Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Use of vasopressors for septic shock in the neonatal intensive care unit

Journal of Perinatology volume 43, pages 1274–1280 (2023)Cite this article

Subjects

Abstract

Objective

To describe outcomes for infants in the neonatal intensive care unit with septic shock based on the vasopressor administered.

Methods

This is a multicenter cohort study of infants with an episode of septic shock. We evaluated the primary outcomes of mortality and pressor-free days alive in the first week after shock using multivariable logistic and Poisson regressions.

Results

We identified 1592 infants. Mortality was 50%. Dopamine was the most used vasopressor (92% of episodes) and hydrocortisone was co-administered with a vasopressor in 38% of episodes. Compared to infants treated with dopamine alone, adjusted odds of mortality were significantly higher for those treated with epinephrine alone (aOR 4.7 [95% CI: 2.3–9.2]). Adjuvant hydrocortisone was associated with significantly lower adjusted odds of mortality (aOR 0.60 [0.42–0.86])

Conclusions

The use of epinephrine as either a solo agent or in combination therapy was associated with significantly worse outcomes, while adjuvant hydrocortisone was associated with decreased mortality.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Vasopressor use.

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

The computer code and Stata do-files used to generate the results of the manuscript are available from the corresponding author on reasonable request.

References

  1. Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, et al. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993–2012. JAMA. 2015;314:1039–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Cailes B, Kortsalioudaki C, Buttery J, Pattnayak S, Greenough A, Matthes J, et al. Epidemiology of UK neonatal infections: the neonIN infection surveillance network. Arch Dis Child Fetal Neonatal Ed. 2018;103:F547–53.

    Article  PubMed  Google Scholar 

  3. Wynn JL, Wong HR. Pathophysiology and treatment of septic shock in neonates. Clin Perinatol. 2010;37:439–79.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Burns ML, Stensvold HJ, Risnes K, Guthe HJ, Astrup H, Nordhov SM, et al. Inotropic therapy in newborns, a population-based national registry study. Pediatr Crit Care Med. 2016;17:948–56.

    Article  PubMed  Google Scholar 

  5. Tsai M-H, Hsu J-F, Chu S-M, Lien R, Huang H-R, Chiang M-C, et al. Incidence, clinical characteristics and risk factors for adverse outcome in neonates with late-onset sepsis. Pediatr Infect Dis J. 2014;33:e7–13.

    Article  PubMed  Google Scholar 

  6. McGovern M, Giannoni E, Kuester H, Turner MA, van den Hoogen A, Bliss JM, et al. Challenges in developing a consensus definition of neonatal sepsis. Pediatr Res. 2020;88:14–26.

    Article  PubMed  Google Scholar 

  7. Verstraete E, Boelens J, De Coen K, Claeys G, Vogelaers D, Vanhaesebrouck P, et al. Healthcare-associated bloodstream infections in a neonatal intensive care unit over a 20-year period (1992-2011): trends in incidence, pathogens, and mortality. Infect Control Hosp Epidemiol. 2014;35:511–8.

    Article  PubMed  Google Scholar 

  8. Fleiss N, Coggins SA, Lewis AN, Zeigler A, Cooksey KE, Walker LA, et al. Evaluation of the neonatal sequential organ failure assessment and mortality risk in preterm infants with late-onset infection. JAMA Netw Open. 2021;4:e2036518.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Baske K, Saini SS, Dutta S, Sundaram V. Epinephrine versus dopamine in neonatal septic shock: a double-blind randomized controlled trial. Eur J Pediatr. 2018;177:1335–42.

    Article  CAS  PubMed  Google Scholar 

  10. Kermorvant-Duchemin E, Laborie S, Rabilloud M, Lapillonne A, Claris O. Outcome and prognostic factors in neonates with septic shock. Pediatr Crit Care Med. 2008;9:186–91.

    Article  PubMed  Google Scholar 

  11. Weiss SL, Peters MJ, Alhazzani W, Agus MSD, Flori HR, Inwald DP, et al. Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Intensive Care Med. 2020;46:10–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ventura AMC, Shieh HH, Bousso A, Goes PF, Fernandes ICFO, de Souza DC, et al. Double-blind prospective randomized controlled trial of dopamine versus epinephrine as first-line vasoactive drugs in pediatric septic shock. Crit Care Med. 2015;43:2292–302.

    Article  CAS  PubMed  Google Scholar 

  13. Ramaswamy KN, Singhi S, Jayashree M, Bansal A, Nallasamy K. Double-blind randomized clinical trial comparing dopamine and epinephrine in pediatric fluid-refractory hypotensive septic shock. Pediatr Crit Care Med. 2016;17:e502–12.

    Article  PubMed  Google Scholar 

  14. Kharrat A, Jain A. Hemodynamic dysfunction in neonatal sepsis. Pediatr Res. 2022;91:413–24.

    Article  PubMed  Google Scholar 

  15. Miller LE, Laughon MM, Clark RH, Zimmerman KO, Hornik CP, Aleem S, et al. Vasoactive medications in extremely low gestational age neonates during the first postnatal week. J Perinatol. 2021;41:2330–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Spitzer AR, Ellsbury DL, Handler D, Clark RH. The Pediatrix BabySteps Data Warehouse and the Pediatrix QualitySteps improvement project system—tools for “meaningful use” in continuous quality improvement. Clin Perinatol. 2010;37:49–70.

    Article  PubMed  Google Scholar 

  17. Wynn JL, Polin RA. A neonatal sequential organ failure assessment score predicts mortality to late-onset sepsis in preterm very low birth weight infants. Pediatr Res. 2020;88:85–90.

    Article  PubMed  Google Scholar 

  18. Sassano-Higgins S, Friedlich P, Seri I. A meta-analysis of dopamine use in hypotensive preterm infants: blood pressure and cerebral hemodynamics. J Perinatol. 2011;31:647–55.

    Article  CAS  PubMed  Google Scholar 

  19. Valverde E, Pellicer A, Madero R, Elorza D, Quero J, Cabañas F. Dopamine versus epinephrine for cardiovascular support in low birth weight infants: analysis of systemic effects and neonatal clinical outcomes. Pediatrics. 2006;117:e1213–22.

    Article  PubMed  Google Scholar 

  20. Osborn D, Evans N, Kluckow M. Randomized trial of dobutamine versus dopamine in preterm infants with low systemic blood flow. J Pediatr. 2002;140:183–91.

    Article  CAS  PubMed  Google Scholar 

  21. Osborn DA, Paradisis M, Evans N. The effect of inotropes on morbidity and mortality in preterm infants with low systemic or organ blood flow. Cochrane Database Syst Rev. 2007;2007:CD005090.

    PubMed  PubMed Central  Google Scholar 

  22. Zimmerman K, Gonzalez D, Swamy GK, Cohen-Wolkowiez M. Pharmacologic studies in vulnerable populations: using the pediatric experience. Semin Perinatol. 2015;39:532–6.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Ibrahim H, Sinha IP, Subhedar NV. Corticosteroids for treating hypotension in preterm infants. Cochrane Database Syst Rev. 2011;2011:CD003662.

    PubMed  PubMed Central  Google Scholar 

  24. Crouchley JL, Smith PB, Cotton CM, Hornik CD, Goldberg RN, Foreman JW, et al. Effects of low-dose dopamine on urine output in normotensive very low birth weight neonates. J Perinatol. 2013;33:619–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Schmatz M, Srinivasan L, Grundmeier RW, Elci OU, Weiss SL, Masino AJ, et al. Surviving sepsis in a referral neonatal intensive care unit: association between time to antibiotic administration and in-hospital outcomes. J Pediatr. 2020;217:59–65.e1.

    Article  PubMed  Google Scholar 

  26. Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34:1589–96.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Erin Campbell, MS, provided editorial review and manuscript submission. Erin Campbell did not receive compensation for her assistance, apart from her employment at the institution where this research was conducted. Carol Hill, PhD, provided informatics assistance with data procurement from Pediatrix. The authors would like to thank Duke Pediatric Research Scholars.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA

    Henry P. Foote, Rachel G. Greenberg & Christoph P. Hornik

  2. Department of Economics, Clemson University, Clemson, SC, USA

    Daniel K. Benjamin

  3. Duke Clinical Research Institute, Durham, NC, USA

    Rachel G. Greenberg & Christoph P. Hornik

  4. Pediatrix Medical Group, Inc., Sunrise, FL, USA

    Reese H. Clark

Authors
  1. Henry P. Foote
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel K. Benjamin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rachel G. Greenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Reese H. Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christoph P. Hornik
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors made substantial contributions to the conception or design of the work, or the acquisition, analysis, or interpretation of data. HPF drafted the work, all authors revised it critically for important intellectual content. All authors approved the final version to be published and agree 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.

Corresponding author

Correspondence to Christoph P. Hornik.

Ethics declarations

Competing interests

RGG received support from the industry for research services (https://dcri.org/about-us/conflict-of-interest/). The authors have no other conflicts of interest relevant to this article to disclose.

Ethics approval and consent to participate

We obtained institutional review board approval from the Duke University Health System IRB with a waiver of informed consent for our study, protocol Pro00112607. The study was performed in accordance with the Declaration of Helsinki.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Foote, H.P., Benjamin, D.K., Greenberg, R.G. et al. Use of vasopressors for septic shock in the neonatal intensive care unit. J Perinatol 43, 1274–1280 (2023). https://doi.org/10.1038/s41372-023-01667-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-023-01667-8

Search

Advanced search

Quick links