Norepinephrine for the management of hypotension in premature and full-term neonates

Hypotension is a common but serious complication in neonates. The primary
etiological factors of hypotension are abnormal peripheral vasoregulation and
myocardial dysfunction. Severe hypotension is associated with a higher
incidence of intraventricular hemorrhage and an adverse neurodevelopmental
outcome Because of these potential serious consequences, early and effective
treatment is essential to increase the chance of improved neurological outcome
and survival.

In case of severe hypotension nonresponsive to fluid resuscitation, initiation
of inotropic and/or vasoactive agents are warranted to increase cardiac output,
maintain adequate blood pressure and thereby oxygen delivery to the tissue.
Dopamine is the most commonly used pharmacological agent in the treatment of
newborn hypotension. Another frequently used drug is dobutamine. Nevertheless,
failure to sustain adequate blood pressure despite high doses have been
reported. Recent findings also suggest that vasopressor resistance can be
treated with a brief course of hydrocortisone. However, due to the short- and
potential long-term side effects of early hydrocortisone treatment, this might
not be the preferred medication.

Norepinephrine can be suggested as an alternative medicine in the treatment of
hypotension. In different studies norepinephrine was found to raise blood
pressure without adverse effect on organ blood flow. However, it is assumed
that use of norepinephrine can lead to an increase of the total peripheral
vascular resistance resulting in decreased cardiac output and tissue perfusion,
hypertension, tachycardia, decreased myocardial oxygen delivery and tissue
necrosis. Nevertheless, at our NICU norepinephrine has been used for the last
years in both premature as full-term neonates without known adverse events
related to the use of norepinephrine.

In adults norepinephrine has recently been recommended as the first-choice
vasopressor agent to correct hypotension. However, only limited information
regarding the clinical effects of norepinephrine in the newborn is available.
Since pharmacokinetics and pharmacodynamics are very different in children and
adults norepinephrine needs to be studied in this specific population.

To investigate if norepinephrine is safe and effective in increasing blood
pressure and systemic blood flow in premature and full-term neonates with shock
and/or hypotension.

A prospective cohort study with a total duration of 1 year conducted at the
neonatal intensive care unit of the Radboudumc in the Netherlands.

Burden
All infants participating in the study are subjected to routine neonatal
intensive care and hemodynamic management is performed according the actual
protocol for neonatal shock/hypotension. Norepinephrine is one of the several
cardiovascular drugs that are routinely used on the neonatal intensive care
unit. This study does require an extra echocardiography, before and after
initiation of treatment with norepinephrine.

Benefits and risks
Norepinephrine may increase the blood pressure and systemic blood flow, improve
the cardiac function and thereby enhance oxygen delivery to the tissue. These
beneficial effects may improve neurodevelopmental outcome. On the other hand,
it is assumed that use of norepinephrine can lead to an increase of the total
peripheral vascular resistance resulting in decreased cardiac output and tissue
perfusion, hypertension, tachycardia, decreased myocardial oxygen delivery and
tissue necrosis.