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]

Evaluation of the Effects of Extracts Containing Valeriana officinalis and Piper methysticum on the Activities of Cytochrome P450 3A and P-Glycoprotein.

This work investigated interactions ascribed to the administration of phytomedicines containing Valeriana officinalis and Piper methysticum with conventional drugs. The phytomedicines were characterized by HPLC and administered per os to male Wistar rats, either concomitantly or not with the CYP3A substrate midazolam. To distinguish between the presystemic or systemic effect, midazolam was given orally and intravenously. The effects on the P-gp substrate fexofenadine uptake by Caco-2 cells were examined. The valerenic acid content was 1.6 ± 0.1 mg per tablet, whereas kavain was 13.7 ± 0.3 mg/capsule. Valerian and kava-kava extracts increased the maximum plasma concentration (Cmax) of midazolam 2- and 4-fold compared to the control, respectively. The area under the plasma concentrations versus time curve (AUC(0-∞)) was enhanced from 994.3 ± 152.3 ng.h/mL (control) to 3041 ± 398 ng.h/mL (valerian) and 4139 ± 373 ng.h/mL (kava-kava). The half-life of midazolam was not affected. These changes were attributed to the inhibition of midazolam metabolism by the enteric CYP3A since the i. v. pharmacokinetic of midazolam remained unchanged. The kava-kava extract augmented the uptake of fexofenadine by 3.5-fold compared to the control. Although Valeriana increased the uptake of fexofenadine, it was not statistically significant to that of the control (12.5 ± 3.7 ng/mg protein vs. 5.4 ± 0.3 ng/mg protein, respectively). Therefore, phytomedicines containing V. officinalis or P. methysticum inhibited the intestinal metabolism of midazolam in rats. Conversely, the P-gp-mediated transport of fexofenadine was preferably affected by kava-kava.

Effects of moderate sedation induced by propofol or midazolam on intracranial pressure / Efeitos da sedação moderada induzida por propofol ou midazolam na pressão intracranial

INTRODUCTION: Propofol and midazolam are the main options for moderate sedation in clinical practice. In addition, these drugs are used to reduce intracranial pressure in cases of intracranial hypertension, and their use in these situations is guided by limited evidence. OBJECTIVE: To compare the effects of propofol and midazolam on intracranial pressure wave morphology in moderate sedation in patients undergoing upper digestive endoscopy. METHODS: Sixty patients were included in this study, being divided into two groups, propofol and midazolam group. Intracranial pressure was monitored during and after upper digestive endoscopy, using non-invasive monitoring equipment developed by the company Brain4care. Arterial pressure was measured before and after the exam. RESULTS: The propofol group had lower intracranial pressure (p=0.037) during moderate sedation compared to intracranial pressure after endoscopy and a significant decrease in systolic (p=0.0001) and diastolic pressure (p=0.001) after sedation. Midazolam, on the other hand, reduced systolic pressure (p=0.001), but didn't change the other parameters after the procedure. There wasn't a significant difference between the propofol and midazolam groups. CONCLUSION: There was no significant difference between the groups studied, however, analyses within the propofol and midazolam groups indicate that propofol, but not midazolam, causes changes in intracranial pressure in moderate sedation.

INTRODUÇÃO: O propofol e o midazolam são as principais opções para sedação moderada na prática clínica. Além disso, esses medicamentos são usados para reduzir a pressão intracraniana em casos de hipertensão intracraniana e seu uso nessas situações é orientado por evidências limitadas. OBJETIVO: Comparar os efeitos do propofol e do midazolam na morfologia da curva de pressão intracraniana na sedação moderada em pacientes submetidos à endoscopia digestiva alta. MÉTODOS: Sessenta pacientes foram incluídos nesse estudo, sendo divididos em dois grupos: propofol e midazolam. A pressão intracraniana foi monitorada durante e após a endoscopia digestiva alta, usando um equipamento de monitoramento não invasivo desenvolvido pela empresa Brain4care. A pressão arterial foi medida antes e depois do exame. RESULTADOS: O grupo do propofol apresentou pressão intracraniana mais baixa (p=0,037) durante a sedação moderada em comparação com a pressão intracraniana após a endoscopia, e uma diminuição significativa na pressão sistólica (p=0,0001) e diastólica (p=0,001) após a sedação. O midazolam, por outro lado, reduziu a pressão sistólica (p=0,001), mas não alterou os outros parâmetros após o procedimento. Não houve diferença significativa entre os grupos propofol e midazolam. CONCLUSÃO: Não houve diferença significativa entre os grupos estudados; entretanto, as análises dentro dos grupos de propofol e midazolam indicam que apenas o propofol causa alterações na pressão intracraniana em sedação moderada.

Comparison of intranasal dexmedetomidine versus oral midazolam for premedication in pediatric patients: an updated meta-analysis with trial-sequential analysis.

BACKGROUND: Midazolam is routinely used as preanesthetic medication in pediatric patients. Recently, dexmedetomidine has emerged as an alternative as a premedicant. We aimed to add more evidence about the efficacy and safety of two common routes of administration for pediatric premedication: oral midazolam versus intranasal dexmedetomidine. METHODS: We systematically searched Randomized Controlled Trials (RCTs) involving patients ≤ 18 years old undergoing preanesthetic medication and comparing intranasal dexmedetomidine with oral midazolam. Risk Ratio (RR) and Mean Difference (MD) with 95% Confidence Intervals (95% CI) were computed using a random effects model. Trial-sequential analyses were performed to assess inconsistency. RESULTS: Sixteen RCTs (1,239 patients) were included. Mean age was 5.5 years old, and most procedures were elective. There was no difference in satisfactory induction or mask acceptance (RR = 1.15, 95% CI 0.97-1.37; p = 0.11). There was a higher incidence of satisfactory separation from parents in the dexmedetomidine group (RR = 1.40; 95% CI 1.13-1.74; p = 0.002). Dexmedetomidine was also associated with a reduction in the incidence of emergence agitation (RR = 0.35; 95% CI 0.14-0.88; p = 0.02). Heart rate and mean arterial pressure were marginally lower in the dexmedetomidine group but without clinical repercussions. CONCLUSION: Compared with oral midazolam, intranasal dexmedetomidine demonstrated better separation from parents and lower incidence of emergence agitation in pediatric premedication, without a difference in satisfactory induction. Intranasal dexmedetomidine may be a safe and effective alternative to oral midazolam for premedication in pediatric patients.

Epidural administration of ropivacaine and midazolam is superior to intra-articular administration as postoperative analgesia after isolated arthroscopic anterior cruciate ligament reconstruction with hamstrings autograft: a randomized controlled clinical trial.

OBJECTIVE: Reconstructive surgery of the anterior cruciate ligament (ACL) is quite common, previous studies have documented that adequate pain control in the early phases of the postoperative period translates into early mobility and a rapid start of rehabilitation. Therefore, the search for new strategies for postoperative pain control is justified. The aim of this study was to compare intra-articular to the epidural administration of ropivacaine and midazolam as postoperative analgesia after arthroscopic ACL reconstruction with hamstring autograft (HA). MATERIAL AND METHODS: Double-blinded, prospective randomized clinical trial included 108 consecutive patients aged from 18 to 50 years that had undergone arthroscopic ACL reconstruction with HA. The patients were randomly assigned to 2 groups. The first group received intraarticular ropivacaine and midazolam. The second group received epidural ropivacaine and midazolam. The need for rescue analgesia, the postoperative pain experienced, side effects and complications of the analgesic drugs were evaluated. RESULTS: The intra-articular group received statistically significantly higher mean doses of rescue analgesia on the first two days (2.8 â€‹± â€‹1.0 vs. 1.3 â€‹± â€‹0.6 in the epidural group; p â€‹= â€‹0.001). Visual Analogue Scale scores at flexion were statistically significantly higher in the intra-articular group over the entire study period. The intra-articular group also reported a statistically significantly lower range-of-motion 87 â€‹± â€‹15 vs. 102 â€‹± â€‹11 in the epidural group (p â€‹= â€‹0.001). CONCLUSIONS: Epidural administration of ropivacaine combined with midazolam in patients undergoing primary ACL reconstruction with HA was clinically and significantly better relative to rescue analgesia and the intensity of pain in the first 48 postoperative hours when compared to intraarticular administration. There was no difference in terms of adverse effects and complications.

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.

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.

EFFECTS OF DETOMIDINE AND DEXMEDETOMIDINE ON PHYSIOLOGICAL PARAMETERS AND ANESTHETIC RECOVERY IN TAPIRUS TERRESTRIS ANESTHETIZED WITH KETAMINE, GLYCERYL GUAIACOL ETHER, AND MIDAZOLAM.

The aim of this study was to compare the effects of two anesthetic induction protocols for long procedures carried out in the field in Tapiridae. Sixteen tapirs were divided into two groups (n=8) receiving either detomidine (DET) or dexmedetomidine (DEX) for anesthetic induction. All animals were anesthetized by intramuscular administration of a combination of ketamine (1.5 mg/kg), midazolam (0.2 mg/kg), plus either DET (0.04 mg/kg) or DEX (0.007 mg/kg). Anesthetic maintenance was by continuous infusion of ketamine, midazolam, and glyceryl guaiacol ether at 2 mg/kg per hour, 0.1 mg/kg per hour, and 100 mg/kg per hour, respectively). The animals were kept anesthetized for a total of 50 min to allow physical examination and collection of biological material as part of a research program, and physiological variables (heart rate [HR], respiratory rate, oxyhemoglobin saturation [SpO2], rectal temperature [RT], mean arterial pressure [MAP], blood glucose [GLI], and cortisol) and electrocardiogram were recorded during anesthesia. Anesthetic recovery was monitored by two researchers who were not informed of the induction protocol group. The recorded results were statistically evaluated. In both groups there was an initial increase in MAP, which subsequently decreased; RT gradually decreased during anesthesia; HR and GLI increased throughout the procedure; SpO2 was below normal throughout the procedure. Cortisol levels were significantly higher in the DEX group than in the DET group. Also, the animals in the DEX group had a longer recovery time than those in the DET group. On the basis of the results, we conclude that the combination of alpha-2 agonists and midazolam, ketamine, and glyceryl guaicol ether is an appropriate protocol for the anesthesia of tapirs in the field. However, in moderately extended procedures oxygen supplementation is recommended. Additionally, DEX resulted in fewer cardiovascular effects and longer-lasting sedation than DET.

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.

Prehospital Seizure Management in Children: An Evaluation of a Nationally Representative Sample.

OBJECTIVE: To describe the characteristics and emergency medical services (EMS) interventions, appropriateness of medication dosing, and factors associated with use of any or multiple doses of benzodiazepines for children with seizures in the prehospital setting from a nationally representative dataset. METHODS: We performed a retrospective study of EMS encounters within the National EMS Information System between 2019 and 2021, including children (<18 years) with an impression of seizures. We identified (1) factors associated with the use of benzodiazepines in a logistic regression model and (2) factors associated with multiple doses of benzodiazepines in an ordinal regression model. RESULTS: We included 361 177 encounters for seizure. Among transports with an Advanced Life Support clinician, 89.9% were given no benzodiazepines and 7.7%, 1.9%, and 0.4% were given 1, 2, and ≥3 doses of benzodiazepines, respectively. Encounters given more doses of benzodiazepines had increased use of supplemental oxygen. A high proportion (43.4%) of EMS-provided initial benzodiazepine doses were inappropriately low. EMS-provided benzodiazepine use was associated with use of benzodiazepine prior to EMS arrival. Provision of multiple doses of EMS-provided benzodiazepines was associated with use of a low initial dose of benzodiazepine and use of lorazepam or diazepam compared with midazolam. CONCLUSION: A large proportion of prehospital pediatric patients with seizure are given inappropriately low dose of benzodiazepines. Use of a low dose of benzodiazepine and use of benzodiazepines other than midazolam are associated with additional benzodiazepine usage. Our findings have implications for future research and quality improvement needs in pediatric prehospital seizure management.

Anesthetic effects of isoflurane and fentanyl infusion in capuchin monkeys (Sapajus sp) undergoing salpingectomy or deferentectomy, previously chemically restrained with ketamine-midazolam or ketamine-dexmedetomidine.

BACKGROUND: This study evaluated the anesthetic and cardiorespiratory effects of two anesthetic protocols for salpingectomy or deferentectomy in capuchin monkeys (Sapajus sp). MATERIALS AND METHODS: Five capuchin monkeys (5 per group) received ketamine (20 mg/kg) combined with midazolam (0.5 mg/kg; group KM) or dexmedetomidine (5 µg/kg; group KD) intramuscularly. Anesthesia is induced with propofol intravenously and maintained with isoflurane. Before the start of surgery, fentanyl 3 µg/kg was administered IV, and continuous infusion (10 µg/kg/min) IV was started. Times and quality of anesthetic recovery were evaluated postoperatively. RESULTS: KM and KD resulted in adequate chemical restraint. KD resulted in bradycardia. Intraoperative heart rate and systolic blood pressure were higher in KM than in KD. Both groups had smooth recovery. Time to standing was longer in KM than in KD. CONCLUSION: Both protocols allowed the performance of surgeries, with few cardiorespiratory effects. Anesthetic recovery was smooth and shorter in KD group.

A fast and simple protocol to anaesthesia in chicken embryos.

Chicken embryos (CE) are an experimental model used as an important life science research tool worldwide, and then, adequate anesthetic protocols must be adopted to avoid the unjustifiable suffering of animals. Thus, our objective was to evaluate different anesthetic protocols in CEs using an easy inoculation route, the shell membrane (SM). We adopted the heart rate by pulse and the CE movements as a parameter of pain by assessing the vase in the chorioallantoic membrane (CAM) through the shell by a sensor of a multiparametric monitor. CEs were distributed into the following groups: (i) association of ketamine (5 mg/CE), midazolam (0.05 mg/CE) and morphine (0.15 mg/CE); (ii) ketamine (5 mg/CE) and xylazine (0.125 mg/CE); (iii) xylazine (0.0125 mg/CE) and morphine (0.15 mg/CE). The stress method used to test the anesthetic potential of the drugs was high temperature stimulation, keeping the CEs 10 cm from the fire of a Bussen nozzle for 30 s. In this experimental model, associations between different drugs decreased the pulse and the movement, indicating possible sedation. After treatment, the CE's submitted to the stress method had the heart rate and movements kept low in the groups ketamine-midazolam-morphine and ketamine-xylazine, while the non-drug-treated group increased heart rate. In a group treated with xylazine-morphine, the heart rate did not decrease, but the movement decreased after the stimulus. As the best results were the combinations of ketamine-midazolam-morphine and ketamine-xylazine, we recommend these associations for use in embryos in the final third of embryonic development in experimental protocols and euthanasia.

Usefulness of Inhaled Sedation in Patients With Severe ARDS Due to COVID-19.

BACKGROUND: Sedation in intensive care is fundamental for optimizing clinical outcomes. For many years the world has been facing high rates of opioid use, and to combat the increasing opioid addiction plans at both national and international level have been implemented.1 The COVID-19 pandemic posed a major challenge for health systems and also increased the use of sedatives and opioid analgesia for prolonged periods of time, and at high doses, in a significant proportion of patients. In our institutions, the shortage of many drugs for intravenous (IV) analgosedation forces us to alternatives to replace out-of-stock drugs or to seek sedation goals, which are difficult to obtain with traditional drugs at high doses.2 METHODS: This was an analytical retrospective cohort study evaluating the follow-up of subjects with inclusion criteria from ICU admission to discharge (alive or dead). Five end points were measured: need for high-dose opioids (≥ 200 µg/h), comparison of inhaled versus IV sedation of opioid analgesic doses, midazolam dose, need for muscle relaxant, and risk of delirium. RESULTS: A total of 283 subjects were included in the study, of whom 230 were administered IV sedation and 53 inhaled sedation. In the inhaled sedation group, the relative risks (RRs) were 0.5 (95% CI 0.4-0.8, P = .045) for need of high-dose fentanyl, 0.3 (95% CI 0.20-0.45, P < .001) for need of muscle relaxant, and 0.8 (95% CI 0.61-1.15, P = .25) for risk of delirium. The median difference of fentanyl dose between the inhaled sedation and IV sedation groups was 61 µg/h or 1,200 µg/d (2.2 ampules/d, P < .001), and that of midazolam dose was 5.7 mg/h. CONCLUSIONS: Inhaled sedation was associated with lower doses of opioids, benzodiazepines, and muscle relaxants compared to IV sedation. This therapy should be considered as an alternative in critically ill patients requiring prolonged ventilatory support and where IV sedation is not possible, always under adequate supervision of ICU staff.

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

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.ß=.ß0.15; I2.ß=.ß80%; GRADE.ß=.ßvery low); satisfactory sedation (1.2 ( 1.10...1.31); p.ß<.ß0.001; I2.ß=.ß71%; GRADE.ß=.ßvery low); behavior during parental separation (1.2 (1.06...1.36); p.ß=.ß0.003; I2.ß=.ß88%; GRADE.ß=.ßvery low); facial mask acceptance (1.13 (1.04...1.24); p.ß=.ß0.007; I2.ß=.ß49%; GRADE.ß=.ßvery low); behavior during venipuncture (1.32 (1.11...1.57); p.ß=.ß0.002; I2.ß=.ß66%; GRADE.ß=.ßvery 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.

The Reversal of Empathy-Induced Hypernociception in Male Mice by Intra-Amygdala Administration of Midazolam and Cannabidiol Depends on 5-HT3 Receptors.

Introduction: Empathy is a fundamental prosocial behavior. It has been defined as perception, awareness, and understanding of others' emotional states, including painful processes. Mice living in pairs with conspecific chronic suffering from constriction injury exhibit pain hypersensitivity mediated by the amygdaloid complex. Nevertheless, the underlying mechanisms in the amygdala responsible for this response remain to be determined. This study investigated if the anxiolytic benzodiazepine midazolam (MDZ) and cannabidiol (CBD), a phytocannabinoid with multiple molecular targets, would attenuate this behavioral change. We also investigated if serotonergic and γ-aminobutyric acid (GABA)ergic mechanisms in the amygdala are involved in this effect. Materials and Methods: Male Swiss mice were housed in pairs for 28 days. The pairs were divided into two groups on the 14th day: cagemate nerve constriction and cagemate sham. On the 24th day, cagemates underwent a stereotaxic surgery and, on the 28th day, were evaluated on the writhing test. Results: The results showed that living with chronic pain leads to hypernociception in the cagemate and increases the expression of 5-HT3 receptor (5-HT3R) and glutamic acid decarboxylase 67 within the amygdala. MDZ (3.0 and 30 nmol) and CBD (30 and 60 nmol) attenuated the hypernociceptive behavior. The 5-HT3R antagonist ondansetron (0.3 nmol) prevented the antinociceptive effects of MDZ and CBD. Conclusion: These findings indicate that 5-HT3R and GABAergic mechanisms within the amygdala are involved in the pain hypersensitivity induced by the empathy for pain model. They also suggest that MDZ and CBD could be a new potential therapy to alleviate emotional pain disorders.