Pain management in children: Part 1 - Pain assessment tools and a brief review of nonpharmacological and pharmacological treatment options.

If pain is not treated quickly and effectively in children, it can cause long-term physical and psychological sequelae. Therefore, it is important for all health care providers to understand the importance of effective pain control in children. This article is divided into 2 parts: Part 1 reviews the pharmacotherapy of pain management in children and Part 2 will review the problems relating to the use of codeine in children, and the rationale for recommending morphine as the opioid of choice in the treatment of moderate to severe pain. There has been growing concern about codeine's lack of efficacy and increased safety concerns in its use in children. Due to the variability of codeine metabolism and unpredictable effects on efficacy and safety, The Hospital for Sick Children in Toronto, Ontario, no longer includes codeine or codeine-containing products on the regular hospital formulary and now recommends oral morphine as the agent of choice for the treatment of moderate to severe pain in children. A knowledge translation (KT) strategy was developed and implemented by the hospital's Pain Task Force to support this practice change.

Once-daily gentamicin dosing in children with febrile neutropenia resulting from antineoplastic therapy.

STUDY OBJECTIVES: To evaluate an existing once-daily gentamicin dosing guideline in children with febrile neutropenia resulting from antineoplastic therapy and, if necessary, to develop a new simulated dosing guideline that would achieve pharmacokinetic targets more reliably after the first dose. DESIGN: Pharmacokinetic analysis of data from a retrospective medical record review. SETTING: Hematology-oncology unit of a university-affiliated pediatric hospital in Canada. PATIENTS: One hundred eleven patients aged 1-18 years who received once-daily gentamicin between April 2006 and January 2008 for the treatment of febrile neutropenia resulting from antineoplastic therapy, and who had plasma gentamicin concentrations determined after their first dose. MEASUREMENTS AND MAIN RESULTS: Demographic data, gentamicin dosing information, blood sampling times, and plasma gentamicin concentrations were noted. Plasma gentamicin concentrations were determined at approximately 3 and 6 hours after the start of the 30-minute infusion of the first dose. Pharmacokinetic parameters were calculated according to standard first-order, one-compartment equations. The proportion of children who achieved pharmacokinetic targets after the first gentamicin dose was used as a measure of dosing guideline performance; the guideline achieved maximum concentration (C(max)) values below the target range (20-25mg/L) in 51% of patients. Ideal dosing guidelines were then developed using the mean dose required to achieved a C(max) of 23 mg/L for each patient. Univariate analysis or the Student t test was used to determine the existence of significant relationships between pharmacokinetic parameters and patient age and sex. The recursive binary partitioning method was used to determine critical values of age for dosage guideline development; analysis of variance was then used to compare the different levels obtained after use of this technique. Simulated administration of once-daily gentamicin in the following doses achieved a C(max) within or above target in 73% of patients: 1 year to < 6 years, 10.5mg/kg/dose; girls > or = 6 years, 9.5mg/kg/dose; and boys > or = 6 years, 7.5mg/kg/dose. Doses were based on actual body weight for children who weighed less than 125% of ideal body weight or based on effective body weight for children 125% or more of ideal body weight. CONCLUSION: The initial gentamicin dosing guidelines were not effective in achieving C(max). The new proposed dosing guidelines are predicted to achieve a C(max) within or above the target range in almost three quarters of patients. Subsequent dosing should be tailored according to plasma gentamicin concentrations.

Pharmacokinetic modelling of a once-daily dosing regimen for intravenous tobramycin in paediatric cystic fibrosis patients.

OBJECTIVES: This study was designed to determine an optimal dose range for the once-daily dosing (ODD) of tobramycin in the treatment of an acute pulmonary exacerbation in paediatric cystic fibrosis (CF) patients. In addition, we aimed to assess whether certain patient characteristics affect tobramycin pharmacokinetics and, therefore, dosing. METHODS: Patient characteristics and pharmacokinetic parameters of patients receiving tobramycin three times daily from 1 January 1992 to 31 October 2005 were analysed using univariate analysis and multiple linear regression to determine statistically significant relationships and to derive dosing models. The binary partitioning method was used to derive critical values to determine stratification within the chosen dosing model. RESULTS: Using multiple linear regression, age and sex were significantly associated with the volume of distribution divided by the body weight (V/kg). By the binary partitioning method, the critical value for age was 13.75 years. CONCLUSIONS: Age and sex were used to derive an ODD regimen for tobramycin in paediatric CF. Using a target peak concentration range of 25-35 mg/L, the initial dose for female CF patients at least 14 years of age was calculated to be 7 mg/kg/day given intravenously as a single daily dose. All other CF patients would receive an initial dose of 9 mg/kg/day given intravenously as a single daily dose. These dosing guidelines will require prospective evaluation for safety and efficacy.