Epinephrine and Norepinephrine in the Hypotensive Newborn

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Epinephrine or norepinephrine in the hypotensive newborn? A clinician's guide to choosing by the lesion — the failing pump versus the dilated circulation — with the doses, risks and evidence.

Neonatal Haemodynamics Vasoactive Pharmacology

When dopamine and volume aren’t enough, the choice comes down to two catecholamines — epinephrine and norepinephrine. Same family, very different jobs. Choosing well means treating the physiology, not the number on the monitor.

The bottom line

Match the drug to the lesion. Epinephrine is the inotrope-plus-pressor for a failing pump (cold shock, myocardial depression); norepinephrine is the selective vasopressor for a dilated circulation (warm shock). Define whether the problem is pump or tone before you reach for either.

01 Two catecholamines, two profiles

Both are endogenous catecholamines acting directly on adrenergic receptors, but their receptor selectivity sets them apart at the bedside.

Epinephrine (adrenaline)Non-selective α1, α2, β1, β2 — dose-dependent
  • Low dose<0.1 µg/kg/min — predominantly a β-mediated inotrope: ↑ contractility, stroke volume and heart rate2
  • Higher dose>0.1 µg/kg/min — recruits α1 vascular receptors: potent vasoconstriction, ↑ SVR and blood pressure3
  • Best forThe failing pump — cold shock, myocardial depression
Norepinephrine (noradrenaline)Selective α1, moderate β1, negligible β2
  • ActionPredominantly a vasopressor: ↑ SVR and systolic BP with little direct effect on heart rate or cardiac output3,2
  • Lung bedMay act as a pulmonary vasodilator where basal pulmonary tone is high, e.g. sepsis with PPHN5,6
  • Best forThe dilated circulation — warm, vasodilatory shock
The afterload caveat. If contractility is already severely impaired, norepinephrine alone raises left-ventricular afterload and myocardial oxygen demand, which can worsen an unsupported ventricle. At very high epinephrine doses (a commonly cited threshold is >0.5 µg/kg/min), excessive vasoconstriction can paradoxically reduce cardiac output and increase ventricular wall stress (expert consensus).

02 Choose by the lesion, not the number

Selecting between these potent agents means defining the exact cardiovascular pathology rather than treating a blood-pressure value.

Warm shock (vasodilated)

Low SVR, high output. After volume and a first inotrope, norepinephrine is added to restore lost systemic vascular resistance.5,2

Cold shock (poor contractility)

Low output, myocardial depression. Epinephrine is favoured for its direct inotropic action; paediatric guidance starts adrenaline and shifts to noradrenaline if shock is vasodilatory.5

HIE & cardiogenic shock

After perinatal asphyxia with myocardial depression, epinephrine is a potent rescue to restore contractility. Avoid where there is dynamic outflow obstruction (HOCM) (expert consensus).

PPHN with dysfunction

Epinephrine can support a failing right ventricle, but use it cautiously in the severely hypoxaemic infant — its α effects can raise pulmonary vascular resistance and worsen right-to-left shunting.2

The de-escalation strategy. In paediatric intensive care, clinicians often add low-dose norepinephrine (around 0.02–0.05 µg/kg/min) once epinephrine climbs past 0.1–0.2 µg/kg/min — supporting both ventricular performance and SVR while allowing epinephrine to be weaned to limit its tachycardic and metabolic cost (expert consensus).

03 The price of potency — metabolic & structural risks

Both agents are powerfully vasoactive and carry real cost, which is a large part of why they are held in reserve.

Epinephrine & metabolism

Strongly linked to hyperglycaemia and hyperlactataemia — it drives glycogenolysis and glycolysis while α-mediated vasoconstriction promotes anaerobic metabolism and lactate.3,7,8

Myocardial cost

Tachycardia and tachyarrhythmia raise myocardial oxygen demand and oxidative stress; sustained high-dose catecholamine exposure is cardiotoxic.3

Norepinephrine & perfusion

Its intense vasoconstriction can compromise regional and organ tissue perfusion in some infants, even as blood pressure rises.2

A gentler side-effect profile

Compared with epinephrine, norepinephrine carries a lower incidence of tachycardia, hyperlactataemia and hyperglycaemia — part of its appeal as a vasopressor.3,7

04 What actually happens at the cot-side

Paediatric septic-shock guidance increasingly favours epinephrine or norepinephrine over dopamine as first-line support5 — yet neonatal practice stays conservative, with dopamine still the usual first choice.1,2

In a cross-sectional survey of Indian Level III NICUs, for sepsis-induced hypotension dopamine was the preferred first-line inotrope, followed by norepinephrine and low-dose epinephrine — while norepinephrine, followed by dobutamine, was the preferred second-line agent.1 In neonatal septic shock specifically, a pilot randomised trial found norepinephrine comparable to adrenaline for resolving shock and for mortality.5

References

  1. Das R, Nagpal R, Deshpande S, et al. A survey on management practices of hypotension in preterm neonates: an Indian perspective. Front Pediatr. 2024;12:1411719. doi.org/10.3389/fped.2024.1411719
  2. Wu TW, Noori S. Recognition and management of neonatal hemodynamic compromise. Pediatr Neonatol. 2021;62(Suppl 1):S22–S29. doi.org/10.1016/j.pedneo.2020.12.007
  3. Jha A, Zilahi G, Rhodes A. Vasoactive therapy in shock. BJA Educ. 2021;21(7):270–277. doi.org/10.1016/j.bjae.2021.03.002
  4. Garvey AA, Kooi EMW, Dempsey EM. Inotropes for preterm infants: 50 years on are we any wiser? Front Pediatr. 2018;6:88. doi.org/10.3389/fped.2018.00088
  5. Garegrat R, Patnaik S, Suryawanshi S, et al. A pilot randomized controlled trial comparing noradrenaline and adrenaline as a first-line vasopressor for fluid-refractory septic shock in neonates. Front Pediatr. 2024;12:1443990. doi.org/10.3389/fped.2024.1443990
  6. Lu P, Sun Y, Gong X, et al. Use of norepinephrine in preterm neonates with dopamine-resistant shock: a retrospective single-centre cross-sectional study. BMJ Paediatr Open. 2023;7(1):e001804. doi.org/10.1136/bmjpo-2022-001804
  7. Myburgh JA. Norepinephrine: more of a neurohormone than a vasopressor. Crit Care. 2010;14(5):196. doi.org/10.1186/cc9246
  8. Boscarino G, Conti MG, Esposito S, et al. Pharmacological hypotensive treatment in very preterm newborns: systematic review and meta-analysis of randomised controlled trials. Acta Paediatr. 2025. doi.org/10.1111/apa.70411
Tiny Taught · Neonatal & Paediatric Education

Educational summary for clinicians and trainees. Referenced to primary sources; items marked expert consensus reflect standard practice rather than trial evidence. Doses are for orientation only — always follow your unit’s formulary and senior review. This supports, and does not replace, local guidelines and individualised clinical judgement.

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