Julie Fitzgerald, MD, PhD, FCCM
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania
Disclosure information not submitted.
Athena Zuppa, MD
Director, Center for Clinical Pharmacology
Children's Hospital of Philadelphia
Medford, NJ, United States
Disclosure information not submitted.
Title: Nephrotoxic Medication Exposures in Critically Ill Children With Sepsis
Introduction: Children with sepsis are at high risk of acute kidney injury (AKI). We hypothesized that critically ill children with sepsis would also have a high burden of therapy with nephrotoxic medications (NTMs).
Methods: Children >8 weeks and < 18 years of age hospitalized in a PICU with suspected sepsis treated with vancomycin and supported with invasive ventilation and/or vasoactive infusions were prospectively enrolled in a study of vancomycin pharmacokinetics. Epidemiologic data were also collected and summarized using standard descriptive statistics. NTMs administered in the first five days of sepsis were recorded. Outcomes included KDIGO stage 2 or 3 AKI by serum creatinine (present for at least two days) or urine output criteria and PICU mortality.
Results: 33 children (52% male) were enrolled. Median age was 10 years (IQR 5-13). 26 children (79%) required invasive ventilation and 26 (79%) required vasoactive infusion support; 19 (58%) required both. The median number of calendar days of vancomycin therapy was 3 (range 2-48). 28 children (85%) were exposed to ≥3 simultaneous NTMs. The maximum number of daily NTMs administered in the first five days of sepsis was a median of 3 (IQR 3-4). The median number of days exposed to ≥3 NTMs was 2 (IQR 1-3). The most common NTMs (in addition to vancomycin, which was an inclusion criterion) were cephalosporin antibiotics, used in 29 children (88%), and furosemide, used in 25 children (76%). 10 children (30%) developed stage 2 or 3 AKI and 4 children (12%) in the cohort died at PICU discharge.
Conclusions: The burden of therapy with NTMs in critically ill children with sepsis was high. Simultaneous exposure to ≥3 NTMs is a known risk factor for AKI, and 85% of the cohort had this risk factor. The rate of AKI and death in this cohort is similar to previously described cohorts of critically ill children with sepsis. Future study of techniques to reduce NTM exposure in this population and the impact on outcomes is needed.