No Requirement for Targeted Theophylline Levels for Diuretic Effect of Aminophylline in Critically Ill Children

OBJECTIVES: To determine the relationship between theophylline trough levels and urine output in critically ill children administered aminophylline as adjunctive diuretic therapy. DESIGN: Retrospective cohort study. SETTING: The PICU of a tertiary care children’s hospital. PATIENTS: A mixed population of medical/surgical including postoperative cardiothoracic surgery patients less than 18 years old. INTERVENTIONS: Electronic medical records of all PICU patients admitted from July 2010 to June 2015 were reviewed, and patients who received aminophylline as diuretic therapy were identified. MEASUREMENTS AND MAIN RESULTS: Patient cohort data including demographics, daily aminophylline, furosemide and chlorothiazide dosing, theophylline trough levels, fluid intake, urine output and total fluid balance, blood urea nitrogen, and creatinine levels were abstracted. Multivariate analysis based on a generalized estimating equations approach demonstrated that aminophylline administration, when analyzed as a categorical variable, was associated with an increase in urine output and decreased fluid balance. However, aminophylline dosing, when analyzed as a continuous variable, was associated with neither an increase in urine output nor decreased fluid balance. Theophylline trough levels were not correlated with urine output at 24 hours (p = 0.78) and were negatively correlated with urine output at 48 hours (r(2) = 0.078; p < 0.005). CONCLUSIONS: Aminophylline administration provided a measure of increased diuresis, regardless of dosage, and theophylline trough levels. Therefore, achieving a prescribed therapeutic trough level may not be necessary for full diuretic effect. Because, as opposed to the diuretic effect, the side effect profile of aminophylline is dose-dependent, low maintenance dosing may optimize the balance between providing adjunctive diuretic effect while minimizing the risk of toxicity.