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.

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.

Health-Related Quality of Life in Chronic Pain Treated With Tapentadol Versus Oxycodone/Naloxone and Its Determinants: A Real-World, Single-Center Retrospective Cohort Study in Spain.

OBJECTIVES: A substantial proportion of patients with chronic noncancer pain (CNCP) are treated with tapentadol (TAP) or oxycodone/naloxone (OXN) to improve their perceived physical and mental health over time. METHODS: A cross-sectional study was conducted in 135 CNCP outpatients with usual prescribing (TAP: n = 58, OXN: n = 77) at a tertiary-care Spanish Hospital to compare health-related quality-of-life (HRQoL) records. Health utility was derived from the EQ-5D-3L. Regression models were performed to search for other HRQoL determinants. Pain intensity, relief, analgesic prescription, adverse events, inpatient stays, emergency department visits, and change to painkiller prescriptions were registered from electronic records. RESULTS: Health utility (0.43 ± 0.24 scores, from -0.654 to 1) was similar for both opioids, although TAP showed a significantly low daily opioid dose requirement, neuromodulators use, and constipation side effect compared with OXN. After multivariable adjustment, the significant predictors of impaired HRQoL were pain intensity (ß = -0.227, 95% CI -0-035 to -0.005), number of adverse events (ß = -0.201, 95% CI -0.024 to -0.004), and opioid daily dose (ß = -0.175, 95% CI -0.097 to -0.012). Male sex (ß = -0.044) and pain relief (ß = 0.158) should be taken into account for future studies. CONCLUSIONS: HRQoL was similar for TAP and OXN in real-world patients with CNCP, albeit with a TAP opioid-sparing effect. More work is needed to explore HRQoL determinants in relation to long-term opioid use in CNCP.

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.

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.

Topical sevofluran: a galenic experience.

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

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

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

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

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.

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.

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.

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.

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.

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.

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.

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.

[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.

Pharmacokinetic Study of Intravenous Acetaminophen Administered to Critically Ill Multiple-Trauma Patients at the Usual Dosage and a New Proposal for Administration.

The pharmacokinetic profile of intravenous acetaminophen administered to critically ill multiple-trauma patients was studied after 4 consecutive doses of 1 g every 6 hours. Eleven blood samples were taken (predose and 15, 30, 45, 60, 90, 120, 180, 240, 300, and 360 minutes postdose), and urine was collected (during 6-hour intervals between doses) to determine serum and urine acetaminophen concentrations. These were used to calculate the following pharmacokinetic parameters: maximum and minimum concentrations, terminal half-life, area under serum concentration-time curve from 0 to 6 hours, mean residence time, volume of distribution, and serum and renal clearance of acetaminophen. Daily doses of acetaminophen required to obtain steady-state minimum (bolus dosing) and average plasma concentrations (continuous infusion) of 10 µg/mL were calculated (10 µg/mL is the presumed lower limit of the analgesic range). Data are expressed as median [interquartile range]. Twenty-two patients were studied, mostly young (age 44 [34-64] years) males (68%), not obese (weight 78 [70-84] kg). Acetaminophen concentrations and pharmacokinetic parameters were these: maximum concentration 33.6 [25.7-38.7] µg/mL and minimum concentration 0.5 [0.2-2.3] µg/mL, all values below 10 µg/mL and 8 below the detection limit; half-life 1.2 [1.0-1.9] hours; area under the curve for 6 hours 34.7 [29.7-52.7] µg·h/mL; mean residence time 1.8 [1.3-2.6] hours; steady-state volume of distribution 50.8 [42.5-66.5] L; and serum and renal clearance 28.8 [18.9-33.7] L/h and 15 [11-19] mL/min, respectively. Theoretically, daily doses for a steady-state minimum concentration of 10 µg/mL would be 12.2 [7.8-16.4] g/day (166 [112-202] mg/[kg·day]); for an average steady-state concentration of 10 µg/mL, they would be 6.9 [4.5-8.1] g/day (91 [59-111] mg/[kg·day]). In conclusion, administration of acetaminophen at the recommended dosage of 1 g per 6 hours to critically ill multiple-trauma patients yields serum concentrations below 10 µg/mL due to increased elimination. To reach the 10 µg/mL target, and from a strictly pharmacokinetic point of view, continuous infusion may be more feasible than bolus dosing. Such a change in dosing strategy requires appropriate, pharmacokinetic-pharmacodynamic and specific safety study.