Pediatric Drugs

, Volume 19, Issue 5, pp 487–495 | Cite as

Understanding the Stability of Dopamine and Dobutamine Over 24 h in Simulated Neonatal Ward Conditions

  • Katherine Kirupakaran
  • Liam Mahoney
  • Heike Rabe
  • Bhavik A. Patel
Original Research Article

Abstract

Objectives

Our objectives were to investigate the possible effects of temperature and light on the stability of dopamine and dobutamine continuous infusions over 24 h when prepared in a variety of dilution vehicles.

Methods

Syringe-driver infusion apparatuses were set up for dopamine and dobutamine diluted with either 0.9% sodium chloride (NaCl) or 5% glucose delivering 3 and 5 μg/kg/min, respectively, via 206-cm extension sets. All infusions were prepared for a neonate weight of 1 kg. Infusions were run over 24 h with approximately half the tubing within an incubator set at 35 °C. Cyclic voltammetry was used to monitor the concentration of the inotrope within the syringe and at the end of the extension set, both initially and after 24 h.

Results

The variation in the concentration of dopamine and dobutamine in the vials (n = 6) was 3.58 and 1.22%, respectively. This variation increased to 10.88% for dopamine and 5.76% for dobutamine in the syringe. After 24 h, a significant reduction in the concentration of dopamine was observed at the end of the extension set when prepared in 0.9% NaCl versus 5% glucose (p < 0.001; n = 6–7) and in dobutamine when prepared in 0.9% NaCl (p < 0.001; n = 6–7). No differences in the concentration of dopamine prepared in 0.9% NaCl were observed after 24 h in light-exposed and light-protected extension sets (n = 6–7).

Conclusions

Dobutamine is more stable in dilution vehicles than dopamine, and inotropes are more stable in the 5% glucose dilution vehicle than in 0.9% NaCl. Such findings will provide guidance on the choice of inotropes.

Notes

Acknowledgements

The authors thank the nursing staff of the Department of Neonatology, Brighton and Sussex University Hospitals, for the valuable advice on the practical part of the study.

Author contributions

Data collection, analysis, and interpretation were conducted by KK. Data interpretation and conception or design of the study was conducted by LM, HR, and BAP. The manuscript was drafted by BAP, with revision for important intellectual content and final approval of the version to be published provided by KK, LM, and HR.

Compliance with Ethical Standards

Funding

The study was partly supported by FP7-HEALTH Grant No. 282533 NEO-CIRCulation.

Conflict of interest

Katherine Kirupakaran, Liam Mahoney, Heike Rabe, and Bhavik A. Patel have no conflicts of interest that might be relevant to the contents of this manuscript.

References

  1. 1.
    Mattia FR. Chronic physiologic instability is associated with neurodevelopmental morbidity at one and two years in extremely premature infants. Pediatrics. 1998;102(3):e35.CrossRefPubMedGoogle Scholar
  2. 2.
    Patwardhan K. Inotropes in term neonates. Infant. 2009;5(1):12.Google Scholar
  3. 3.
    Paradisis M, Osborn DA. Adrenaline for prevention of morbidity and mortality in preterm infants with cardiovascular compromise. Cochrane Database Syst Rev. 2004;(1):CD003958. doi:10.1002/14651858.CD003958.pub2.
  4. 4.
    Seri I, Evans J. Controversies in the diagnosis and management of hypotension in the newborn infant. Curr Opin Pediatr. 2001;13(2):116–23.CrossRefPubMedGoogle Scholar
  5. 5.
    Mahoney L, Crook D, Walter KN, Sherman E, Rabe H. What is the evidence for the use of adrenaline in the treatment of neonatal hypotension? Cardiovasc Hematol Agents Med Chem. 2012;10(1):50–98.CrossRefPubMedGoogle Scholar
  6. 6.
    Mahoney L, Shah G, Crook D, Rojas-Anaya H, Rabe H. A literature review of the pharmacokinetics and pharmacodynamics of dobutamine in neonates. Pediatr Cardiol. 2016;37(1):14–23.CrossRefPubMedGoogle Scholar
  7. 7.
    Lasky T, Greenspan J, Ernst FR, Gonzalez L. Dopamine and dobutamine use in preterm or low birth weight neonates in the premier 2008 database. Clin Ther. 2011;33(12):2082–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Volpe JJ. Intraventricular hemorrhage in the premature infant—current concepts. Part I. Ann Neurol. 1989;25(1):3–11.CrossRefPubMedGoogle Scholar
  9. 9.
    Tsuji M, Saul JP, du Plessis A, Eichenwald E, Sobh J, Crocker R, et al. Cerebral intravascular oxygenation correlates with mean arterial pressure in critically ill premature infants. Pediatrics. 2000;106(4):625–32.CrossRefPubMedGoogle Scholar
  10. 10.
    O’Leary H, Gregas MC, Limperopoulos C, Zaretskaya I, Bassan H, Soul JS, et al. Elevated cerebral pressure passivity is associated with prematurity-related intracranial hemorrhage. Pediatrics. 2009;124(1):302–9.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Bhatt-Mehta V, Nahata M. Stability of dopamine hydrochloride injection in the presence of dobutamine hydrochloride, tolazoline hydrochloride, and theophylline injections. J Perinatol. 1990;10(2):129–33.PubMedGoogle Scholar
  12. 12.
    Grillo JA, Gonzalez ER, Ramaiya A, Karnes HT, Wells B. Chemical compatibility of inotropic and vasoactive agents delivered via a multiple line infusion system. Crit Care Med. 1995;23(6):1061–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Allen EM, Van Boerum DH, Olsen AF, Dean JM. Difference between the measured and ordered dose of catecholamine infusions. Ann Pharmacother. 1995;29(11):1095–100.CrossRefPubMedGoogle Scholar
  14. 14.
    Patel N, Taki M, Tunstell P, Forsey P, Forbes B. Stability of dobutamine 500 mg in 50 ml syringes prepared using a Central Intravenous Additive Service. Eur J Hosp Pharm Sci Pract. 2012;19(1):52–6.CrossRefGoogle Scholar
  15. 15.
    Allwood M. The stability of four catecholamines in 5% glucose infusions. J Clin Pharm Ther. 1991;16(5):337–40.CrossRefPubMedGoogle Scholar
  16. 16.
    Braenden J, Stendal T, Fagernaes C. Stability of dopamine hydrochloride 0.5 mg/mL in polypropylene syringes. J Clin Pharm Ther. 2003;28(6):471–4.CrossRefPubMedGoogle Scholar
  17. 17.
    British Medical Association and Royal Pharmaceutical Society of Great Britain. British National Formulary for children. London: BMJ Group; 2009.Google Scholar
  18. 18.
    British Pharmacopoeia Commission. British Pharmacopoeia 2016. London: The Stationery Office Ltd.; 2016.Google Scholar
  19. 19.
    Bullock J, Jordan D, Gawlinski A, Henneman EA. Standardizing IV infusion medication concentrations to reduce variability in medication errors. Crit Care Nurs Clin North Am. 2006;18(4):515–21.CrossRefPubMedGoogle Scholar
  20. 20.
    Moyen E, Camiré E, Stelfox HT. Clinical review: medication errors in critical care. Crit Care. 2008;12(2):1.CrossRefGoogle Scholar
  21. 21.
    Roberts NB, Higgins G, Sargazi M. A study on the stability of urinary free catecholamines and free methyl-derivatives at different pH, temperature and time of storage. Clin Chem Lab Med. 2010;48(1):81–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Barros DP, Fonseca FLA, Pedreira MDLG, Peterlini MAS. Hydrogen profiles of dobutamine hydrochloride and fentanyl citrate solutions according to intravenous administration systems, temperature, and luminosity conditions. J Infus Nurs. 2014;37(5):362–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Dandurand K, Stennett D. Stability of dopamine hydrochloride exposed to blue-light phototherapy. Am J Health Syst Pharm. 1985;42(3):595–7.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Katherine Kirupakaran
    • 1
  • Liam Mahoney
    • 1
    • 2
  • Heike Rabe
    • 1
    • 2
  • Bhavik A. Patel
    • 3
  1. 1.Brighton and Sussex Medical SchoolBrightonUK
  2. 2.Department of NeonatologyBrighton and Sussex University Hospital NHS TrustBrightonUK
  3. 3.School of Pharmacy and Biomolecular SciencesUniversity of BrightonBrightonUK

Personalised recommendations