ABSTRACT
BACKGROUND: Intravenous salbutamol is used to treat children with refractory status asthmaticus, however insufficient pharmacokinetic data are available to guide initial and subsequent dosing recommendations for its intravenous use. The pharmacologic activity of salbutamol resides predominantly in the (R)-enantiomer, with little or no activity and even concerns of adverse reactions attributed to the (S)-enantiomer. OBJECTIVE: Our aim was to develop a population pharmacokinetic model to characterize the pharmacokinetic profile for intravenous salbutamol in children with status asthmaticus admitted to the pediatric intensive care unit (PICU), and to use this model to study the effect of different dosing schemes with and without a loading dose. METHODS: From 19 children (median age 4.9 years [range 9 months-15.3 years], median weight 18 kg [range 7.8-70 kg]) treated with continuous intravenous salbutamol at the PICU, plasma samples for R- and S-salbutamol concentrations (111 samples), as well as asthma scores, were collected prospectively at the same time points. Possible adverse reactions and patients' clinical data (age, sex, weight, drug doses, liver and kidney function) were recorded. With these data, a population pharmacokinetic model was developed using NONMEM 7.2. After validation, the model was used for simulations to evaluate the effect of different dosing regimens with or without a loading dose. RESULTS: A two-compartment model with separate clearance for R- and S-salbutamol (16.3 L/h and 8.8 L/h, respectively) best described the data. Weight was found to be a significant covariate for clearance and volume of distribution. No other covariates were identified. Simulations showed that a loading dose can result in higher R-salbutamol concentrations in the early phase after the start of infusion therapy, preventing accumulation of S-salbutamol. CONCLUSIONS: The pharmacokinetic model of intravenous R- and S-salbutamol described the data well and showed that a loading dose should be considered in children. This model can be used to evaluate the pharmacokinetic-pharmacodynamic relationship of intravenous salbutamol in children, and, as a next step, the effectiveness and tolerability of intravenous salbutamol in children with severe asthma.
Subject(s)
Adrenergic beta-2 Receptor Agonists/pharmacokinetics , Albuterol/pharmacokinetics , Status Asthmaticus/drug therapy , Administration, Intravenous , Adolescent , Adrenergic beta-2 Receptor Agonists/administration & dosage , Adrenergic beta-2 Receptor Agonists/blood , Adrenergic beta-2 Receptor Agonists/pharmacology , Albuterol/administration & dosage , Albuterol/blood , Albuterol/pharmacology , Child , Child, Preschool , Female , Hospitalization/statistics & numerical data , Humans , Infant , Intensive Care Units, Pediatric/statistics & numerical data , Male , Models, Theoretical , Prospective Studies , Status Asthmaticus/metabolismABSTRACT
PURPOSE: We sought to establish the reliability and validity of the Dutch version of the Vancouver Symptom Score for Dysfunctional Elimination Syndrome for children with dysfunctional voiding and their parents. MATERIALS AND METHODS: For this cross-sectional multicenter study the Vancouver Symptom Score for Dysfunctional Elimination Syndrome was translated and cross-culturally adapted to Dutch following a standardized process. Patients 16 years or younger with dysfunctional voiding and their parents were recruited at pediatric, pediatric urology and pelvic floor physical therapy outpatient clinics. The reference group consisted of children 6 to 16 years old without dysfunctional voiding and their parents. All groups completed questionnaires. The evaluated measurement properties included discriminative ability, internal consistency, test-retest reliability, interrater agreement, criterion validity using the Pediatric Incontinence Questionnaire and construct validity. A cutoff value for diagnosis of dysfunctional voiding was determined. RESULTS: A total of 50 patients and 60 references and their parents were included in the study. The Vancouver Symptom Score for Dysfunctional Elimination Syndrome showed good discriminative ability. A moderate internal consistency was found (Cronbach alpha 0.37-0.55). Test-retest reliability was moderate to good, and interrater agreement demonstrated good correlation between children and parents (ICC 0.85, 95% CI 0.79-0.89). A weak correlation with the Pediatric Incontinence Questionnaire was found in patients and construct validity was confirmed. Cutoff scores for dysfunctional voiding were 11 and 9 for patients and parents, respectively. CONCLUSIONS: The Dutch Vancouver Symptom Score for Dysfunctional Elimination Syndrome displayed moderate to good reliability and validity properties for the patient and parent versions. Use of this instrument in clinical practice will support the assessment of dysfunctional voiding and facilitate international reporting of research results.
Subject(s)
Severity of Illness Index , Urination Disorders/diagnosis , Adolescent , Case-Control Studies , Child , Cross-Sectional Studies , Female , Humans , Male , Netherlands , Prospective Studies , Psychometrics , Reproducibility of Results , TranslationsABSTRACT
A 5-year-old boy presented with vomiting and dyspnoea. His chest X-ray showed two round consolidations in his right lung, one of them with air bronchograms, which were caused by round pneumonia. Round pneumonia presents with multiple lesions in only 2% of cases.
