Cardiac output and the pharmacology of general anesthetics: a narrative review

The relationship between cardiac output and anesthetic drugs is important to anesthesiologists, since cardiac output determines the speed with which a drug infused into the bloodstream reaches its target and the intensity of the drug's effect. But rather than focus on how anesthetic drugs affect cardiac output, this narrative review focuses on how changes in cardiac output affect the pharmacokinetics and pharmacodynamics of general anesthetics during the three phases of anesthesia. At induction, an increase in cardiac output shortens both the onset time of propofol for hypnosis and the neuromuscular blocking effect of rapid-acting neuromuscular blockers, favoring the conditions for rapid sequence intubation. During maintenance, changes in cardiac output are followed by opposite changes in the drug plasma concentration of anesthetic drugs. Thus, an increase in cardiac output followed by a decrease in the plasma concentration of the anesthetic could expose the patient to a real risk of intraoperative awakening, which can be avoided by increasing the dose of hypnotic drugs. At emergence, an increase in cardiac output secondary to an increase in pC02 allows for a more rapid recovery from anesthesia. The pC02 can be increased by adding CO2 to the respiratory circuit, lowering the ventilatory rate, or placing the patient on partial rebreathing. Finally, the reversal action of sugammadex for rocuronium-induced neuromuscular block can be shortened by increasing the cardiac output.

La relación entre el gasto cardíaco y los fármacos anestésicos es importante para los anestesiólogos puesto que el gasto cardíaco determina la velocidad con la cual un medicamento que se infunde al torrente sanguíneo llega a su diana y la intensidad del efecto del agente. Pero en lugar de concentrarnos en cómo los fármacos anestésicos afectan el gasto cardíaco, esta revisión narrativa se enfoca en cómo los cambios en el gasto cardíaco afectan la farmacocinética y la farmacodinámica de los agentes anestésicos generales durante las tres fases de la anestesia. En el momento de la inducción, un incremento en el gasto cardíaco acorta tanto el tiempo de inicio del efecto del propofol para la hipnosis como el efecto del bloqueo neuromuscular causado por los bloqueadores neuromusculares de acción rápida, favoreciendo las condiciones para la intubación de secuencia rápida. Durante la fase de mantenimiento, los cambios en el gasto cardíaco vienen seguidos de cambios opuestos en la concentración plasmática del medicamento de los agentes anestésicos. Por lo tanto, un aumento del gasto cardíaco, seguido de una reducción en la concentración plasmática del anestésico, podría exponer al paciente a un riesgo real de despertar intraoperatorio, lo cual puede evitarse aumentando la dosis de los fármacos hipnóticos. En la educción, un aumento en el gasto cardíaco secundario al incremento en el pCO2 permite una recuperación más rápida de la anestesia. El pCO2 puede aumentar agregando CO2 al circuito de la respiración, reduciendo la tasa ventilatoria, o colocando al paciente en re-inhalación parcial. Finalmente, la acción de reversión de sugammadex en caso de bloqueo neuromuscular inducido por rocuronio, puede acortarse aumentando el gasto cardíaco.

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.

In vitro assessment of the direct hemolytic effect of the volatile halogenated anesthetics sevoflurane, isoflurane, and desflurane.

Sevoflurane is being repurposed as a topical analgesic for painful wounds. Providing pre-charged sevoflurane syringes to irrigate wounds implies a potential risk of accidental intravenous injections. We assessed the potential of two concentrations (33% and 50% v/v) of three anesthetics, isoflurane, desflurane and sevoflurane, to produce hemolysis in vitro. Spectrophotometric absorbance was read at 576 nm. For both concentrations, the percentage of hemolysis (mean ± SD) was higher for isoflurane (29.7 ± 3.4% and 39.5 ± 5.3%), mild for desflurane (8.0 ± 0.5% and 6.5 ± 0.9%) and negligible for sevoflurane (0.7 ± 0.0% and 0.6 ± 0.1%), respectively. In conclusion, in contrast to isoflurane and desflurane, sevoflurane did not display hemolytic potential in vitro. However, the use of syringes preloaded with sevoflurane may still be problematic if it increases the possibility of inadvertent intravenous administration through increased risk of gas embolism and severe central nervous system depression.

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.

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.

Analgesic effectiveness and improvement in quality of life after using topical sevoflurane for an extremely painful anal fissure / Eficácia analgésica e melhoria da qualidade de vida com o uso tópico de sevoflurano em fissura anal extremamente dolorosa

Painful anal fissures could be distressing conditions that severely impair the patients' quality of life. The analgesic effectiveness of topical drugs, such as calcium-antagonists and nitrates is quite variable. The inhalational anesthetic sevoflurane is being repurposed as a topical analgesic for painful chronic wounds.We report a pioneer experience treating a painful chronic anal fissure with topical sevoflurane. A young adult male was suffering from an extremely painful chronic anal fissure, which severely affected his quality of life. The topical treatment with nitroglycerine and diltiazem gels failed. The patient agreed to the treatement with topical sevoflurane as an off-label medication, and it produced an immediate, intense, and long-lasting analgesic effect. An intense but rapidly transient burning sensation, as well as persistent but well-tolerated flatulence were the only adverse effects. The quality of life was greatly improved, and the cost of the treatment was affordable. Therefore, the off-label use of topical sevoflurane appears to be an effective alternative for the symptomatic treatment of painful anal fissures (AU)

As fissuras anais dolorosas podem ser condições angustiantes que prejudicam gravemente a qualidade de vida dos pacientes. A eficácia analgésica de medicamentos tópicos, como antagonistas de cálcio e nitratos, é bastante variável. O anestésico inalatório sevoflurano está sendo reaproveitado como analgésico tópico para feridas crônicas dolorosas. Relatamos uma experiência pioneira de tratamento com sevoflurano tópico em fissura anal crônica dolorosa. Umjovemadulto do sexomasculino sofria de uma fissura anal crônica extremamente dolorosa, que afetava gravemente sua qualidade de vida. O tratamento tópico com nitroglicerina e géis de diltiazem foi ineficaz. O paciente concordou com o tratamento com sevoflurano tópico como medicamento off-label, ou seja, com uso diferente do aprovado embula. O sevoflurano tópico produziu um efeito analgésico imediato, intenso e duradouro. Uma sensação de ardência intensa, mas transitória, e flatulência persistente, embora bem tolerada, foram os únicos efeitos adversos. A qualidade de vidamelhorou significativamente, e o custo do tratamento revelou-se acessível. Portanto, o uso off-label de sevoflurano tópico pode ser uma alternativa analgésica eficaz em casos de fissuras anais dolorosas. (AU)

Assessment of glomerular and tubular function to guide fluid management in a pre-eclamptic critical patient with oliguria and volume overload: case report.

Oliguria in the setting of critically ill patients is usually treated by admini-stering fluids and furosemide [1]. Invasive therapies, namely renal replacement therapies (RRT), are reserved for patients in whom less invasive measures have failed [2], especially if acute pulmonary oedema complicates the clinical picture [1]. Intravascular volume depletion elicits a kidney response consisting of augmented sodium retention at Henle's loop and water at the collecting tubules. In such conditions, loop diuretics such as furosemide would be less effective to improve diuresis and water loss than osmotic diuretics such as mannitol [3, 4]. This case report aims to highlight the utility of the assessment of the glomerular and tubular functions to identify an ineffective diuretic strategy and to select a successful one, which prevented the use of invasive RRT. A 33-year-old female patient suffering from preeclampsia (gestational age was 35 + 6 weeks) was admitted to our Post-surgical Intensive Care Unit (PICU) after an urgent caesarean section performed under spinal anaesthesia, without further incidents.

Development of an experimental model of septic knee arthritis in rats through intra-articular inoculation of Staphylococcus aureus.

Haematogenous models of septic arthritis have some inherent disadvantages, such as the manifestation of arthritis relies on chance, the size of the inoculum is unknown and the number of animals to be studied cannot be reduced because the animals cannot serve as their own controls. This study aimed to develop a rat model of knee septic arthritis by injecting a known inoculum of Staphylococcus aureus into the joint. The left knees of 27 Sprague Dawley rats were injected with four different inoculum concentrations of a sensitive strain of S. aureus (30,000 colony-forming units (CFUs), n = 3; 18,550 CFUs, n = 6; 15,500 CFUs, n = 9; and 7700 CFUs, n = 9); the right knees served as controls. Clinical, microbiological and histological variables were assessed two and seven days later. The main criterion for diagnosing septic arthritis was a positive culture of synovial fluid. The rate of microbiologically confirmed septic arthritis was high for all inoculum concentrations (3/3, 6/6, 8/9 and 7/9, respectively), and the rate of bacteraemia was also high. Animal welfare was better for the two lowest inoculum concentrations. No animal reached the pre-established humane end points. Overall, the third inoculum was considered the most suitable. Thus, acute septic arthritis can be caused in rats by inoculating 15,000 CFUs of an ATCC strain of S. aureus directly into the knee joint. Overall, the model seems to be useful for studying the effectiveness of drugs for the treatment of acute septic arthritis.

Sevoflurano tópico como tratamiento alternativo fuera de indicación para una úlcera por presión en paciente frágil / Off-label topical sevoflurane as an alternative treatment for a pressure ulcer in a frail patient

Una paciente frágil tetraparética presentaba una úlcera por presión sacra que se había mostrado resistente al tratamiento conservador tópico, consistente en higiene postural y curas con sulfadiazina de plata. Fue programada para cirugía de cobertura con colgajo glúteo, pero ante el elevado riesgo anestésico se le ofertó intentar curar la herida con sevoflurano tópico, lo cual fue aceptado. El sevoflurano fue aplicado diariamente en domicilio, y la herida evolucionó satisfactoriamente, con reducción progresiva de la superficie y la profundidad hasta cerrar por completo en pocas semanas, evitándose así una intervención quirúrgica. El empleo fuera de indicación de sevoflurano irrigado tópicamente sobre el lecho de heridas complejas aparece como una herramienta muy ventajosa, pues supone una alternativa a medidas más invasivas y es de fácil aplicación

A frail tetraparetic patient suffered from a sacral pressure ulcer which had been refractory to conservative topical treatment, consisting in postural hygiene and application of silver sulfadiazine cream. A gluteal flap surgery had been scheduled but, due to the high anesthetic risk, the patient was offered to try to heal the ulcer with topical sevoflurane, which was accepted. Sevoflurane was daily applied at home, and the wound condition successfully improved, showing a progressive reduction in its size and deepness until it was considered fully healed after few weeks; as a consequence, the scheduled surgery was avoided. Off-label use of topical sevoflurane on complicated wounds seems to be valuable, since it represents a noninvasive alternative and it is very easy to perform

Bayesian Regression Model for a Cost-Utility and Cost-Effectiveness Analysis Comparing Punch Grafting Versus Usual Care for the Treatment of Chronic Wounds.

Punch grafting is a traditional technique used to promote epithelialization of hard-to-heal wounds. The main purpose of this observational study was to conduct a cost-utility analysis (CUA) and a cost-effectiveness analysis (CEA) comparing punch grafting (n = 46) with usual care (n = 34) for the treatment of chronic wounds in an outpatient specialized wound clinic from a public healthcare system perspective (Spanish National Health system) with a three-month time horizon. CUA outcome was quality-adjusted life years (QALYs) calculated from EuroQoL-5D, whereas CEA outcome was wound-free period. One-way sensitivity analyses, extreme scenario analysis, and re-analysis by subgroups were conducted to fight against uncertainty. Bayesian regression models were built to explore whether differences between groups in costs, wound-free period, and QALYs could be explained by other variables different to treatment. As main results, punch grafting was associated with a reduction of 37% in costs compared to usual care, whereas mean incremental utility (0.02 ± 0.03 QALYs) and mean incremental effectiveness (7.18 ± 5.30 days free of wound) were favorable to punch grafting. All sensitivity analyses proved the robustness of our models. To conclude, punch grafting is the dominant alternative over usual care because it is cheaper and its utility and effectiveness are greater.

Sevoflurano tópico como terapia de rescate para paciente frágil afecta de úlceras crónicas en piernas con dolor refractario y sobreinfectadas por Staphylococcus aureus resistente a meticilina y Pseudomonas aeruginosa sensible. Caso clínico / Topical sevofl urane as rescue therapy in a frail patient suffering from leg ulcers causing refractory pain and superinfected by methicillin-resistant Staphylococcus aureus and sensitive Pseudomonas aeruginosa. A case report

Una paciente frágil afecta de úlceras crónicas en piernas sobreinfectadas por Staphylococcus aureus resistente a meticilina y Pseudomonas aeruginosa sensible, y causantes de dolor somático y neuropático refractario a los analgésicos sistémicos, aceptó ser tratada con sevoflurano tópico como terapia fuera de indicación. La primera irrigación se siguió de un control completo e inmediato del dolor que persistía entre las irrigaciones diarias, por lo que la paciente pudo descansar y dormir ya desde el primer día. Los cultivos del exudado de las heridas tomados al cuarto día de tratamiento con sevoflurano ya resultaron negativos. Al alta hospitalaria tres semanas después la herida izquierda estaba ya cerrada y la derecha cerró dos semanas después aplicando sevoflurano como tratamiento extrahospitalario. El sevoflurano ejerció efectos analgésico, antimicrobiano y cicatrizante, sin efectos adversos severos, por lo que aparece como una nueva estrategia de futuro muy interesante para el ámbito de los cuidados paliativos

A frail patient was suffering from chronic leg ulcers superinfected by methicillin-resistant Staphylococcus aureus and sensitive Pseudomonas aeruginosa, and causing severe somatic and neuropathic pain, which was refractory to conventional systemic analgesics. The patient accepted to be treated with topical sevoflurane as off-label treatment. Pain completely disappeared after the first irrigation with sevoflurane and the analgesic effect persisted between daily irrigations, so that the patient could regain night resting. Cultures of the ulcer exudate taken after 4 days with sevoflurane yielded negative results. The patient was discharged 3 weeks later with the left ulcer healed; the right ulcer healed after 2 more weeks of outpatient treatment with sevoflurane. Therefore, sevoflurane caused analgesic, antimicrobial, and pro-healing effects without noticeable adverse effects, making this new alternative very promising for the care of palliative patients

Interchangeability of the EQ-5D and the SF-6D, and comparison of their psychometric properties in a spinal postoperative Spanish population.

OBJECTIVE: EuroQol-5D (EQ-5D) and Short-Form Six-Dimensions (SF-6D) are widely used to calculate quality-adjusted life-years in cost-utility analysis. The choice of the instrument could influence the results of cost-utility analysis. Our objective was to compare the psychometric properties of the EQ-5D and SF-6D in a postoperative Spanish population, as well as assess their interchangeability in a cost-utility analysis. DESIGN: Ambispective study. SETTING: Tertiary public hospital. PARTICIPANTS: 275 Spanish patients who had undergone surgery for lumbar disc herniation. INTERVENTION(S): Patients completed EQ-5D-3L and Short-Form 36 (SF-36v2) questionnaires. Internal consistency, floor and ceiling effects, agreement, and construct validity (convergent validity, including dimension-to-dimension correlations, and "known groups" validity) were assessed. The Spanish tariffs were applied. MAIN OUTCOME MEASURE(S): Cronbach's α coefficient, Spearman's rank correlation coefficient, Lin's concordance correlation coefficient, intraclass correlation coefficient and Bland-Altman plot. RESULTS: Main findings were: (a) lack of agreement between EQ-5D and SF-6D utilities (Lin's concordance correlation coefficient: 0.664 [95% CI: 0.600-0.720]; the Bland-Altman plot showed a mean difference of 0.0835 and wide limits of agreement [- 0.2602-0.4272]). (b) Lack of correlation between domains that theoretically measure similar aspects of quality of life, with the exception of "pain" domain. CONCLUSIONS: The preference-based EQ-5D and SF-6D instruments showed valid psychometric properties to assess generic outcome in a Spanish population who had undergone surgery for lumbar disc herniation; however, utility scores derived from the measures were different. Thus, these two instruments cannot be used interchangeably to perform a cost-utility analysis, and they should both be included in sensitivity analyses.

Sevoflurano tópico como tratamiento analgésico y antimicrobiano de tenosinovitis piógena de los flexores de la mano. Caso clínico / Topical sevoflurane as analgesic and antimicrobial treatment of pyogenic flexor tenosynovitis of the hand. Case report

Presentamos el caso de un paciente con una tenosinovitis piógena del 5° dedo de la mano, tratado inicialmente con desbridamiento quirúrgico y antibioterapia empírica. La evolución fue desfavorable, pues el dedo presentaba un defecto de cobertura con signos infecciosos en la herida y las curas resultaban muy dolorosas. Al paciente se le ofertaron varias opciones quirúrgicas y, mientras se decidía por alguna, aceptó por escrito iniciar curas con sevoflurano líquido tópico (según protocolo vigente para uso de fármacos fuera de indicación). El efecto analgésico del sevoflurano apareció rápidamente, y la evolución posterior de la herida fue muy favorable, pues los signos infecciosos desaparecieron y el defecto de cobertura se había cerrado tras tres semanas de empleo de sevoflurano tópico, sin necesidad de nuevas cirugías. Este caso ejemplifica que el uso fuera de indicación de sevoflurano tópico para tratar heridas complejas puede evitar actuaciones quirúrgicas, mucho más agresivas para los pacientes.

The clinical case is presented on a patient suffering from pyogenic tenosynovitis affecting the 5th finger of the hand, which was initially treated with surgical debridement and empirical antibiotic treatment. The clinical outcome was unfavourable, since the finger presented with a coverage defect, and the wound seemed to be infected. Wound cleaning and dressings were very painful. The patient was asked to choose between several surgical therapeutic alternatives, but he gave written informed consent to be treated with topical sevoflurane, following an approved protocol for the off-label use of this drug. Pain was accurately controlled after sevoflurane application, and the wound exhibited a very good outcome with disappearance of the clinical signs of infection and complete closure of the defect coverage after three weeks of sevoflurane, with no new surgical procedures. The present clinical case illustrates how the off-label use of topical sevoflurane for the treatment of complicated wounds could be useful to avoid surgical procedures that are more aggressive for patients.

Silvoflurano tópico en infección superficial por SARM tras artroplastia de rodilla: caso clínico / Topical sevoflurane for superficial MRSA infection after knee arthroplasty: case report

Intentar el tratamiento retentivo de material protésico ante heridas quirúrgicas infectadas por gérmenes resistentes es objeto de debate, especialmente cuando el agente causal es un Staphylococcus aureus resistente a meticilina (SARM). Una paciente diabética y con obesidad tipo I sufrió infección de la herida quirúrgica tras artroplastia de rodilla que no evolucionó bien con antibioterapia empírica y terapia hiperosmolar. Se planificó una reintervención que fue demorada por motivos extramédicos (falta de terapia de presión negativa para cubrir la herida postoperatoria, pues se preveía no poder realizar cierre primario). Mientras se conseguía este material, y tras obtener el consentimiento de la paciente, se iniciaron irrigaciones de la herida con sevoflurano tópico off-label, pues ese fármaco ha mostrado capacidad antimicrobiana. La evolución clínica fue excelente desde el inicio a pesar de que en el cultivo se aisló un SARM resistente a la antibioterapia empírica, por lo que se desestimó la reintervención y se continuó con sevoflurano tópico junto a la antibioterapia dirigida por antibiograma, lográndose la curación completa de la herida tras 6 semanas. Durante ese tiempo, la paciente no experimentó ningún efecto adverso atribuible al sevoflurano. El sevoflurano tópico aparece como una valiosa nueva opción terapéutica ante heridas postoperatorias infectadas, especialmente cuando los gérmenes causantes son resistentes a los antibióticos convencionales.

It is challenging to try a retentive treatment of prosthetic material superinfected by resistant microorganisms, especially when the causative agent is a methicillin-resistant Staphylococcus aureus (MRSA). A diabetic, obese female patient suffered from a postoperative wound infection after a knee arthroplasty. Initial treatment with antibiotics and hyperosmolar therapy failed and clinical evolution was no good. Surgery was scheduled, but it was delayed due to nonmedical reasons (lack of negative-pressure therapy to cover the wound since primary wound closure was anticipated to be very improbable to perform). While waiting for this therapy, off-label irrigations with topical sevoflurane were started after obtaining written consent, since this drug has exhibited antimicrobial properties. Clinical evolution turned out to be excellent since the very beginning, even though a MRSA resistant to the antibiotics empirically administered was isolated. Thus, surgery was discarded, and culture-guided antibiotic therapy was added to topical sevoflurane, which was followed by a complete healing of the wound after 6 weeks. Sevoflurane treatment was well tolerated as the patient reported no adverse effects. Therefore, treating postsurgical wounds with topical sevoflurane appears as a valuable new alternative, especially when infections are caused by microorganisms resistant to conventional antibiotics.

Uncooperative Patient With an Infected Elbow Osteosynthesis: Alternative Management With Topical Sevoflurane.

INTRODUCTION: Treatment of an infected osteosynthesis is usually a complicated process, with its complexity increasing when unforeseen situations appear. Typically, the therapeutic management of such situations is challenging because they are not anticipated in the medical literature and physicians have to look for and adapt novel solutions to a specific patient condition. CASE REPORT: A 41-year-old, uncooperative, homeless man, presented to the emergency room with a left olecranon fracture. After planned surgery, the surgical wound became infected with a methicillin-sensitive Staphylococcus aureus because the treatment took place in an unhygienic outpatient hospital setting. The patient refused to remain in the hospital and also failed to complete antibiotic courses prescribed (culture-guided rifampicin 600 mg daily plus levofloxacin 500 mg daily). Instead of removing the osteosynthesis material, the infection was successfully treated by repeated applications of 5 mL of sevoflurane into the surgical wound. Subsequently, wound healing was achieved with a combination of a brief course of negative pressure wound therapy (NPWT), use of silver-impregnated dressings, and irrigation of the wound with sevoflurane. Sevoflurane also provided topical analgesic to ameliorate the pain caused by removing the NPWT sponge. Interestingly, despite extremely poor compliance by the patient to all standard treatment regimens, and the clinical decision to retain the implant, the infection was resolved, and the fracture was consolidated. CONCLUSIONS: Local application of sevoflurane in the wound bed appears to exhibit analgesic, antimicrobial, and positive healing effects. It could be a promising alternative treatment to be included as a therapeutic option for wound care.

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.