Early targeted therapy treatment of patent ductus arteriosus with ibuprofen and hydrocortisone in premature infants with low cortisol level

Abstract

Objective To evaluate the role of ibuprofen and hydrocortisone in early treatment of patent ductus arteriosus (PDA) in premature infants with low cortisol level. Method A prospective randomized controlled trial on 144 very low birth weight infants in the Hospital within 24 hours after birth with gestational age of 28~32 weeks and birth weight of 1 000~1 499 grams, who had asymptomatic PDA diagnosed by echocardiography, introducing early administration of drugs including ibuprofen and/or hydrocortisone within the first 24~48 hours after birth. According to the baseline of serum cortisol level measured prior to the administration of drugs, the preterm were assigned into two groups. The low cortisol level group (the cortisol level <150 μg/L) were further subdivided into four groups each being allocated to hydrocortisone or ibuprofen or both of hydrocortisone and ibuprofen combined or placebo treatment. The high cortisol level group (the cortisol level≥150 μg/L) were allocated to either ibuprofen or placebo treatment in randomization. Diameter of ductus arteriosus and cortisol value were measured again after treatment, and the follow-ups were undertaken till discharge. All data was collected and analyzed by statistical software. Result A total of 91 cases were in low cortisol level group (22 cases of hydrocortisone, 23 cases of ibuprofen, 21 cases of both hydrocortisone and ibuprofen, and 25 cases of placebo) and 53 cases in high cortisol level group (26 cases of placebo and 27 cases of Ibuprofen). Low cortisol level group, combined therapy, closure of the ductus at a rate of 81.0%, was higher than other methods of therapy (P<0.05); high cortisol level group, the ductus arteriosus closed in 20 patients of ibuprofen therapy (74.1%) and in 13 patients of placebo treatment (50.0%) (P<0.05). Early treatment did not significantly increase the drug adverse effects, including impaired renal function, gastrointestinal bleeding, hyperglycemia and others. After comparisons between laboratory changes in early targeted groups and non-early targeted groups after treatment, findings were as follows: decrease in the incidence of apnea, myocardial damage, feeding intolerance, intraventricular hemorrhage and reduce the duration of phototherapy. Conclusion This trial proved the efficacy and safety of early therapy with ibuprofen and hydrocortisone for closure of ductus arteriosus in premature infants with low cortisol level and the decreasing incidence of complications due to PDA without increasing the risk of adverse effects. Key words: Ductus arteriosus, patent; Cortisol; Hydrocortisone; Infant, premature