Uso de sedación endovenosa en pacientes con COVID-19 crítico en ventilación mecánica invasiva / Use of intravenous sedation in patients with critical COVID-19 in invasive mechanical ventilation

ANTECEDENTES: El objetivo del presente informe es: Describir el proceso para la elaboración de recomendaciones por el grupo de trabajo designado por el Ministerio de Salud, en adelante denominado grupo de trabajo. Trasladar las Recomendaciones efectuadas por dicho grupo de trabajo en atención al uso de sedación endovenosa en pacientes con COVID-19 crítico en ventilación mecánica invasiva, según la pregunta PICO (P: Población, I: Intervención, C: Comparador, O: Outcome o desenlaces) priorizada por el grupo de trabajo. La metodología considerada para arribar a la recomendación fue el Marco de Evidencia a la Decisión/Recomendación (EtD) desarrollado por el Grupo de Trabajo GRADE (1,2). ANALISIS: Formulación de la pregunta: En personas con COVID-19 crítico en ventilación mecánica invasiva, ¿cuál es el medicamento que debe administrarse para la sedación endovenosa? Y ¿Cuál pauta de dosificación? Identificación de la evidencia para la pregunta PICO: Se siguieron las orientaciones establecidas en el documento interno de UNAGESP: Orientaciones para el soporte metodológico otorgado al grupo de trabajo designado por el MINSA. Se describe a continuación los resultados del proceso: Se efectuó la búsqueda de guías de práctica clínica (GPC) que incluyeran recomendaciones respecto al uso de sedación endovenosa en la población de interés, con fecha de búsqueda 22 de octubre de 2021 en las siguientes plataformas: eCOVID-19 living map of recommendations (eCovid-19 RecMap), Base internacional de Guías GRADE (BIGG) , Guidelines International Network (GIN), COVID-19 Guidelines Dashboard, National Institute for Health and Care Excellence - UK (NICE) y Trip database, identificándose 7 guías de práctica clínica (Ver Anexo 1). En base a criterios como fecha de búsqueda de la evidencia, uso de metodología GRADE para evaluar la certeza de la evidencia, disponibilidad de la tabla Perfil de evidencia o Resumen de hallazgos, disponibilidad de los criterios o Tabla EtD y tipo de recomendación. Se identificaron tres guías de la Organización Panamericana de la Salud y una de la Society of Critical Care Medicine (SCCM)(3­6), sin embargo, las guías de OPS no brindan recomendaciones especificas para responder directamente a todas las alternativas de intervenciones planteadas por SOPEMI. Por otro lado, las guías de SCCM contienen recomendaciones respecto al uso de todas las alternativas de intervenciones planteadas en pacientes no COVID. La búsqueda se realizó en MEDLINE/ vía PubMed, plataforma L·OVE de Epistemonikos (7) y en MedRxiv, con fecha 22 de octubre de 2021. Los criterios de selección de los estudios fueron: ensayos clínicos aleatorizados, cohortes o casos y control que evalúen la PICO planteada y reportaran al menos uno de los desenlaces de interés. La certeza de la evidencia fue realizada según el enfoque GRADE que toma en cuenta los siguientes criterios: diseño del estudio, riesgo de sesgo, inconsistencia en los resultados, ausencia de evidencia directa, imprecisión, sesgo de publicación, tamaño de efecto, gradiente dosis-respuesta, y efecto de los potenciales factores de confusión residual (los tres últimos aplicables en estudios observacionales) (8,9). Los resultados fueron presentados utilizando la Tablas de Resumen de Hallazgos (SOF, por sus siglas en inglés) construidas a partir del software en línea GRADEpro (https://gradepro.org/)(10) a partir de la adaptación de tablas SoF de la guía de SCCM (6) para pacientes no críticos. Metodología considerada para la elaboración de las recomendaciones: Marco de Evidencia a la Decisión/Recomendación (EtD: Evidence to decisión framework): Los marcos EtD (1,2) son una herramienta del Enfoque GRADE, que tiene como finalidad fomentar el uso de la evidencia de una manera estructurada y transparente para informar decisiones relacionadas al manejo clínico de una enfermedad, salud pública, políticas del sistema de salud o en situaciones como el contexto actual de pandemia acerca de acciones con repercusión socio-económica entre otras. Se aplicaron los principios del enfoque "GRADE-ADOLOPMENT" para identificar guías de práctica clínica orientadas a las preguntas PICO propuestas por el grupo de trabajo de MINSA, además que tener disponibles los perfiles de evidencia GRADE o Tablas de resumen de hallazgos y los marcos EtD. Dependiendo de la evaluación, estas pueden ser consideradas para la adaptación con contextualización o para la adopción (11). Los siguientes criterios del marco EtD fueron seleccionados para la discusión y juicio por el grupo de trabajo: Efectos deseables, Efectos indeseables, Certeza de la evidencia, Valores y preferencias de los pacientes, Balance de efectos, Recursos necesarios, Equidad, Aceptabilidad y Factibilidad. En caso de no haber consenso en la valoración del juicio, se efectuó una votación, determinándose la valoración por mayoría simple. La perspectiva fue del sistema de salud. Elaboración de las Recomendaciones: La metodología EtD considera determinar la fuerza y dirección de una recomendación (12). Ambas, como resultado del juicio acerca del balance beneficio-riesgo, calidad global de la evidencia, confianza en los valores y preferencias de los pacientes, uso de recursos, equidad en salud, aceptabilidad, y factibilidad. En este sentido, existirán recomendaciones "a favor de la intervención" o "en contra de la intervención" (a favor de la alternativa u opción). Asimismo, las recomendaciones fueron determinadas como fuertes o condicionales. Una recomendación será fuerte si existe una clara diferencia entre los efectos deseables e indeseables de la intervención, la certeza global de la evidencia alta o moderada, todos o casi todos los pacientes informados toman la misma decisión, el costo de la intervención está plenamente justificado, existe un impacto favorable en la equidad en salud, la intervención es aceptable para los usuarios interesados (pacientes y personal de salud) y la implementación de dicha intervención es viable. Una recomendación será condicional si alguna de las consideraciones siguientes está presente: Exista poca diferencia entre los efectos deseables e indeseables de la intervención, la calidad de la evidencia es baja o muy baja, existe variabilidad o incertidumbre respecto de lo que decidirán los pacientes informados o el costo de la intervención pudiera no estar justificado en algunas circunstancias. Diálogo Deliberativo para la valoración de los criterios del Marco EtD y elaboración de las recomendaciones: El Diálogo deliberativo se llevó a cabo el día 27 de octubre de 2021, reunión virtual a través de la herramienta Zoom, con la participación de: 1. Profesionales del Grupo de trabajo designado por el Ministerio de Salud: integrantes de la Sociedad Peruana de Medicina Intensiva y Representantes del Ministerio de Salud, en su calidad de panel de expertos, habilitados para emitir los juicios para cada criterio, votar en caso de ser necesario y elaborar la recomendación. 2. Representantes de la Unidad de Análisis y Generación de Evidencias en Salud Pública (UNAGESP) del INS, quienes efectuaron la identificación de la evidencia presentada ante los expertos, en calidad de facilitadores y conductores de los aspectos metodológicos de la reunión. RECOMENDACIÓN: Se sugiere el uso de Propofol sobre benzodiazepinas para la sedación en pacientes con COVID 19 críticos en ventilación mecánica invasiva. Recomendación condicional, basada en evidencia de muy baja calidad: Consideraciones adicionales: La sedación en pacientes COVID 19 críticos en ventilación mecánica invasiva debe ser precedida por una adecuada analgesia. En los pacientes COVID 19 críticos en ventilación mecánica invasiva que no se alcance el objetivo de sedación con las dosis adecuadas de Propofol, o se tenga efectos colaterales, se podría considerar el uso de otro sedante. No se ha establecido la seguridad de Propofol en el embarazo, porque atraviesa la barrera placentaria y puede causar depresión neonatal. Se sugiere usar dexmedetomidina sobre benzodiazepinas para la sedación en pacientes COVID 19 críticos en ventilación mecánica durante la fase de destete. Recomendación condicional, calidad de la evidencia muy baja: Consideraciones adicionales: Tener precaución sobre los efectos adversos como bradicardia e hipotensión. Evitar su uso en pacientes inestables hemodinámicamente. No se recomienda dar dosis de carga de dexmedetomidina. Se sugiere el uso de dexmedetomidina sobre Propofol para la sedación en pacientes COVID 19 críticos en ventilación mecánica durante la fase de destete.

Síndrome De Cotard Y Catatonía: Reporte De Un Caso / Cotard's Syndrome And Catatonia: A Case Report

Resumen El Síndrome de Cotard es una condición neuropsiquiátrica poco frecuente, descrito inicialmente por Jules Cotard como un delirio hipocondríaco y luego como Delirio de negación, en que el paciente niega la existencia de partes de su cuerpo, la propia existencia y/o del mundo entero. La aparición de un Síndrome Catatónico junto al Síndrome de Cotard es aún más infrecuente. Se presenta el caso de una paciente de 72 años con una Depresión psicótica, que desarrolla un Síndrome de Cotard y posteriormente Catatonía. Logra buena respuesta tras la adición de Lorazepam y Venlafaxina al esquema farmacológico en curso, por lo que se desestima el uso de Terapia Electroconvulsiva. Se constata remisión total de síntomas y posterior recuperación funcional ad integrum, siendo evaluada a través de entrevista clínica, Hamilton Depression Rating Scale, Bush-Francis Catatonia Rating Scale e Índice de Barthel. Además, se revisan otros reportes de caso sobre esta comorbilidad, y a diferencia de la mayoría de éstos, se destaca la favorable evolución de la paciente sin necesidad de Terapia Electroconvulsiva. Aún no se ha dilucidado la relación entre ambos síndromes, aunque algunos autores han planteado la hipótesis de vías neurobiológicas compartidas y otros han postulado la aparición de síntomas catatónicos como la progresión del Síndrome de Cotard. Para aclarar estas interrogantes, son necesarios más estudios al respecto que permitan conocer la etiopatogenia de esta inusual combinación.

Cotard's Syndrome is a rare neuropsychiatric condition, initially described by Jules Cotard as a hypochondriacal delusion and then as Delusion of negation, in which the patient denies the existence of parts of his body, his own existence and / or the entire world. The appearance of a Catatonic Syndrome together with Cotard Syndrome is even more infrequent. We present the case of a 72-year-old patient with a psychotic depression, who developed Cotard's Syndrome and later Catatonia. She achieves good response after the addition of Lorazepam and Venlafaxine to the current pharmacological treatment, so the use of Electroconvulsive Therapy is dismissed. Total remission of symptoms and subsequent functional recovery ad integrum was observed, being evaluated through clinical interview, Hamilton Depression Rating Scale, Bush-Francis Catatonia Rating Scale and Barthel Index. In addition, other case reports on this comorbidity are reviewed, and unlike most of these, the favorable evolution of the patient stands out without the need for Electroconvulsive Therapy. The relationship between the two syndromes has not been elucidated, although some authors have proposed the hypothesis of shared neurobiological pathways and others have postulated the appearance of catatonic symptoms such as the progression of Cotard's Syndrome. To clarify these questions, more studies are needed in order to know the etiopathogenesis of this unusual combination.

Prescripción de lorazepam dentro de la caja Costarricense del seguro social / Prescription of lorazepam within the Costa Rican social insurance Prescrição de lorazepam no fundo de seguro social da Costa Rica / Prescrição de lorazepam no fundo de seguro social da Costa Rica

Objetivo: describir la prescripción de lorazepam dentro de la caja Costarricense del seguro social. Método: el estudio es descriptivo y retrospectivo, de enero de 2011 a diciembre de 2015. La investigación consistió en 339,484 prescripciones de lorazepam. El tratamiento estadístico de los datos se centró en las estadísticas descriptivas de las cinco unidades generadas a partir de las variables, que fueron analizadas por el programa R. Resultados: se observó un aumento exponencial en la prescripción de lorazepam durante el período investigado. El lorazepam ha sido indicado principalmente para adultos mayores de 60 años. Para todos los grupos de población se encontraron recetas por encima de la dosis diaria definida. Las prescripciones fueron realizadas principalmente por médicos generales y en áreas rurales. Conclusión: en vista de este escenario, es necesario revisar las estrategias de prescripción, dispensación y seguimiento para los usuarios de este medicamento, a fin de evitar efectos adversos y daños a la salud de la clientela.

Objective: to describe the prescription of lorazepam in the social insurance fund of Costa Rica. Method: the study is descriptive and retrospective, from January 2011 to December 2015. The investigation consisted of 339,484 lorazepam prescriptions. The statistical treatment of the data was focused on the descriptive statistics of the five units generated from the variables, which were analyzed by the R program. Results: exponential increase in lorazepam prescription was observed during the investigated period. Lorazepam has been mainly indicated for adults over 60 years old. For all population groups prescriptions above the defined daily dose were found. The prescriptions were performed mainly by general practitioners and in rural areas. Conclusion: In view of this scenario, there is a need to review the prescription, dispensing and follow-up strategies for users of this medication, in order to avoid adverse effects and harm to clientele's health.

Objetivo: descrever a prescrição de lorazepam no fundo de seguro social da Costa Rica. Método: o estudo é descritivo e retrospectivo. A investigação foi constituída por 339.484 prescrições de lorazepam. O tratamento estatístico dos dados foi focado na estatística descritiva das cinco unidades geradas, a partir das variáveis, que foram analisadas pelo programa R. Resultados: foi verificado aumento exponencial na prescrição de lorazepam durante o periodo investigado. O lorazepam foi indicado principalmente para idosos de 60 anos. Para todos os grupos populacionais foram encontradas prescrições acima da dose diária definida. As prescrições foram realizadas principalmente por médicos generalistas e em áreas rurais. Conclusão: frente a este cenário, há necessidade de rever as estratégias de prescrição, dispensação e acompanhamento aos usuários dessa medicação, a fim de evitar efeitos adversos e prejuízos para a saúde da clientela.

An easy and reliable way to prevent electrocardiographic deteriorations of patients undergoing off-pump coronary artery bypass surgery: preoperative anxiolytic treatment

Abstract Objective: To investigate the effects of preoperative anxiety relieving on electrophysiological changes in patients undergoing off-pump coronary artery bypass surgery. Methods: A total of 61 patients at ASA III risk group in the age range of 18-65 years were enrolled in the present study. Patients were randomly divided into two groups. Group S (Sedation group) was administered 0.04 mg/kg lorazepam per os (PO) twice before the operation. Group C (control group) was not administered with any anxiolytic premedication. State Trait Anxiety Inventory (STAI-I) and Beck Anxiety Inventory (BAI) were used to evaluate the level of anxiety. Electrocardiography (ECG), pulse oximeter and standard monitoring were performed for each patient. QT and P dispersions in each derivation of all ECGs were calculated. Results: Preoperative STAI-I scores were significantly lower in sedation group compared to the controls. Mean values of QT dispersion measured before induction, at the 1st minute of induction, 30th second of intubation and 4th minute of intubation in sedation group were significantly reduced compared to controls (P=0.024; P=0.027; P=0.001; P=0.033, respectively). The mean values of P dispersion measured before induction, at the 3rd minute of induction, 30th second of intubation and 4th minute of intubation in sedation group were significantly reduced compared to controls (P=0.001; P=0.020; P=0.023; P=0.005, respectively). Conclusion: Elevated anxiety levels in patients undergoing coronary bypass surgery have a negative effect through prolonged QT and P-wave dispersion times. Anxiolytic treatment before surgery may be useful to prevent ventricular and atrial arrhythmias and associated complications through decreasing the QT and P-wave dispersion duration.

A Case of Clozapine-induced Corneal and Lenticular Pigmentation

PURPOSE: To report a case of corneal and lenticular pigmentation after prolonged clozapine therapy. CASE SUMMARY: A 56-year-old male visited our hospital with a progressive decline in vision that affected both eyes. He had a history of schizophrenia. He was being treated with 200 mg clozapine and 1 mg lorazepam daily, and had been treated with clozapine for 5 years. At the first visit, his best-corrected-visual acuity was 20/32 in both eyes. Slit lamp examination of the corneas showed bright, fine, grayish-brown deposits on the endothelium, and on dilation, bilateral central stellate opacity of the anterior portion of the lens capsule was revealed. CONCLUSIONS: Clozapine may induce corneal and lenticular pigmentation and thus may lead to a decline in vision. Patients on long-term clozapine therapy should be considered for regular ophthalmic review.

Use of Haloperidol and Lorazepam for Intractable Symptoms in the Hospice Palliative Care Unit

BACKGROUND: Terminally ill cancer patients suffer from refractory symptoms, and the last option of treatment is to consider sedatives. However, due to concerns that sedation may shorten survival time, some people prefer not to take sedatives. The purpose of this study was to investigate the effects of sedative administration on survival time among terminally ill cancer patients.METHODS: Two hundreds and thirty-seven patients who were hospitalized to the hospice care unit of public hospitals in Seoul from January, 2015 to March, 2016 were analyzed retrospectively. The univariate and multivariate Cox's proportional hazard regression model was used to determine independent factors related to survival time.RESULTS: The usage of sedation was necessary because the incidence of insomnia was 61.4% in the lorazepam only group, and the incidence of delirium was highest in the haloperidol group and the haloperidol with lorazepam group. Interestingly, multivariate analysis showed that male (HR, 1.766; P < 0.001), decreased consciousness (HR, 1.803; P=0.003), anorexia (HR, 1.506; P=0.012), resting dyspnea (HR, 1.757; P < 0.001), elevated serum bilirubin (HR, 1.657; P=0.001), and the haloperidol with lorazepam group (HR, 0.535, P < 0.001) were each significantly associated with survival time. Furthermore, patients in the haloperidol with lorazepam group survived longer than patients with no such medications.CONCLUSION: There is no evidence that treatment with sedative medication shortens the survival time of patients with terminally ill cancer with refractory symptoms.

Negative myoclonus associated with pregabalin / 영남의대학술지

Negative myoclonus (NM) is a jerky, shock-like involuntary movement caused by a sudden, brief interruption of muscle contraction. An 80-year-old man presented with multifocal NM and confusion. Two days before the onset of NM, he commenced the intake of pregabalin at a dose of 150 mg/day for neuropathic pain. His NM resolved completely and mental status improved gradually after the administration of lorazepam intravenously and the discontinuation of pregabalin. Our study suggests that pregabalin can cause NM even in patients without a history of seizures.

TeleCondutas: avaliação e manejo da insônia / TeleGuides: evaluation and management of insomnia

A insônia é o mais prevalente dos transtornos do sono. É definida como a insatisfação com a qualidade ou a quantidade de sono, que ocorre a despeito de adequada oportunidade para dormir e que impõe ao indivíduo algum tipo de prejuízo durante o dia. A prevalência da insônia crônica em sociedades industrializadas é de 5 a 10%. Entre pessoas portadoras de doença crônica (psiquiátricas ou não) e idosos, a prevalência é significativamente maior. Trata-se de queixa frequente na Atenção Primária à Saúde (APS). Este material contempla as situações mais comumente associadas a insônia na APS, assim como o manejo inicial desta queixa. Está baseado em extensa revisão das evidências disponíveis na literatura, em boas práticas clínicas e adaptado à realidade brasileira, considerando as intervenções terapêuticas disponíveis. Esta guia apresenta informação que orienta a conduta para casos de avaliação e manejo da insônia no contexto da Atenção Primária à Saúde, incluindo: Avaliação Geral, Avaliação Objetiva, Avaliação e Manejo em situações específicas, Intervenções Não-Farmacológicas, Manejo Farmacológico na APS, Retirada de benzodiazepínico, Preocupações com uso de amitriptilina, Fármacos não recomendados na APS, Avaliação longitudinal da insônia, Fluxograma para avaliação e manejo da insônia.

Benzodiazepine-Associated Carcinogenesis: Focus on Lorazepam-Associated Cancer Biomarker Changes in Overweight Individuals

OBJECTIVE: Cellular, animal, and human epidemiological studies suggested that benzodiazepines increase the risk of cancer and cancer mortality. Obesity is also clearly linked to carcinogenesis. However, no human studies have examined benzodiazepine-associated carcinogenesis as assessed by changes in cancer biomarkers. METHODS: A total of 19 patients were recruited, and received a 6-week treatment of 0.5 mg lorazepam. The measured cancer biomarkers were angiopoietin-2 (ANG-2), soluble CD40 ligand, epidermal growth factor, endoglin, soluble Fas ligand (sFASL), heparin-binding EGF-like growth factor (HB-EGF), insulin-like growth factor binding protein, interleukin (IL)-6, IL-8, IL-18, plasminogen activator inhibitor (PLGF), placental growth factor, transforming growth factor (TGF)-α, tumor necrosis factor (TNF)-α, urokinase-type plasminogen (uPA), vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D. RESULTS: Six cancer biomarkers were significantly increased in all patients as a whole. The subgroup analysis revealed a distinct pattern of change. Overweight patients showed a significant increase in 11 cancer biomarkers, including ANG-2, sFASL, HB-EGF, IL-8, PLGF, TGF-α, TNF-α, uPA, VEGF-A, VEGF-C, and VEGF-D. However, normal-weight patients did not show any changes in cancer biomarkers. CONCLUSION: Adiposity may have primed the carcinogenic potential, leading to lorazepam-associated carcinogenesis in overweight patients. Epidemiological studies addressing this issue should consider the potential modulator contributing to benzodiazepine-associated carcinogenesis.

Síndrome catatónico: ¿síndrome neuropsiquiátrico o enfermedades sistémicas? / Catatonic syndrome: neuropsychiatric syndrome or systemic diseases?

Descubierto por el psiquiatra Karl Ludwig Kahlbaum en 1868. Durante muchos años la observación de síntomas y signos del síndrome catatónico se asoció a enfermedad psiquiátrica y particularmente con la esquizofrenia. Kraepelin (1896): incluye a la catatonia dentro de la "demencia precoz", junto a la hebefrenia y paranoia. Bleuler (1924): Subtipo de Esquizofrenia. Schneider los define como trastornos de las tendencias y la voluntad. Jaspers separa los trastornos de la voluntad de los de la motricidad. "Durante más de 125 años después de que Karl Kahlbaum clasificó la catatonía como una entidad psicopatológica distinta, se ha informado abrumadoramente en relación con muchas condiciones" (Fink M., (2010) 1. Definición actual: Los trastornos catatónicos son un grupo de síntomas caracterizados por alteraciones en el comportamiento motor (movimiento muscular) que pueden tener una base psicológica o fisiológica. (Enciclopedia de los trastornos mentales) 2. "Con los grandes avances en las neurociencias básicas y clínicas que han transcurrido durante la última década, finalmente estamos dilucidando los mecanismos que subyacen a la complejidad y la diversidad desconcertante de la fenomenología catatónica" (Stowe R. (2002) 3. La fisiopatología de la catatonía es compleja e incluye alteraciones en la dopamina y otros sistemas neurotransmisores, posibles anomalías de los canales iónicos y disfunción de los circuitos frontal-neocortical, límbico e incluso del tronco cerebral.

Psychogenic non-epileptic seizures in the post-anesthesia recovery unit / Convulsões não epilépticas psicogênicas em sala de recuperação pós-anestésica

Abstract Introduction: Psychogenic non-epileptic seizures (PNES or “pseudoseizures”) remain an obscure topic in the peri-operative setting. They are sudden and time-limited motor and cognitive disturbances, which mimic epileptic seizures, but are psychogenically mediated. Pseudoseizures occur more frequently than epilepsy in the peri-operative setting. Early diagnosis and management may prevent iatrogenic injury. Case: 48 year-old female with a history of depression and “seizures” presented for gynecologic surgery. She described her seizure history as “controlled” without anticonvulsant therapy. The patient underwent uneventful general anesthesia and recovered neurologically intact. During the first two postoperative hours, the patient experienced 3 episodes of seizure-like activity with generalized shaking of extremities and pelvic thrusting; her eyes were firmly closed. No tongue biting or incontinence was noted. The episodes lasted approximately 3 min each, one of which resolved spontaneously and the other two following intravenous lorazepam. During these episodes, the patient had stable hemodynamics and adequate ventilation such that endotracheal intubation was deemed unwarranted. Post-ictally, the patient was neurologically intact. Computed axial tomography of the head, metabolic assay, and electroencephalogram showed no abnormalities. A presumptive diagnosis of PNES was made. Discussion: Psychogenic non-epileptic seizures mimic shivering, and should be considered early in the differential diagnosis of postoperative shaking, as they may be more likely than epilepsy in this setting. Pseudoseizure patterns include asynchronous convulsive episodes lasting more than 90 s, forced eye closure with resistance to opening, and retained pupillary responses. Autonomic manifestations such as tachycardia, cyanosis and incontinence are usually absent. A psychiatric background is common. Knowledge and correct diagnosis of pseudoseizures is of great importance for anesthesiologists to prevent morbidity and iatrogenic injury such as respiratory arrest caused by anticonvulsant therapy, in addition to the risks associated with endotracheal intubation and prolonged hospital stays. The diagnosis of pseudoseizures must be thoroughly documented and relayed in transfer of care to avoid misdiagnosis and iatrogenic complications. Treatment recommendations are anecdotal; psychiatric interventions are the hallmark of treatment. Anesthetic recommendations include techniques involving the minimum required short-acting agents, along with high levels of peri-operative psychological support and reassurance.

Resumo Introdução: As convulsões não epilépticas psicogênicas (CNEP ou “pseudoconvulsões”) permanecem como tema obscuro no cenário perioperatório. Trata-se de distúrbios motores e cognitivos súbitos, mas por tempo limitado, que imitam as convulsões epilépticas, mas que são psicogenicamente mediados. Pseudoconvulsões ocorrem com mais frequência do que epilepsia em cenário perioperatório. O diagnóstico e o tratamento precoces podem evitar lesões iatrogênicas. Caso: Paciente do sexo feminino, 48 anos, com história de depressão e “convulsões”, apresentou-se para cirurgia ginecológica. A paciente descreveu sua história de convulsões “controladas” sem o uso de terapia anticonvulsivante. Foi submetida à anestesia geral sem intercorrências e recuperou-se neurologicamente intacta. Durante as duas primeiras horas de pós-operatório, apresentou três episódios semelhantes à convulsão, com tremores generalizados das extremidades e impulso pélvico; seus olhos estavam bem fechados. Não observamos mordedura da língua ou incontinência. Os episódios duraram cerca de três minutos cada; um dos episódios resolveu espontaneamente e os outros dois após a administração de lorazepam por via intravenosa. Durante os episódios, a condição hemodinâmica da paciente era estável e a ventilação adequada, de modo que a intubação traqueal foi considerada injustificável. Após a convulsão, a paciente estava neurologicamente intacta. Tomografia axial da cabeça, teste metabólico e eletroencefalograma não mostraram alterações. O diagnóstico de provável CNEP foi feito. Discussão: As convulsão não epilépticas psicogênicas imitam o tremor e devem ser inicialmente consideradas no diagnóstico diferencial de tremor pós-operatório, pois podem ser mais prováveis do que a epilepsia nesse cenário. Os padrões da pseudoconvulsão incluem episódios convulsivos assíncronos que duram mais de 90 segundos, olhos forçadamente fechados com resistência à abertura e respostas pupilares mantidas. Manifestações autonômicas, como taquicardia, cianose e incontinência, normalmente estão ausentes. Uma história psiquiátrica é comum. O conhecimento e o diagnóstico correto de pseudoconvulsões são muito importantes para os anestesiologistas para a prevenção de morbidade e lesões iatrogênicas, como a parada respiratória causada por terapia anticonvulsivante, além dos riscos associados à intubação orotraqueal e internação prolongada. O diagnóstico de pseudoconvulsões deve ser cuidadosamente documentado e retransmitido nas trocas de equipes médicas para evitar erros de diagnóstico e complicações iatrogênicas. As recomendações de tratamento são anedóticas; intervenções psiquiátricas são o pilar do tratamento. As recomendações anestésicas incluem técnicas que envolvem o uso de agentes de ação curta, juntamente com altos níveis de apoio e amparo psicológico no período perioperatório.

Malignant catatonia responsive to low doses of lorazepam: case report / Catatonia maligna responsiva a baixas doses de lorazepam: relato de caso

Abstract CONTEXT: Catatonia can be divided into non-malignant or malignant. The latter is characterized by autonomic instability, exhibiting high fever, tachycardia and hypertension, and is regarded as a fulminant and rapidly progressive subtype. CASE REPORT: This article reports a case of malignant catatonia in a 43-year-old patient who had been presenting psychiatric disorders for the last three years. The patient was stable, maintaining mutism, immobility and autonomic abnormalities. Oral lorazepam (1 mg every eight hours) was introduced and, in a few hours, the patient became afebrile. Two days later, the patient was already responding to verbal commands. CONCLUSIONS: Early intervention with lorazepam reduced the evolution of this patient to a fatal complication. Therefore, this case report sought to show that early diagnosis and intervention reduced the occurrence of serious and irreversible clinical outcomes.

Resumo CONTEXTO: A catatonia pode ser dividida em não maligna ou maligna. A maligna se caracteriza pela instabilidade autonômica, exibindo febre elevada, taquicardia e hipertensão, além de ser considerada um subtipo fulminante e rapidamente progressivo. RELATO DE CASO: Este artigo relata um caso de catatonia maligna em paciente de 43 anos, com transtornos psiquiátricos há três anos. A paciente estava estável, mantendo o mutismo, a imobilidade e as anormalidades autonômicas. Foi introduzido lorazepam, via oral, 1 mg de oito em oito horas, e em algumas horas, a paciente ficou afebril. Em dois dias, já estava respondendo a comandos verbais. CONCLUSÕES: Intervenção precoce com lorazepam preveniu a evolução desta paciente para um desfecho fatal. Portanto, este relato de caso mostrou que o diagnóstico e a intervenção precoces reduziram a ocorrência de desfechos graves e irreversíveis.

Low Plasma Insulin Level Prolonged Hypoglycemia after High dose Insulin Lispro Injection

Increased plasma insulin levels are often observed in exogenous insulin overdose patients. However, plasma insulin level may decrease with time. We report a case of low plasma insulin level hypoglycemia after insulin lispro overdose. The patient was a 37-year-old man with no previous medical history who suspected insulin lispro overdose. Upon arrival, his Glasgow coma scale was 3 points and his blood sugar level (BSL) was 24 mg/dl. We found five humalog-quick-pen (insulin lispro) in his bag. There was no elevation of glucose level, despite an initial 50 ml bolus of 50% glucose and 150 cc/hr of 10% dextrose continuous intravenous infusion. He also suffered from generalized tonic-clonic seizure, which was treated with lorazepam and phenytoin. We conducted endotracheal intubation, after which he was admitted to the intensive care unit (ICU). There were recurrent events of hypoglycemia below BSL<50 mg/dl after admission. We repeatedly infused 50 ml 50% glucose 10 times and administered 1 mg of glucagon two times. The plasma insulin level was 0.2 uU/ml on initial blood sampling and 0.2 uU/ml after 5 hours. After 13 hours, his BSL stabilized but his mental status had not recovered. Diffuse brain injury was observed upon magnetic resonance imaging (MRI) and severe diffuse cerebral dysfunction was found on electroencephalography (EEG). Despite 35 days of ICU care, he died from ventilator associated pneumonia.

The Efficacy and Safety of Clonazepam in Patients with Anxiety Disorder Taking Newer Antidepressants: A Multicenter Naturalistic Study

OBJECTIVE: This study compared the efficacy and tolerability of clonazepam with other benzodiazepines in patients with anxiety disorders. METHODS: Inclusion criteria were as follows: age >20 years, diagnosis of anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition, text revision (DSM-IV-TR) criteria, taking only one type of antidepressant, and prescribed one of three oral benzodiazepines (alprazolam, clonazepam, or lorazepam). At baseline and week 6, clinical benefit was evaluated using the Clinical Global Impression-Severity Scale (CGI-S), Clinical Global Impression-Anxiety Scale (CGI-anxiety), and Clinical Global Impression-Sleep Scale (CGI-sleep). RESULTS: Among 180 patients, no differences in demographic characteristics among the three benzodiazepine groups were noted. After six weeks of treatment, all benzodiazepine groups showed significant improvements in CGI-S, CGI-anxiety, and CGI-sleep scores (p<0.001). There were no differences in mean changes in CGI-S, CGI-anxiety and CGI-sleep among the three benzodiazepine groups. The incidence of side effects was significantly lower in the clonazepam group than with the other benzodiazepines. The incidences of adverse events for the clonazepam, alprazolam, and lorazepam groups were 26.7% (n=20), 48.4% (n=31), and 43.9% (n=18), respectively. CONCLUSION: The present study suggests that clonazepam is as efficacious as other benzodiazepines for the treatment of various anxiety disorders. Furthermore, the safety profile of clonazepam was superior to the other benzodiazepines in this study.

Impact of High Dose Lorazepam on Seizure Threshold in Catatonia: Experience from a Case Study

No abstract available.

Tendencias de consumo de medicamentos ansiolíticos e hipnóticos en una población colombiana, 2008-2013 / Trends in the consumption of anxiolytic and hypnotic drugs in a Colombian population

Introducción: En Latinoamérica, los psicofármacos son el tercer grupo de medicamentos más comercializados, especialmente antidepresivos (35%) y ansiolíticos (5%). El objetivo es determinar el comportamiento del consumo y los costos de los ansiolíticos e hipnóticos en una población de pacientes afiliados al Sistema General de Seguridad Social en Salud de Colombia. Material y métodos: Estudio descriptivo observacional. Los datos para el análisis fueron las prescripciones de cualquier ansiolítico o hipnótico, realizadas a pacientes ambulatorios en el periodo comprendido entre enero de 2008 y diciembre de 2013 en una población de 3,5 millones de personas. Se consideraron variables sociodemográficas, farmacológicas, costos globales y costos por mil habitantes y día (CHD). Resultados: El número de pacientes que recibieron los medicamentos estudiados varió de 11.097 a 19.231 entre 2008 y 2013. Los medicamentos más utilizados fueron clonazepam (el 44,1% de las formulaciones), alprazolam (31,2%) y lorazepam (13,2%). El valor facturado de ansiolíticos pasó de 207.673,63 dólares en 2008 a 488.977 dólares en 2013, con un crecimiento del 135,4%. El CHD fue de 0,31 dólares para las benzodiazepinas y 0,02 dólares para los medicamentos Z en 2008 y 0,36 y 0,02 dólares en 2013 respectivamente. Los CHD se redujeron después del año 2010, tras la introducción de medicamentos genéricos. Conclusiones: Los pacientes que reciben benzodiazepinas en Colombia son en su mayoría mujeres, con 55 años de edad promedio, con muy baja frecuencia expresada en CHD comparada con la de otros países.

Introduction: In Latin America, psychotropic medications are the third most marketed drug group, especially antidepressants (35%) and anxiolytics (5%). The objective of this study was to determine the trends in the consumption and the costs of anxiolytic and hypnotic drugs in a population of patients enrolled in the Health System of Colombia. Material and methods: A descriptive, observational study was performed using the data recorded inprescriptions for any anxiolytic or hypnotic drug prescribed to outpatients in the period between January 2008 and December 2013 in a population of 3.5 million people. Sociodemographic, pharmacological variables, overall costs, and cost per thousand inhabitants per day (CHD), were also recorded. Results: The number of patients who received the drugs studied varied from 11,097 to 19,231 between 2008 and 2013. The most used drugs were clonazepam (44.1% of formulations), alprazolam (31.2%), and lorazepam (13.2%). The invoiced value of anxiolytics increased from US$ 207,673.63 in 2008 to US$ 488,977 in 2013, an increase of 135.4%. The CHD was US$ 0.31 for benzodiazepines, and US$ 0.02 for zaleplon, zolpidem and zopiclone (Z drugs) for 2008, and US$ 0.36 and US$ 0.02 in 2013 respectively. The CHD declined after 2010 following the introduction of generic drugs. Conclusions: Patients receiving benzodiazepines in Colombia are mostly women, average age 55 years, with very low frequency in defined daily doses per thousand inhabitants when compared with other countries.

Efectividad y seguridad del clorhidrato de dexmedetomidina comparado con midazolam, lorazepam, propofol y ketamina para pacientes que requieren sedación en unidad de cuidados intensivos / Effectiveness and safety of dexmedetomidine hydrochloride compared to midazolam, lorazepam, propofol and ketamine for patients requiring sedation in the intensive care unit

Introducción: Múltiples procedimientos en la unidad de cuidados intensivos requieren sedación. La sedación ideal, debe reducir la ansiedad, facilitar la monitorización, mejorar la tolerancia a la ventilación mecánica, reducir los tiempos de estancia y la morbilidad, además, ofrecer seguridad frente a la presentación de eventos adversos asociados con la administración de los agentes sedantes. Estudios recientes presentan al clorhidrato de dexmedetomidina como un agente seguro en sedación con mejor rendimiento y menor presentación de desenlaces no deseables que otros agentes sedantes en estos pacientes. Sus aparentes ventajas hacen necesaria una revisión de la evidencia actual al respecto. Objetivo: Evaluar la efectividad y seguridad del uso de dexmedetomidina en pacientes que requieren sedación en unidad de cuidados intensivos (UCI). Metodología: Se realizó una búsqueda sistemática de revisiones sistemáticas de la literatura (RSL) utilizando las bases de datos MEDLINE (In-Process & Other Non-Indexed Citations y Daily Update) EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects ­ DARE, LILACS y la revisión de publicaciones obtenidas por otros medios comparando el uso de dexmedetomidina en UCI con otros agentes sedantes, considerando los resultados en cuanto a estancia en UCI, tiempo de extubación, mortalidad, delirium y bradicardia. Resultados: Se obtuvieron 27 publicaciones, 11 fueron tamizadas para valoración de los criterios de inclusión. Cuatro cumplieron con estos y se evaluaron con la herramienta AMSTAR. Solo una fue considerada de alta calidad, base de esta revisión. Esta, incluyó 24 estudios con 2419 pacientes. Dexmedetomidina estuvo asociado a una reducción significativa de la estancia en UCI (Diferencia ponderada de medias -0.48 días IC95% -0.18 a ­ 0.78 p = 0.002), también se asoció a un incremento en el riesgo de bradicardia que requirió intervención cuando se usó una dosis de carga o mantenimiento > 0.7µ/kg/hr (RR= 7.3 IC95% 1.73 ­ 30.81 p= 0.007). Conclusiones: Basándose en evidencia de moderada calidad, el clohidrato de dexmedetomidina reduce los tiempos de estancia en unidad de cuidados intensivos sin tener efecto en los tiempo de ventilación mecánica, está asociada a un incremento en la bradicardia sintomática que requiere intervenciones cuando se usan dosis de carga o mantenimiento superiores a > 0.7µ/kg/hr, no hay diferencia en otros desenlaces de interés como mortalidad, delirium, hipotensión, auto extubación, infarto del miocardio o fibrilación auricular. Con estos hallazgos es razonable sugerir el uso de dexmedetomidina como agente sedante en los pacientes que así lo requieren en UCI.(AU)

Opioids and the Gastrointestinal Tract: A Case of Narcotic Bowel Syndrome and Literature Review

The worldwide use of opiates is increasing yet there is little evidence that in long-term, non-cancer patients, they have an efficacious effect on functional outcomes and quality of life measures. Although it seems paradoxical, chronic opiate use may lead to a pro-nociceptive state. Mechanisms for the development of the hyperalgesic state include activation of the opiate bimodal regulatory systems, dynorphin and spinal cord glia. A potential consequence of chronic opiate usage is the development of narcotic bowel syndrome, which is characterized by chronic or intermittent colicky abdominal pain or discomfort that worsens after the narcotic effects of opiates wear off. It is likely that this is an under-recognized diagnosis. We describe here a case of 26-year old female who had visited our institution multiple times with intractable chronic abdominal pain in the context of normal findings on haematological, biochemical, metabolic, endoscopic and radiological investigations. She had been treated with a multitude of opioid agonists with escalating doses. A diagnosis of narcotic bowel syndrome was made. On elective admission her daily analgesic requirements were 150 microg/hr fentanyl, 100 mg oramorph and 400 mg tramadol (equating to 740 mg oral morphine/24 hr). A detoxification regimen was prescribed which included rapid opiate withdrawal couple with the commencement of methadone, lorazepam, clonidine and duloxetine. She was discharged opiate free, with no abdominal pain, 14 days after admission. Clinicians must be aware of narcotic bowel syndrome, which is often erroneously labelled as a functional gastrointestinal disorder, in patients who have been on long-term opiates.

Anti-Intrusion Effect of Lorazepam: An Experimental Study

OBJECTIVE: Easy triggering of trauma-related episodic memory fragments caused by perceptual cues is tied to strong perceptual priming in the implicit memory system. And among benzodiazepines, only lorazepam has been consistently reported to have an atypical suppression effect on perceptual priming processes. The aim of this study was to investigate the effects of single doses of lorazepam, diazepam, and a placebo on intrusive memories after exposure to a distressing videotape and to explore whether the anti-intrusive effect of lorazepam is acquired as a result of the suppression of perceptual but not conceptual priming processes. METHODS: Under prospective, randomized, and double-blind conditions, we compared the anti-intrusion effect of a single dose of lorazepam (n=22) with that of diazepam (n=22) and a placebo (n=21) in young healthy Korean college students following exposure to a traumatic videotape. RESULTS: We present the first finding for an anti-intrusion effect of lorazepam. One day after the medication, lorazepam, rather than diazepam or the placebo, significantly reduced the extent of intrusion and data-driven processing of the traumatic information. There were no differences among the three conditions in state anxiety, depression, and an arousal scale throughout the experiment. CONCLUSION: Results from this study suggest the possibility of lorazepam as a candidate anti-intrusion drug, as well as the cautious use of diazepam in the treatment of PTSD patients. The anti-intrusive effect of lorazepam is directly related to its atypical inhibitory effect on implicit perceptual priming processes. The present study provides support for the enhanced perceptual priming hypothesis of PTSD.