Outcomes of a Vial-Sparing Antithrombin III Protocol in Pediatric Extracorporeal Membrane Oxygenation.

Exogenous antithrombin III (AT3) may be administered to pediatric patients supported by extracorporeal membrane oxygenation (ECMO) to achieve a greater systemic response to heparin. Antithrombin III administration and dosing practices vary between ECMO centers. This study compared the outcomes of two different AT3 replacement protocols used by a single pediatric ECMO center for 47 patients between December 2013 and August 2021. In May 2016, a weight-based continuous infusion protocol (WBP) was transitioned to a vial-sparing protocol (VSP) as a cost-saving measure. No difference was observed in the percentage of heparin monitoring levels within goal range, with a median of 56.5% therapeutic levels on the WBP compared with a median of 60.7% on the VSP ( p = 0.170). No significant differences were observed in amount of exogenous blood products administered, number of hemorrhagic or thrombotic events, number of mechanical failures, or number of circuit changes required. The VSP resulted in fewer AT3 dispenses ( p < 0.001) and units dispensed ( p = 0.005), resulting in a significant median cost reduction from $15,610.62 on the WBP to $7,765.56 on the VSP ( p = 0.005). A vial-sparing AT3 replacement protocol resulted in significant cost savings with similar efficacy and safety outcomes.

Valproic Acid Serum Concentration and Incidence of Toxicity in Pediatric Patients.

In certain pediatric patients on valproic acid, therapeutic range (50-100 µg/mL) is maximized or exceeded to achieve better seizure control. This study compared incidence of common valproic acid adverse effects (thrombocytopenia, hepatotoxicity, and hyperammonemia) across maintenance concentration and age group. One hundred twenty-four children on maintenance valproic acid between January 2013 and January 2021 were eligible for inclusion. Fifty-six patients were maintained in concentration range 50 to 80 µg/mL, an additional 44 between 80 and 100 µg/mL and 24 between 100 and 120 µg/mL. Forty-one patients were prepubescent, 57 pubescent, and 26 postpubescent. There were no statistically significant differences observed in the primary endpoint of thrombocytopenia across serum concentration range (P = .093) or age group (P = .628). No significant differences in hepatic dysfunction (P = .099) or hyperammonemia (P = .548) were observed in serum concentration groups. Similarly, age group analysis observed no difference in hepatic dysfunction (P = .615) or hyperammonemia (P = .369). Serum valproic acid levels >100 µg/mL can be considered in select pediatric patients based on this study.

Incidence of nephrotoxicity with prolonged aminoglycoside exposure in patients with cystic fibrosis.

Cystic fibrosis (CF) patients, with Pseudomonas aeruginosa infection, often require repeated aminoglycoside courses for the management of acute pulmonary exacerbations (APEs). Acute kidney injury (AKI) due to aminoglycosides has been reported; little data exist regarding long-term nephrotoxicity with repeated exposure. The objective of this study was to describe the incidence of acute and chronic nephrotoxicity due to cumulative intravenous (IV) aminoglycoside exposure. This is a retrospective, observational study of pediatric and adult CF patients admitted to an academic medical center between January 1, 2006 and October 1, 2018 for APE management. Patients were eligible for inclusion if they received at least five courses of an IV aminoglycoside for at least 7 days each. Cumulative weight-based aminoglycoside dose was reported in milligrams per kilogram. For each admission, baseline and highest serum creatinine were collected to assess the incidence of AKI. The baseline and final estimated glomerular filtration rate (eGFR) were calculated to assess long-term effects on renal function. Sixty-six patients, representing greater than 700 courses, were included in the final analysis. The median cumulative weight-based aminoglycoside dose was 1183 mg/kg of tobramycin or tobramycin equivalent. Twenty percent of courses resulted in AKI; 86% were Stage 1. A repeated measure multivariate model showed colistin, piperacillin/tazobactam, vancomycin, and age were significant AKI risk factors. There was no correlation between cumulative aminoglycoside dose and change in eGFR. AKI from IV aminoglycoside exposure occurred in 20% of courses. Cumulative exposure to IV aminoglycosides in APE management was not correlated with long-term renal dysfunction.