Published online February 1, 2006
PEDIATRICS Vol. 117 No. 2 February 2006, pp. 367-375 (doi:10.1542/peds.2005-0869)
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A Double-Blind, Randomized, Controlled Study of a "Stress Dose" of Hydrocortisone for Rescue Treatment of Refractory Hypotension in Preterm Infants

Pak C. Ng, FRCPCH, MDa, Cheuk H. Lee, FRCP (Edin)a, Flora Liu Bnura, Iris H.S. Chan, PhDb, Anthony W.Y. Lee, MScc, Eric Wong, MScd, Hin B. Chan, MRCP (UK)e, Christopher W.K. Lam, PhDb, Benjamin S.C. Lee, PhDc and Tai F. Fok, FRCPCH, MDa

a Department of Pediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
b Department of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
c Pharmacy, Prince of Wales Hospital, Hong Kong
d Center of Epidemiology and Biostatistics, The Chinese University of Hong Kong, Hong Kong
e Department of Pediatrics and Adolescent Medicine, United Christian Hospital, Hong Kong

Objective. To assess the effectiveness of a "stress dose" of hydrocortisone for rescue treatment of refractory hypotension and adrenocortical insufficiency of prematurity in very low birth weight (VLBW) infants. We hypothesized that significantly more VLBW infants who were receiving dopamine ≥10 µg/kg per min could wean off vasopressor support 72 hours after treatment with hydrocortisone.

Methods. A double-blind, randomized, controlled study was conducted in a university neonatal center. Forty-eight VLBW infants who had refractory hypotension and required dopamine ≥10 µg/kg per min were randomly assigned to receive a stress dose of hydrocortisone (1 mg/kg every 8 hours for 5 days; n = 24) or an equivalent volume of the placebo solution (isotonic saline; n = 24).

Results. The baseline clinical characteristics were similar between the groups. Serum cortisol concentrations were very low immediately before randomization in both groups of infants. Significantly more VLBW infants who were treated with hydrocortisone weaned off vasopressor support 72 hours after starting treatment. The use of volume expander, cumulative dose of dopamine, and dobutamine were significantly less in hydrocortisone-treated infants compared with control infants. In addition, the median duration of vasopressor treatment was halved in hydrocortisone-treated patients. Two versus 11 infants in the hydrocortisone and control groups required a second vasopressor for treatment of refractory hypotension. The trend (linear and quadratic) of the mean arterial blood pressure was also significantly and consistently higher in hydrocortisone-treated infants.

Conclusions. A stress dose of hydrocortisone was effective in treating refractory hypotension in VLBW infants. Although routine and prophylactic use of systemic corticosteroids could not be recommended because of their potential adverse effects, this relatively low dose of hydrocortisone would probably be preferable to high-dose dexamethasone for treatment of refractory hypotension in emergency and life-threatening situations.

Key Words: adrenocortical insufficiency • hydrocortisone • hypotension • preterm infants

Abbreviations: VLBW—very low birth weight • HPA—hypothalamic-pituitary-adrenal • BP—blood pressure

Accepted Jun 10, 2005.




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