Association of weight with drug dosing guideline adherence in children hospitalized with asthma

Abstract

Background: Obesity can result in physiologic alterations that may be important to drug disposition. Despite this, dosing recommendations for hospitalized children with obesity remain limited, including drugs for asthma exacerbations. This knowledge gap may lead to variability in prescribing practices in children with obesity, posing a serious risk of under or over-exposure to drugs. Objectives: To examine the prevalence of non-guideline adherent drug dosing by weight in children hospitalized with asthma who are prescribed one of the following commonly used steroid drugs: prednisone, prednisolone, methylprednisolone, or dexamethasone. Methods and Analysis: We performed a retrospective cohort study of children aged 2-17 years who were prescribed steroids during hospitalization for asthma in the years 2010-2017 using the Cerner Health Facts® (HF) database. The HF database contains de-identified data from more than 500 health care facilities across the US. Doses of 4 commonly prescribed steroid drugs for asthma exacerbation (prednisone, prednisolone, methylprednisolone, and dexamethasone) were categorized as either guideline adherent or non-guideline adherent based on NHLBI asthma guidelines. Non-guideline adherent doses were defined as: doses > recommended maximum daily dose, 2) total mg/kg/day ≥ 110% of the maximum recommended weight-based dose, or 3) total mg/kg/day ≤ 90% of the minimum recommended weight-based dose. Total daily doses were calculated based on prescribed drug doses and frequencies. Body mass index (BMI) was calculated from documented height and weight; weight categories were defined using age- and sex-specific BMI percentile guidelines established by the CDC. Chi-square tests determined statistical differences in non guideline adherent doses of all included steroid drugs between weight categories. Results: We identified 24,155 patients hospitalized for asthma exacerbations who received at least 1 of the included drugs. The majority of patients admitted with asthma exacerbations were aged 6-10 years (44.8%), male (59.8%), African American (51.0%), and had government insurance (55.8%). The majority of children (54%) were a healthy weight. Approximately 38.6% were overweight or obese (n= 9,325); there were 3,648 patients with class I obesity (15.1%), 1,353 with class II obesity (5.6%), and 770 with class III obesity (3.2%). A substantial number of children overall received non-guideline adherent drug doses (27.8%), rising significantly as weight category increased, from 25.2% of the healthy weight group to 41.6% of those with Class III obesity (p<0.0001). Weight category remained a significant independent predictor of receiving a non-guideline adherent dose in adjusted logistic regression models (p<0.0001). Conclusion: The association between weight and receipt of non-guideline adherent steroid prescriptions for patients hospitalized with asthma exacerbation increases with increasing weight category, disproportionately affecting children with severe obesity. Future studies should attempt to address differences in hospital clinical and utilization outcomes between patients with and without obesity based on drug dosing differences.