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. 2016 Aug;40(6):860-8.
doi: 10.1177/0148607115572193. Epub 2015 Feb 19.

Safety and Dose Escalation Study of Intravenous Zinc Supplementation in Pediatric Critical Illness

Natalie Z Cvijanovich  1 , Janet C King  2 , Heidi R Flori  3 , Ginny Gildengorin  2 , Alexander A Vinks  4 , Hector R Wong  5
Affiliations

Safety and Dose Escalation Study of Intravenous Zinc Supplementation in Pediatric Critical Illness

Natalie Z Cvijanovich et al. JPEN J Parenter Enteral Nutr. 2016 Aug.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: IV zinc supplementation at 500 mcg/kg/d restores pZn to near the 50th percentile and is well tolerated.

Keywords: critical illness; hyperglycemia; inflammation; lymphopenia; pediatrics; zinc.

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Figures

Figure 1
Figure 1
Mean plasma Zn and Cu concentrations over time. A. Plasma zinc (pZn) concentration by group. Single horizontal line represents 50th percentile (75 μg/dL) Day 1 to Day 7 change: *No Zn, p=0.54; **Zn250, p=0.01; #Zn500, p=0.03; ##Zn750, p<0.001 B. Plasma copper (pCu) concentration by group. Single horizontal line represents 50th percentile (65 μg/dL). Day 1 to Day 7 change *p=0.03; **NS=not significant
Figure 1
Figure 1
Mean plasma Zn and Cu concentrations over time. A. Plasma zinc (pZn) concentration by group. Single horizontal line represents 50th percentile (75 μg/dL) Day 1 to Day 7 change: *No Zn, p=0.54; **Zn250, p=0.01; #Zn500, p=0.03; ##Zn750, p<0.001 B. Plasma copper (pCu) concentration by group. Single horizontal line represents 50th percentile (65 μg/dL). Day 1 to Day 7 change *p=0.03; **NS=not significant
Figure 2
Figure 2
Median daily glucose homeostasis score (GHOS) by study group. Higher number indicates greater degree of hyperglycemia. *p=0.08 for change in score among groups
Figure 3
Figure 3
Pharmacokinetic profiles of a representative patient from each supplemented study group. Dashed horizontal lines represent 2.5th, 50th, and 97.5th percentile [pZn]. Open circles represent specific time points of measurement. A. Zn250 patient; B. Zn 500 patient; C. Zn750 patient. Note: Scale in C has been widened to optimize graph
See this image and copyright information in PMC

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