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.

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)

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.

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

Abstract 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 4.081 s 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.

Resumo Justificativa e objetivos: O propofol é comumente usado como agente hipnótico na terapia eletroconvulsiva, mas apresenta também propriedades anticonvulsivantes. O objetivo principal foi avaliar o efeito da dose de propofol ajustada ao peso na duração da convulsão elétrica. Os objetivos secundários foram avaliar o efeito da dose total de propofol na duração da convulsão elétrica, o efeito da dose tanto total quanto ajustada ao peso nos valores do índice bispectral e a influência da bioquímica do sangue no efeito anticonvulsivante. Métodos: Após aprovação do Comitê de Ética em Pesquisa, foi feita uma revisão retrospectiva dos prontuários de todos os pacientes que fizeram pelo menos uma sessão de eletroconvulsoterapia. Análise de regressão linear múltipla ajustada para potenciais confundidores foi feita para explorar o efeito da dosagem de propofol sobre os valores do índice bispectral e a duração da convulsão; análises de correlação bivariada foram previamente feitas para identificar as variáveis que atendem aos critérios de confusão, especificamente valores de r de Spearman > 0,10. Os resultados da análise de regressão foram expressos como coeficiente B com intervalo de confiança de 95%. Resultados: Setenta e seis pacientes receberam 631 sessões de fase aguda. Propofol mostrou um efeito negativo estatisticamente significativo sobre a duração da convulsão (especificamente uma redução de 4,081 segundos para cada mg.kg−1 de propofol; IC de 95%: -7906 para -0,255, p = 0,037), mas não para os valores do índice bispectral. Anemia leve e hipoalbuminemia foram condições muito raras e o efeito anticonvulsivante não foi influenciado por esses parâmetros. Conclusões: A dose de propofol ajustada ao peso está negativamente relacionada com a duração das crises convulsivas, deve ser cuidadosamente titulada quando usada na terapia eletroconvulsiva.

Blastoma pleuropulmonar: reporte de un caso / Pleuropulmonary blastoma: case report

El blastoma pleuropulmonar corresponde a una neoplasia primaria de pulmón, exclusiva de la edad pediátrica, poco frecuente y de características agresivas. La edad de diagnóstico varía entre 1 mes y 12 años. No se identifica una distinción de sexos. Se localiza en la pleura o el pulmón. Suele presentarse como dificultad respiratoria, con o sin neumotórax, dolor torácico y fiebre, por lo que es mal diagnosticada como neumonía. Radiológicamente, suele hallarse una masa de gran tamaño cercana a la pleura en la base pulmonar derecha sin broncograma aéreo. Cuenta con tres tipos histológicos: tipo I (quístico), tipo II (mixto), tipo III (sólido). Su tratamiento incluye resección y quimioterapia multimodal. El tipo I tiene un pronóstico favorable, pero los tipos II y III tienen mal pronóstico. Se presenta un caso de blastoma pleuropulmonar en una niña de 2 años, con énfasis en su diagnóstico clínico-radiológico.

Pleuropulmonary Blastoma corresponds to a malignant primary lung disorder, exclusive of pediatric age, infrequent and of aggressive characteristics. Age on diagnosis is 1 month-12 years. Rates per sex are equal. It can be found inside pleura or lungs. Respiratory distress associated or not with pneumothorax, chest pain and fever are classical clinical signs. These symptoms could be misdiagnosed as pneumonia. Radiologically, a large mass near the pleura at the base of the right lung without air bronchogram is its most common form. It has three histological types: type I (cystic), type II (mixed) and type III (solid). Its treatment requires tumor excision and multimodal chemotherapy. Pleuropulmonary Blastoma type I has good prognosis; type II and III variants have lower survival. We report a 2-year-old girl, pointing to the clinical-radiological diagnosis.

Intraoperative awareness as an example of the influence of cardiac output on anesthetic dosing: case report / Despertar intraoperatorio como ejemplo de la influencia del gasto cardíaco en la dosificación anestésica. Reporte de caso

Abstract A case of intraoperative awareness during ablation of pulmonary veins-one of the most widely used techniques in interventional cardiology-is discussed. An infusion of isoproterenol was administered following the ablation of ectopic foci. A few seconds after the infusion the patient experienced increased heart rate and intraoperative awareness manifested as an abrupt patient movement and bispectral index elevation. This has been described in similar procedures, following the administration of isoproterenol. In our opinion, the isoproterenol infusion caused the increased heart rate and subsequent abrupt rise in cardiac output. As an inversely proportional relationship between the propofol concentrations and cardiac output has been described, we believe that this rise in cardiac output could have favored the decline in the concentrations of propofol, leading to an intraoperative awareness episode.

Resumen Presentamos un caso de despertar intraoperatorio durante la ablación de venas pulmonares, una de las técnicas más empleadas por los cardiólogos intervencionistas. Tras la ablación de focos ectópicos se procede a la infusión de isoproterenol. Segundos después de la infusión se produce un aumento de la frecuencia cardíaca seguido de un despertar intraoperatorio traducido como un movimiento brusco del paciente y un aumento en el índice bi-espectral (BIS). Esto ha sido descrito en procedimientos similares tras la administración de isoproterenol. En nuestra opinión, la infusión de isoproterenol provocó un aumento de la frecuencia cardiaca y secundariamente del gasto cardíaco de forma brusca. Dado que se ha descrito una relación inversamente propocional entre las concentraciones de propofol y el gasto cardíaco, pensamos que este aumento del gasto cardíaco pudo condicionar un descenso de las concentraciones de propofol y esto causar el episodio de despertar intraoperatorio.

Papel de los roedores en la transmisión de Leptospira spp. en granjas porcinas / The role of rodents in the transmission of Leptospira spp. in swine farms

RESUMEN Diferentes especies de roedores son potenciales transmisores de múltiples agentes zoonóticos como Leptospira spp., espiroqueta causante de la Leptospirosis, que es una enfermedad infecciosa que tiene un impacto negativo en la porcicultura debido a que genera grandes pérdidas productivas, reproductivas y económicas. En las granjas porcinas, las especies de roedores más comunes son el ratón doméstico (Mus musculus), la rata parda (Rattus norvegicus) y la rata negra (Rattus rattus), que actúan como huéspedes de mantenimiento de diferentes serovares de Leptospira spp., contaminando con orina el ambiente, los alimentos y el agua, poniendo en riesgo la salud humana y animal. Por esta razón, el objetivo de este artículo es describir el papel de los roedores en la transmisión de Leptospira en granjas porcinas. Para esto, se realizó una búsqueda bibliográfica en diferentes bases de datos como Science Direct, Scopus, Redalyc, PubMed y SciELO. Los resultados de la revisión de literatura, demuestran que son escasos los estudios que reportan la importancia de los roedores en la transmisión de Leptospira en granjas porcinas. La presentación de la enfermedad depende en gran parte de la presencia, el contacto y el control de roedores en las granjas, aunque también se deben tener en cuenta factores ambientales, de supervivencia del agente y las medidas de higiene, entre otros.(AU)

ABSTRACT Different species of rodents are potential transmitters of multiple zoonotic agents such as Leptospira spp., a spirochete that causes leptospirosis. This is an infectious disease that has a negative impact on pig production because it generates large productive, reproductive and economic losses. In swine farms, the most common rodent species are house mice (Mus musculus), brown rats (Rattus norvegicus) and black rats (Rattus rattus), which act as maintenance hosts for different serovars of Leptospira, contaminating the environment, food and water through urine, and putting human and animal health at risk. For this reason, the objective of this article is to describe the role of rodents in the transmission of Leptospira in swine farms. For this purpose, a bibliographic search was carried out in different databases such as Science Direct, Scopus, Redalyc, PubMed and SciELO. The results of the literature review show that there are few studies that report the importance of rodents in the transmission of Leptospira in swine farms. The onset of the disease depends to a large extent on the presence, contact and control of rodents in farms, although environmental factors, agent survival and hygiene, among others, must also be considered.(AU)