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Optimising insulin aspart practices in a neonatal intensive care unit: a clinical and pharmaco-technical study

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Abstract

Neonatal hyperglycaemia is frequent and requires insulin therapy. To resolve the difficulties encountered by paediatricians in stabilising glycaemia, the preparation and administration of insulin aspart were assessed and optimised. After high-performance liquid chromatography (HPLC-UV) assessment of insulin aspart preparations made according to the old protocol, a new protocol was drawn up. Dosage reliability of solutions prepared by paediatric nurses was evaluated by HPLC-UV. This new protocol was also tested in a Y-infusion situation and the need to saturate infusion tubes assessed. Wide deviations in insulin aspart concentrations were found between theoretical concentrations and preparations made according to the old protocol. Glycated insulin aspart was found in the majority of these preparations. The new protocol significantly reduced the variability of data and relative deviations around the target value. It also eliminated the formation of glycated insulin even in the case of co-infusion of parenteral nutrition and confirmed the need to saturate infusion tubes.

Conclusion: The revision of the insulin therapy protocol reduced the variability of insulin concentration in preparations and avoided the administration of glycated derivatives potentially toxic for neonates.

What is Known:

• Insulin preparation in NICUs is a risky task because it is a two-step preparation

• Diluted in dextrose, insulin aspart is unstable, with formation of potentially toxic glycated derivatives

What is New:

• This work proposes a new insulin therapy protocol validated by HPLC-UV for NICU allowing suppression of the formation of glycated insulin, to significantly reduce deviations from theoretical concentrations and to limit adsorption phenomena

• This protocol is validated in case of co-infusion of parenteral nutrition

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Data availability

Data and materials are not in a public depository and are available upon request.

Code availability

N/A

Abbreviations

D5%:

Dextrose

D50%:

50% dextrose

HPLC-UV:

High-performance liquid chromatography

IPN:

Individualised parenteral nutrition

NICUs:

Neonatal intensive care units

Q1:

1st quartile

Q3:

3rd quartile

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Acknowledgements

We thank Alexandra Tavernier (M.A. University of Glasgow, Professeur Agrégée, France) for English language and editing assistance.

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Authors and Affiliations

  1. ULR 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, University of Lille, CHU Lille, F-59000, Lille, France

    Laure-Hélène Préta, Stéphanie Genay, Natacha Carta, Pascal Odou & Bertrand Décaudin

  2. Institut de Pharmacie, CHU Lille, F-59000, Lille, France

    Laure-Hélène Préta, Stéphanie Genay, Cécile Malat, Pascal Odou & Bertrand Décaudin

  3. Hôpital Jeanne de Flandre, Département de néonatologie, CHU Lille, F-59000, Lille, France

    Mohamed Riadh Boukhris, Julie Verspieren & Laurent Storme

  4. ULR 4489 - Environnement Périnatal et Santé, University of Lille, F-59000, Lille, France

    Laurent Storme

Authors
  1. Laure-Hélène Préta
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  2. Stéphanie Genay
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  3. Cécile Malat
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  4. Natacha Carta
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  5. Mohamed Riadh Boukhris
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  6. Julie Verspieren
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  7. Pascal Odou
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  8. Laurent Storme
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  9. Bertrand Décaudin
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Contributions

All the authors made substantial contributions to conception and design of the study and/or acquisition of data and/or analysis and interpretation of data; all the authors participated in drafting or critically revising the manuscript; all the authors gave final approval of the version submitted.

• Conducted the study and carried out the experiments, acquired and analysed the data and drafted the first version of the manuscript: Laure-Hélène Préta

• Supervised the work by contributing to design of the study, interpreting the data and revising the manuscript: Stéphanie Genay, Pascal Odou, Laurent Storme and Bertrand Décaudin

• Assisted in data collection and contributed to the development and execution of the analyses and revised the manuscript: Cécile Malat and Natacha Carta

• Participated in the development of the protocol and interpretation of the data and revised the manuscript: Mohamed Riadh Boukhris and Julie Verspieren

• Approved the final manuscript version: all the authors

Corresponding author

Correspondence to Laure-Hélène Préta.

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Conflict of interest

The authors declare no competing interests.

Additional information

Communicated by Daniele De Luca

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Supplementary information

ESM 1

Representation of the infusion set-up performed with the medical devices detailed in Suppl mat 2 (PNG 243 kb)

High resolution image (TIFF 1872 kb)

ESM 2

Medical devices used in infusion set-up (PDF 226 kb)

ESM 3

Regression parameters of the validation method for the range. The given parameters are: a (the slope of the line), b (the intercept at the origin) in mean value ± standard deviation and R2 (the coefficient of determination). The limits of detection (LOD) and quantification (LOQ) are expressed in μg/mL for phenol and metacresol and U/mL for insulin (DOCX 12 kb)

ESM 4

New protocol for the preparation and administration of insulin aspart in NICUs. Changes from the previous protocol are highlighted in red boxes. (PDF 61 kb)

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Préta, LH., Genay, S., Malat, C. et al. Optimising insulin aspart practices in a neonatal intensive care unit: a clinical and pharmaco-technical study. Eur J Pediatr 180, 2985–2992 (2021). https://doi.org/10.1007/s00431-021-04041-y

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  • DOI: https://doi.org/10.1007/s00431-021-04041-y

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