title: Safety and Dose Escalation Study of Intravenous Zinc Supplementation in Pediatric Critical Illness.
abstract: Critically ill children have low plasma zinc (pZn), correlating with organ failure. Since Zn influences inflammation, immune function, and glucose control, Zn supplementation is a plausible therapeutic modality. We sought to determine a safe dose of intravenous (IV) Zn to restore pZn in critically ill children.
  
  
  
  Stepwise dose escalation study of IV Zn supplementation at a tertiary children's hospital. All children (<10 years) admitted to the pediatric intensive care unit with a Pediatric Risk of Mortality III score >5, or ≥1 new organ failure were eligible. After consent, patients were sequentially enrolled into 4 dosing groups: (1) no zinc, (2) Zn250: 250 mcg/kg/d ZnSO4, (3) Zn500: 500 mcg/kg/d ZnSO4, or (4) Zn750: 750 mcg/kg/d ZnSO4 ZnSO4 was administered 3 times daily for 7 days. pZn was measured at baseline, end of first ZnSO4 infusion, 1 hour postinfusion, and 7 hours postinfusion on day 1, then daily through days 2-7. Interleukin-6 (IL-6), C-reactive protein (CRP), and lymphocyte subsets were measured on days 1 and 3. Glucose was measured 3 times daily for 7 days.
  
  
  
  Twenty-four patients were enrolled. Baseline demographics were similar among groups. Baseline pZn was low in all patients (mean [SD], 41.8 [16.0] mcg/dL). pZn increased over the study period in supplemented groups; however, mean pZn in the Zn750 group exceeded the 50th percentile. pZn was not associated with IL-6, CRP, or lymphocyte subsets among groups. Degree of hyperglycemia did not differ among groups. No patient had a study-related adverse event.
  
  
  
  IV zinc supplementation at 500 mcg/kg/d restores pZn to near the 50th percentile and is well tolerated.
authors.affiliation: Division of Critical Care, Children's Hospital and Research Center Oakland, Oakland, California, USA NCvijanovich@mail.cho.org.
authors.forename: Natalie Z
authors.initials: NZ
authors.lastname: Cvijanovich
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California, USA.
authors.forename: Janet C
authors.initials: JC
authors.lastname: King
authors.affiliation: Division of Critical Care, Children's Hospital and Research Center Oakland, Oakland, California, USA.
authors.forename: Heidi R
authors.initials: HR
authors.lastname: Flori
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California, USA.
authors.forename: Ginny
authors.initials: G
authors.lastname: Gildengorin
authors.affiliation: Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Vinks
authors.affiliation: Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA Division of Critical Care, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Hector R
authors.initials: HR
authors.lastname: Wong
mesh_terms: D061605:Administration, Intravenous; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness / Q000628:therapy*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D015278:Intensive Care Units, Pediatric; D008297:Male; D010372:Pediatrics; D011446:Prospective Studies; D015032:Zinc / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood
chemical_list: D015032:Zinc
keywords: critical illness; hyperglycemia; inflammation; lymphopenia; pediatrics; zinc