High incidence of persistent subtherapeutic levels of the most common AEDs in children with epilepsy receiving polytherapy.

BACKGROUND: Low levels of AEDs can be secondary drug-drug interactions or related to irregular intake due to poor treatment adherence. This latter behavior is highly suspected in ambulatory pediatric epileptic patients when controls of AEDs are subtherapeutic. However, it cannot be considered for inpatients during long periods of hospitalization. A few isolated case reports have documented persistent low levels (PLL) of AEDs in hospitalized epileptic children, but no population study has currently been reported. OBJECTIVE: The aim of this study was to document the incidence of PLL of the most common AEDs - phenytoin (PHT), phenobarbital (PHB), valproic acid (VA), and carbamazepine (CBZ) - in pediatric epileptic in- and outpatients (PEP). METHODS: 21,040 plasma levels of the aforementioned AEDs from 3279 PEP were retrospectively analyzed. Plasma levels of AEDs were measured by an automated method using trademarked commercial kits with their corresponding quality control programs. Randomized samples were also controlled by HPLC methods. Only cases with more than 3 controls were included in the study. RESULTS: A high rate of PLL of PHT was detected in in- (71.7%) and outpatients (74.1%), while PLL of PHB, VA, and CBZ were detected in a lower proportion. Rates of PLL of PHT were similar in in- and outpatients. PLL of PHB was more commonly observed in outpatients while PLL of VA and CBZ were more frequently seen in inpatients. In some hospitalized patients receiving polytherapy, PLL of at least one AED were documented during a long time. DISCUSSION: Treatment non-adherence could be present in part of the outpatients, but cannot explain the PLL observed in a group of inpatients as described here. The recently described "pharmacokinetic hypothesis" of pharmaco-resistant epilepsy should be addressed in cases with AEDs-PLL, particularly in hospitalized cases. Perhaps, instead of stopping the subtherapeutic medication, the increasing doses of this AED and/or administration of inhibitors of CYP and P-glycoprotein, could help to achieve its therapeutic range, allowing a better pharmacologic effect and avoiding the development of more severe complications, such as status epilepticus or SUDEP.

Péptido natriurético tipo B: utilidad en el manejo de recién nacidos críticamente enfermos / B-type natriuretic peptide: Usefulness in the management of critically-ill neonates

El péptido natriurético B (PNB) es un péptido responsable de los cambios durante la organogénesis del corazón y en la transición a la vida extrauterina. En la primera semana de vida, los niveles de PNB son altos y se normalizan con el descenso fisiológico del peso. Valores elevados de PNB se han asociado a diferentes patologías. Objetivo. Establecer la relación entre los niveles de PNB y la criticidad y evolución a corto plazo en pacientes internados en la Unidad de Cuidados Intensivos Neonatales. Método. Estudio observacional analítico de una cohorte prospectiva. Se definió criticidad como requerimientos de asistencia respiratoria con fracción inspirada de oxígeno mayor del 50% y/o inotrópicos. Se extrajeron 2 muestras de sangre con 72 h de diferencia. Resultados. Ingresaron 73 pacientes. Según la evolución al séptimo día del ingreso, se los dividió en 2 grupos: pacientes con buena evolución o con evolución grave persistente. La mediana del PNB inicial fue similar en ambos grupos (p: 0,15). La mediana de PNB a las 72 h fue mayor en los pacientes con evolución grave persistente (p: 0,005). Se calculó la diferencia entre ambos valores de PNB (ΔPNB: valor de PNB a las 72 h - valor de PNB a la hora cero). El ΔPNB presentó valores positivos en los pacientes con evolución grave persistente (X= 1260 pg/ml; rango: 4262094) y valores negativos en el grupo con buena evolución (X= -967 pg/ml; rango: -1656/-278) (p: 0,0002); sensibilidad: 87%; especificidad: 86%; valor predictivo positivo: 74%; y valor predictivo negativo: 93%. Conclusión. En este grupo de pacientes, el delta de PNB reflejó la evolución a corto plazo.

B-type natriuretic peptide (BNP) is responsible for changes in the heart organogenesis and is associated with transition to extrauterine life. In the first week of life, BNP levels are high and return to normal with the physiological loss in weight. High BNP levels are associated with different conditions. Objective. To establish the relationship between BNP levels and criticality and the short-term clinical course among patients hospitalized in the neonatal intensive care unit. Method. Observational and analytical study conducted in a prospective cohort. Criticality was defined as a requirement for assisted mechanical ventilation with a fraction of inspired oxygen of more than 50% and/or inotropes. Two blood samples were collected 72 hours apart. Results. Seventy-three patients were included in the study. Depending on their clinical course on day 7, they were divided into 2 groups: patients with a good clinical course or a persistent, severe clinical course. The median baseline BNP level was similar in both groups (p: 0.15). The median BNP level at 72 hours was higher among patients with a persistent, severe clinical course (p: 0.005). The difference between both BNP values was calculated (ΔBNP: BNP level at 72 hours - BNP level at 0 hours). The ΔBNP was positive among patients with a persistent, severe clinical course (X= 1260 pg/mL; range: 426-2094) and negative in the group with a good clinical course (X= -967 pg/mL; range: -1656/-278) (p: 0.0002); sensitivity: 87%; specificity: 86%; positive predictive value: 74%; and negative predictive value: 93%. Conclusion. In this group of patients, the delta-BNP value reflected the short-term clinical course.

B-type natriuretic peptide: Usefulness in the management of critically-ill neonates. / Péptido natriurético tipo B: utilidad en el manejo de recién nacidos críticamente enfermos.

INTRODUCTION: B-type natriuretic peptide (BNP) is responsible for changes in the heart organogenesis and is associated with transition to extrauterine life. In the first week of life, BNP levels are high and return to normal with the physiological loss in weight. High BNP levels are associated with different conditions. OBJETIVE: To establish the relationship between BNP levels and criticality and the short-term clinical course among patients hospitalized in the neonatal intensive care unit. METHOD: Observational and analytical study conducted in a prospective cohort. Criticality was defined as a requirement for assisted mechanical ventilation with a fraction of inspired oxygen of more than 50% and/or inotropes. Two blood samples were collected 72 hours apart. RESULTS: Seventy-three patients were included in the study. Depending on their clinical course on day 7, they were divided into 2 groups: patients with a good clinical course or a persistent, severe clinical course. The median baseline BNP level was similar in both groups (p: 0.15). The median BNP level at 72 hours was higher among patients with a persistent, severe clinical course (p: 0.005). The difference between both BNP values was calculated (ΔBNP: BNP level at 72 hours - BNP level at 0 hours). The ΔBNP was positive among patients with a persistent, severe clinical course (X= 1260 pg/mL; range: 426-2094) and negative in the group with a good clinical course (X= -967 pg/mL; range: -1656/-278) (p: 0.0002); sensitivity: 87%; specificity: 86%; positive predictive value: 74%; and negative predictive value: 93%. CONCLUSION: In this group of patients, the delta-BNP value reflected the short-term clinical course.

INTRODUCCIÓN: El péptido natriurético B (PNB) es un péptido responsable de los cambios durante la organogénesis del corazón y en la transición a la vida extrauterina. En la primera semana de vida, los niveles de PNB son altos y se normalizan con el descenso fisiológico del peso. Valores elevados de PNB se han asociado a diferentes patologías. OBJETIVO: Establecer la relación entre los niveles de PNB y la criticidad y evolución a corto plazo en pacientes internados en la Unidad de Cuidados Intensivos Neonatales. MÉTODO: Estudio observacional analítico de una cohorte prospectiva. Se definió criticidad como requerimientos de asistencia respiratoria con fracción inspirada de oxígeno mayor del 50% y/o inotrópicos. Se extrajeron 2 muestras de sangre con 72 h de diferencia. RESULTADOS: Ingresaron 73 pacientes. Según la evolución al séptimo día del ingreso, se los dividió en 2 grupos: pacientes con buena evolución o con evolución grave persistente. La mediana del PNB inicial fue similar en ambos grupos (p: 0,15). La mediana de PNB a las 72 h fue mayor en los pacientes con evolución grave persistente (p: 0,005). Se calculó la diferencia entre ambos valores de PNB (ΔPNB: valor de PNB a las 72 h - valor de PNB a la hora cero). El ΔPNB presentó valores positivos en los pacientes con evolución grave persistente (X= 1260 pg/ml; rango: 4262094) y valores negativos en el grupo con buena evolución (X= -967 pg/ml; rango: -1656/-278) (p: 0,0002); sensibilidad: 87%; especificidad: 86%; valor predictivo positivo: 74%; y valor predictivo negativo: 93%. CONCLUSIÓN: En este grupo de pacientes, el delta de PNB reflejó la evolución a corto plazo.