Reacción paradojal secundaria a ingesta accidental de benzodiazepinas. Serie de casos / Paradoxical reaction secondary to accidental ingestion of benzodiazepines. Case series

Resumen Globalmente, los fármacos son el tipo de agente más frecuentemente implicado en las intoxicaciones pediátricas y las Ben-zodiacepinas el grupo farmacológico más frecuente. La reacción paradojal, secundaria a la exposición a Benzodiacepinas se caracteriza por la presencia de signosintomatología contraria a los efectos sedativos hipnóticos esperados, pudiendo presentarse con inquietud, ansiedad, hostilidad y alteraciones de la conducta, entre otros. La mayoría de los trabajos hallados acerca de este síndrome en pediatría lo describen secundario a Midazolam endovenoso, en contexto de sedación consciente para la realización de diferentes procedimientos. Las causas por los cuales se puede generar este fenómeno de desinhibición no han sido clarificadas, postulándose tres hipótesis: la desregulación colinérgica central, el aumento del tono gabaérgico en el sistema límbico, tálamo e hipotálamo y el desbalance de serotonina. Se expone una serie de 15 pacientes de entre 1 año y 5 años, expuestos accidentalmente a Benzodiacepinas, principalmente Clonazepam y Lorazepam, a fin de describir las características de esta reacción. En esta serie se observó con latencia breve y duración variable, de hasta 11 horas, la presencia en orden de frecuencia, de: ansiedad, irritabilidad, gritos, hostilidad y conductas agresivas, llanto inconsolable, incapacidad de contención por familiares, conductas irracionales, excitación psicomotriz, desinhibición emocional, alucinaciones y aumento de locuacidad, asociado frecuentemente a ataxia.

Abstract Globally, medicines are the most frequently toxins involved in pediatric poisonings, and Benzodiazepines are the most fre-quent pharmacological group in those poisonings. The paradoxical reaction, secondary to Benzodiazepines exposure, is characterized by the presence of contrary expected sedative-hypnotic effects, and may present with restlessness, increased anxiety, hostility, and behav-ioral alterations, among others. The studies we found about this syndrome in pediatric patients describe it most frequently secondary to endovenous Midazolam, in the context of the conscious sedation to perform different procedures. The reasons why this reaction is generated have not been clarified, three hypotheses are postulated: the central cholinergic dysregulation, the increased Gabaergic tone in the limbic system, thalamus and hypothalamus and the serotonin imbalance. A series of 15 patients, between 1 year and 5 years old, accidentally exposed to Benzodiazepines, mainly Clonazepam and Lorazepam, to describe the characteristics of the paradoxical reaction secondary to Benzodiazepines exposure. In this case series, we observed with short latency and variable duration, up to 11 hours, the presence in order of frequency of: anxiety, irritability, screams, hostility and aggressive behaviors, inconsolable crying, inability to con-tain by their family members, irrational behaviors and psychomotor excitement, emotional disinhibition, hallucinations and increased talkativeness, frequently associated with ataxia.

Tratamiento de meningitis tuberculosa en paciente HIV negativo, posible reacción paradojal / Possible paradoxical reaction to treatment of tubercular meningitis in an HIV negative patient

La respuesta paradojal al tratamiento tuberculoso es la aparición de manifestaciones clínico-radiológicas nuevas, o el empeoramiento de las previas, luego de una mejoría inicial con el tratamiento específico. Se puede observar en 6-30% de los casos de tuberculosis meníngea. Es una reacción inmunológica exagerada y debe tenerse presente ya que su tratamiento se basa en el uso de inmunomoduladores y no en el cambio de las drogas antituberculosas. Presentamos el caso de una paciente adulta HIV negativa con meningitis tuberculosa que, luego de una adecuada respuesta inicial al tratamiento, intercurre a las 10 semanas con una reacción paradojal tratada satisfactoriamente con corticoides.

The paradoxical response to tuberculosis treatment consists in the appearance of new clinical or radiologic manifestations or worsening of previous injuries after an initial improvement with anti-tuberculosis therapy. It can be observed in 6 to 30 percent of the cases of tubercular meningitis. It is the consequence of an exaggerated immune reaction that should be considered since the treatment is based on the use of immunomodulators and not in the change of anti-tuberculous drugs. We present the case of an HIV negative adult with tuberculous meningitis with a good initial response to specific therapy who showed, 10 weeks later, a paradoxical reaction to treatment that responded successfully to corticosteroids.

Reacciones paradójicas en el tratamiento de la tuberculosis ganglionar / Paradoxical reactions during tuberculosis lymphadenitis treatment

Lymphadenitis tuberculosis is the most frequent form of non pulmonary tuberculosis. Its incidence has increased in the last years probably because HIV co-infection. Usually manifests like a swelling of lymph nodes in the cervical region without constitutional symptoms. Diagnostics tests yields are poorer than in pulmonary tuberculosis probably due to the scarce bacillus population. Treatment is the same of pulmonary tuberculosis, but paradoxical reactions are far more frequent. These reactions, specially the latest presentations ones very often are treated as recurrence of the disease. Although this is always a possibility, in most cases they are due to an hypersensitivity reaction. In this article we present an illustrative case, an update on tuberculosis lymphadenitis and a review of the paradoxical reactions during its treatment.

La tuberculosis ganglionar es la forma más frecuente de tuberculosis extrapulmonar. Su incidencia ha aumentado, probablemente por la co-infección con VIH. Su presentación clínica más habitual es con un aumento de volumen de los ganglios cervicales sin síntomas constitucionales. Las pruebas diagnósticas tienen menos rendimiento que en la tuberculosis pulmonar por ser una enfermedad con menor población bacilar. Para el tratamiento se utilizan las mismas drogas y duración que en tuberculosis pulmonar, pero existe mayor incidencia de reacciones paradojales, las que pueden ser de difícil manejo. En este artículo presentamos primero un caso clínico particularmente ilustrativo, seguido de una puesta al día sobre tuberculosis ganglionar, incluyendo una revisión sobre el manejo de sus reacciones paradójicas.

Reacción paradojal en meningitis tuberculosa: presentación de un caso / Paradoxical reaction in tuberculous meningitis: a case report

La afectación del sistema nervioso central es una de las localizaciones extrapulmonares de la tuberculosis con peor pronóstico. El retraso en el diagnóstico y tratamiento es uno de los factores relacionados con mayor tasa de mortalidad y secuelas. Se describe la "reacción paradojal" como un deterioro sintomático de grado variable, durante el tratamiento efectivo de la tuberculosis. El aumento de la resistencia del Mycobacterium tuberculosis a fármacos observado en los últimos años genera mayor preocupación ante la aparición de una reacción paradojal durante el tratamiento. Se presenta el caso de un niño con meningitis tuberculosa que, luego de un mes de tratamiento, presentó empeoramiento clínico y nuevas lesiones en la tomografía y resonancia magnética nuclear de cerebro. Se excluyeron patologías asociadas, se verificó que la toma de medicamentos haya sido supervisada, y la sensibilidad del bacilo a fármacos antituberculosos de primera línea fue confirmada. El paciente no requirió cambios en el esquema de tratamiento antituberculoso y se administraron esteroides para el alivio sintomático. La reacción paradojal durante el tratamiento antituberculoso es infrecuente y debida a una reacción de hipersensibilidad entre el huésped y el bacilo tuberculoso. Cuando aparece, se debe asegurar la efectividad y el cumplimiento del tratamiento administrado.

The central nervous system is one of the locations of extrapulmonary tuberculosis with worse prognosis. The delay in diagnosis and treatment is one of the factors associated with higher mortality and sequelae. The "paradoxical reaction" is described as a variable degree of symptomatic deterioration during the effective treatment of tuberculosis. The increased resistance of Mycobacterium tuberculosis to drugs observed in recent years generates greater concern about the emergence of a paradoxical reaction during treatment. The case of a child with tuberculous meningitis that after one month of treatment presented clinical worsening and new lesions in CT and MRI images of the brain is presented. Comorbidities were excluded, it was verified that taking drugs has been monitored, and the sensitivity of the bacillus to first-line antituberculosis drugs was confirmed. The patient required no change in the pattern of tuberculosis treatment and steroids were administered for symptomatic relief. The paradoxical reaction during antituberculosis treatment is rare and due to a hypersensitivity reaction between the host and the tuberculous bacillus. When it appears you must ensure the effectiveness and compliance of the treatment.

Reacción paradojal al tratamiento antituberculoso en un paciente inmunocompetente: a propósito de un caso / Paradoxical reaction during tuberculosis treatment in immunocompetent children: case report

Tuberculosis is an important public health problem. It is estimated that around 5-10% of patients with tuberculosis present with central nervous system involvement; meningitis and tuberculoma being two of the most frequent manifestations. The paradoxical reaction in patients undergoing antituberculosis treatment is infrequent, nevertheless it is an important consideration in patients, who after an appropriate initial response to specific treatment, present with worsening clinical and radiological signs or the appearance of new lesions.

La tuberculosis (TBC) es un problema de importancia en salud pública. Se estima que alrededor de 5 a 10% de los pacientes con TBC presentan compromiso de sistema nervioso central, siendo la meningitis y el tuberculoma las manifestaciones más frecuentes. La reacción paradojal en pacientes con tratamiento antituberculoso es infrecuente, sin embargo, es importante considerarla en pacientes que durante la terapia, luego de una respuesta inicial apropiada, presentan un empeoramiento clínico y/o radiológico o aparición de nuevas lesiones.

Rebound effect of drugs: fatal risk of conventional treatment and parmacological basis of homeopathic treatment / Efeito rebote das drogas: riscos fatais do tratamento convencional e bases farmacológicas do tratamento homeopático / Efecto rebote de drogas: riesgos fatales del tratamiento convencional y bases farmacológicas del tratamiento homeopático

The homeopathic model applies the secondary action or vital reaction of the organism as a therapeutic method and thus prescribes treatment by similitude, which consists in administering to ill individuals substances that cause similar symptoms in healthy individuals. The vital, homeostatic or paradoxical reaction of the organism might be explained scientifically by means of the rebound effect of modern drugs, which might cause fatal iatrogenic events after discontinuation of antipathic (a term used in alternative medicine for palliative treatment, also known as enantiopathic) treatment. Although the rebound effect is studied by modern pharmacology, it is poorly communicated to and discussed among healthcare professionals, who are thus deprived of information needed for the safe management of modern drugs. This article presents an up-to-date review on the rebound effect of modern drugs that grounds the homeopathic principle of healing and calls the attention of doctors to this type of adverse effect that is usually unnoticed. The rebound effect of modern palliative drugs, which was pointed out by Hahnemann more than two centuries ago, might cause fatal adverse events and is illustrated by the examples of acetylsalicylic acid, anti-inflammatory agents, bronchodilators, antidepressants, statins, proton-pump inhibitors, etc. Although the rebound effect is expressed by a small fraction of (susceptible) individuals and might be avoided by gradual tapering of antipathic drugs, it exhibits epidemiologic importance as a function of the massive use of such palliative drugs and the lack of knowledge in its regard.

O modelo homeopático aplica a ação secundária ou reação vital do organismo como método terapêutico. Assim, propõe o tratamento por semelhança, que consiste em administrar aos doentes substâncias que produzem sintomas similares em pessoas sadias. A reação vital, homeostática ou paradoxal do organismo pode ser explicada cientificamente com base no efeito rebote das drogas modernas. Este pode produzir eventos iatrogênicos fatais depois da suspensão do tratamento antipático (ou enantiopático, termo utilizado em medicina alternativa para se referir ao tratamento paliativo). Embora o efeito rebote é abordado pela farmacologia moderna, é pouco difundido e discutido pelos profissionais da saúde que, assim, são privados de informação necessária para o manejo seguro das drogas modernas. Este artigo apresenta uma revisão atualizada do efeito rebote das drogas modernas e que também embasa o princípio homeopático da cura. Apontado por Hahnemann mais de dois séculos atrás, o efeito rebote das drogas paliativas modernas pode causar efeitos adversos fatais, como ilustram os exemplos do ácido salicílico, anti-inflamatórios, broncodilatadores, antidepressivos, estatinas, inibidores da bomba de prótons, etc. Embora o efeito rebote seja expressado por uma pequena parte de indivíduos (suscetíveis) e possa ser evitando através da retirada gradual das drogas antipáticas, atinge importância epidemiológica devido ao uso maciço dessas drogas e do desconhecimento a seu respeito.