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BACKGROUND: The effect of anesthetic techniques on cancer recurrence has been the subject of intensive research in the past years, as it affects a large proportion of the population. The use of opioids and halogenated agents in cancer patients during the perioperative period may be related to higher rates of cancer recurrence and reduced disease-free survival. METHODS: This was a prospective study. The sample was composed of 100 patients who underwent a radical cystectomy for infiltrating bladder cancer in a reference center. We compared disease-free survival associated with combined anesthesia versus opiate-based analgesia. The relationship between the administered hypnotic and disease-free survival was also investigated. RESULTS: The median disease-free survival of the patients who received combined anesthesia was 585 (240-1,005) days versus 210 (90-645) days in the other group. A significant difference was observed between the two groups (p = 0.01). Combined analysis of all groups revealed significant differences in disease-free survival between patients who received combined anesthesia with propofol (510 [315-1,545] disease-free days) and those who received sevoflurane and opioids (150 [90-450] disease-free days) (p = 0.02). CONCLUSIONS: Anesthesia may play a crucial role in tumor relapse, as it is administered at the moment of the greatest risk of dissemination: surgical handling of the tumor. Opioids and volatile agents have been related to an increased risk for cancer recurrence. We compared the use of propofol + local anesthesia versus sevoflurane + opioids and also found that disease-free survival was longer among patients who received propofol + local anesthesia. Disease-free survival increases with the use of propofol in combination with epidural anesthesia in patients who undergo surgery for infiltrating bladder cancer.
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Analgésicos Opioides/administración & dosificación , Anestesia por Inhalación , Anestesia Intravenosa , Anestésicos Intravenosos/administración & dosificación , Cistectomía , Propofol/administración & dosificación , Neoplasias de la Vejiga Urinaria/cirugía , Analgésicos Opioides/efectos adversos , Anestesia por Inhalación/efectos adversos , Anestesia por Inhalación/mortalidad , Anestesia Intravenosa/efectos adversos , Anestesia Intravenosa/mortalidad , Anestésicos Intravenosos/efectos adversos , Cistectomía/efectos adversos , Cistectomía/mortalidad , Supervivencia sin Enfermedad , Humanos , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Propofol/efectos adversos , Estudios Prospectivos , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Introduction: Our case is unique because the differential diagnosis was a challenge. At first, the patient presented with septic shock and multi-organ failure in the context of a suspected lymphoproliferative syndrome. Once the lymphoproliferative process had been ruled out, hemophagocytic syndrome due to COVID-19 infection was suspected, so he is probably one of the few patients with such an exhaustive study that could contribute to our understanding of COVID-19. We followed therapeutic guidelines that differ from the usual, using adrenalin and levosimendan. Corticosteroids helped to modulate the cytokine storm. Case report: A 16-year-old adolescent was admitted to the intensive care unit with fever, diarrhea, multiorgan failure and septic shock. He was IgG positive for COVID-19 and IgM negative. Thoraco-abdominal computed tomography demonstrated multiple para-aortic and peri-pancreatic lymphadenopathy and acute respiratory distress syndrome. The first suspected diagnosis was a lymphoproliferative syndrome and bacterial infection. The second possibility was a hemophagocytic syndrome in a patient recovering from COVID-19. He was treated with broad spectrum antibiotics because the differential diagnosis was difficult, and we removed them when the microbiological screening was negative. During the course of the disease he presented with severe biventricular dysfunction, probably due to the cytokine storm, so we used inotropic drugs (adrenaline, levosimendan). Infection with Salmonella species group B was diagnosed later, when the patient was in the Internal Medicine ward, although he was asymptomatic. Conclusion: The severity of COVID-19 infection ranges from mild to severe, causing serious disease in some people. Although the pathophysiology is not well known, it seems that in some cases an immune storm is triggered, and it is related to more serious and prolonged disease. In our case, heart failure was important, because it could have worsened the prognosis. Fortunately, the response to levosimendan and corticosteroids was adequate and he recovered favorably until discharge.
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COVID-19 , Insuficiencia Cardíaca , Linfohistiocitosis Hemofagocítica , Choque Séptico , Masculino , Adolescente , Humanos , COVID-19/complicaciones , Simendán/uso terapéutico , Síndrome de Liberación de Citoquinas , SARS-CoV-2 , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológico , Corticoesteroides/uso terapéuticoRESUMEN
BACKGROUND: The pre- and post-conditioning effects of halogenated anesthetics make them most suitable for cardiac surgery. Several studies have demonstrated that the mechanism of drug-induced myocardial conditioning is enzyme-mediated via messenger RNA and miRNA regulation. The objective of this study was to investigate the role that miRNAs play in the cardioprotective effect of halogenated anesthetics. For such purpose, we reviewed the literature to determine the expression profile of miRNAs in ischemic conditioning and in the complications prevented by these phenomena. METHODS: A review was conducted of more than 100 studies to identify miRNAs involved in anesthetic-induced myocardial conditioning. Our objective was to determine the miRNAs that play a relevant role in ischemic disease, heart failure and arrhythmogenesis, which expression is modulated by the perioperative administration of halogenated anesthetics. So far, no studies have been performed to assess the role of miRNAs in anesthetic-induced myocardial conditioning. The potential of miRNAs as biomarkers and miRNAs-based therapies involving the synthesis, inhibition or stimulation of miRNAs are a promising avenue for future research in the field of cardiology. RESULTS: Each of the cardioprotective effects of myocardial conditioning is related to the expression of several (not a single) miRNAs. The cumulative evidence on the role of miRNAs in heart disease and myocardial conditioning opens new therapeutic and diagnostic opportunities. CONCLUSION: Halogenated anesthetics regulate the expression of miRNAs involved in heart conditions. Further research is needed to determine the expression profile of miRNAs after the administration of halogenated drugs. The results of these studies would contribute to the development of new hypnotics for cardiac surgery patients.
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Anestésicos , Procedimientos Quirúrgicos Cardíacos , Humanos , MicroARNs , MiocardioRESUMEN
BACKGROUND: Low-cardiac output syndrome (LCOS) after cardiac surgery secondary to systemic hypoperfusion is associated with a higher incidence of renal and neurological damage. A range of effective therapies are available for LCOS. The beneficial systemic effects of levosimendan persist even after cardiac output is restored, which suggests an independent cardioprotective effect. METHODS: A double-blind clinical trial was conducted in patients with a confirmed diagnosis of LCOS randomized into two treatment groups (levosimendan vs. dobutamine). Monitoring of hemodynamic (cardiac index, systolic volume index, heart rate, mean arterial pressure, central venous pressure, central venous saturation); biochemical (e.g. creatinine, S100B protein, NT-proBNP, troponin I); and renal parameters was performed using acute kidney injury scale (AKI scale) and renal and brain ultrasound measurements [vascular resistance index (VRI)] at diagnosis and during the first 48 h. RESULTS: Significant differences were observed between groups in terms of cardiac index, systolic volume index, NT-proBNP, and kidney injury stage at diagnosis. In the levosimendan group, there were significant variations in AKI stage after 24 and 48 h. No significant differences were observed in the other parameters studied. CONCLUSION: Levosimendan showed a beneficial effect on renal function in LCOS patients after cardiac surgery that was independent from cardiac output and vascular tone. This effect is probably achieved by pharmacological postconditioning. CLINICAL TRIAL REGISTRATION: EUDRA CT, identifier 2014-001461-27. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001461-27.
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Numerous studies have studied the effect of halogenated agents on the myocardium, highlighting the beneficial cardiac effect of the pharmacological mechanism (preconditioning and postconditioning) when employed before and after ischemia in patients with ischemic heart disease. Anesthetic preconditioning is related to the dose-dependent signal, while the degree of protection is related to the concentration of the administered drug and the duration of the administration itself. Triggers for postconditioning and preconditioning might have numerous pathways in common; mitochondrial protection and a decrease in inflammatory mediators could be the major biochemical elements. Several pathways have been identified, including attenuation of NFκB activation and reduced expression of TNFα, IL-1, intracellular adhesion molecules, eNOS, the hypercontraction reduction that follows reperfusion, and antiapoptotic activating kinases (Akt, ERK1/2). It appears that the preconditioning and postconditioning triggers have numerous similar paths. The key biochemical elements are protection of the mitochondria and reduction in inflammatory mediators, both of which are developed in various ways. We have studied this issue, and have published several articles on cardioprotection with halogenated gases. Our results confirm greater cardioprotection through myocardial preconditioning in patients anesthetized with sevoflurane compared with propofol, with decreasing levels of troponin and N-terminal brain natriuretic peptide prohormone. The difference between our studies and previous studies lies in the use of sedation with sevoflurane in the postoperative period. The results could be related to a prolonged effect, in addition to preconditioning and postconditioning, which could enhance the cardioprotective effect of sevoflurane in the postoperative period. With this review, we aim to clarify the importance of various mechanisms involved in preconditioning and postconditioning with halogenated gases, as supported by our studies.
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Cardiotónicos/farmacología , Gases/farmacología , Éteres Metílicos/farmacología , Isquemia Miocárdica/prevención & control , Propofol/farmacología , Animales , Cardiotónicos/administración & dosificación , Gases/administración & dosificación , Humanos , Éteres Metílicos/administración & dosificación , Isquemia Miocárdica/cirugía , Propofol/administración & dosificación , SevofluranoAsunto(s)
Anestesia por Circuito Cerrado/instrumentación , Anestésicos por Inhalación/administración & dosificación , Éteres Metílicos/administración & dosificación , Óxido Nítrico/administración & dosificación , Complicaciones Posoperatorias/terapia , Respiración Artificial/instrumentación , Vasodilatadores/administración & dosificación , Absorción , Administración por Inhalación , Anestesia por Circuito Cerrado/efectos adversos , Disponibilidad Biológica , Regulación hacia Abajo , Diseño de Equipo , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Complicaciones Posoperatorias/fisiopatología , Respiración Artificial/efectos adversos , Sevoflurano , Vasodilatadores/química , Vasodilatadores/metabolismoRESUMEN
PURPOSE: To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV) dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and neuronal enolase. METHODS: This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels. RESULTS: After surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL), neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng/mL), or mean ± SD creatinine (1.06±0.24 mg/dL vs 1.25±0.37 mg/dL at 48 hours). RV dilatation decreased from 4.23±0.7 mm to 3.45±0.6 mm and pulmonary artery pressure from 58±18 mmHg to 42±19 mmHg at 48 hours. CONCLUSION: Preoperative administration of levosimendan has shown a protective role against cardiac, renal, and neurological damage in patients with a high risk of multiple organ dysfunctions undergoing cardiac surgery.
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Insuficiencia Cardíaca/prevención & control , Implantación de Prótesis de Válvulas Cardíacas/métodos , Hidrazonas/administración & dosificación , Cuidados Preoperatorios/métodos , Piridazinas/administración & dosificación , Disfunción Ventricular Derecha/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Ecocardiografía/métodos , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/diagnóstico por imagen , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Infusiones Intravenosas , Masculino , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/prevención & control , Medición de Riesgo , Simendán , España , Resultado del Tratamiento , Disfunción Ventricular Derecha/diagnósticoRESUMEN
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