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.

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)

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.

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.

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.

Cost-utility Analysis for Recurrent Lumbar Disc Herniation: Conservative Treatment Versus Discectomy Versus Discectomy With Fusion.

STUDY DESIGN: This study was an ambispective long-term cost-utility analysis with retrospective chart review and included the prospective completion of health questionnaires by patients. OBJECTIVE: This was a cost-utility analysis, comparing conservative treatment, discectomy, and discectomy with spinal fusion for patients with recurrent lumbar disc herniation after a previous discectomy. SUMMARY OF BACKGROUND DATA: Lumbar disc herniation is an important health problem, with recurrence rates ranging from 5% to 15%. Management of recurrences is controversial due to a lack of high-level evidence. Cost-effectiveness analyses are useful when making clinical decisions. There are economic assessments for first herniations, but not in the context of recurrent lumbar disc herniations. MATERIALS AND METHODS: Fifty patients with disc herniation recurrence underwent conservative treatment (n=11), discectomy (n=20), or discectomy with fusion (n=19), and they completed the Short-Form 36, EuroQol-5D, and Oswestry Disability Index.Baseline case quality-adjusted life year (QALY) values, cost-utility ratios, and incremental cost-utility ratios were calculated on the basis of the SF-36. Direct health costs were calculated by applying the health care system perspective. Both QALY and costs were discounted at a rate of 3%. One-way sensitivity analyses were conducted for uncertainty variables, such as other health surveys or 2-year follow-up. RESULTS: Cost-utility analysis of conservative treatment versus discectomy showed that the former is dominant, mainly because it is significantly more economical (&OV0556;904 vs. &OV0556;6718, P<0.001), while health results were very similar (3.48 vs. 3.18, P=0.887). Cost-utility analysis of discectomy versus discectomy with fusion revealed that discectomy is dominant, showing a trend to be both more economical (&OV0556;6718 vs. &OV0556;9364, P=0.054) and more effective (3.18 vs. 1.92 QALY, P=0.061). CONCLUSIONS: This cost-utility analysis showed that conservative treatment is more cost-effective than discectomy in patients with lumbar disc herniation recurrence. In cases of recurrence in which conservative treatment is not feasible, and another surgery must be performed for the patient, discectomy is a more cost-effective surgical alternative than discectomy with fusion. LEVEL OF EVIDENCE: Level II.

Analgesic effectiveness of topical sevoflurane to perform sharp debridement of painful wounds.

OBJECTIVE: Analgesic topical options to perform wound debridement are scarce. The purpose of this study was to communicate our experience using topical sevoflurane as analgesic for wound debridement. METHODS: After approval by our institutional review board, medical records were reviewed for those patients who had previously accepted to be treated with off-label topical sevoflurane (1 mL/cm2) as an analgesic for sharp debridement of painful wounds, because it was previously approved by our institutional Pharmacy Regulatory Commission and Medical Management. According to this protocol, pain scores were measured by using a numerical rating scale (from 0 to 10 points) over a 10-hour period. Wound debridement was performed following routine procedures. RESULTS: Medical records from 152 patients were reviewed. Baseline pain was severe (median, 7 points). After topical sevoflurane application, the analgesic effect was rapid (median pain score of 2 points at 5 minutes), and full debridement was feasible in most wounds (93%). The initial intense analgesic effect lasted for 30 minutes and then it subsided gradually over time to nearly reach baseline values after 10 hours. The patients estimated that the analgesic effect lasted several hours (median, 9 hours), and their overall satisfaction was high (median of 8 points on a scale ranging from 0 to 10). Fifty-two patients (34%) experienced itching. CONCLUSIONS: Topical application of sevoflurane to painful wounds produced a rapid, robust, and long-lasting analgesic effect, which allowed for a high degree of wound debridement.

Psychometric Properties Study of the Oswestry Disability Index in a Spanish Population With Previous Lumbar Disc Surgery: Homogeneity and Validity.

STUDY DESIGN: Evaluation of the psychometric properties of a questionnaire. OBJECTIVE: To assess the psychometric properties of the Spanish version of the Oswestry Disability Index (ODI) in a Spanish population with previous lumbar disc surgery. SUMMARY OF BACKGROUND DATA: ODI is frequently used for measuring disability in spinal disorders. In 1995, ODI was translated and transculturally adapted into the Spanish context; its content and apparent validity, internal consistency and test-retest reliability were demonstrated for a Spanish population with lumbar pain. However, this score has not been tested in terms of discriminative capacity (floor and ceiling effects) and construct validity. METHODS: Two hundred seventy-five patients who had previously undergone surgical treatment for disc lumbar herniation completed the ODI, Short-Form 36 (SF36), EuroQol-5D (EQ5D), and Numerical Rating Scale for Back Pain. Internal consistency, floor and ceiling effects and construct validity (convergent, divergent, and "known-groups" validities) were assessed. RESULTS: Spanish ODI showed a very good internal consistency: Cronbach-α coefficient for ODI score was 0.928; Cronbach-α coefficient, if the item was deleted, did not increase by more than 0.1 for each item; and Item-total correlations ranged from strong to very strong. There was floor effect for both ODI score and for all individual items. There was no ceiling effect. Spanish ODI showed very good construct validity because 88% (7/8) of the hypotheses about convergent, divergent and "known-groups" validities were supported. Concerning convergent validity, ODI was strongly correlated with the Numerical Rating Scale for Back Pain (0.717; P < 0.001), SF36-Utility (rho = -0.786; P < 0.001), Physical Component Summary score SF36 (rho = -0.787; P < 0.001), Mental Component Summary score SF36 (rho = -0.605; P < 0.001), EQ5D-Utility (rho = -0.833; P < 0.001) and some EQ5D physical components. CONCLUSION: Spanish ODI showed good psychometric properties (internal consistency and construct validity), similar to others validation studies. Spanish ODI is a valid instrument for the measurement of disability in Spanish patients with previous lumbar disc surgery, specifically in patients with moderate/intense disability. LEVEL OF EVIDENCE: 4.

[Influence of propofol dose and blood components on duration of electrical seizures in electroconvulsive therapy]. / Influência da dose de propofol e dos componentes sanguíneos na duração das convulsões elétricas em eletroconvulsoterapia.

BACKGROUND AND OBJECTIVES: Propofol is commonly employed as a hypnotic agent to perform electroconvulsive therapy, but it exhibits also anticonvulsant properties. The main objective was to study the effect of the weight-adjusted dose of propofol on duration of the electrical seizure. Secondary objectives were to study the effect of absolute dose of propofol on duration of electrical seizure, the effect of both absolute and weight-adjusted doses on values of bispectral index, and the influence of blood chemistry on anticonvulsant effect. METHODS: After approval of the Institutional Review Board, a retrospective chart review was performed of all patients who underwent at least one electroconvulsive therapy session. Multiple lineal regression analysis adjusted for potential confounders was employed to explore the effect of propofol dosage on values of bispectral index and on duration of seizure; bivariate correlation analyses were previously performed to identify variables fulfilling confounding criteria, specifically values of Spearman's rho >0.10. Results of regression analysis were expressed as B coefficient with its 95% confident interval. RESULTS: 76 patients received 631 acute phase sessions. Propofol showed a statistically significant negative effect on duration of seizure (specifically a reduction of 4.081s for every mg.kg-1 of propofol; CI95%: -7906 to -0.255, p=0.037) but not on bispectral index values. Slight anemia and hypoalbuminemia were very infrequent conditions, and the anticonvulsant effect was not influenced by these parameters. CONCLUSIONS: Propofol weight-adjusted dose is negatively related to duration of seizures. It should be carefully titrated when employed to perform electroconvulsive therapy.

The Psychiatric Patient as a Health Resource Consumer: Costs Associated with Electroconvulsive Therapy.

BACKGROUND: Clinical practice protocols should consider both the psychological criteria related to a patient's satisfaction as a consumer of health services and the economic criteria to allocate resources efficiently. An electroconvulsive therapy (ECT) program was implemented in our hospital to treat psychiatric patients. The main objective of this study was to determine the cost associated with the ECT sessions implemented in our hospital between 2008 and 2014. A secondary objective was to calculate the cost of sessions that were considered ineffective, defined as those sessions in which electrical convulsion did not reach the preset threshold duration, in order to identify possible ways of saving money and improving satisfaction among psychiatric patients receiving ECT. METHODS: A descriptive analysis of the direct health costs related to ECT from the perspective of the public health system between 2008 and 2014 was performed using a retrospective chart review. All of the costs are in euros (2011) and were discounted at a rate of 3%. Based on the base case, a sensitivity analysis of the changes of those variables showing the greatest uncertainty was performed. RESULTS: Seventy-six patients received 853 sessions of ECT. The cumulative cost of these sessions was €1409528.63, and 92.9% of this cost corresponded to the hospital stay. A total of €420732.57 (29.8%) was inefficiently spent on 269 ineffective sessions. A sensitivity analysis of the economic data showed stable results to changes in the variables of uncertainty. CONCLUSION: The efficiency of ECT in the context outlined here could be increased by discerning a way to shorten the associated hospital stay and by reducing the number of ineffective sessions performed.

Irrigation with Liquid Sevoflurane and Healing of a Postoperative, Recurrent Epidural Infection: A Potential Cost-Saving Alternative.

BACKGROUND: The general inhalation anesthetic sevoflurane can be used for the topical treatment of complicated wounds. It is applied in liquid form and may be used to irrigate the inside of cavities. Sevoflurane also exhibits in vitro antimicrobial activity. Therefore, sevoflurane may be used as an alternative to typical antibiotic or surgical treatment of complicated, localized infections. CASE DESCRIPTION: The case of a 61-year-old male patient who suffered a cranioencephalic trauma 18 years previously is presented. The patient underwent surgeries related to the trauma on numerous occasions. To date, he has suffered various recurrent epidural abscesses, which have been treated with surgical cleaning and antibiotic treatment. In the most recent episode, he presented a frontal epidural abscess 25 mm in diameter with fistulization of the skin. The patient gave written informed consent to be treated with sevoflurane irrigation, and the Pharmacy Service authorized the off-label use. Sevoflurane was applied via a catheter placed inside the cavity during weekly outpatient procedures. The procedures began 8 weeks after the clinically and radiologically verified recovery of the abscess. By avoiding surgery and the associated hospital admission, this novel alternative may prevent patient morbidity and, furthermore, may produce important economic savings. CONCLUSIONS: The treatment of complicated wounds with liquid sevoflurane may be an effective and economically efficient clinical alternative for some patients.