Population Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Children Undergoing Ambulatory Surgery.

BACKGROUND: Dexmedetomidine (DEX) is an α-2 adrenergic agonist with sedative and analgesic properties. Although not approved for pediatric use by the Food and Drug Administration, DEX is increasingly used in pediatric anesthesia and critical care. However, very limited information is available regarding the pharmacokinetics of DEX in children. The aim of this study was to investigate DEX pharmacokinetics and pharmacodynamics (PK-PD) in Mexican children 2-18 years of age who were undergoing outpatient surgical procedures. METHODS: Thirty children 2-18 years of age with American Society of Anesthesiologists physical status score of I/II were enrolled in this study. DEX (0.7 µg/kg) was administered as a single-dose intravenous infusion. Venous blood samples were collected, and plasma DEX concentrations were analyzed with a combination of high-performance liquid chromatography and electrospray ionization-tandem mass spectrometry. Population PK-PD models were constructed using the Monolix program. RESULTS: A 2-compartment model adequately described the concentration-time relationship. The parameters were standardized for a body weight of 70 kg by using an allometric model. Population parameters estimates were as follows: mean (between-subject variability): clearance (Cl) (L/h × 70 kg) = 20.8 (27%); central volume of distribution (V1) (L × 70 kg) = 21.9 (20%); peripheral volume of distribution (V2) (L × 70 kg) = 81.2 (21%); and intercompartmental clearance (Q) (L/h × 70 kg) = 75.8 (25%). The PK-PD model predicted a maximum mean arterial blood pressure reduction of 45% with an IC50 of 0.501 ng/ml, and a maximum heart rate reduction of 28.9% with an IC50 of 0.552 ng/ml. CONCLUSIONS: Our results suggest that in Mexican children 2-18 years of age with American Society of Anesthesiologists score of I/II, the DEX dose should be adjusted in accordance with lower DEX clearance.

Determination of blood dexmedetomidine in dried blood spots by LC-MS/MS to screen therapeutic levels in paediatric patients.

Dexmedetomidine is an imidazole derivative, with high affinity for α2 adrenergic receptors, used for sedation, analgesia and adjuvant anaesthesia. In this study, an analytical method for the quantification of dexmedetomidine in dried blood spots was developed, validated and applied. The drug was extracted from dried blood spot by liquid extraction; the separation was carried out by ultra high-resolution liquid chromatography in reverse phase coupled to tandem mass spectrometry method. An X Select cyano 5 µm HSS column (2.1 X 150 mm, Waters) and a mobile phase composed of 0.1% formic acid: acetonitrile [50:50 v/v], were used. The test was linear over the concentration range of 50 to 2000 pg/mL. The coefficients of variation for the intra and interday trials were less than 15%. The drug was stable under the conditions tested. The method was successfully applied for the quantification of 6 patients, aged 0 to 2 years, with classification ASA I, who underwent ambulatory surgeries, receiving a dose of 1 µg/Kg dexmedetomidine IV. The drug concentrations in the different sampling times were in the range of 76 to 868 pg/mL.

Buprenorphine and pain treatment in pediatric patients: an update.

INTRODUCTION: The usual management of moderate to severe pain is based on the use of opioids. Buprenorphine (BPN) is an opioid with an analgesic potency 50 times greater than that of morphine. It is widely used in various pain models and has demonstrated efficacy and safety in adult patients; however, there are insufficient clinical trials in pediatric populations. PURPOSE: The aim of this study was to perform an updated meta-analysis on the implementation of BPN in the treatment of pain in the pediatric population. METHODS: A bibliographic search was carried out in different biomedical databases to identify scientific papers and clinical trials with evidence of BPN use in children and adolescents. RESULTS: A total of 89 articles were found, of which 66 were selected. Analysis of these items revealed additional sources, and the final review included a total of 112 publications. CONCLUSION: Few studies were found regarding the efficacy and safety of BPN use in children. In recent years, the use of this drug in the pediatric population has become widespread, so it is imperative to perform clinical trials and pharmacological and pharmacovigilance studies, which will allow researchers to develop dosage schemes based on the evidence and minimize the risk of adverse effects.

Neurological complications and death in children with dengue virus infection: report of two cases.

BACKGROUND: Dengue virus infection can have different complications; the best known is hemorrhagic dengue fever. However, other effects such as neurological disorders may endanger the lives of patients. Dengue neurological manifestations can be confused with encephalitis symptoms and can lead to cerebral edema and death. Therefore, we consider important in the endemic areas to take into account the diagnosis of dengue encephalitis in patients with neurological disorders, and to request the determination of serology in cerebrospinal fluid for the NS1 antigen test. CASE PRESENTATION: We present the cases of two patients from the state of Morelos, Mexico, with 17 and 14 years of age. Both cases presented a rapid evolution characterized by fever, seizures and neurological deterioration secondary to severe cerebral edema that evolved to cerebral death in both cases. The diagnosis of brain death was confirmed by electroencephalogram in both patients. The two patients were submitted to serology for NS1 that tested positive in both cases. They died between the second and fifth day after admission. CONCLUSIONS: Retrospective studies have found that up to 4% of the patients have dengue virus infections, which leads us to believe that in endemic areas, this infection should be suspected in cases of encephalic and febrile symptoms. RT-PCR should be performed to identify cases of encephalitis caused by the dengue virus, and early interventions should be performed to attempt to reduce the morbidity and mortality of these cases.

Neurological complications and death in children with dengue virus infection: report of two cases

Background Dengue virus infection can have different complications; the best known is hemorrhagic dengue fever. However, other effects such as neurological disorders may endanger the lives of patients. Dengue neurological manifestations can be confused with encephalitis symptoms and can lead to cerebral edema and death. Therefore, we consider important in the endemic areas to take into account the diagnosis of dengue encephalitis in patients with neurological disorders, and to request the determination of serology in cerebrospinal fluid for the NS1 antigen test. Case presentation We present the cases of two patients from the state of Morelos, Mexico, with 17 and 14 years of age. Both cases presented a rapid evolution characterized by fever, seizures and neurological deterioration secondary to severe cerebral edema that evolved to cerebral death in both cases. The diagnosis of brain death was confirmed by electroencephalogram in both patients. The two patients were submitted to serology for NS1 that tested positive in both cases. They died between the second and fifth day after admission. Conclusions Retrospective studies have found that up to 4% of the patients have dengue virus infections, which leads us to believe that in endemic areas, this infection should be suspected in cases of encephalic and febrile symptoms. RT-PCR should be performed to identify cases of encephalitis caused by the dengue virus, and early interventions should be performed to attempt to reduce the morbidity and mortality of these cases.(AU)

Neurological complications and death in children with dengue virus infection: report of two cases

Abstract Background Dengue virus infection can have different complications; the best known is hemorrhagic dengue fever. However, other effects such as neurological disorders may endanger the lives of patients. Dengue neurological manifestations can be confused with encephalitis symptoms and can lead to cerebral edema and death. Therefore, we consider important in the endemic areas to take into account the diagnosis of dengue encephalitis in patients with neurological disorders, and to request the determination of serology in cerebrospinal fluid for the NS1 antigen test. Case presentation We present the cases of two patients from the state of Morelos, Mexico, with 17 and 14 years of age. Both cases presented a rapid evolution characterized by fever, seizures and neurological deterioration secondary to severe cerebral edema that evolved to cerebral death in both cases. The diagnosis of brain death was confirmed by electroencephalogram in both patients. The two patients were submitted to serology for NS1 that tested positive in both cases. They died between the second and fifth day after admission. Conclusions Retrospective studies have found that up to 4% of the patients have dengue virus infections, which leads us to believe that in endemic areas, this infection should be suspected in cases of encephalic and febrile symptoms. RT-PCR should be performed to identify cases of encephalitis caused by the dengue virus, and early interventions should be performed to attempt to reduce the morbidity and mortality of these cases.

Las directrices que rigen la terapéutica farmacológica en el recién nacido / The basis that guide pharmacological theraphy in newborn

El proceso de la vida se divide en distintas etapas vitales, una de las que más cambios sufre es la etapa de recién nacido (RN). Los cambios de origen corporal y fisiológico que se presentan en los primeros días de vida, alteran la farmacocinética y farmacodinamia de los fármacos. Además, debido a lo impredecible del desarrollo de los órganos que regulan la disposición de los medicamentos en el RN, es necesario conocer la farmacocinética de ciertos medicamentos, mientras el RN alcanza su madurez orgánica, para así ajustar la dosis de los medicamentos, sobre la base de parámetros farmacocinéticos individuales. En el presente trabajo se revisan las bases clínicas y farmacocinéticas, así como los instrumentos de control útiles para el establecimiento de una terapéutica farmacológica racional y segura en el RN.

Farmacocinética bayesiana de cefuroxima en niños infectados gravemente enfermos / Bayesian pharmacokinetics of cefuroxime in critically ill septic children

Objetivo. Estimar los párametros farmacocinéticos de cefuroxima en el paciente pediátrico críticamente enfermo utilizando un método farmacocinético bayesiano y un número limitado de muestras por paciente. Diseño. Estudio transversal de pacientes pediátricos gravemente enfermos que recibieron tratamiento y monitoreo de concentraciones séricas de cefuroxima. Lugar. Centro de atención de tercer nivel. Pacientes. Nueve pacientes pediátricos sépticos gravemente enfermos. Métodos. Se midió la cefuroxima a diferentes tiempos y se estimaron los parámetros Vd(volumen de distribución) y Kel(constante de eliminación) utilizando un algoritmo iterativo en dos etapas hayesiano y la información de tres muestras de cada paciente. El Vd y la Kel fueron también estimados por el método tradicional de regresión no lineal en 8 muestras. Resultados. La comparación de algunos métodos mostró que la Vd bayesiano fue muy similar al tradicional (r=0.99 y sesgo de -0.04 l/kg) mientras que para la Kel la correlación fue de 0.90 y el sesgo de -0.29 h. el Vd bayesiano promedio fue de 0.68 l/kg, un valor mayor que el reportado para pacientes no críticamente enfermos. Conclusiones. Ofrecemos un modelo farmacocinético de cefuroxima para niños sépticos gravemente enfermos que puede ser integrado a un predictor bayesiano para establecer dosis individualizadas. Asimismo, ilustran la utilidad de un abordaje farmacocinético bayesiano para establecer dosis individualizadas. Asimismo, ilustran la utilidad de un abordaje farmacocinético bayesiano como herramienta de investigación clínica

Predición bayesiana de las concentraciones séricas de clorafenicol en niños con sepsis y desnutrición / Evaluation on the performance of bayesian adaptive control system to forecast the chloramphenicol serum concentrations in pediatric patients with sepsis and malnutrition

Objetivo. Validar los parámetros farmacocinéticos de cloranfenicol en pacientes pediátricos con sepsis y desnutrición (PPSD) por medio de un programa de predicción bayesiano para cloranfenicol en PPSD. Lugar. Hospital Pediátrico de Enseñanza de Tercer Nivel. Pacientes. Quince PPSD y diez pacientes pediátricos con sepsis sin desnutrición (PPSN), que recibieron tratamiento con cloranfenicol. Método y resultados principales. En la primera parte del estudio, los expedientes clínicos de 10 PPSD y 10 PPSN quienes habían recibido tratamiento con cloranfenicol fueron revisados. Los parámetros farmcocinéticos poblacionales para cada grupo fueron estimados por medio de un algoritmo no paramétrico de maximización de expectativas (NPEM). En la segunda parte, cinco pacientes independientes con indicadores similares de desnutrición que recibieron cloranfenicol fueron utilizados para probar el desempeño predictivo de los modelos poblacionales, utilizados éstos como distribución a priori en un programa de control adaptado bayesiano. Las concentraciones séricas de cloranfenicol predichas por el método bayesiano fueron comparadas con las concentraciones observadas. El modelo específico para PPSD permitió pronosticar las concentraciones pico y valle de cloranfenicol con menor sesgo y con una mayor precisión, comparado con el modelo poblacional de PPSN. Conclusiones. Estos datos indican que la farmacocinética de cloranfenicol en PPSD puede predecirse con un sesgo mínimo y una buena precisión utilizando un programa bayesiano, permitiendo así, un mejor control sobre el grado de exposición a esta droga y con el beneficio económico adicional de requerir de un número limitado de muestras por paciente