135 Early Ibuprofen Intervention for Preterm Infants Under 28 Gestational Weeks

Abstract

Background: Three cases of pulmonary hypertension with severe hypoxaemia were reported in 2002 after prophylactic ibuprofen administration during a randomized controlled trial of prophylactic treatment of patent ductus arteriosus (PDA) in very preterm infants (Gournay et al., Lancet 2002; 359: 1486–88). In a monocentre open study we investigated whether curative treatment with ibuprofen for a haemodynamically significant PDA induced pulmonary hypertension when administered between 24 and 72 h of life in preterm infants under 28 weeks of gestational age (GA). Methods: 29 preterm newborns below 28 weeks of GA were screened between 24 and 72 h of life for the presence of a haemodynamically relevant PDA, defined as one or more of the following criteria: left atrium/aortic root ratio > 1.4, reduction in diastolic flow in the anterior cerebral artery (resistance index > 0.8) or respiratory step back. Exclusion criteria were: ductus-dependent cardiopathy, right-to-left shunt over the PDA, intra-ventricular haemorrhage grade III or IV or thrombocytopenia < 50.000/nl. Intravenous ibuprofen was started after confirmation of a relevant PDA with 10 mg/kg bodyweight and was continued with two doses of 5 mg/kg in 24 h intervals. Besides determination of a haemodynamically relevant PDA echocardiographic measurements included the following parameters for the evaluation of pulmonary vascular resistance: shunt direction and flow velocity via the ductus and foramen ovale, estimation of the right systolic ventricular pressure (RSVP) in the presence of a tricuspid regurgitation and mean pulmonary artery pressure. In the treated infants these measurements were obtained serially during the ibuprofen course. Results: Of the 29 screened patients 14 were excluded from the study: 3 patients with severe IVH, 3 with pulmonary hypertension, and 8 due to non-relevant PDA. Among the 15 treated infants 8 showed a tricuspid regurgitation before the first ibuprofen dose with an estimated pulmonary vascular pressure (RSVP median 31 mmHg; range 23–43 mmHg) below systemic systolic pressure (median 41 mmHg; range 32–51 mmHg). The RSVP resolved during ibuprofen administration. In the treatment group PDA-closure rate 24 h after the third ibuprofen dose was 53.3%. Conclusion: In preterm infants below 28 weeks GA curative treatment with ibuprofen for a haemodynamically significant PDA was not associated with the occurrence of pulmonary hypertension when administered after 24 h of life.