ulcers. / Tratamiento crónico ambulatorio con sevoflurano tópico en pacientes con úlceras vasculares.

OBJECTIVE: To show the effectiveness and safety of topical sevoflurane after ambulatory and prolonged administration in patients with refractory vascular ulcers. METHODS: Retrospective observational study analyzing clinical improvement and vascular ulcers surface area variation after topical application of sevoflurane. Inclusion criteria were patients with painful vascular ulcers refractory to usual therapies and who were treated with topical sevoflurane for at least 36 months. The following variables were collected: age, sex, medical history, associated comorbidity, ulcer etiology and medical treatment. The visual analog scale was used to measure baseline and break through pain intensity before and after treatment. RESULTS: Nine patients met the inclusion criteria of the total number of patients treated whose median age was 74.8 ± 7.5 years. Cases 2 and 9 died during follow-up. In all cases, the analgesic action of topical sevoflurane was rapid (3.1 ± 2.1 minutes), intense (visual analog scale: 7 ± 1.1 to 1.4 ± 1.1 points) and long-lasting (6 to 24 h). With the exception of case 4, all patients experienced a large reduction in vascular ulcers surface area (15.1 ± 5.0 a 2.7 ± 4.2) and tolerance was not observed over time. CONCLUSION: Topical application of sevoflurane is an analgesic and re-epithelializing strategy for vascular ulcers with a successful safety profile.

Sevoflurane topical analgesia for intractable pain with suicidal ideation.

Proper symptom management to improve quality of dying is mandatory in palliative care patients. Home-based control of pain caused by leg ulcers is challenging, especially when the pain is severe and refractory to conventional analgesics, the patient is intolerant to opioids and refuses invasive measures. This was the case for an 87-year-old woman under oncological palliative care who suffered from a leg ulcer causing refractory pain, which produced suicidal ideation. Leg amputation was indicated, but she had signed a living will refusing any invasive measures. After obtaining written informed consent, sevoflurane was applied topically on the ulcer, which resulted in a rapid and long-lasting reduction of pain. Daily self-administration of sevoflurane successfully controlled the wound pain and the patient abandoned her suicidal ideation, the wound healed 35 days later, and her quality of dying improved remarkably. Topical sevoflurane deserves further research on ulcers of vascular and also neoplastic aetiology.

Pain management & opioid dose reduction with topical sevoflurane instillations in intractable venous ulcers: a case report

Abstract Vascular ulcers (VU) constitute a major cause of pain and disability, and significantly compromise quality of life. VU have a natural tendency to become chronic and in many cases exhibit anunsatisfactoryresponse to many of the standard therapeutic options.The case of a 73 year-old Caucasian female with severe pain and poorly-controlled pain (Visual Analogic Scale-VAS- of 8-9) due to three lower leg long-standing VUs is reported and discussed herein. The patient was treated with topical instillations of undiluted sevoflurane as per institutional off-label protocol (starting doses of 1mL/cm2 twice a day, and up-titrated according to response to a maximum of 7 mL twice daily). The VAS score dropped to 0-1 shortly after initiation of therapy and remained stable throughout treatment up until the closure of the observations. Subsequently, opioid therapy was gradually tapered down and ultimately abandoned.Sevoflurane application resulted on adequate and sustained pain management of refractory VU, with no significant side effects. On account of its beneficial effectivity and safety profiles, topical sevoflurane emerges as an add-on alternative for the long-term management of VU, and potentially other painful conditions.

Topical sevofluran: a galenic experience.

Sevoflurane is a volatile liquid from the family of ether-derived alogenated hydrocarbons that is approved for the induction and  maintenance of inhalational general anesthesia in the hospital setting. This review describes the pioneering experience of a Spanish Pain Unit in the  home treatment of complicated painful wounds using topical sevoflurane  instillations according to a protocol approved for off-label use. Aspects of  safety and efficacy, both analgesic, antimicrobial and pro-healing are  addressed, and some future lines of research are discussed in terms of  new formulations for topical use. After more than seven years of use of the protocol, an experience of over 70,000 applications of topical sevoflurane  has been gained. In general terms, the analgesic effect appears quickly, is  highly intense and persists for several hours. As a result, patients can  reduce their consumption of systemic analgesics and benefit from an  improvement in their quality of life. In addition, there are signs that  suggest sevoflurane also possesses antimicrobial and pro-healing  properties. Regarding safety, pruritus at the level of the periulcerous skin  is the most frequently reported adverse effect, although it is usually  transient and well-tolerated, and no systemic toxicity has been reported.  Overall, the risk-benefit balance of the drug has so far been very  favorable. To avoid manipulation of this volatile liquid, we have developed  a new formulation of sevoflurane in gel form, which has made it possible  to successfully apply sevoflurane in the context of painful pathologies  where the skin remains intact. Furthermore, these types of new  formulations, including sevoflurane microspheres, which we have also  developed, could improve the efficacy and safety of topical sevoflurane  while reducing the occupational exposure of healthcare staff. This means  that the development of new formulations is a field with a very promising  future.

El sevoflurano es un líquido volátil de la familia de los hidrocarburos  alogenados derivados del éter que está aprobado para realizar la inducción y el mantenimiento de la anestesia general inhalatoria en ambiente  exclusivamente hospitalario. En esta revisión se expone la experiencia  pionera de nuestra Unidad del Dolor en el tratamiento domiciliario de  heridas dolorosas complejas mediante irrigaciones de sevoflurano tópico  según un protocolo aprobado para su uso fuera de ficha técnica. Se  abordan aspectos de seguridad y eficacia, tanto analgésica como  antimicrobiana y procicatrizante, y se comentan algunas líneas de futuro  en cuanto a nuevas formulaciones para uso tópico. Tras más de 7 años de  vigencia del referido protocolo, contamos con una experiencia acumulada  de más de 70.000 aplicaciones de sevoflurano tópico. En líneas generales,  el efecto analgésico aparece rápidamente en cuestión de minutos, es de  gran intensidad, y de duración prolongada por espacio de varias horas;  gracias a ello los pacientes pueden reducir el consumo de analgésicos sistémicos y, en general, su calidad de vida mejora. Además,  existen indicios que sugieren que también ejerce acción antimicrobiana y  procicatrizante. En cuanto a seguridad, el prurito a nivel de la piel  periulcerosa es el efecto adverso más frecuentemente comunicado,  aunque suele ser transitorio y bien tolerado, y no hay signos sugerentes  de toxicidad sistémica. Globalmente, el balance beneficio-riesgo es muy  favorable para los pacientes hasta el momento. Para evitar la manipulación de la presentación líquida y volátil hemos desarrollado una nueva  formulación de sevoflurano en tipo gel, lo cual ha permitido tratar  satisfactoriamente patologías dolorosas que cursan con piel íntegra;  además, este tipo de nuevas formulaciones, incluyendo las microesferas de sevoflurano que también desarrollamos, podrían mejorar la eficacia y la  seguridad del fármaco tópico a la vez que se reduce la exposición  ocupacional del personal sanitario, por lo que el desarrollo de nuevas  formulaciones es un campo con un futuro muy prometedor.

Cost-effectiveness analysis of domiciliary topical sevoflurane for painful leg ulcers.

OBJECTIVES: The general anesthetic sevoflurane is being repurposed as a topical analgesic for painful chronic wounds. We conducted a Bayesian cost-effectiveness analysis (CEA) comparing the addition of domiciliary topical sevoflurane to conventional analgesics (SEVOFLURANE, n = 38) versus conventional analgesics alone (CONVENTIONAL, n = 26) for the treatment of nonrevascularizable painful leg ulcers in an outpatient Pain Clinic of a Spanish tertiary hospital. METHODS: We used real-world data collected from charts to conduct this CEA from a public healthcare perspective and with a one-year time horizon. Costs of analgesics, visits and admissions were considered, expressed in €2016. Analgesic effectiveness was measured with SPID (Sum of Pain Intensity Difference). A Bayesian regression model was constructed, including "treatment" and baseline characteristics for patients ("arterial hypertension") and ulcers ("duration", "number", "depth", "pain") as covariates. The findings were summarized as a cost-effectiveness plane and a cost-effectiveness acceptability curve. One-way sensitivity analyses, a re-analysis excluding those patients who died or suffered from leg amputation, and an extreme scenario analysis were conducted to reduce uncertainty. RESULTS: Compared to CONVENTIONAL, SEVOFLURANE was associated with a 46% reduction in costs, and the mean incremental effectiveness (28.15±3.70 effectiveness units) was favorable to SEVOFLURANE. The estimated probability for SEVOFLURANE being dominant was 99%. The regression model showed that costs were barely influenced by any covariate, whereas effectiveness was noticeably influenced by "treatment". All sensitivity analyses showed the robustness of the model, even in the extreme scenario analysis against SEVOFLURANE. CONCLUSIONS: SEVOFLURANE was dominant over CONVENTIONAL as it was less expensive and much more effective.

Pain reduction of topical sevoflurane vs intravenous opioids in pressure ulcers.

Recently, it has been reported that topical irrigations of liquid sevoflurane on the bed of painful wounds produce a rapid, intense, and lasting analgesic effect. In this paper, A cohort of 112 patients with painful pressure ulcers who were refractory to opioids (or who exhibited undesirable adverse events to them) was treated with topical sevoflurane as per local institutional policy. These patients were recruited from an intensive care unit for a period of 3 years. The main aim was to determine the effectiveness of topical sevoflurane in reducing the pain of PUs and reducing the ulcer area. Study findings are reported and discussed herein and suggest that sevoflurane is a viable and promising treatment option for PUs.

Palliative analgesia with topical sevoflurane in cancer-related skin ulcers: a case report.

A Caucasian 39-year-old male patient with a poorly-differentiated infiltrating epidermoid penile carcinoma with urethral invasion was diagnosed. The patient received concomitant adjuvant chemotherapy with radiotherapy in the palliative setting, which produced painful ulceration of tumour lesions at loco-regional level (Numerical Rate Scale, NRS=9). The patient consented for treatment with direct topical sevoflurane instillations, at initial doses of 1 mL/cm2 of ulcerated area, as per unit protocol. The local use of undiluted sevoflurane achieved a marked reduction of the pain score in both nociceptive and irruptive pains (average NRS=3 immediately post-application). This improvement was corroborated by a decline in total morphine needs, any adverse events associated with major opiates. PGI-I and CGI-I scales were used before and after treatment with topical sevoflurane to assess patient and clinician perceptions of improvement in the quality of life. The pharmacy of our hospital had the responsibility to elaborate pre-loaded syringes with sevoflurane so that the patient was instilled simply and comfortably.