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Vancomycin Prescribing and Therapeutic Drug Monitoring in Children With and Without Acute Kidney Injury After Cardiac Arrest

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Abstract

Background

Acute kidney injury (AKI) commonly occurs after cardiac arrest. Those subsequently treated with vancomycin are at additional risk for drug-induced kidney injury.

Objective

We aimed to determine whether opportunities exist for improved drug monitoring after cardiac arrest.

Methods

This was a retrospective cohort study of children aged 30 days–17 years treated after cardiac arrest in an intensive care unit from January 2010 to September 2014 who received vancomycin within 24 h of arrest. Vancomycin dosing and monitoring were compared between those with and without AKI, with AKI defined as pRIFLE (pediatric risk, injury, failure, loss, end-stage renal disease) stage 2–3 AKI at day 5 using Schwartz formula-calculated estimated glomerular filtration rate (eGFR).

Results

Of 43 children, 16 (37%) had AKI at day 5. Age, arrest duration, median time to first vancomycin dose, and the number of doses before and time to first vancomycin concentration measurement were similar between groups. Children with AKI had higher initial vancomycin concentrations than those without AKI (median 16 vs. 7 mg/L; p = 0.003). A concentration was not measured before the second dose in 44% of children with AKI. Initial eGFR predicted day 5 AKI. In children with AKI, the initial eGFR was lower in those with than those without a concentration measurement before the second dose (29 mL/min/1.73 m2 [interquartile range (IQR) 23–47] vs. 52 [IQR 50–57]; p = 0.03) but well below normal in both.

Conclusions

In children with AKI after cardiac arrest, decreased vancomycin clearance was evident early, and early monitoring was not performed universally in those with low initial eGFR. Earlier vancomycin therapeutic drug monitoring is indicated in this high-risk population.

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Authors and Affiliations

  1. Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia and The University of Pennsylvania Perelman School of Medicine, 3401 Civic Center Blvd, 6th Floor Wood Building, Room 6117, Philadelphia, PA, 19104, USA

    Julie C. Fitzgerald, Adam S. Himebauch, Alexis A. Topjian & Athena F. Zuppa

  2. Center for Clinical Pharmacology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Nicole R. Zane, Kevin J. Downes & Athena F. Zuppa

  3. Department of Pharmacy, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA

    Michael D. Reedy

  4. Department of Pediatrics, Children’s Hospital of Philadelphia and The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Kevin J. Downes & Susan L. Furth

  5. Department of Pediatrics, Penn State Hershey Children’s Hospital, Penn State University College of Medicine, Hershey, PA, USA

    Neal J. Thomas

  6. Department of Pharmacy Practice, Pharmacometric Center of Excellence, Midwestern University, Downers Grove, IL, USA

    Marc H. Scheetz

Authors
  1. Julie C. Fitzgerald
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  2. Nicole R. Zane
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  3. Adam S. Himebauch
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  4. Michael D. Reedy
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  5. Kevin J. Downes
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  6. Alexis A. Topjian
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  7. Susan L. Furth
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  8. Neal J. Thomas
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  9. Marc H. Scheetz
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  10. Athena F. Zuppa
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Corresponding author

Correspondence to Julie C. Fitzgerald.

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Funding

This study was supported by the Division of Critical Care Medicine Russell Raphaely Endowed Chair of Critical Care Medicine at the Children’s Hospital of Philadelphia.

Conflict of interest

Dr. Zane is supported by National Institutes of Health (NIH) Grant 2T32GM008562; Dr. Downes is supported by NIH Grant K23 HD091365, and he has received research support from Merck and Co. and Pfizer, Inc. unrelated to the current work; Dr. Topjian was previously supported by the NIH and Sage Therapeutics and currently receives support from Laerdal Medical; Dr. Furth is supported by NIH Grants U19 AR069525, U01 DK066174, P50 DK114786, and U01 HL125295; Dr. Scheetz was supported by NIH, National Institute of Allergy and Infectious Diseases Grant R15 AI105742, performs consulting for Achaogen, Paratek, and SIGA, and is a Grant Investigator for the CARE Foundation and Merck and Co.; and Dr. Zuppa is supported by the following NIH Grants: National Institute of Child Health and Human Development Grants UG1HD063108 and 1R21HD093369, National Institute of General Medical Sciences Grant R01GM094203, National Heart Lung and Blood Institute UG3HL141736; as well as Department of Defense Grant W81XWH-17-1-0668, and Zelda Therapeutics. JCF, ASH, MDR, and NJT have no conflicts of interest that are directly relevant to the content of this article.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Fitzgerald, J.C., Zane, N.R., Himebauch, A.S. et al. Vancomycin Prescribing and Therapeutic Drug Monitoring in Children With and Without Acute Kidney Injury After Cardiac Arrest. Pediatr Drugs 21, 107–112 (2019). https://doi.org/10.1007/s40272-019-00328-8

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  • DOI: https://doi.org/10.1007/s40272-019-00328-8

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