European Journal of Pediatrics

, Volume 177, Issue 9, pp 1335–1342 | Cite as

Epinephrine versus dopamine in neonatal septic shock: a double-blind randomized controlled trial

  • Kishore Baske
  • Shiv Sajan SainiEmail author
  • Sourabh Dutta
  • Venkataseshan Sundaram
Original Article


We compared epinephrine and dopamine as a first-line vasoactive drug in 40 neonates (enrolled in two gestational age strata ≤ 306/7 and ≥ 310/7 weeks) with fluid-refractory septic shock. Epinephrine or dopamine was initiated at 0.2 or 10 μg/kg/min, respectively. If shock persisted after 15 min, epinephrine or dopamine was increased to 0.3 or 15 μg/kg/min, respectively (16–30 min), and thereafter to 0.4 or 20 μg/kg/min (31–45 min). Proportion of neonates achieving ‘reversal of shock’ (defined as systolic and diastolic BP > fifth centile and capillary filling time < 3 s and left ventricular output ≥ 150 mL/kg/min) by 45 min [5 (25%) vs 6 (30%), RR 0.83 (95% CI 0.30, 2.29)]; haemodynamic stability (shock reversal for ≥ 120 min without escalation of vasoactive drugs) anytime during therapy [10 (50%) vs 6 (30%), RR 1.67 (95% CI 0.75, 3.71)]; and all-cause mortality by 28 days [14 (70%) vs 16 (80%), RR 0.87 (95% CI 0.61, 1.26)] were comparable in the epinephrine and dopamine groups, respectively. On stratified analysis, we observed an interaction of gestational age strata with the group of allocation favouring epinephrine in neonates ≤ 306/7 weeks.

Conclusion: Epinephrine (0.2–0.4 μg/kg/min) and dopamine (10–20 μg/kg/min) had comparable efficacy and safety in neonatal septic shock.

Clinical Trial registry name and registration number: The study was registered with Clinical Trial Registry of India CTRI/2015/10/006285.

What is Known:

The choice of vasoactive drugs in neonatal septic shock is empirical and dopamine is the conventional first-line vasoactive drug.

There are no randomized controlled trials comparing dopamine and epinephrine in neonatal septic shock.

What is New:

In this study, epinephrine and dopamine had comparable efficacy and safety as a first-line vasoactive drug in management of neonatal septic shock.

On stratified analysis in a limited sample, epinephrine was associated with better outcomes in neonates ≤ 306/7 weeks.


Dopamine Epinephrine Neonate Septic shock Vasoactive agents 



Blood pressure


Bronchopulmonary dysplasia


Capillary filling time


Cardiac output


Clinical risk index for babies score


Diastolic blood pressure


Heart rate


Left ventricular output


Intra-ventricular haemorrhage


Necrotising enterocolitis


Retinopathy of prematurity


Systolic blood pressure


Systemic vascular resistance


Authors’ contributions

• Dr. Kishore Baske: designed the data collection instruments, enrolled the patients, collected the data, drafted the initial manuscript and approved the final manuscript as submitted.

• Dr. Shiv Sajan Saini: conceptualized and designed the study, coordinated and supervised data collection, performed functional echocardiography, performed the data analysis, reviewed and revised the manuscript and approved the final manuscript as submitted

• Dr. Sourabh Dutta: critically reviewed the manuscript and approved the final manuscript as submitted

• Venkataseshan Sundaram: coordinated and supervised data collection, reviewed and revised the manuscript and approved the final manuscript as submitted

Compliance with ethical standards

Conflict of interest

There is no potential, perceived, or real conflict of interest. The sponsor had no role in planning, conduct, analysis or publication of the study.

Research involving human participants and/or animals

Human participants.

Informed consent

Obtained from one of the parents of all neonates.


  1. 1.
    Barrington K, Chan W (1993) The circulatory effects of epinephrine infusion in the anesthesized piglet. Pediatr Res 33(2):190–194CrossRefPubMedGoogle Scholar
  2. 2.
    Chiesa C, Natale F, Pascone R, Osborn JF, Pacifico L, Bonci E, De Curtis M (2011) C reactive protein and procalcitonin: reference intervals for preterm and term newborns during the early neonatal period. Clin Chim Acta 412(11–12):1053–1059CrossRefPubMedGoogle Scholar
  3. 3.
    Davis AL, Carcillo JA, Aneja RK, Deymann AJ, Lin JC, Nguyen TC, Okhuysen-Cawley RS, Relvas MS, Rozenfeld RA, Skippen PW, Stojadinovic BJ, Williams EA, Yeh TS, Balamuth F, Brierley J, de Caen AR, Cheifetz IM, Choong K, Conway E Jr, Cornell T, Doctor A, Dugas MA, Feldman JD, Fitzgerald JC, Flori HR, Fortenberry JD, Graciano AL, Greenwald BM, Hall MW, Han YY, Hernan LJ, Irazuzta JE, Iselin E, van der Jagt EW, Jeffries HE, Kache S, Katyal C, Kissoon NT, Kon AA, Kutko MC, MacLaren G, Maul T, Mehta R, Odetola F, Parbuoni K, Paul R, Peters MJ, Ranjit S, Reuter-Rice KE, Schnitzler EJ, Scott HF, Torres A Jr, Weingarten-Abrams J, Weiss SL, Zimmerman JJ, Zuckerberg AL (2017) American College of Critical Care Medicine Clinical Practice Parameters for hemodynamic support of pediatric and neonatal septic shock. Crit Care Med 45(6):1061–1093CrossRefPubMedGoogle Scholar
  4. 4.
    de Waal K, Evans N (2010) Hemodynamics in preterm infants with late-onset sepsis. J Pediatr 156(6):918–922 22 e1CrossRefPubMedGoogle Scholar
  5. 5.
    Eriksen VR, Hahn GH, Greisen G (2014) Dopamine therapy is associated with impaired cerebral autoregulation in preterm infants. Acta Paediatr 103(12):1221–1226CrossRefPubMedGoogle Scholar
  6. 6.
    Evans N, Kluckow M (1996) Early determinants of right and left ventricular output in ventilated preterm infants. Arch Dis Child Fetal Neonatal Ed 74(2):F88–F94CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Ezaki S, Suzuki K, Kurishima C, Miura M, Moriwaki K, Arakawa H, Kunikata T, Sobajima H, Tamura M (2009) Levels of catecholamines, arginine vasopressin and atrial natriuretic peptide in hypotensive extremely low birth weight infants in the first 24 hours after birth. Neonatology 95(3):248–255CrossRefPubMedGoogle Scholar
  8. 8.
    Fowlie PW, Schmidt B (1998) Diagnostic tests for bacterial infection from birth to 90 days--a systematic review. Arch Dis Child Fetal Neonatal Ed 78(2):F92–F98CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Goldstein B, Giroir B, Randolph A (1995) International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 6(1):2–8CrossRefGoogle Scholar
  10. 10.
    Hatjis CG, McLaughlin MK (1982) Identification and ontogenesis of beta-adrenergic receptors in fetal and neonatal rabbit myocardium. J Dev Physiol 4(6):327–338PubMedGoogle Scholar
  11. 11.
    Investigators of the Delhi Neonatal Infection Study (DeNIS) collaboration (2016) Characterisation and antimicrobial resistance of sepsis pathogens in neonates born in tertiary care centres in Delhi, India: a cohort study. Lancet Glob Health 4(10):e752–e760CrossRefGoogle Scholar
  12. 12.
    Jobe AH, Bancalari E (2001) Bronchopulmonary dysplasia. Am J Respir Crit Care Med 163(7):1723–1729CrossRefPubMedGoogle Scholar
  13. 13.
    Kermorvant-Duchemin E, Laborie S, Rabilloud M, Lapillonne A, Claris O (2008) Outcome and prognostic factors in neonates with septic shock. Pediatr Crit Care Med 9(2):186–191CrossRefPubMedGoogle Scholar
  14. 14.
    Kim MY, Finch AM, Lumbers ER, Boyce AC, Gibson KJ, Eiby YA, Lingwood BE (2014) Expression of adrenoceptor subtypes in preterm piglet heart is different to term heart. PLoS One 9(3):e92167CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Levene ML, Kornberg J, Williams TH (1985) The incidence and severity of post-asphyxial encephalopathy in full-term infants. Early Hum Dev 11(1):21–26CrossRefPubMedGoogle Scholar
  16. 16.
    Li J, Zhang G, Holtby H, Humpl T, Caldarone CA, Van Arsdell GS, Redington AN (2006) Adverse effects of dopamine on systemic hemodynamic status and oxygen transport in neonates after the Norwood procedure. J Am Coll Cardiol 48(9):1859–1864CrossRefPubMedGoogle Scholar
  17. 17.
    Ma M, Noori S, Maarek JM, Holschneider DP, Rubinstein EH, Seri I (2015) Prone positioning decreases cardiac output and increases systemic vascular resistance in neonates. J Perinatol 35(6):424–427CrossRefPubMedGoogle Scholar
  18. 18.
    Mahoney L, Crook D, Walter KN, Sherman E, Rabe H (2012) What is the evidence for the use of adrenaline in the treatment of neonatal hypotension? Cardiovasc Hematol Agents Med Chem 10(1):50–98CrossRefPubMedGoogle Scholar
  19. 19.
    Noori S, Seri I (2012) Neonatal blood pressure support: the use of inotropes, lusitropes, and other vasopressor agents. Clin Perinatol 39(1):221–238CrossRefPubMedGoogle Scholar
  20. 20.
    Phillipos EZ, Barrington KJ, Robertson MA (1996) Dopamine versus epinephrine for inotropic support in the neonate: a randomized double blinded controlled trial. Pediatr Res 39:238AGoogle Scholar
  21. 21.
    Saini SS, Kumar P, Kumar RM (2014) Hemodynamic changes in preterm neonates with septic shock: a prospective observational study. Pediatr Crit Care Med 15(5):443–450CrossRefPubMedGoogle Scholar
  22. 22.
    Seri I (1995) Cardiovascular, renal, and endocrine actions of dopamine in neonates and children. J Pediatr 126(3):333–344CrossRefPubMedGoogle Scholar
  23. 23.
    Valverde E, Pellicer A, Madero R, Elorza D, Quero J, Cabanas F (2006) Dopamine versus epinephrine for cardiovascular support in low birth weight infants: analysis of systemic effects and neonatal clinical outcomes. Pediatrics 117(6):e1213–e1222CrossRefPubMedGoogle Scholar
  24. 24.
    Wynn JL, Wong HR (2010) Pathophysiology and treatment of septic shock in neonates. Clin Perinatol 37(2):439–479CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Zaidi AK, Huskins WC, Thaver D, Bhutta ZA, Abbas Z, Goldmann DA (2005) Hospital-acquired neonatal infections in developing countries. Lancet 65(9465):1175–1188CrossRefGoogle Scholar
  26. 26.
    Zubrow AB, Hulman S, Kushner H, Falkner B (1995) Determinants of blood pressure in infants admitted to neonatal intensive care units: a prospective multicenter study. Philadelphia neonatal blood pressure study group. J Perinatol 15(6):470–479PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Neonatology, Department of PediatricsPost Graduate Institute of Medical Education and ResearchChandigarhIndia

Personalised recommendations