RESUMEN
OBJECTIVE: Literature in pediatric patients suggests dosing sirolimus 1.6 mg/m2/day divided twice daily for lymphatic disorders with limited evidence available for dosing in neonates and infants. The objective of this research was to determine the sirolimus dose required to achieve therapeutic trough concentrations in infants with lymphatic disorders at Children's Hospital of Philadelphia. METHODS: This retrospective review included patients <1 year of age at Children's Hospital of Philadelphia who were initiated on sirolimus for lymphatic disorder. Patients were included if they received at least 5 days of consecutive sirolimus therapy prior to trough concentration monitoring. Measures of central tendency and variability were used for statistical analysis. RESULTS: A total of 16 patients met criteria for inclusion. The median initial sirolimus dose was 1 mg/m2/day (IQR, 0.5-1.6 mg/m2/day). Fourteen patients (87.5%) achieved therapeutic trough concentrations on a median sirolimus dose of 0.5 mg/m2/day. Dosing frequency to achieve therapeutic trough concentrations included 1 patient (6.25%) on twice daily dosing, 12 patients (75%) on once daily dosing, and 1 patient (6.25%) requiring every 48-hour dosing. The median time to first therapeutic trough was 15.5 days (IQR, 5.5-18.5 days), and patients required a median of 1 dose adjustment. CONCLUSIONS: A median sirolimus dose to achieve therapeutic sirolimus trough concentrations in infants with lymphatic disorders was 0.5 mg/m2/day with a median of 1 dose adjustment. Sirolimus was well tolerated in the study population.
RESUMEN
OBJECTIVE: Ketorolac-related adverse events are not yet elucidated in neonates and infants given paucity of data. The objective of this research is to determine the incidence of major bleed in postsurgical neonates and infants treated with ketorolac, and to describe characteristics of ketorolac therapy and its effect on renal function. METHODS: This retrospective review assessed postsurgical patients younger than 6 months of age, without renal and/or coagulation dysfunction, who received ketorolac for postoperative pain during the study period. Major bleed was defined as a decrease in hemoglobin by ≥ 2 g/dL in a 24-hour period and/or intracranial, intraventricular, gastrointestinal, or pulmonary hemorrhage. Renal injury was identified per pediatric-modified RIFLE (risk, injury, failure, loss, end stage renal disease) criteria. RESULTS: One hundred twenty-five patients were analyzed, having a mean dosing weight of 5.6 kg, gestational age of 37.2 weeks, and postnatal age of 3.8 months. Ketorolac therapy was most frequently 0.5 mg/kg intravenously every 6 hours with a mean of 6.7 doses administered. The primary endpoint of major bleed occurred in 2 (1.6%) 2-month-old patients of 39 weeks' gestation. Both bleeds were characterized by decrease in hemoglobin without evidence of clinically significant bleeding. One (0.8%) and 3 (2.4%) patients experienced a decrease in glomerular filtration rate and urine output, respectively. Sixty-two (49.6%) patients received a concomitant medication associated with decreased bleeding risk. CONCLUSIONS: Ketorolac appears to have low incidence of major bleeds in postsurgical patients younger than 6 months of age without renal and/or coagulation dysfunction. Larger, prospective studies are needed to confirm safety of ketorolac use in this population.