Manifestaciones clínicas post supresión de sedoanalgesia en pacientes adultos de una terapia intensiva / Clinical manifestations after suppression of sedoanalgesia in adult patients in intensive care

Introducción: en la unidad de cuidados intensivos (UCI), las personas asistidas con patologías relevantes se encuentran bajo sedación, una vez que estas se encuentran bajo los principios de supresión de la sedación, es importante identificar cuáles son las manifestaciones que presentan, propias de las sedaciones. Objetivo: describir las manifestaciones clínicas del síndrome de supresión de la sedoanalgesia presentes en pacientes asistidos en un Hospital Público de la Ciudad de Corrientes de enero a diciembre del 2022. Metodología: estudio cuantitativo, descriptivo, transversal y observacional. La muestra incluyó pacientes adultos de UCI. El cálculo del tamaño muestral se realizó a través del método probabilístico aleatorio simple resultando de éste una muestra de 100 historias clínicas. Para la recolección de datos se utilizó la observación y como instrumento un formulario semiestructurado, de carácter anónimo. Cada formulario contenía datos específicos donde se categorizan las variables en estudio como ser edad, sexo, comorbilidades, tiempo de sedoanalgesia, tipo de sedación, sedoanalgesia utilizada, agitación, confusión, alucinación, diaforesis, taquicardia. Resultados: en cuanto a la edad se obtuvo un promedio de 49 años, el sexo predominante fue el masculino con 52%, en cuanto a las comorbilidades más frecuentes, el 20% presentó Insuficiencia Respiratoria Aguda y el 16% Insuficiencia renal. El motivo de ingreso a UCI en mayor medida con el 33% fue por dificultad respiratoria y Post Quirúrgicos complicados 32%. Los fármacos de mayor elección fueron midazolam 94%, seguido del fentanilo 80%. En cuanto al tiempo de sedación de los pacientes, se encontró una media de 1265 horas. Las manifestaciones clínicas que se observaron en la muestra en mayor medida corresponden a taquicardia 70%, agitación 52%, un 37% confusión e hipertensión y un 24% alucinación. Conclusión: las manifestaciones que se presentaron con mayor frecuencia fueron taquicardia, agitación, confusión, hipertensión y con menor frecuencia alucinación[AU]

Introduction: in the intensive care unit (ICU), people treated with relevant pathologies are under sedation. Once they are under the principles of sedation suppression, it is important to identify the manifestations they present, typical of sedations. Objective: To describe the clinical manifestations of sedation suppression syndrome present in patients treated at a Public Hospital in the City of Corrientes from January to December 2022. Methodology: quantitative, descriptive, cross-sectional and observational study. The sample included adult ICU patients. The calculation of the sample size was carried out through the simple random probabilistic method, resulting in a sample of 100 medical records. Manifestaciones clínicas post supresión de sedoanalgesia en pacientes adultos de una terapia intensiva. Observation was used to collect data and a semi-structured, anonymous form was used as an instrument. Each form contained specific data where the variables under study were categorized, such as age, sex, comorbidities, sedation time, type of sedation, sedation used, agitation, confusion, hallucination, diaphoresis, tachycardia. Results: regarding age, an average of 49 years was obtained, the predominant sex was male with 52%, regarding the most frequent comorbidities, 20% presented Acute Respiratory Failure and 16% Renal failure. The reason for admission to the ICU to a greater extent with 33% was due to respiratory difficulty and complicated Post-Surgeries 32%. The drugs of greatest choice were midazolam 94%, followed by fentanyl 80%. Regarding the sedation time of the patients, an average of 1265 hours was found. The clinical manifestations that were observed in the sample to a greater extent correspond to tachycardia 70%, agitation 52%, confusion and hypertension 37% and hallucination 24%. Conclusion: the manifestations that occurred most frequently were tachycardia, agitation, confusion, hypertension and, less frequently, hallucination[AU]

Introdução: na unidade de terapia intensiva (UTI), as pessoas tratadas com patologias relevantes estão sob sedação. Uma vez sob os princípios da supressão da sedação, é importante identificar as manifestações que apresentam, típicas das sedações. Objetivo: Descrever as manifestações clínicas da síndrome de supressão da sedação presentes em pacientes atendidos em um Hospital Público da Cidade de Corrientes no período de janeiro a dezembro de 2022. Metodologia: estudo quantitativo, descritivo, transversal e observacional. A amostra incluiu pacientes adultos internados em UTI. O cálculo do tamanho amostral foi realizado pelo método probabilístico aleatório simples, resultando em uma amostra de 100 prontuários. A observação foi utilizada para a coleta de dados e um formulário semiestruturado e anônimo foi utilizado como instrumento. Cada formulário continha dados específicos onde foram categorizadas as variáveis em estudo, como idade, sexo, comorbidades, tempo de sedação, tipo de sedação, sedação utilizada, agitação, confusão, alucinação, sudorese, taquicardia. Resultados: em relação à idade obteve-se uma média de 49 anos, o sexo predominante foi o masculino com 52%, quanto às comorbidades mais frequentes, 20% apresentavam Insuficiência Respiratória Aguda e 16% Insuficiência Renal. O motivo de internação na UTI em maior proporção com 33% foi por dificuldade respiratória e pós-cirúrgicos complicados 32%. Os medicamentos de maior escolha foram midazolam 94%, seguido de fentanil 80%. Quanto ao tempo de sedação dos pacientes, foi encontrada uma média de 1265 horas. As manifestações clínicas mais observadas na amostra correspondem a taquicardia 70%, agitação 52%, confusão e hipertensão 37% e alucinação 24%. Conclusão: as manifestações que ocorreram com maior frequência foram taquicardia, agitação, confusão, hipertensão e, menos frequentemente, alucinação[AU]

Revisión de la sedación continua en el paciente crítico. Evidencias de la efectividad de nuevos fármacos respecto a los esquemas farmacológicos tradicionales / Review of continuous sedation in the critical ill patient. Evidence of the effectiveness of new drugs compared to traditional pharmacological schemes

Introducción: La sedación es uno de los pilares fundamentales del manejo del paciente crítico internado en la Unidad de Terapia Intensiva (UTI), sobre todo en aquellos que requieren Asistencia Ventilatoria Mecánica (AVM). Los fármacos que se utilizan con este propósito tienen el objetivo de lograr un adecuado nivel de conciencia en el paciente, de forma tal que se encuentre confortable y tolere la AVM. Los esquemas de sedación utilizados se encontraban basados en Benzodiacepinas, aunque, su uso no está exento de efectos adversos. El presente estudio pretende realizar una Revisión y Síntesis de la evidencia existente sobre la efectividad y seguridad del uso de dos nuevos fármacos, Propofol y Dexmedetomidina, para sedación continua en UTI y su comparación con los esque- mas tradicionales. Los Resultados respecto a la reducción de días en UTI resultó siempre significativa a favor del uso de propofol o dexmedetomidina en comparación a benzodiacepinas; lo mismo ocurrió con los días vinculados a la AVM. Estos resultados fueron encontrados en revisiones tanto de alta calidad como moderada o baja. Sin embargo, todos los estudios tuvieron en común que la calidad de la evidencia utilizada fue baja a moderada. Según la evidencia identificada, el uso de dexmedetomidina o propofol disminuiría de manera estadísticamente significativa los días de estadía en UTI y los requerimientos de AVM en pacientes adultos. Se debe tener en cuenta que la mayoría de las Revisiones encontradas fueron de calidad baja, siendo solamente 2 (dos) de calidad alta y una moderada. Es por esto último que la recomendación del uso de sedación basada en Dexmedetomidina o Propofol es condicional, ya que la calidad de la evidencia que la soporta es baja, en la mayoría de los casos.

Introductión: Sedation is one of the fundamental pillars of the management of critically ill patients admitted to the Intensive Care Unit (ICU), especially in those who require mechanical ventilatory assistance (MVA). The drugs used for this purpose have the objective of achieving an adequate level of consciousness in the patient, so that they are comfortable and tolerate AVM. The sedation schemes used were based on Benzodiazepines, however, their use is not free of adverse effects. The present work aims to carry out a review and synthesis of the existing evidence on the effectiveness and safety of the use of two new drugs Propofol and Dexmedetomidine for continuous sedation in ICU and its comparison with traditional regimens. The results regarding the reduction of days in ICU were always significant in favor of the use of Propofol or Dexmedetomidine compared to benzodiazepines; The same happened with the days linked to the AVM. These results were found in reviews of both high and moderate or low quality. However, what they all had in common was that the quality of the evidence used was low to moderate. According to the evidence identified, the use of Dexmedetomidine or Propofol would statistically significantly reduce the days of ICU stay and AVM requirements in adult patients. It should be taken into account that most of the reviews found were of low quality, with only 2 being of high quality, and 1 of moderate quality. It is for this last reason that the recommendation for the use of sedation based on Dexmedetomidine or Propofol is conditional, since the quality of the evidence supporting it is, for the most part, low.

Anesthetic challenges during endobronchial brachytherapy: A case report

@#Lung cancer is the leading cause of cancer death worldwide. It may present as airway obstruction in a patient with endobronchial masses. Endobronchial brachytherapy (EBBT) has been shown to provide palliative therapy. It is the insertion of a radioactive material near the mass to reduce tumor size, thereby improving airway obstruction. This is the first case of EBBT done in our institution during the COVID-19 pandemic. A 53-year-old male, 60 kg, ASA Physical Status 2 for hypertension, smoker, malignancy, and previous pulmonary tuberculosis patient, presented with a cough and dyspnea. An endobronchial mass almost obstructing the right mainstem bronchus was seen on a computed tomography (CT) scan. He was diagnosed with squamous cell carcinoma of the lung and underwent radiotherapy and erlotinib chemotherapy. On repeat CT scan, there was no noted decrease in the size of the mass. EBBT was suggested, and a multi-disciplinary team was formed for the planned procedure. Pulmonology, radiation oncology, and anesthesiology teams were identified, and thorough planning was done prior to the actual procedure. Three fractions of EBBT were done under sedation using midazolam, fentanyl, and dexmedetomidine infusion. Lidocaine spray and transtracheal block were also performed as adjuncts prior to sedation. The procedure went as planned, and points for improvement were discussed for subsequent fractions. Due to persistent cough and discomfort from the catheter, additional ipratropium nebulization for minimization of secretions, and oral dextromethorphan for cough suppression were incorporated. After each fraction, the patient was monitored post-procedure for any side effects both from the radiotherapy and anesthetic technique. Qualitative reduction in mass size was noted in subsequent fractions. The patient was able to complete 3 fractions and was advised to follow-up after a month. EBBT is an emerging palliative and treatment modality for lung cancer, especially for intraluminal masses. Anesthetic considerations will depend on each case’s characteristics such as airway anatomy, patient comfort and capacity, and procedural requirements. Conscious sedation with topical anesthesia is an adequate and appropriate anesthetic option, especially in cases where severe airway obstruction may compromise ventilation if airway reflexes are blunted. A multidisciplinary approach with different services and stakeholders is important for the proper planning, execution, and management of such patients.

Anestesia balanceada em gato palheiro (Leopardus braccatus) para realização de gastrotomia e enterotomia ­ relato de caso / Balanced anesthesia in pamps cat (Leopardus braccatus) for gastrotomy and enterotomy ­ case report / Anestesia balanceada en gato palheiro (Leopardus braccatus) para gastrotomía y enterotomía ­ reporte de caso

Foi atendido no Hospital Veterinária da Universidade Federal de Mato Grosso (HOVET-UFMT) - Campus Cuiabá, um gato palheiro (Leopardus braccatus), macho, filhote e pesando 1,8kg. Após avaliação clínica e exames complementares diagnosticou-se presença de corpo estranho solido gástrico e intestinal. Como medicação pré-anestésica optou-se pela associação de cetamina (1mg/kg) e midazolam (0,2mg/kg), seguiu-se com a indução com propofol (à efeito) e manutenção anestésica por meio do fornecimento de isofluorano. Como técnica adicional utilizou-se epidural, com uma associação de lidocaína (4,5mg/kg) e morfina (0,1mg/kg). Durante o procedimento anestésico notou-se estabilidade das variáveis cardiovasculares e respiratórias, além de recuperação satisfatória ao final do procedimento.

Was attended to in the Veterinary Hospital of the Federal University of Mato Grosso (HOVET-UFMT) - Campus Cuiabá, a pantanal cat (Leopardus braccatus), male, puppy and weighing 1.8 kg. After clinical evaluation and complementary exams, the presence of a solid gastric and intestinal foreign body was diagnosed. As pre-anesthetic medication, the association of ketamine (1mg/kg) and midazolam (0.2mg/kg) was chosen, followed by induction with propofol (for effect) and anesthetic maintenance by supplying isoflurane. As an additional technique, an epidural was used, with an association of lidocaine (4.5mg/kg) and morphine (0.1mg/kg). During the anesthetic procedure, stability of cardiovascular and respiratory variables was observed, in addition to satisfactory recovery at the end of the procedure.

Ingresó en el Hospital Veterinario de la Universidad Federal de Mato Grosso (HOVET-UFMT) · Campus Cuiabá, un gato palheiro (Leopardus braccatus), macho, cachorro y con un peso de 1,8 kg. Luego de evaluación clínica y exámenes complementarios se diagnosticó la presencia de cuerpo extraño sólido gástrico e intestinal. Como medicación preanestésica se optó por la asociación de ketamina (1 mg/kg) y midazolam (0,2 mg/kg), seguida de inducción con propofol (por efecto) y mantenimiento anestésico mediante suministro de isoflurano. Como técnica adicional se utilizó epidural, con asociación de lidocaína (4,5 mg/kg) y morfina (0,1 mg/kg). Durante el procedimiento anestésico se observó estabilidad de variables cardiovasculares y respiratorias, además de recuperación satisfactoria al final del procedimiento.

Comparison of Efficacy and Safety of Midazolam versus Nitrous Oxide as Sedative Agents during Paediatric Dental Treatment: A Systematic Review / Comparison of Efficacy and Safety of Midazolam versus Nitrous Oxide as Sedative Agents during Paediatric Dental Treatment: A Systematic Review

ABSTRACT Objective: To identify and study the existing literature on the efficacy and safety of midazolam compared to inhalation of nitrous oxide in children undergoing dental treatment. Material and Methods: Electronic resources such as PubMed Central, Cochrane Database of Systematic Reviews, Lilacs, Science Direct, and SIGLE were thoroughly searched. The title scan was used to find randomised controlled trials reviewed for inclusion by reading the abstract. Studies comparing the sedative, behavioural, and anxiolytic effects and safety in children undergoing dental treatment under midazolam and nitrous oxide inhalation were included. The Cochrane Reviews system software, Revman 5.4.1, was used to assess the quality of the included studies. Results: 11328 articles were identified by screening the electronic databases, of which 10906 were eliminated after titles were read and duplicates were removed. Ten full-text articles were examined, of which three were excluded as they did not match the eligibility criteria. Hence, a total of 7 studies were included. Midazolam and nitrous oxide inhalation were not statistically different in terms of the success of treatment and behaviour modification. However, midazolam showed a deeper level of sedation and resulted in amnesia in more children when compared to nitrous oxide sedation. All of the included studies were found to have a high risk of bias. Conclusion: Though all the studies included showed an increased risk of bias, midazolam and nitrous oxide inhalation seem equally effective sedative agents for controlling behaviour in children undergoing dental treatment. Midazolam shows a deeper sedation level when given orally and produces a higher rate of anterograde amnesia.

Control de síntomas al final de la vida con Dexmedetomidina: Estudio observacional de centro único / End-of-life symptom control with dexmedetomidine: A single-center observational study

Introducción: El manejo de los síntomas refractarios con dexmetomidina (DXM) es una alternativa en pacientes oncológicos en la atención al final de la vida (AFV) lo que puede convertirse en un gran desafío, ante la necesidad de iniciar sedación paliativa. El objetivo del presente estudio es determinar el efecto de la DXM comparado con el midazolam (MDZ) en el control de síntomas refractarios en pacientes con cáncer avanzado AFV, como parte de una estrategia asistencial de sedación paliativa. Metodología: Estudio observacional, longitudinal, se revisaron los informes médicos en las historias clínicas de pacientes hospitalizados con diagnóstico de cáncer avanzado terminal y síntomas refractarios (dolor, disnea y delirio), que recibieron sedación paliativa con DXM o MDZ. Se utilizaron los registros de Escala de Evaluación de Síntomas de Edmonton - revisada (ESAS-r) para intensidad de síntomas y la Escala de Sedación/Agitación de Richmond (RASS) para respuesta a la sedación. Resultados: Un total de 35 pacientes recibieron DXM y 18 MDZ. El dolor (32 %) y delirio (30 %) fueron los síntomas refractarios más identificados. Dolor intenso en 89.3 % antes del inicio de DXM. A las 72 horas, el grupo DXM presentó disminución de la intensidad del delirio a leve y moderado, mientras que la mayoría de los pacientes del grupo MDZ fallecieron antes de las 72 horas. Conclusiones: El uso clínico de la DXM permite un enfoque multimodal, ampliando su utilidad en la atención al final de la vida para el manejo del dolor y delirio, ya que permite un estado de respuesta para la interacción con los miembros de la familia, función relevante en cuidados paliativos.

Introduction: Managing refractory symptoms with dexmedetomidine (DXM) is an alternative for cancer patients in end-of-life care (EOLC), which can become a great challenge, given the need to start palliative sedation. This study aims to determine the effect of DXM compared to midazolam (MDZ) in controlling refractory symptoms in patients with advanced EOLC cancer as part of a palliative sedation care strategy. Methodology: In this observational, longitudinal study, the medical reports in the medical records of hospitalized patients diagnosed with terminal advanced cancer and refractory symptoms (pain, dyspnea, and delirium) who received palliative sedation with DXM or MDZ were reviewed. The Edmonton Symptom Assessment Scale-revised (ESAS-r) scores for symptom intensity and the Richmond Sedation/Agitation Scale (RASS) for response to sedation were used. Results: A total of 35 patients received DXM, and 18 received MDZ. Pain (32%) and delirium (30%) were the most identified refractory symptoms. Intense pain in 89.3% before DXM started; at 72 hours in 64.3%, the pain was reported as mild. Delirium was severe in 77.7%, DXM was used in 59.3%, and MDZ was used in 40.7%. At 72 hours, the DXM group presented a decrease in delirium intensity to mild and moderate, while most of the patients in the MDZ group died before 72 hours. Conclusions: The clinical use of DXM allows a multimodal approach, expanding its usefulness in end-of-life care for managing pain and delirium since it provides a state of response for interaction with family members, a function relevant in palliative care.

Comparison between oral midazolam versus oral ketamine plus midazolam as preanesthetic medication in autism spectrum disorder: double-blind randomized clinical trial

Abstract Background: Conventional dental care is often impossible in patients with Autism Spectrum Disorder (ASD). Non-collaborative behaviors, sometimes associated with aggressiveness, are usual justifications for premedication in this population. Thereby, this research focuses on the effects of oral midazolam versus oral ketamine plus midazolam as preanesthetic medication in ASD. Methods: The sample included 64 persons with ASD, aged 2-59 years, scheduled for dental care under general anesthesia. The primary objective of this study was to compare degrees of sedation between two parallel, double-blinded, equally proportional groups randomized to receive oral midazolam (0.5 mg.kg−1, maximum 15 mg) or oral midazolam (0.5 mg.kg−1) associated with oral S(+)-ketamine (3 mg.kg−1, maximum 300 mg). The secondary outcomes were the need of physical stabilization to obtain intravenous line, awakening time, and occurrence of adverse events. Results: According to the dichotomous analysis of sedation level (Ramsay score 1 and 2 versus Ramsay ≥ 3), oral association of S(+)-ketamine and midazolam improved sedation, with increased probability of Ramsay ≥ 3, Relative Risk (RR) = 3.2 (95% Confidence Interval [95% CI] = 1.32 to 7.76) compared to midazolam alone. Combined treatment also made it easier to obtain venous access without physical stabilization, RR = 2.05 (95% CI = 1.14 to 3.68). There were no differences between groups regarding awakening time and the occurrence of adverse events. Conclusion: The association of oral S(+)-ketamine with midazolam provides better preanesthetic sedation rates than midazolam alone and facilitates intravenous line access in patients with autism.

Tétanos de l'enfant au Centre Hospitalier Universitaire Mère­Enfant de Libreville, Gabon / Child tetanus at the Mother and Child University Hospital Center, Libreville, Gabon

L'objectif de cette étude était de déterminer les aspects épidémiologique, clinique, thérapeutique et évolutif du tétanos de l'enfant au service de réanimation du Centre Hospitalier Universitaire Mère-Enfant de Libreville, au Gabon. Méthodes : Etude rétrospective de type descriptif menée du 1er janvier 2019 au 31 décembre 2022. Les dossiers des enfants âgés de 0 à 16 ans, admis en réanimation pour tétanos, ont constitué la base des données. Les variables étudiées étaient épidémiologiques, cliniques, thérapeutiques et évolutives. Résultats : Parmi les 561 enfants hospitalisés en réanimation durant la période, il y'avait 12 cas de tétanos, soit une prévalence de 2,1%. Le sexe ratio était de 2. Les enfants âgés de 10 ans et plus représentaient la moitié de l'effectif (n=6). La porte d'entrée la plus retrouvée était une plaie du pied soit 50%, suivie d'une plaie céphalique dans 25% des cas. Tous les enfants avaient un état vaccinal incorrect, un trismus et des troubles d'alimentation. Le score pronostique de Dakar était à 2 chez six enfants (50%) et de 3 chez les 6 autres. Les molécules les plus utilisées étaient le Midazolam (92%), le Métronidazole (100%), le sérum et vaccin antitétanique (100%). Cinq patients (42%) ont bénéficié d'une ventilation assistée. La durée moyenne de séjour était de 13,6 jours ±9,9 et la létalité de 42%. Conclusion : le tétanos prédomine chez le grand enfant n'ayant pas de couverture vaccinale. Des mesures de sensibilisation des populations sur la vaccination antitétanique sont indispensables pour baisser la létalité.

Analysis of the effect of midazolam on pain in a rat model of lumbar disc herniation based on the p38 MAPK signaling pathway / 中国骨伤

OBJECTIVE@#To investigate the effect of midazolam on pain in lumbar disc herniation model rats based on p38 MAPK signaling pathway.@*METHODS@#Fifty SPF-grade Sprague-Dawley healthy rats, half male and half female, were selected and randomly divided into normal group, model group, and low-dose, medium-dose, high-dose groups. Model group and low-dose, medium-dose, high-dose groups were initially modeled for lumbar disc herniation. Intraperitoneal injection of saline was performed in rats of normal and model groups; and in the low-dose, medium-dose, and high-dose groups, intraperitoneal injection of midazolam was performed with doses of 30, 60, and 90 mg/kg, respectively. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT), β-endorphin (β-EP), substance P (SP), neuropeptide Y (NPY) were detected in the serum of rats by enzyme-linked immunoassay. The expression of p38 MAPK and matrix metalloproteinase-3(MMP-3) protein were detected by Western blot in the tissues of rats of each group.@*RESULTS@#The levels of TNF-α, IL-1β and β-EP were higher and the level of 5-HT was lower in the model group than in the normal group(P<0.05);the levels of TNF-α, IL-1β and β-EP were lower and the level of 5-HT was higher in the low-dose, medium-dose and high-dose groups than in the model group(P<0.05). The levels of SP and NPY increased in the model group compared with the normal group (P<0.05) and the levels of SP and NPY decreased in the low-dose, medium-dose and high-dose groups compared with the model group (P<0.05). The expression of p38 MAPK and MMP-3 increased in the model group compared with the normal group (P<0.05); the expression of p38 MAPK and MMP-3 decreased in the low-dose, medium-dose and high-dose compared with the model group(P<0.05).@*CONCLUSION@#Midazolam may ameliorate the immune inflammatory response in rats with a model of lumbar disc herniation, possibly regulated through the p38MAPK signaling pathway.

Effect of combined sedation using multiple drugs on inflammatory cytokines in patients with acute respiratory distress syndrome

Abstract he innate immune response plays an important role in the pathophysiology of acute respiratory distress syndrome (ARDS); however, no drug has been proven to be beneficial in the management of ARDS. Therefore, the aim of this study was to investigate the effects of using combined sedatives on systemic inflammatory responses in patients with ARDS. A total of 90 patients with ARDS and an intubation time of > 120 h were randomly divided into the propofol group (group P), midazolam group (group M), and combined sedation group (group U). Patients in groups P and M were sedated with propofol and midazolam, respectively, whereas patients in group U were sedated with a combination of propofol, midazolam, and dexmedetomidine. The dosage of sedatives and vasoactive drugs, duration of mechanical ventilation, and incidence of sedative adverse reactions were documented. The dosage of sedatives and vasoactive drugs, as well as the incidence of sedative adverse reactions in group U, was significantly lower than those in groups P and M. Similarly, the duration of mechanical ventilation in group U was significantly shorter than that in groups P and M. Hence, inducing sedation through a combination of multiple drugs can significantly reduce their adverse effects, improve their sedative effect, inhibit systemic inflammatory responses, and improve oxygenation in patients with ARDS

Accidente cerebrovascular por COVID-19 en una lactante de 6 meses / Stroke due to COVID-19 in a Six-month-old infant

Introducción: En de la población adulta predomina la enfermedad pulmonar, pero el coronavirus infantil grave parece más tipificado por una respuesta inflamatoria inmunomediada, con o sin síndrome inflamatorio multisistémico asociado. Objetivo: Examinar un paciente pediátrico con accidente cerebrovascular, como consecuencia de la enfermedad producida por el coronavirus tipo 2. Presentación del caso: Lactante femenina de 6 meses, que se presentó a emergencia con historia de fiebre de 39 oC, sin predominio de horario, de 10 días de evolución que no cedió con antipiréticos tipo acetaminofén, y dificultad respiratoria en los 3 días previos a su presentación en emergencia del hospital. Antecedentes familiares patológicos positivos, por la enfermedad del coronavirus en su padre. En la radiografía de tórax se observó infiltrado alveolar derecho y se ingresó con diagnóstico de neumonía por síndrome respiratorio agudo grave por coronavirus tipo 2. La tomografía de cráneo registró foco isquémico frontal parasagital derecho y parietal izquierdo; posteriormente se confirmó con resonancia magnética, en cuyo informe se definió la presencia de infartos en fase aguda a nivel frontal derecho y parietal izquierdo. Conclusiones: Se expuso una manifestación infrecuente en población pediátrica asociada a la enfermedad por coronavirus. La tasa de eventos tromboembólicos en el curso de las infecciones virales no es baja, y por coronavirus no es la excepción. Se requieren mayores estudios y pruebas para determinar el papel del síndrome respiratorio agudo severo por coronavirus tipo 2 en el accidente cerebrovascular pediátrico(AU)

Introduction: Pulmonary disease predominates in the adult population, but severe infantile coronavirus appears more typified by an immune-mediated inflammatory response, with or without associated multisystem inflammatory syndrome. Objective: To examine a pediatric patient with stroke resulting from coronavirus type 2 disease. Case presentation: 6-month-old female infant presenting to emergency with history of fever of 39 ℃ with no hourly predominance, of 10 days of evolution that did not subside with acetaminophen-type antipyretics and respiratory distress in the three days prior to presentation to hospital emergency. Positive family history of coronavirus disease in his father. Chest X-ray showed right alveolar infiltrate and she was admitted with a diagnosis of severe acute respiratory syndrome pneumonia due to coronavirus type 2. The cranial tomography recorded a right frontal parasagittal and left parietal ischemic focus, later confirmed by magnetic resonance imaging whose report defined the presence of acute phase infarcts at the right frontal and left parietal levels. Conclusions: An infrequent manifestation in pediatric population associated with coronavirus disease is exposed. The rate of thromboembolic events in the course of viral infections is not low and coronavirus is no exception. Further studies and evidence are required to determine the role of severe acute respiratory syndrome due to coronavirus type 2 in pediatric stroke(AU)

Oral preanesthetic medication in children - comparison between midazolam alone and in combination with ketamine: a systematic review and meta-analysis

Abstract Background Up to 60% of pediatric surgical patients develop high levels of preoperative anxiety. This study compared the effects of oral combinations of midazolam and ketamine with oral midazolam alone for pediatric preanesthetic medication. Methods The study protocol was registered in PROSPERO as CRD42020172920. A systematic literature search was conducted using Medline, Cochrane, EMBASE, CENTRAL, and Web of Science for randomized controlled trials comparing oral combinations of midazolam and ketamine with midazolam alone as preanesthetic medication in elective surgical pediatric patients. Meta-analyses included the following outcomes: anxiety and sedation levels, child's behavior during separation from parents, face mask acceptance, and venipuncture. The quality of evidence was assessed using GRADE criteria. Results Twenty studies were included. The following effects (RR (95% CI)) were observed for combinations of ketamine and midazolam relative midazolam alone: anxiolysis (1.2 (0.94-1.52); p= 0.15; I2 = 80%; GRADE = very low); satisfactory sedation (1.2 ( 1.10-1.31); p< 0.001; I2 = 71%; GRADE = very low); behavior during parental separation (1.2 (1.06-1.36); p= 0.003; I2 = 88%; GRADE = very low); facial mask acceptance (1.13 (1.04-1.24); p= 0.007; I2 = 49%; GRADE = very low); behavior during venipuncture (1.32 (1.11-1.57); p= 0.002; I2 = 66%; GRADE = very low). Conclusions While similar probabilities of obtaining anxiolysis were found, adequate sedation, calm behavior during child's separation from parents, low levels of fear during face mask adaptation, and cooperative behavior during peripheral venous cannulation were more likely with midazolam-ketamine combinations.

Inhibitory Effects and Mechanisms of Three Benzodiazepines on Helicobacter pylori / 中国医学科学院学报

Objective To explore the inhibitory effects and mechanisms of benzodiazepines on Helicobacter pylori (Hp).Methods The Hp international standard strain ATCC43504 was treated with benzodiazepines diazepam,midazolam,and remimazolam,respectively.The treatments with amoxicillin and clarithromycin were taken as the positive controls,and that with water for injection as the negative control.The inhibition zone of each drug was measured by the disk diffusion method.The minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of each drug against Hp were determined.Hp suspension was configured and treated with diazepam and midazolam,respectively.The bacterial suspension without drug added was used as the control group.The concentration of K+ in each bacterial suspension was measured by an automatic biochemical analyzer before drug intervention(T0)and 1(T1),2(T2),3(T3),4(T4),5(T5),6(T6),and 7 h(T7)after intervention.Hp urease was extracted and treated with 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,2 MIC midazolam,1 mg/ml acetohydroxamic acid,and water for injection,respectively.The time required for the rise from pH 6.8 to pH 7.7 in each group was determined by the phenol red coloring method.Results The inhibition zones of diazepam,midazolam,remimazolam,amoxicillin,clarithromycin,and water for injection against Hp were 52.3,42.7,6.0,72.3,60.8,and 6.0 mm,respectively.Diazepam and midazolam showed the MIC of 12.5 μg/ml and 25.0 μg/ml and the MBC of 25 μg/ml and 50 μg/ml,respectively,to Hp.The concentrations of K+ in the diazepam,midazolam,and control groups increased during T1-T7 compared with those at T0(all P<0.01).The concentration of K+ in diazepam and midazolam groups during T1-T4 was higher than that in the control group(all P<0.01).The time of inhibiting urease activity in the 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,and 2 MIC midazolam groups was(39.86±5.11),(36.52±6.65),(38.58±4.83),(39.25±6.19),(36.36±4.61),and(35.81±6.18)min,respectively,which were shorter than that in the acetohydroxamic acid group(all P<0.01)and had no significance differences from that in the water for injection group(all P>0.05).Conclusion Diazepam and midazolam exerted inhibitory effects on Hp,which may be related to the cleavage of Hp cells rather than inhibiting urease.

Child Stress and Behaviour During Restorative Treatment under Non-Pharmacological Techniques and Sedation: A Case Series

ABSTRACT Objective: To evaluate the behaviour and stress of children undergoing restorative treatment with and without sedation. Material and Methods: Participants were 14 healthy children aged between 2.5 and 6 years and with a history of dental behavioural management problems. In the dental treatment visit, the child was treated with non-pharmacological techniques, and in the second, moderate sedation was added. The child received the same procedure performed by a paediatric dentist in both visits: composite resin restoration using local anaesthesia and rubber dam isolation. In both visits, saliva was collected at the children's arrival at the dental clinic, during local anaesthesia and at the end of treatment. The visits were filmed for later analysis of behaviour according to the Ohio State University Behavioural Rating Scale. Results: About 78.5% of children improved their behaviour from the first to the second visit. The salivary cortisol curve of the first visit was maintained in the second visit for 21.4% of children but varied in the remaining participants. Conclusion: Most children presented better behaviour and less stress when sedation was added to non-pharmacological techniques during dental care.

Comparative study between S-(+)-ketamine­midazolam and fentanyl­droperidol in black-tufted marmosets (Callithrix penicillata) / Estudo comparativo entre S-(+)cetamina-midazolam e fentanil-droperidol em saguis-de-tufo-preto (Callithrix penicillata)

Sedative and antinociceptive effects of two anesthetic protocols in black-tufted marmosets were compared in this study. Twenty-six marmosets underwent chemical immobilization for physical examination, blood sampling, tattooing, and microchipping. Animals were randomly treated with S-(+)-ketamine (10 mg/kg) and midazolam (1 mg/kg) (KM) or fentanyl (12.5 µg/kg) and droperidol (625 µg/kg) (FD) given by intramuscular injection. Heart and respiratory rates were recorded. Sedation, antinociception, muscle relaxation, posture, auditory, and visual responses were evaluated using a scoring system. Sedation in KM was achieved faster (p < 0.001) and lasted for a shorter period of time (p = 0.0009). KM was similar to FD in its cardiorespiratory effects, auditory and visual responses. Both protocols promoted adequate sedation to allow manipulation. Animals in KM assumed lateral recumbency while animals in FD maintained a quadrupedal posture during evaluation. FD produced less intense sedation and muscle relaxation but a higher degree of antinociception compared to KM and is suitable for procedures that require analgesia in black-tufted marmosets.(AU)

O presente estudo comparou os efeitos cardiorrespiratórios, sedativos e antinociceptivos de dois protocolos anestésicos em saguis-de-tufo-preto (Callithrix penicillata). Vinte e seis saguis foram submetidos à contenção química para exame físico, coleta de sangue, tatuagem de identificação e microchip. Os animais foram tratados aleatoriamente com a associação de S-(+)-cetamina (10 mg/kg) e midazolam (1 mg/kg) (KM) ou fentanil (12,5 µg/kg) e droperidol (625 µg/kg) (FD), administrados por injeção intramuscular. Foram avaliadas frequência cardíaca, frequência respiratória, sedação, antinocicepção, relaxamento muscular, postura e resposta ao estímulo auditivo e visual. A sedação em KM foi alcançada mais rapidamente (p <0,001) e teve um tempo hábil mais curto (p = 0,0009). KM foi semelhante a FD nos efeitos cardiorrespiratórios, respostas auditivas e visuais. Os dois protocolos promoveram sedação adequada para manipulação. Os animais do grupo KM permaneceram em decúbito lateral durante a avaliação, enquanto os animais em FD mantiveram postura quadrupedal. FD resultou em sedação e relaxamento muscular de menor intensidade, porém com maior escore de antinocicepção em comparação com KM, sendo adequada para procedimentos que requerem analgesia em saguis-de-tufo-preto.(AU)

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.

Uma análise de custo-efetividade de propofol versus midazolam para sedação de pacientes adultos admitidos à unidade de terapia intensiva / A cost-effectiveness analysis of propofol versus midazolam for the sedation of adult patients admitted to the intensive care unit

RESUMO Objetivo: Construir um modelo de custo-efetividade para comparar o uso de propofol com o de midazolam em pacientes críticos adultos sob uso de ventilação mecânica. Métodos: Foi construído um modelo de árvore decisória para pacientes críticos submetidos à ventilação mecânica, o qual foi analisado sob a perspectiva do sistema privado de saúde no Brasil. O horizonte temporal foi o da internação na unidade de terapia intensiva. Os desfechos foram custo-efetividade por hora de permanência na unidade de terapia intensiva evitada e custo-efetividade por hora de ventilação mecânica evitada. Foram obtidos os dados do modelo a partir de metanálise prévia. Assumiu-se que o custo da medicação estava incluído nos custos da unidade de terapia intensiva. Conduziram-se análises univariada e de sensibilidade probabilística. Resultados: Pacientes mecanicamente ventilados em uso de propofol tiveram diminuição de sua permanência na unidade de terapia intensiva e na duração da ventilação mecânica, respectivamente, em 47,97 horas e 21,65 horas. Com o uso de propofol, ocorreu redução média do custo de U$2.998,971 em comparação ao uso do midazolam. A custo-efetividade por hora de permanência na unidade de terapia intensiva evitada e por hora de ventilação mecânica evitada foi dominante, respectivamente, em 94,40% e 80,8% do tempo. Conclusão: Ocorreu diminuição significante do custo associado ao uso de propofol, no que se refere à permanência na unidade de terapia intensiva e à duração da ventilação mecânica para pacientes críticos adultos.

ABSTRACT Objective: To build a cost-effectiveness model to compare the use of propofol versus midazolam in critically ill adult patients under mechanical ventilation. Methods: We built a decision tree model for critically ill patients submitted to mechanical ventilation and analyzed it from the Brazilian private health care system perspective. The time horizon was that of intensive care unit hospitalization. The outcomes were cost-effectiveness per hour of intensive care unit stay avoided and cost-effectiveness per hour of mechanical ventilation avoided. We retrieved data for the model from a previous meta-analysis. We assumed that the cost of medication was embedded in the intensive care unit cost. We conducted univariate and probabilistic sensitivity analyses. Results: Mechanically ventilated patients using propofol had their intensive care unit stay and the duration of mechanical ventilation decreased by 47.97 hours and 21.65 hours, respectively. There was an average cost reduction of US$ 2,998.971 for propofol when compared to midazolam. The cost-effectiveness per hour of intensive care unit stay and mechanical ventilation avoided were dominant 94.40% and 80.8% of the time, respectively. Conclusion: There was a significant reduction in costs associated with propofol use related to intensive care unit stay and duration of mechanical ventilation for critically ill adult patients.

Factores de riesgo de reacción paradójica asociados a sedación endovenosa con midazolam / Paradoxical reactions associated with midazolam conscious sedation

Background: Benzodiazepines are used for perioperative conscious sedation. However, its use may be associated with paradoxical reactions. The known risk factors for these reactions are age, alcohol and drug abuse and psychiatric disorders. Aim: To assess the incidence and impact of risk factors of paradoxical reactions to midazolam. Material and Methods: Cross sectional study of 218 patients aged 50 ± 16 years (51% women) scheduled for elective surgical procedures under regional anesthesia and midazolam sedation. The paradoxical reactions were classified according to their severity in three categories. Results: The incidence of paradoxical reactions to midazolam was 8.3% (95% confidence interval (CI) 5.0-12.7). All were mild and only 28% of the affected patients required pharmacological treatment, none of them flumazenil. A multivariable logistic regression model showed that the variables independently associated with a paradoxical reaction to midazolam were the use of psychoactive medications (Odds Ratio (OR) = 3.4 [1.1-11], p = 0.04, and the dose of midazolam (OR 1.35 [1.03-1.78], p = 0.03. Conclusions: The incidence of paradoxical reactions to midazolam was 8,3% and all were mild. Their risk factors are the use of psychoactive medications and the use of higher doses of midazolam.

Safety and efficacy of dexmedetomidine hydrochloride combined with midazolam in fiberoptic bronchoscopy in children: a prospective randomized controlled study / 中国当代儿科杂志

OBJECTIVES@#To study the safety and efficacy of dexmedetomidine hydrochloride combined with midazolam in fiberoptic bronchoscopy in children.@*METHODS@#A total of 118 children who planned to undergo fiberoptic bronchoscopy from September 2018 to February 2021 were enrolled. They were divided into a control group (@*RESULTS@#Compared with the control group, the observation group had significantly decreased MAP at T@*CONCLUSIONS@#Dexmedetomidine hydrochloride combined with midazolam is a safe and effective way to administer general anesthesia for fiberoptic bronchoscopy in children, which can ensure stable vital signs during examination, reduce intraoperative adverse reactions and postoperative agitation, shorten examination time, and increase amnesic effect.