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Physical compatibility of alprostadil with selected drugs commonly used in the neonatal intensive care units

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Abstract

This study aimed to determine the physical compatibility of alprostadil with 17 continuous infusion drugs commonly administered in neonatal intensive care units. Test samples were prepared in a laminar airflow hood. Alprostadil 20 mcg/ml was mixed with each drug in a 1:1 ratio, in two orders of mixing. Physical stability of the admixtures was assessed by visual examination and by measuring turbidity. Visual examination was conducted by two observers by two methods: visual examination against a black and white background under normal fluorescent light and using a high-intensity monodirectional light. pH was measured as chemical stability predictor. Evaluations were performed immediately and 4 h after mixing. An additional visual control was performed at 24 h. Visual examination was positive or doubtful for the four drug combinations not considered compatible. Turbidity values were under 0.5 NTU throughout the study in all samples. No modifications of one pH unit or more was detected in any drug pair over time.

Conclusion: Alprostadil was considered physical compatible with 13 drugs (adrenalin, amiodarone, calcium gluconate, dobutamine, dopamine, fentanyl, flecainide, furosemide, heparin, ketamine, midazolam, milrinone and morphine). Incompatibility could not be ruled out for 3 drugs (cisatracurium, dexmedetomidine and noradrenalin), and insulin was considered incompatible with alprostadil.

What is Known:

• Y-site administration is common in neonatal intensive care units, and volume of diluents and rate of infusions in newborns were lower than in adults which might result in high concentrations and prolonged contact time at Y-site administration.

• Available data about compatibility of alprostadil with other drugs was scarce.

What is New:

• Alprostadil was compatible with 13 drugs commonly used in neonatal intensive care units.

• Insulin was considered incompatible with alprostadil, and incompatibility cannot be ruled out for cisatracurium, dexmedetomidine and noradrenalin with alprostadil.

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Data availability

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

Abbreviations

IV:

Intravenous

NTU:

Nephelometric turbidity unit

NICUs:

Neonatal intensive care units

References

  1. Alprostadil 500 mcg/ml ampoule Product Information, Laboratory Pfizer, June 2019. Available at: https://cima.aemps.es/cima/dochtml/ft/56120/FT_56120.html. Accessed October 2020

  2. Kalikstad B, Skjerdal Å, Hansen TWR (2010) Compatibility of drug infusions in the NICU. Arch Dis Child 95:745–748. https://doi.org/10.1136/adc.2009.174268

    Article  PubMed  Google Scholar 

  3. Trissel LA (2011) Drug stability and compatibility issues in drug delivery. In: ASHP (ed) Handbook on injectable drugs, 11th edn, pp 17–22

    Google Scholar 

  4. Staven V, Wang S, Grønlie I, Tho I (2016) Development and evaluation of a test program for Y-site compatibility testing of total parenteral nutrition and intravenous drugs. Nutr J 15:1–18. https://doi.org/10.1186/s12937-016-0149-x

    Article  CAS  Google Scholar 

  5. Walter WV, Trissel LA, Baker MB et al (2008) Compatibility of medications with 3-in-1 parenteral nutrition admixtures. J Parenter Enter Nutr 23:67–74. https://doi.org/10.1177/014860719902300267

    Article  Google Scholar 

  6. Leopoldino RW, Costa HT, Costa TX, Martins RR, Oliveira AG (2018) Potential drug incompatibilities in the neonatal intensive care unit: a network analysis approach. BMC Pharmacol Toxicol 19:1–6. https://doi.org/10.1186/s40360-018-0265-7

    Article  CAS  Google Scholar 

  7. Kanji S, Lam J, Johanson C, Singh A, Goddard R, Fairbairn J, Lloyd T, Monsour D, Kakal J (2010) Systematic review of physical and chemical compatibility of commonly used medications administered by continuous infusion in intensive care units. Crit Care Med 38:1890–1898. https://doi.org/10.1097/CCM.0b013e3181e8adcc

    Article  CAS  PubMed  Google Scholar 

  8. D’Huart E, Vigneron J, Demoré B (2019) Physical compatibility of intravenous drugs commonly used in intensive care units: an observational study and physical compatibility laboratory tests on anti-infective drugs. Pharm Technol Hosp Pharm 4:29–40. https://doi.org/10.1515/pthp-2019-0005

    Article  Google Scholar 

  9. Langille SE (2013) Particulate matter in injectable drug products. PDA J Pharm Sci Technol 67:186–200. https://doi.org/10.5731/pdajpst.2013.00922

    Article  CAS  PubMed  Google Scholar 

  10. Benlabed M, Perez M, Gaudy R, Genay S, Lannoy D, Barthélémy C, Odou P, Lebuffe G, Décaudin B (2019) Clinical implications of intravenous drug incompatibilities in critically ill patients. Anaesth Crit Care Pain Med 38:173–180. https://doi.org/10.1016/j.accpm.2018.04.003

    Article  PubMed  Google Scholar 

  11. Doessegger L, Mahler HC, Szczesny P, Rockstroh H, Kallmeyer G, Langenkamp A, Herrmann J, Famulare J (2012) The potential clinical relevance of visible particles in parenteral drugs. J Pharm Sci 101:2635–2644. https://doi.org/10.1002/jps.23217

    Article  CAS  PubMed  Google Scholar 

  12. Dice JE (2006) Physical compatibility of alprostadil with commonly used IV solutions and medications in the neonatal intensive care unit. J Pediatr Pharmacol Ther 11:233–236. https://doi.org/10.5863/1551-6776-11.4.233

    Article  PubMed  PubMed Central  Google Scholar 

  13. De Basagoiti A, Fernández A, Mendiola S et al (2019) Intravenous drug use in neonatal intensive care units. Eur J Hosp Pharm 1–5. https://doi.org/10.1136/ejhpharm-2019-001939

  14. De Basagoiti A, Antón X, Calleja A et al (2020) Analysis of standard concentrations of continuous infusions in nine Spanish neonatal intensive care units. Eur J Hosp Pharm 1–5. https://doi.org/10.1136/ejhpharm-2019-002194

  15. Newton DW (2009) Drug incompatibility chemistry. Am J Heal Pharm 66:348–357. https://doi.org/10.2146/ajhp080059

    Article  CAS  Google Scholar 

  16. Allen LV, Levinson RS, Phisutsinthop D (1977) Compatibility of various admixtures with secondary additives at Y-injection sites of intravenous administration sets. Am J Heal Pharm 34:939–943

    Article  CAS  Google Scholar 

  17. Staven V, Wang S, Grønlie I, Tho I (2018) Physical stability of an all-in-one parenteral nutrition admixture for preterm infants upon mixing with micronutrients and drugs Eur J Hosp Pharm ejhpharm-2018-001562. https://doi.org/10.1136/ejhpharm-2018-001562

  18. Trissel LA, Martinez JF (1993) Physical compatibility of melphalan with selected drugs during Y-site administration. Am J Heal Pharm 50:2359–2363

    Article  CAS  Google Scholar 

  19. Nemec K, Kopelent-Frank H, Greif R (2008) Standardization of infusion solutions to reduce the risk of incompatibility. Am J Heal Pharm 65:1648–1654. https://doi.org/10.2146/ajhp070471

    Article  Google Scholar 

  20. Monogue ML, Almarzoky Abuhussain SS, Kuti JL, Nicolau DP (2018) Physical compatibility of fosfomycin for injection with select i.v. drugs during simulated Y-site administration. Am J Heal Pharm 75:e36–e44. https://doi.org/10.2146/ajhp170123

    Article  Google Scholar 

  21. Foushee JA, Fox LM, Gormley LR, Lineberger MS (2015) Physical compatibility of cisatracurium with selected drugs during simulated Y-site administration. Am J Heal Pharm 72:483–486. https://doi.org/10.2146/ajhp140165

    Article  CAS  Google Scholar 

  22. Bardin C, Astier A, Vulto A et al (2012) Guidelines for the practical stability studies of anticancer drugs: A european consensus conference. Eur J Hosp Pharm 19:278–285. https://doi.org/10.1136/ejhpharm-2012-000112

    Article  Google Scholar 

  23. Siu E, Sadasivam K, Christiansen N (2016) Creating and auditing a new electronic continuous infusion prescription chart for a paediatric critical care unit. Arch Dis Child 101:e2. https://doi.org/10.1136/archdischild-2016-311535.3

    Article  PubMed  Google Scholar 

  24. Staven V, Waaseth M, Wang S, Gronlie I, Tho I (2015) Utilization of the Tyndall effect for enhanced visual detection of particles in compatibility testing of intravenous fluids: validity and reliability. PDA J Pharm Sci Technol 69:270–283. https://doi.org/10.5731/pdajpst.2015.01020

    Article  PubMed  Google Scholar 

  25. Veggeland T, Brandl M (2010) Study of a simple method for visual detection of microprecipitates in blends of parenteral drug solutions using a focussed (Tyndall) light beam. Int J Pharm Compd 14:78–81

    PubMed  Google Scholar 

  26. Trissel LA (2014) Alprostadil monography. In: ASHP (ed) Handbook on injectable drugs, 18th edn, pp 25–26

    Google Scholar 

  27. Greenhill K, Hornsby E, Gorman G (2019) Investigations of physical compatibilities of commonly used intravenous medications with and without parenteral nutrition in pediatric cardiovascular intensive care unit patients. Pharmaceuticals 12:1–9. https://doi.org/10.3390/ph12020067

    Article  CAS  Google Scholar 

  28. Staven V, Iqbal H, Wang S, Grønlie I, Tho I (2017) Physical compatibility of total parenteral nutrition and drugs in Y-site administration to children from neonates to adolescents. J Pharm Pharmacol 69:448–462. https://doi.org/10.1111/jphp.12647

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We wish to thank M Urrutia and C Olalde (Hospital Universitario Araba), A Aguirre (Hospital Universitario Basurto), E Guerra and B Loureiro (Hospital Universitario Cruces) and A Montoro (Hospital Universitario Donostia) for their contribution in the drugs and their administration condition selection and by answering the initial survey. We would also like to express our gratitude to I Tho and their research group in the University of Oslo for sharing their knowledge and experience in stability studies which has contributed to improve this work.

Funding

Financial support was obtained for research projects of the Department of Health of the Basque Government: physical stability study of alprostadil with Y-site-administrated drugs in neonatal intensive care units: code 2018111014; 2018–2020. This work was supported by the Maternal and Child Health and Development Research Network (SAMID), RETICS funded by the PN I+D+I 2013–2016 (Spain), ISCIII-Sub-Directorate General for Research Assessment and Promotion and the European Regional Development Fund (ERDF), ref. RD16/0022.

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Authors and Affiliations

  1. Biocruces Bizkaia Health Research Institute, Pharmacotherapy and Drug Safety Group, Barakaldo, Bizkaia, Spain

    Amaya De Basagoiti, Alberto Katsumiti, Monike De Miguel & Ainara Campino

  2. Osakidetza Basque Health Service, Cruces University Hospital, Department of Hospital Pharmacy, Barakaldo, Bizkaia, Spain

    Amaya De Basagoiti, Silvia Abascal, Leocadio R. López-Giménez, Pilar Pascual, Monike De Miguel & Ainara Campino

  3. Biocruces Bizkaia Health Research Institute, Barakaldo, Bizkaia, Spain

    Alazne Bustinza

Authors
  1. Amaya De Basagoiti
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  2. Alberto Katsumiti
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  3. Silvia Abascal
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  4. Alazne Bustinza
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  6. Pilar Pascual
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  7. Monike De Miguel
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  8. Ainara Campino
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Contributions

All authors made substantial contributions to conception and design of the study, and/or acquisition of data and/or analysis and interpretation of data; all authors participated in drafting or critically revising the manuscript for important intellectual content; all authors gave final approval of the version submitted; and all authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Conceived the idea and developed the project: Amaya de Basagoiti (AdB) and Ainara Campino (AC)

Designed the study protocol: AdB, AC and Alberto Katsumiti (AK)

Prepared the study samples and collected the related data: AdB, AK, AC, Alazne Bustinza (AB), Silvia Abascal (SA), Pilar Pascual (PP)

Conducted the experimental studies in laboratory and collected the data: AdB, AC, AK, AB, Leocadio R López-Giménez (LRL) and Monike de Miguel (MdM)

Analysed and interpreted the results: AdB, AC, AK

Wrote the manuscript: AdB

Reviewed the manuscript drafts and approved the final version: AC

Approved the final manuscript version: all authors

Corresponding author

Correspondence to Ainara Campino.

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De Basagoiti, A., Katsumiti, A., Abascal, S. et al. Physical compatibility of alprostadil with selected drugs commonly used in the neonatal intensive care units. Eur J Pediatr 180, 1169–1176 (2021). https://doi.org/10.1007/s00431-020-03854-7

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  • DOI: https://doi.org/10.1007/s00431-020-03854-7

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