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.

At-home Topical Sevoflurane Added to the Conventional Analgesic Treatment for Painful leg Ulcers Greatly Improved the Analgesic Effectiveness and Reduced Opioid Consumption in a Single-Center Retrospective Comparative Study with one-Year Follow-up.

The general anesthetic sevoflurane is being repurposed as a topical analgesic for painful chronic wounds. This study was aimed to compare the analgesic effectiveness and safety of systemic analgesics alone or plus at-home topical sevoflurane for the management of patients with painful nonrevascularizable leg ulcers who were referred to a Pain Clinic by their attending vascular surgeons. We reviewed charts of patients treated in a single Pain Clinic with analgesic Standard of Care either alone (group SoC) or plus at-home topical sevoflurane (group SoC + Sevo), according to safety criteria. The area under the curve of pain over a year (AUC-Pain) was the primary outcome for analgesic effectiveness. Opioids were converted into Oral Morphine Milligram Equivalents. Groups SoC (n = 26) and SoC + Sevo (n = 38) were similar in baseline characteristics. Compared to SoC, median values [interquartile range] of area under the curve of pain for one-year follow-up were markedly lower for SoC + Sevo (54 [35-65] vs. 15 [11-23]; p < 0.000001, U Mann-Whitney test). Oral Morphine Milligram Equivalents were similar at baseline (SoC: 78.5 [22.5-135] vs. SoC + Sevo: 101.3 [30-160]; p = 0.753), but significantly lower for SoC + Sevo at three (120 [22.5-202.5] vs. 30 [0-80]; p = 0.005), six (120 [11.3-160] vs. 20 [0-67.5]; p = 0.004), nine (114.4 [0-154] vs. 0 [0-37]; p = 0.018), and 12 months (114.4 [0-154] vs. 0 [0-20]; p = 0.001). Multiple linear regression analysis revealed the addition of sevoflurane to be the most likely variable to explain this difference in outcome (ß:-33.408; p < 0.000001). Nine patients (24%) in SoC + Sevo had adverse effects attributed to sevoflurane, but only one patient needed to stop using sevoflurane due severe dermatitis. In conclusion, the addition of topical sevoflurane to the analgesic standard of care in patients with painful nonrevascularizable leg ulcers was a well-tolerated therapy that significantly improved pain control and allowed for a significant reduction in opioid consumption.

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.

Sevoflurano tópico: una experiencia galena / Topical sevoflurane: a galenic experience

El sevoflurano es un líquido volátil de la familia de los hidrocarburos halogenados derivados del éter que está aprobado para realizar la inducción y elmantenimiento de la anestesia general inhalatoria en ambiente exclusivamentehospitalario. En esta revisión se expone la experiencia pionera de nuestra Unidad del Dolor en el tratamiento domiciliario de heridas dolorosas complejasmediante irrigaciones de sevoflurano tópico según un protocolo aprobadopara su uso fuera de ficha técnica. Se abordan aspectos de seguridad y eficacia, tanto analgésica como antimicrobiana y procicatrizante, y se comentanalgunas líneas de futuro en cuanto a nuevas formulaciones para uso tópico.Tras más de 7 años de vigencia del referido protocolo, contamos con unaexperiencia acumulada de más de 70.000 aplicaciones de sevoflurano tópico.En líneas generales, el efecto analgésico aparece rápidamente en cuestión deminutos, es de gran intensidad, y de duración prolongada por espacio de variashoras; gracias a ello los pacientes pueden reducir el consumo de analgésicossistémicos y, en general, su calidad de vida mejora. Además, existen indiciosque sugieren que también ejerce acción antimicrobiana y procicatrizante. (AU)

Sevoflurane is a volatile liquid from the family of ether-derived halogenated hydrocarbons that is approved for the induction and maintenance ofinhalational general anesthesia in the hospital setting. This review describes the pioneering experience of a Spanish Pain Unit in the home treatmentof 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, andsome future lines of research are discussed in terms of new formulationsfor topical use. After more than seven years of use of the protocol, anexperience of over 70,000 applications of topical sevoflurane has beengained. In general terms, the analgesic effect appears quickly, is highlyintense and persists for several hours. As a result, patients can reduce theirconsumption of systemic analgesics and benefit from an improvement intheir quality of life. In addition, there are signs that suggest sevofluranealso possesses antimicrobial and pro-healing properties. Regarding safety,pruritus at the level of the periulcerous skin is the most frequently reportedadverse effect, although it is usually transient and well-tolerated, and nosystemic toxicity has been reported. Overall, the risk-benefit balance of thedrug has so far been very favorable. To avoid manipulation of this volatileliquid, we have developed a new formulation of sevoflurane in gel form,which has made it possible to successfully apply sevoflurane in the contextof painful pathologies where the skin remains intact. Furthermore, thesetypes of new formulations, including sevoflurane microspheres, which wehave also developed, could improve the efficacy and safety of topicalsevoflurane while reducing the occupational exposure of healthcare staff.This means that the development of new formulations is a field with a verypromising future. (AU)

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.

Revisión de mezclas binarias, ternariasy cuaternarias para inducción y mantenimiento de anestesia libre de opiáceos / Review of binary, ternary and quaternary mixtures for induction and maintenance of opioid free anesthesia

Objetivo: Describir y estructurar la información actual disponible sobremezclas binarias, ternarias y/o cuaternarias empleadas en una “anestesialibre de opiáceos”, así como su estabilidad fisicoquímica, para facilitar sucorrecta administración, optimizar su uso y prevenir posibles problemasde efectividad o seguridad.Método: Revisión sistemática de la literatura sobre anestesia libre deopiáceos en PubMed/Medline, Trissel, Micromedex, Lexicomp, AHFS DrugInformation, Extended Stability for Parenteral Drugs y Stabilis Web. Artículos publicados en inglés o español hasta mayo de 2020 y con acceso atexto completo. Se emplearon los términos MeSH: “Drug Incompatibility”AND “Opioid Free Anesthesia” AND “Administration, Intravenous” AND“Dexmedetomidine” AND “Lidocaine” AND “Ketamine” AND “SulphateMagnesium” OR “Infusions, Intravenous”. Se realizó una primera búsquedaen PubMed/Medline incluyendo casos clínicos de anestesia general tipoanestesia libre de opiáceos. Los resultados obtenidos se estructuraron enuna base de datos. La segunda búsqueda fue sobre incompatibilidadesde las mezclas intravenosas. Se recogieron medicamentos compatibles/incompatibles; concentraciones de referencia; tiempo de estabilidad a temperatura ambiente (23 ± 2 °C) y en refrigeración (4 ± 2 °C); tipo de administración recomendada y resultados y conclusiones relevantes. Se crearon dos tablas bidimensionales de la compatibilidad de cada combinación defármacos para la administración en Y o en mezcla en una sola solución.Resultados: Se identificaron 780 artículos; se accedió al texto completo de 203. Se recogieron de forma cronológica los 4.762 casos tratados en 32 diferentes publicaciones con protocolos de anestesia librede opiáceos. El uso de dos fármacos fue la asociación más frecuente(42,4%). Los fármacos más empleados fueron dexmedetomidina (25 trabajos), clorhidrato de ketamina (25 trabajos) y lidocaína (14 trabajos). (AU)

Objective: To describe and organize the current information availableon binary, ternary and/or quaternary mixtures used in opioid-free anesthesia (OFA), as well as their physicochemical stability, in order to facilitate itscorrect administration, optimize its use, and prevent potential effectivenessand safety issues.Method: A systematic review of the literature on OFA was conductedin PubMed/Medline, Trissel, Micromedex, Lexicomp, www.ahfsdruginformation.com, ASHP’s Extended Stability for Parenteral Drugs, and www.stabilis.org. Only articles published in English or Spanish until May 2020and with access to full text were considered. MeSH terms used included:“drug incompatibility” AND “opioid-free anesthesia” AND “administration,intravenous” AND “dexmedetomidine” AND “lidocaine” AND “ketamine”AND “magnesium sulphate” OR “infusions, intravenous. A first search wascarried out in PubMed/Medline that included OFA clinical cases. Theresults obtained were collected in a database. A second search wascarried out on the incompatibilities of intravenous mixtures. Informationwas compiled on mutually-compatible/incompatible drugs, reference concentrations, stability time at room temperature (23 ± 2 °C) and under refrigeration (4 ± 2 ºC), type of administration recommended, and relevantresults and conclusions. Two two-dimensional tables on the compatibility of each drug combination were created for administration as Y-site infusionor as a mixture in a single solution. (AU)

Review of binary, ternary and quaternary mixtures for induction and maintenance of opioid free anesthesia.

OBJECTIVE: To describe and organize the current information available on  binary, ternary and/or quaternary mixtures used in opioid-free anesthesia (OFA), as well as their physicochemical stability, in order to  facilitate its correct administration, optimize its use, and prevent potential  effectiveness and safety issues. METHOD: A systematic review of the literature on OFA was conducted in  PubMed/Medline, Trissel, Micromedex, Lexicomp,  ww.ahfsdruginformation.com, ASHP's Extended Stability for Parenteral Drugs, and www.stabilis.org. Only articles published in English or Spanish until May 2020 and with  access to full text were considered. MeSH terms used included: "drug  incompatibility" AND "opioid-free anesthesia" AND "administration, intravenous" AND "dexmedetomidine" AND "lidocaine"  AND "ketamine" AND "magnesium sulphate" OR "infusions, intravenous. A  first search was carried out in PubMed/Medline that included OFA clinical cases. The results obtained were collected in a database. A second search  was carried out on the incompatibilities of intravenous mixtures.  Information was compiled on mutually-compatible/incompatible drugs,  reference concentrations, stability time at room temperature (23 ± 2 °C)  and under refrigeration (4 ± 2 ºC), type of administration recommended,  and relevant results and conclusions. Two two-dimensional tables on the  compatibility of each drug combination were created for administration as  Y-site infusion or as a mixture in a single solution. RESULTS: Seven hundred and eighty articles were identified, with the full  text of 203 being accessed. A total of 4,762 cases treated with OFA  protocols were chronologically collected from 32 different publications. Administration of two concomitant drugs was the most usual  regimen (42.4%). The most frequently drugs were dexmedetomidine (25  studies), ketamine hydrochloride (25 studies) and lidocaine (14 studies).  Compatibility/incompatibility data was collected for 11 drugs, associated to  7 pharmacological groups; compatibility with Y-site administration was  found in 43 of 55 combinations (78.18%) and with integration into one  single solution in 13 of 55 drug combinations (23.63%). None of the  sources reviewed reported any adverse results related to potential  pharmacological incompatibilities. CONCLUSIONS: Despite the availability of multiple OFA protocols, few studies analyze the compatibility between binary drug mixtures. No  information exists as yet regarding compatibilities in the context of ternary and quaternary mixtures.  Despite the availability of multiple OFA  protocols, few studies analyze the compatibility between binary drug  mixtures. No information exists as yet regarding compatibilities in the  context of ternary and quaternary mixtures.

Objetivo: Describir y estructurar la información actual disponible sobre mezclas binarias, ternarias y/o cuaternarias empleadas en una  "anestesia libre de opiáceos", así como su estabilidad fisicoquímica, para  facilitar su correcta administración, optimizar su uso y prevenir posibles  problemas de efectividad o seguridad.Método: Revisión sistemática de la literatura sobre anestesia libre de opiáceos en PubMed/Medline, Trissel, Micromedex, Lexicomp, AHFS  Drug Information, Extended Stability for Parenteral Drugs y Stabilis Web.  Artículos publicados en inglés o español hasta mayo de 2020 y con acceso  a texto completo. Se emplearon los términos MeSH: "Drug Incompatibility" AND "Opioid Free Anesthesia" AND "Administration,  Intravenous" AND "Dexmedetomidine" AND "Lidocaine" AND "Ketamine"  AND "Sulphate Magnesium" OR "Infusions, Intravenous". Se realizó una  primera búsqueda en PubMed/Medline incluyendo casos clínicos de  anestesia general tipo anestesia libre de opiáceos. Los resultados  obtenidos se estructuraron en una base de datos. La segunda búsqueda  fue sobre incompatibilidades de las mezclas intravenosas. Se recogieron  medicamentos compatibles/ incompatibles; concentraciones de referencia; tiempo de estabilidad a temperatura ambiente (23 ± 2 °C) y en  refrigeración (4 ± 2 °C); tipo de administración recomendada y resultados  y conclusiones relevantes. Se crearon phardos tablas bidimensionales de la compatibilidad de cada combinación de fármacos para la administración en Y o en mezcla en una sola solución.Resultados: Se identificaron 780 artículos; se accedió al texto completo de 203. Se recogieron de forma cronológica los 4.762 casos  tratados en 32 diferentes publicaciones con protocolos de anestesia libre de opiáceos. El uso de dos fármacos fue la asociación más frecuente (42,4%). Los fármacos más empleados fueron dexmedetomidina (25 trabajos), clorhidrato de ketamina (25 trabajos) y lidocaína (14  trabajos). Se recopiló información de compatibilidad/incompatibilidad de  11 medicamentos, asociados a 7 grupos farmacológicos, encontrándose  compatibilidad en Y en 43 de 55 combinaciones (78,18%) y en mezcla en  una sola solución en 13 de 55 combinaciones de fármacos (23,63%). En  ningún trabajo publicado se expone algún tipo de evento adverso en  relación con una posible incompatibilidad farmacológica.Conclusiones: Existen múltiples protocolos de anestesia libre de  piáceos, pero los estudios de compatibilidad entre las diferentes mezclas  de fármacos empleadas son muy limitados cuando se trata de mezclas  binarias, y no existe información en el caso de mezclas ternarias y  cuaternarias.

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.

Occupational exposure to sevoflurane following topical application to painful wounds.

BACKGROUND: Occupational exposure to halogenated anesthetics employed for general anesthesia has been extensively studied. Conversely, a new modality of treatment of painful wounds with topical sevoflurane lacks exposure studies. OBJECTIVES: To evaluate the magnitude of acute occupational exposure to sevoflurane following topical application to painful wounds. METHODS: Four patients with chronic painful wounds were treated with topical sevoflurane (20, 20, 20 and 10 mL) following an approved therapeutic protocol in our Pain Management Unit. Eight passive dosimeters were placed at different locations of a treatment room with a volume of 163 m3 and 3.3 air changes per hour: 3 for near peak (for 20-50 min) and 1 overall exposure (for 3.4 h) at the nurse's breathing zone, and 4 for area exposure (for 3-3.4 h). Worst-case scenario theoretical concentrations of sevoflurane were also calculated. RESULTS: The highest levels were obtained for two dosimeters worn by the nurse at the breathing zone (8.28 and 9.12 ppm-TWA [parts per million-Time-Weighted Average]), while the lowest level was obtained from the dosimeter placed on the most distant wall from patients (0.73 ppm-TWA). Theoretical concentrations were calculated from standard volatilization principles and were in agreement with the concentrations measured. Discussion-Conclusions: All air concentrations measured were lower than exposure limits set by occupational safety agencies from Finland, Sweden and Norway, which range from 10 ppm for a TWA of 8 hours to 20 ppm for short-term exposures (15 min). Application of topical sevoflurane on wounds seems to be environmentally safe for health-care professionals as it produces exposure levels lower than the established limits for anesthetic procedures.

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.

Opioids and immunosupression in oncological postoperative patients / Opioides e imunossupressão em pacientes oncológicos pós-cirúrgicos

Summary Introduction: Recent animal studies demonstrated immunosuppressive effects of opioid withdrawal resulting in a higher risk of infection. The aim of this study was to determine the impact of remifentanil discontinuation on Post-Anesthesia Care Unit (PACU)-acquired infection after a schedule of sedoanalgesia of at least 6 days. Method: All patients over 18 years of age with a unit admission of more than 4 days were consecutively selected. The study population was the one affected by surgical pathology of any origin where sedation was based on any hypnotic and the opioid remifentanil was used as analgesic for at least 96 hours in continuous perfusion. Patients who died during admission to the unit and those with combined analgesia (peripheral or neuroaxial blocks) were excluded. Bivariate analysis was performed to determine risk factors for infection acquired in the unit. A comparative study between periods of 6 days before and after the cessation of remifentanil was performed. Paired samples test and McNemar test was used for quantitative and categorical variables, respectively. Results: There were 1,789 patients admitted to the PACU during the study and the population eligible was constituted for 102 patients. The incidence rate of PACU-acquired infection was 38 per 1,000 PACU days. Ventilator-associated pneumonia was the most frequently diagnosed PACU-acquired infection. Pseudomona aeruginosa was the most frequently isolated microorganism. Hospital mortality was 36.27%. No statistically significant differences were seen in the incidence of HAI in cancer patients in relation to discontinuation of remifentanil (p=0.068). Conclusion: The baseline state of immunosuppression of cancer patients does not imply a higher incidence of HAI in relation to the interruption of remifentanil. It would be of interest to carry out a multicenter PACU study that included immunological patterns.

Resumo Introdução: Recentes pesquisas utilizando animais demonstraram efeitos imunossupressores depois da suspensão de opiáceos, associados a um maior risco de infecção nosocomial. O objetivo desta investigação foi determinar o impacto da interrupção do opioide remifentanilo em uma Unidade de Reanimação Pós-cirúrgica (URP) nas infecções associadas aos cuidados da saúde depois de uma pauta de sedoanalgesia de ao menos 6 dias. Método: Foram relacionados de forma consecutiva todos os pacientes maiores de 18 anos com internação na unidade superior a 4 dias. A população investigada foi aquela afetada por patologia cirúrgica de qualquer origem, na qual a sedação esteve baseada em qualquer hipnótico e como analgésico, foi utilizado o opioide remifentanilo durante pelo menos 96 horas em perfusão contínua. Foram excluídos os pacientes que faleceram durante a internação na unidade e aqueles com analgesia combinada (bloqueios periféricos ou neuroaxiais). Foi realizada uma análise bivariante para determinar fatores de risco para a infecção adquirida na unidade. Foi realizada uma investigação comparativa entre períodos dos 6 dias anteriores e posteriores à interrupção de remifentanilo. Utilizamos o teste de amostras pareadas e a prova de McNemar para as variáveis quantitativas e categóricas, respectivamente. Resultados: O número de pacientes internados na URP durante o período de investigação foi de 1.789. Depois de aplicar os critérios de inclusão e exclusão, a população elegível ficou constituída por 102 pacientes. A densidade de incidência de infecção de forma global foi de 38 por cada 1.000 dias de internamento. A pneumonia associada à ventilação mecânica foi a infecção adquirida mais frequente e Pseudomona aeruginosa, o micro-organismo mais frequentemente isolado. A mortalidade hospitalar foi de 36,27%. Não foram observadas diferenças estatisticamente significativas na incidência de IACS em pacientes oncológicos em relação à descontinuação de remifentanilo (p=0,068). Conclusão: O estado basal de imunossupressão dos pacientes oncológicos não implica uma maior incidência de IACS em relação à interrupção do remifentanilo. Seria interessante a realização de uma investigação multicêntrica de URP que incluísse padrões imunológicos.

Opioids and immunosupression in oncological postoperative patients.

INTRODUCTION: Recent animal studies demonstrated immunosuppressive effects of opioid withdrawal resulting in a higher risk of infection. The aim of this study was to determine the impact of remifentanil discontinuation on Post-Anesthesia Care Unit (PACU)-acquired infection after a schedule of sedoanalgesia of at least 6 days. METHOD: All patients over 18 years of age with a unit admission of more than 4 days were consecutively selected. The study population was the one affected by surgical pathology of any origin where sedation was based on any hypnotic and the opioid remifentanil was used as analgesic for at least 96 hours in continuous perfusion. Patients who died during admission to the unit and those with combined analgesia (peripheral or neuroaxial blocks) were excluded. Bivariate analysis was performed to determine risk factors for infection acquired in the unit. A comparative study between periods of 6 days before and after the cessation of remifentanil was performed. Paired samples test and McNemar test was used for quantitative and categorical variables, respectively. RESULTS: There were 1,789 patients admitted to the PACU during the study and the population eligible was constituted for 102 patients. The incidence rate of PACU-acquired infection was 38 per 1,000 PACU days. Ventilator-associated pneumonia was the most frequently diagnosed PACU-acquired infection. Pseudomona aeruginosa was the most frequently isolated microorganism. Hospital mortality was 36.27%. No statistically significant differences were seen in the incidence of HAI in cancer patients in relation to discontinuation of remifentanil (p=0.068). CONCLUSION: The baseline state of immunosuppression of cancer patients does not imply a higher incidence of HAI in relation to the interruption of remifentanil. It would be of interest to carry out a multicenter PACU study that included immunological patterns.

Sevoflurano tópico: una nueva opción terapéutica paliativa en las úlceras cutáneas / Topical sevoflurane: A new palliative therapeutic option for skin ulcers

La presencia de úlceras cutáneas, con tendencia a la cronicidad y con mala respuesta al arsenal terapéutico-analgésico clásico, conllevan un alto grado de dolor, discapacidad y merma en la calidad de vida. Presentamos el caso de una paciente terminal con un cuadro álgico debido a la presencia de múltiples úlceras vasculares en miembros inferiores de 3 meses de evolución y de difícil manejo por mala tolerancia a anticomiciales y opioides mayores. Las instilaciones tópicas de forma periódica del anestésico halogenado sevoflurano sobre el lecho ulceroso lograron un excelente control del dolor basal e irruptivo a los pocos minutos de su administración, y una progresiva mejoría en la cicatrización de las úlceras sin evidenciar efectos secundarios asociados

The presence of cutaneous ulcers, with a tendency to become chronic and without a response to the therapeutic-analgesic arsenal available, carry a heightened degree of pain and disability and significantly compromise patient quality of life. A case is reported of a terminally ill woman with a painful condition due to the presence of multiple vascular ulcers of 3 months onset in lower right limb, and difficult to manage because of poor tolerance to anticonvulsants and major opioids. Periodically administered topical applications of halogenated anaesthetic sevoflurane on the ulcer bed achieved good results in baseline and breakthrough pain management within a few minutes after application and a progressive improvement in the healing of ulcers without associated adverse effects

Efficacy and safety of topical sevoflurane in the treatment of chronic skin ulcers.

PURPOSE: Results of efficacy and safety assessments of topical sevoflurane use in patients with long-term treatment-refractory vascular ulcers are reported. METHODS: Patients were randomly assigned to receive sevoflurane instillations (1 mL per cm2 of ulcer area 1-4 times daily) plus standard wound care (ulcer cleaning, debridement, and dressing changes) or standard care only. Topical sevoflurane was initiated during hospitalization, with self- or nurse-administered instillations continued after discharge. Study participants were evaluated at least once weekly for 1 month and then every 2 weeks for up to 90 days. The primary efficacy measures were debridement-related and overall pain (assessed using a 10-point visual analog scale), daily opioid use, and ulcer size; secondary measures were patient and clinician impressions of improvement and ulcer-related admissions during treatment. The primary safety endpoint was intolerable sevoflurane-related adverse effects. RESULTS: Compared with the group receiving standard care alone (n = 5), the sevoflurane group (n = 10) had significant (p = 0.001) reductions in mean ± S.D. scores for debridement-related pain on day 1 of treatment and at subsequent time points; the sevoflurane group also had significant reductions in overall pain, daily opioid use, and ulcer size. Outcomes in terms of patient- and clinician-rated improvement and emergency admissions also favored the sevoflurane group. Mild localized reddening in the area surrounding ulcers occurred in 4 sevoflurane-treated patients. CONCLUSION: Direct application of sevoflurane onto vascular ulcers resulted in an intense and long-lasting analgesia and was associated with a progressive reduction of ulcer size.

Tratamiento con enjuagues de ketaminaketamina asociado o no a fentanilo transmucoso en el dolor oncológico orofacial resistente a opiáceos mayores / Treatment with ketamine mouthwashes with and without transmucosal fentanyl in major opiate-resistant orofacial cancer pain

Objetivo: Evaluar la efectividad de los enjuagues de ketamina asociados o no a fentanilo transmucoso en una serie de diversos dolores orofaciales de etiología neoplásica de difícil control analgésico. Material y métodos: Estudio prospectivo de 20 pacientes, con 8 pacientes que recibieron enjuagues de ketamina (40 mg = 4 ml), 8 pacientes que recibieron ketamina asociada a citrato de fentanilo por vía transmucosa oral a dosis de 200 mcg y 4 pacientes con opiáceos sistémicos para el dolor orofacial y mucositis refractaria. Resultados: Un total de16 de los 20 pacientes tenían dolor orofacial o mucositis refractaria al tratamiento con lidocaína y opiáceos. La tasa de éxito del empleo de enjuagues de ketamina fue del 50% (8/16 pacientes). La asociación ketamina y fentanilo transmucoso obtuvo una tasa de éxito del 94,1% (15/16 pacientes). Los efectos adversos se asocian al uso de la ketamina; todos los efectos secundarios fueron transitorios y desaparecieron cuando se suspendieron los enjuagues con ketamina. Conclusión: Los enjuagues de ketamina son una opción eficaz para el tratamiento del dolor orofacial secundario al cáncer. En caso de presencia de episodios de dolor irruptivo recurrente, la asociación de ketamina en enjuague bucal y citrato de fentanilo oral transmucoso puede ser una opción viable en dolor refractario a otros tratamientos (AU)

Purpose: The objective of this study was to determine if an oral ketamine mouth wash and expectorant, that may or may not rinse transmucosal fentanyl, was a safe and effective method to alleviate a series of various difficult to control orofacial pain of cancer origin. Material and methods: A prospective review was made of the medical charts of 20 patients, finding 8 patients who received ketamine mouthwash (40 mg = 4 ml), 8 patients who received ketamine mouthwash and oral transmucosal fentanyl citrate 200 mcg, and 4 patients with systemic opioids for refractory orofacial and mucositis pain. Results: Of the 20 patients, 16 had orofacial or mucositis pain refractory to a mixture of lidocaine and opioids. The effectiveness of ketamine mouthwash was 50% (8/16 patients). The combination of ketamine and/or fentanyl transmucosal had an analgesic efficacy of 94.1% (15/16 patients). The adverse effects were associated with the ketamine mouthwash; all side effects were transient and subsided when the ketamine mouthwash was stopped. Conclusion: Ketamine mouthwash for orofacial pain due to cancer may be an effective treatment option. In cases of reported episodes of breakthrough pain, the combination of a ketamine mouthwash and oral transmucosal fentanyl citrate may be a viable treatment option in refractory mucositis pain (AU)

Evaluación de la lesión neurológica y complicaciones médicas en una cohorte histórica de pacientes con lesión medular aguda traumática tras tratamiento con megadosis de metilprednisolona / Assessment of neurologic function and complications in a retrospective cohort of patients with acute spinal cord injury due to trauma treated with large-dose methylprednisolone

Introducción: El uso de metilprednisolona para el tratamiento de lesiones traumáticas de médula espinal se utilizó para mejorar la recuperación neurológica en The National Acute Spinal Corel Injury Studies-NASClS. La controversia sobre este protocolo, llevó a investigaciones posteriores y un informe de 2002, lo considera de una evidencia insuficiente para ser considerado un estándar de tratamiento. Nuestro objetivo fue valorar retrospectivamente su aplicación en una cohorte de pacientes con trauma medular. Métodos: Estudio retrospectivo de una cohorte de pacientes ingresados en una unidad de críticos entre 1997-2007 con diagnóstico de lesión de médula espinal traumática. Los pacientes fueron agrupados de acuerdo con el tratamiento médico recibido (grupo metilprednisolona frente a grupo no-metilprednisolona). Se evaluó la variación de la función neurológica mediante la escala ASIA al ingreso y alta, así como la aparición de complicaciones médicas en función del tratamiento con o sin metilprednisobna. Se realizó estudio estadístico mediante regresión múltiple de Cox para el tratamiento o no con el fármaco. Resultados: No hubo diferencias entre grupos de tratamiento en la evolución neurológica al alta de la unidad de cuidados críticos (OR = 1,57, IC 95%: 0,69 a 3,54). El grupo metilprednisolona presentó un aumento de complicaciones médicas como hiperglucemia (OR = 5,67, IC 95%: 1,85-17,31) y hemorragia gastrointestinal (OR = 19,16, IC 95%: 1,64-223,30) en comparación con el grupo no tratado con metalprednisolona. Conclusiones: En este estudio retrospectivo, el uso de metilprednisolona en pacientes con lesión aguda de la médula espinal no se asocia con una mejoría en el resultado de la función neurológica al alta en la unidad de críticos y un mayor riesgo de complicaciones metabólicas (AU)

BACKGROUND AND OBJECTIVE: Methylprednisolone was used to improve neurologic recovery from spinal cord injury in the National Acute Spinal Cord Injury Studies (NASCIS). Debate over this use led to further research and a 2002 report stating that there was insufficient evidence to support this application as a standard therapy. Our aim was to retrospectively assess this application in a cohort of patients with spinal cord injury. METHODS: Retrospective cohort study of patients admitted to the intensive care unit (ICU) between 1997 and 2007 with a diagnosis of spinal cord injury due to trauma. The patients were grouped according to medical treatment received into a methylprednisolone group and a no-methylprednisolone group. We assessed change in neurologic function on the impairment scale of the American Spinal Injury Association on ICU admission and on discharge. We also recorded medical complications in each group. Cox multiple regression analysis was used to analyze differences between treatments. RESULTS: No significant differences were detected in neurologic outcome on discharge from the ICU (odds ratio [OR], 1.57; 95% confidence interval [CI], 0.69-3.54). The methylprednisolone-treated patients had more medical complications such as hyperglycemia (OR, 5.67; 95% CI, 1.85-17.31) or gastrointestinal bleeding (OR, 19.16; 95% CI, 1.64-223.30) than the patients who did not receive methylprednisolone. CONCLUSIONS: In this retrospective study, methylprednisolone was unrelated to improvement in neurologic outcome after acute spinal cord injury on ICU discharge although the patients treated with this drug were at greater risk of metabolic complications (AU)