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There have been several reports of very low birthweight
(VLBW) infants who experience systemic hypotension that is unresponsive to
volume expansion and inotropic agents, but very responsive to corticosteroids.
Ng et al have performed a prospective study of the pituitary adrenal axis in
137 VLBW infants, of whom 78 had refractive hypotension (group 2) and 59
remained normotensive (group 1). Human corticotropin releasing hormone (hCRH)
(1mcg/kg IV bolus) was administered between 08:00 h and 10:00 h on days 7 and
14 of life. Serial samples for ACTH and cortisol were obtained at baseline, 15,
30, and 60 minutes after injection. Inclusion criteria were gestational age
<32 weeks, birthweight <1500 grams, no postnatal systemic or inhaled
corticosteroids, and an indwelling arterial line. Exclusion criteria were
persistent hypoglycemia, systemic infection, necrotizing enterocolitis, or
major surgery.
Results from groups 1 and 2 combined, showed that basal and
peak cortisol and change in cortisol over the first 30 minutes after hCRH
injection correlated significantly with the lowest recorded BP during the first
14 days of life and the BP measured at the initiation of the study on day 7. In
contrast, ACTH levels on days 7 and 14 and cortisol on day 14 did not correlate
with the lowest BP. Serum cortisol levels (after hCRH) on day 7 correlated
negatively with the total dose of inotropic agents, while plasma ACTH levels
were positively correlated.
The ACTH response to
hCRH was significantly greater on both days 7 and 14 in group 2 infants, but
cortisol responses were greater in group 1 than group 2 on day 7. Day 14
cortisol responses were similar in both groups. The authors state that this
study demonstrates adrenal hyporesponsiveness in group 2 infants at day 7.
Those were the infants with significant hypotension requiring ionotropic
agents. By day 14, the transient nature of this endocrine dysfunction was
evident as there were no significant differences between the two groups of
infants. The authors term this dysfunction, transient adrenocortical
insufficiency of prematurity or TAP.
Ng PC, Lee CH, Lam CW, Ma KC, Fok TF, Chan IH, Wong E. Transient adrenocortical insufficiency of prematurity and systemic hypotension in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2004;89:F119-126.
Editor’s Comment: This is an interesting,
well-conducted prospective study of a problem that is relatively common in many
NICUs. Neonatologists have been using small doses of hydrocortisone in premature
babies with hypotension refractory to inotropic agents for some time. However,
the definition of the defect responding to this non-replacement, non-stress
level of hydrocortisone administration has not been clarified. Ng et al have
provided a clear demonstration that these infants have a transient adrenal, not
pituitary immaturity, which requires hydrocortisone administration. They note
that a previously reported trial of hydrocortisone versus dopamine for the
routine treatment of hypotension failed to confirm its benefit. This is not
surprising, given the distinct differences in the 2 groups of infants studied.
A short course of hydrocortisone in premature infants with hypotension
refractory to inotropic agents seems a reasonable therapeutic maneuver. Data
now show that these corticosteroids do not need to be given for prolonged
periods.
William L. Clarke, MD
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Current GGH - Vol. 24 No. 1
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