Persistent pulmonary hypertension of the newborn in the era before nitric oxide: Practice variation and outcomes

Objectives. In the era before widespread use of inhaled nitric oxide, to de termine the prevalence of persistent pulmonary hypertension (PPHN) in a mul ticenter cohort, demographic descriptors of the population, treatments used , the outcomes of those treatments, and variation in practice among centers . Study Design. A total of 385 neonates who received greater than or equal to 50% inspired oxygen and/or mechanical ventilation and had documented evide nce of PPHN (2D echocardiogram or preductal or postductal oxygen difference ) were tracked from admission at 12 Level III neonatal intensive care units . Demographics, treatments, and outcomes were documented. Results. The prevalence of PPHN was 1.9 per 1000 live births (based on 71 5 58 inborns) with a wide variation observed among centers (.43-6.82 per 1000 live births). Neonates with PPHN were admitted to the Level III neonatal i ntensive care units at a mean of 12 hours of age (standard deviation: 19 ho urs). Wide variations in the use of all treatments studied were found at th e centers. Hyperventilation was used in 65% overall but centers ranged from 33% to 92%, and continuous infusion of alkali was used in 75% overall, wit h a range of 27% to 93% of neonates. Other frequently used treatments inclu ded sedation (94%; range: 77%-100%), paralysis (73%; range: 33%-98%), and i notrope administration (84%; range: 46%-100%). Vasodilator drugs, primarily tolazoline, were used in 39% (range: 13%-81%) of neonates. Despite the wid e variation in practice, there was no significant difference in mortality a mong centers. Mortality was 11% (range: 4%-33%). No specific therapy was cl early associated with a reduction in mortality. To determine whether the therapies were equivalent, neonates treated with h yperventilation were compared with those treated with alkali infusion. Hype rventilation reduced the risk of extracorporeal membrane oxygenation withou t increasing the use of oxygen at 28 days of age. In contrast, the use of a lkali infusion was associated with increased use of extracorporeal membrane oxygenation (odds ratio: 5.03, compared with those treated with hyperventi lation) and an increased use of oxygen at 28 days of age. Conclusions. Hyperventilation and alkali infusion are not equivalent in the ir outcomes in neonates with PPHN. Randomized trials are needed to evaluate the role of these common therapies.