Hydrocortisone is effective in treatment of vasopressor-resistant hypotension in very low birth weight neonates

Article Outline

• Copyright

Ng PC, Lee CH, Bnur FL, Chan IHS, Lee AWY, Wong E, et al. A double-blind, randomized, controlled study of a “stress dose” of hydrocortisone for rescue treatment of refractory hypotension in preterm infants. Pediatrics 2006;117:367-75.

Question Among premature very low birth weight (VLBW) infants with refractory hypotension and adrenocortical insufficiency, does the use of a “stress dose” of hydrocortisone allow weaning from vasopressor support within 72 hours of treatment?

Design Double-blind, randomized, controlled study.

Setting University neonatal center in Hong Kong.

Participants 48 VLBW infants who had refractory hypotension and required dopamine ≥10 μg/kg per minute.

Intervention Infants 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).

Outcomes The primary outcome was the ability to wean off dopamine within 72 hours after treatment.

Results The baseline clinical characteristics were similar between the groups. Serum cortisol concentrations were very low immediately before randomization in both groups of infants. More VLBW infants who were treated with hydrocortisone were weaned off vasopressor support 72 hours after starting treatment (79% vs 33%, P =.001, Number Needed to Treat [NNT] = 2). 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 patients treated with hydrocortisone-treated. Fewer infants in the hydrocortisone group required a second vasopressor for treatment of refractory hypotension (8.3% vs 45.8%, P =.009, NNT = 3). The trend (linear and quadratic) of the mean arterial blood pressure was also significantly and consistently higher in infants treated with hydrocortisone.

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.

Comment Although the association between blood pressure and organ blood flow is complex in the VLBW neonate during the first 24 to 48 postnatal hours, most neonatologists attempt to maintain blood pressure in the perceived gestational- and postnatal-age dependent “normal” range using dopamine, epinephrine, and/or dobutamine. As close to 50% of the VLBW neonates become dependent on vasopressor/inotrope support or do not respond at all, and because findings of observational and retrospective studies suggest that low-dose hydrocortisone may be effective in stabilizing their cardiovascular status, hydrocortisone has been used with increasing frequency to treat vasopressor resistance in this patient population. This study is the first, prospective, randomized clinical trial (RCT) assessing the effectiveness of relatively low doses of hydrocortisone on increasing blood pressure and decreasing vasopressor requirement in VLBW neonates during the immediate postnatal period. The findings demonstrate that hydrocortisone increases blood pressure and decreases the need vasopressor/inotrope support by 72 hours of hydrocortisone treatment. As the study was not designed to evaluate the safety of early hydrocortisone administration, the findings that the beneficial cardiovascular effects were not accompanied by apparent side effects such as hyperglycemia, systemic infections, or intestinal perforation should be viewed with caution, and it remains to be seen whether this treatment modality improves mortality and/or long-term outcomes such as neurodevelopmental outcome. Thus, despite the findings of this RCT, there is no evidence yet to support the widespread and indiscriminate use of early hydrocortisone in the VLBW patient population with vasopressor resistance.