Evaluation of Sirolimus Dosing in Neonates and Infants With Lymphatic Disorders: A Case Series.

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.

Evaluation of the Safety of Ketorolac in Postsurgical Infants Less Than Six Months of Age.

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.

Pediatric Emergency Medicine Simulation Curriculum: Vitamin K Deficiency in the Newborn.

Introduction: The American Academy of Pediatrics recommends vitamin K prophylaxis at birth for all newborns to prevent vitamin K deficiency bleeding (VKDB). Despite a lack of evidence for serious harms, barriers to prophylaxis, including parental refusal, are rising, as are cases of VKDB. Methods: This simulation involved an infant presenting to the emergency department who decompensated due to a cerebral hemorrhage caused by VKDB and was treated by pediatric and emergency providers. The case was incorporated into the fellow and division monthly curricula, and participants completed postsimulation surveys. The patient required a secure airway, seizure management, vitamin K, and a fresh frozen plasma infusion upon suspicion of the diagnosis, plus a coordinated transfer to definitive care. The case included a description of the simulated case, learning objectives, instructor notes, an example of the ideal flow of the scenario, anticipated management mistakes, and educational materials. Results: The simulations were carried out with 48 total participants, including 40 fellows and eight attendings, from five different training institutions over 1 year. In surveys, respondents gave overall positive feedback. Ninety-four percent of participants gave the highest score on a Likert scale indicating that the simulation was relevant, and over 80% gave the highest score indicating that the experience helped them with medical management. Discussion: This simulation trained physicians how to recognize and treat a distressed infant with VKDB. The case was perceived to be an effective learning tool for both fellow and attending physicians.

Compatibility of treprostinil sodium and dopamine hydrochloride during simulated Y-site administration.

PURPOSE: To evaluate the physical and chemical compatibilities of treprostinil sodium and dopamine hydrochloride. METHODS: Treprostinil sodium (4,000, 76,000, and 500,000 ng/mL) were mixed with dopamine hydrochloride (0.6, 3.2, 6, and 40 mg/mL). Samples were obtained at hours 0, 1, 2, and 4 for physical compatibility and chemical stability testing. Physical compatibility was assessed by visual examination and measurements of turbidity and pH. Drug concentrations were assessed using stability-indicating liquid chromatography mass spectrophotometry (LCMS) for treprostinil sodium and stability-indicating high-performance liquid chromatography (HPLC) for dopamine hydrochloride. RESULTS: Treprostinil sodium 4,000 and 76,000 ng/mL, when mixed with dopamine hydrochloride 0.6, 3.2, 6, and 40 mg/mL, were stable for 4 hours. Treprostinil sodium 500,000 ng/mL was stable when mixed with dopamine hydrochloride 0.6 mg/mL for 4 hours, but when mixed with dopamine hydrochloride 3.2, 6, and 40 mg/mL, significant precipitation was seen. CONCLUSION: Treprostinil sodium 4,000 and 76,000 ng/mL were stable for 4 hours during simulated Y-site coadministration with dopamine hydrochloride 0.6, 3.2, 6, and 40 mg/mL. Treprostinil sodium 500,000 ng/mL is stable when mixed with dopamine hydrochloride 0.6 mg/mL.