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Diuréticos del asa y ototoxicidad
Abstract
Loop diuretics are quite often used in medical practice. In spite of a wide security, there are several adverse events that should be known, in order to be early recognised as soon as they appear. Ototoxicity associated to furosemide is infrequent and reversible. However, permanent deafness associated with furosemide administration has been previously reported.
... Es de suma importancia conocer y actuar sobre estas alteraciones, dadas las complicaciones futuras en el desarrollo psicomotor, en especial en el área del lenguaje, que se puedan presentar en este tipo de patologías. Los niños que no son diagnosticados tempranamente padecen deterioro de habilidades del lenguaje verbal si no se inician en un programa de rehabilitación auditivo, de ahí la importancia del diagnóstico temprano (10,(12)(13). ...
... De los factores de riesgo encontrados en la población, el mayor porcentaje lo ocuparon los ototóxicos, con 63,81%, y entre los pacientes con alteraciones en las pruebas auditivas, los varones ocuparon el segundo lugar, con 4,76%. Es tal vez el factor de riesgo que más se manifestó en los estudios de prevalencia de alteraciones auditivas (12), y se conoce que son fuertes factores de riesgo, no solo en este grupo etario; de ahí la importancia del seguimiento y cuidados en la población a la que se administra este tipo de medicamentos (13). Sin embargo, algunos autores han discutido su asociación con la presentación de alteraciones auditivas (14). ...
... Es importante el seguimiento en estos niños, con el fin de establecer el diagnóstico definitivo y el tratamiento apropiado. También es necesario concientizar a los familiares en la reconsulta, para diagnóstico definitivo y seguimiento de las recomendaciones, con el fin de evitar secuelas a largo plazo y complicaciones asociadas, conociendo que una de las limitantes para el adecuado manejo es la falta de interés o conocimiento de la patología en sí por parte de los padres (13,(16)(17). ...
Propósito: Determinar la prevalencia de alteraciones auditivas detectadas a través de tamizaje en la población de recién nacidos con factores de riesgo, en la Unidad Neonatal (UCIN) del Hospital de San José. Materiales y métodos: Se trató de un estudio observacional descriptivo, tipo corte transversal, donde se tomaron 106 participantes con al menos un factor de riesgo para alteraciones auditivas. Se determinaron medidas de tendencia central, de dispersión, proporciones y frecuencias. Se establecieron asociaciones estadísticas a través de chi2 y F de Fisher. Resultados: La edad media gestacional de nacimiento fue de 35,5 semanas, peso promedio de 2.286 gramos. Con respecto al sexo, 59 (55,66%) fueron del masculino. Diez (9,52%) presentaron emisiones otoacústicas alteradas. Sobre los factores de riesgo, en 17 (16,50%) se encontraron bilirrubinas por encima de 20 mg/dl, a diez (20,83%) se les realizó exanguinotransfusión, 17 (16,19%) se diagnosticaron con Storch, seis (5,83%) presentaron alteraciones craneofaciales y a 67 (63,81%) se les administró al menos un ototóxico. Se encontró una asociación estadísticamente significativa entre hipoacusia y el peso (p = 0,005), alteraciones craneofaciales (p = 0,044) e historia de infecciones maternoperinatales (Storch) (p = 0,002). Conclusiones: Se debe continuar con la investigación de los factores de riesgo para el desarrollo de hipoacusia en nuestra población, con el fin de identificarlos tempranamente y establecer un proceso de rehabilitación adecuado. Conviene implementar un programa de tamizaje auditivo obligatorio.
... La información disponible sobre esta asociación es diversa: Swartz indica que ciertos medicamentos pueden provocar súbitamente una hipoacusia bilateral, es decir, una pérdida rápida e inexplicable de la audición. Medicamentos ototóxicos como los aminoglucósidos -estreptomicina y gentamicina-pueden destruir las células pilosas del órgano de Corti y provocar una sordera permanente; los salicilatos y diuréticos -como la furosemida o el ácido etacrínico-pueden provocar una pérdida transitoria de la audición a dosis altas; y otros, como el quimioterápico cisplatino, también están asociados con ototoxicidad (34,39). Como se ha descrito en la literatura, la ototoxicidad depende de varios factores, como la concentración del fármaco en el oído interno, las características del paciente, el uso concomitante de otros fármacos ototóxicos y el tratamiento previo con aminoglucósidos (40). ...
Introducción.
La salud auditiva es un tema de interés en salud pública que afecta la calidad de vida y que puede afectarse por la exposición continua al ruido, un factor de riesgo que genera síntomas auditivos y extraauditivos.
Objetivo.
Identificar el estado de salud auditiva de adultos que viven en Bogotá, y su asociación con factores de exposición a ruido ambiental, individuales y otológicos.
Materiales y métodos.
Se realizó un estudio transversal mediante el análisis de una base de datos con 10.311 registros, obtenidos entre los años 2014 y 2018, producto de una encuesta estructurada de percepción de ruido y tamizaje auditivo. Se hizo un análisis descriptivo bivariado y una regresión logística binaria.
Resultados.
El 35,4 % de los participantes presentó disminución auditiva. En el componente de percepción: 13,0 % refirió no escuchar bien, 28,8 % informó síntomas extraauditivos, 53,3 % tenía antecedentes otológicos, y 69,0 % manifestó molestia por ruido extramural. En la regresión logística, las variables más asociadas con disminución auditiva fueron: de las ambientales, vivir en zonas de mayor ruido (OR = 1,50) (IC95%: 1,341,69); de las individuales, ser hombre (OR = 1,85) (IC95%: 1,64-2,09) y la edad (por cada año de vida, el riesgo de disminución auditiva aumentó 6 %); y de las otológicas, tener antecedente de síntomas otológicos (OR = 1,86) (IC95%: 1,66-2,08).
Conclusiones.
La disminución auditiva es multicausal en la población evaluada. Los factores que aumentan su prevalencia son incremento de la edad, ser hombre, tabaquismo, medicamentos ototóxicos, vivir en zonas de mayor exposición a ruido y presentar síntomas extraauditivos.
The suppression tuning of distortion-product otoacoustic emissions (DPOAEs) is commonly assumed to measure frequency selectivity, because the dominant features of suppression-tuning curves (STCs) are similar to the principal properties of the neural-tuning curves (NTCs) of single auditory-nerve fibers. In the present study, several common loop diuretics were used to affect the DPOAE-generation process to determine if reversible ototoxicity could adversely modify the characteristics of STCs, in a manner similar to that shown previously for NTCs. Contour plots of DPOAE level in the presence of a series of variable-level suppressor tones were obtained before and after administering diuretic drugs that reversibly reduced or eliminated DPOAEs. Primary-tone pairs were centered at 2.8 or 4 kHz, with L1 = L2, or L2 < L1. From the resulting plots, STC parameters including tip frequency, threshold at the tip frequency, and Q10 dB measures of tuning were extracted for four suppression criteria of 3, 6, 9, and 12 dB. In the pre-drug nonototoxic state, suppression tuning depended on both primary-tone level (L1, L2), and the relative levels of the primaries (L1-L2), with tuning being sharper for lower- than for higher-level equilevel primaries, and sharpest for offset-level primary tones. Following drug injection, the expected decrease in sharpness of tuning evidenced by changes in Q10 dB as well as the dramatically elevated tip thresholds normally seen for NTCs under similar conditions, were not observed. Overall, Q10 dB increased or decreased more or less randomly, with a slight tendency for STCs to become sharper than prior to drug dosing, for the two highest suppression criteria. The STC-tip frequencies demonstrated significant decreases following diuretic administration that were weakly correlated with the associated decreases in DPOAE amplitude. The most consistent changes in response to the drug-induced reduction in DPOAE level were increases in the STC-tip thresholds. However, these changes were relatively small and rarely exceeded 10 dB. In the absence of notable changes in overall STC shape, a major finding was a change in the effectiveness of suppression following ototoxic insult. However, when the amount of suppression was expressed as a percentage of the DPOAE remaining, the effects of diuretic dosing were often almost completely obscured. Overall, the results demonstrated that when the generation of DPOAEs was interfered with by the introduction of a suppressor tone to produce STCs that resemble NTCs, STCs behaved quite differently following reversible cochlear insult than their previously documented neural counterparts. These findings imply that STCs do not assess the frequency-selective aspects of the cochlear amplification process in a manner similar to NTCs.
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Six cases of hearing impairment have been presented. Furosemide was administered to all of these patients at the time of the alleged onset of the deafness. None of the known or suspected causes of deafness occurring in transplant patients was evident in these cases. With the experimental evidence that furosemide does induce stria damage and the absence of other recognized causes of deafness in this series of patients, furosemide must be considered the etiologic agent responsible for the permanent sensorineural hearing loss. A characteristic audiometric pattern of hearing impairment emerged and a possible explanation for these features has been given. Certain precautionary steps in the use of ototoxic drugs are suggested.
The rat is an altricial animal which serves as a useful model for human auditory development. The purpose of the present study was to investigate the effects of furosemide on cochlear function and the stria vascularis ultrastructure at various postnatal ages. Rat pups anesthetized with ketamine hydrochloride/xylazine hydrochloride received furosemide 35 mg/kg intravenously (IV), and the endocochlear potential and compound action potential of the eighth nerve were recorded. The stria vascularis was removed and prepared for transmission electron microscopy. Rat pups 9 to 28 days of age had a much greater reduction of endocochlear potential and elevation of the compound action potential threshold than animals older than 30 days. These physiologic changes were accompanied by edema of the stria on transmission electron microscopy only in animals at susceptible ages. These findings support the concept of a critical period of susceptibility to ototoxic drugs during development and could have important clinical implications in premature infants.
As the preceding review demonstrates, the true incidence of ototoxicity of various drug is difficult to establish. This stems as much from our inability to assess labyrinthine function in a sensitive and accurate fashion as it does from the lack of universally acceptable definitions of significant dysfunction. Until these difficulties are overcome, we will be able to talk about ototoxicity only in broad generalities. This review also suggests that monitoring for ototoxicity must be individualized to the particular drug being employed, and that a uniform method of monitoring for all drugs is not reasonable or practical. The early development of subjective symptomatology seen with erythromycin, acetylsalicylic acid, and quinine obviates the need for formal clinical testing of inner ear function each time the drug is employed. The profound and sometimes irreversible ototoxic effects of aminoglycosides and cisplatinum require much more formal monitoring. The role of more sensitive measures of vestibular function, such as harmonic acceleration, has yet to be firmly established.
Single doses of gentamicin and furosemide given in combination result in a rapid and profound loss of cochlear function. In this study, measurement of three gross cochlear potentials (cochlear microphonics, compound action potentials and the endocochlear potential) were carried out in order to determine the ototoxic sites of action of the drugs given in combination. The rapidity and severity of the cochlear deficit is dose dependent and with the doses employed in this study (80 mg/kg gentamicin i.v. 80 mg/kg furosemide i.v.), complete loss of cochlear function is seen after about 72 hours. Twenty-four hours after i.v. administration of the drugs, significant increases in compound action potential thresholds between 6 and 32 kHz were seen. In contrast, over this frequency range the generation of cochlear microphonics in response to stimulus levels of 70 dB SPL appeared to be unaffected. The endocochlear potential remained unaffected at 24 and 72 hours after administration. These findings are taken as evidence that the primary site of ototoxic action of the two drugs in combination may be at the level of the inner hair cells and/or the afferent synapse.
This study aimed to investigate the differential effect of the loop diuretic furosemide on the auditory and vestibular (otolith) end organs in the same animals simultaneously.
Auditory nerve-brain stem-evoked responses (ABR-generated in the cochlea) and short latency vestibular-evoked responses to linear acceleration impulses (L-VsEP-generated in the otolith organs) were recorded from albino Sabra rats both before and at minute intervals after intravenous injections of the loop diuretic furosemide. In some animals, an equal volume of saline was injected to control for the effect of the injection itself. In most animals, more than one injection of saline or furosemide was possible (furosemide, N = 17 injections in 10 rats; saline, N = 18 injections in 9 rats). Peak-to-peak amplitude and peak latency changes in the first wave in each recording (representing end-organ activity) as a function of postinjection time were compared between the two evoked potentials using analysis of variance and repeated t-tests.
Saline injections caused only minor changes in the amplitude of the ABR and the L-VsEP. After administration of furosemide, the amplitude of the L-VsEP hardly changed. However, there was a noticeable decrease in the amplitude of the ABR.
Although furosemide has a major depressant effect on cochlear function, vestibular end-organ activity is hardly altered.
Medicinal iatrogenics are responsible for hospital admissions but also occur in hospitals. In view of the lack of knowledge, prevalence and nature of the adverse drug-related events (ADE) in the Bichat-Claude Bernard hospital group in Paris, and because of the potential severity of the latter, the Local drug committee has decided to develop a policy to manage these risks.
The first stage consisted in a transversal study on a given day in the departments in which patients are hospitalised for more than 24 hours, in order to assess the prevalence, severity and preventability of ADE and to search for factors of risk.
107 ADE were observed in 89 patients on the day of the survey (9.9% global prevalence of ADE [CI 95%: 8.8% - 11.0%]). Among the latter, 57 patients had exhibited at least one adverse event during their hospitalisation, i.e., a prevalence of 6.3% ([CI 95%: 4.7% - 7.9%] ). Two thirds of these patients were hospitalised in medical departments. These nosocomial ADE (nosocomial adverse drug events) were serious or severe in 73% of cases and 25% could have been avoided. The only clearly identified risk factor was the number of drugs prescribed.
This review has drawn the attention of the medical and paramedical community to the need to define vigilance markers, and has provided some elements of response that should be further completed by a prospective cohort study.
Hearing loss is a significant morbidity in survivors of the neonatal intensive care unit (NICU). The overall prevalence of hearing loss in neonates is 0.93 per 1000 live births, whereas in neonates weighing less than 2000 g, it is as high as 15.5 per 1000 live births. The increased incidence of hearing loss in NICU graduates has been attributed to their underlying disease process as well as exposure to ototoxic drugs including furosemide. A retrospective chart review of all neonatal intensive care survivors was done to evaluate the potential effect of furosemide on hearing loss. From July 2000 to January 2002, there were 57 neonates who received and 207 neonates who did not receive furosemide. The incidence of abnormal hearing screen was 15.5% in the furosemide group and 15.9% in the nonfurosemide group ( p = 0.9). Although the incidence of hearing loss is significantly higher in NICU graduates in comparison with the general neonatal population, it does not seem to be directly related to the use of furosemide.
08025 Barcelona E-mail: hugomar2@yahoo.es Información artículo: Nota clínica Trabajo recibido: septiembre
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E-mail: hugomar2@yahoo.es
Información artículo: Nota clínica
Trabajo recibido: septiembre 2006
Trabajo aceptado: noviembre 2007