Objective To evaluate the safety of intravenous (IV) sildenafil, an inhibitor of cyclic guanosine monophosphate–specific phosphodiesterase, in treating near-term and term newborns with persistent ...pulmonary hypertension of the newborn (PPHN). Study design This was an open-label, dose-escalation trial in newborns with PPHN and an oxygenation index (OI) > 15. Sildenafil was delivered by continuous IV infusion for at least 48 hours and up to 7 days. Results Five centers enrolled a total of 36 neonates with PPHN at a mean of 34 ± 17 hours of age; 29 of these neonates were already receiving inhaled nitric oxide (iNO). A significant improvement in OI (28.7 to 19.3; P = .0002) was observed after 4 hours of sildenafil infusion in the higher dose cohorts. Thirty-five neonates survived; 1 neonate required extracorporeal membrane oxygenation (ECMO) support. In 4 neonates, sildenafil was stopped due to adverse events. Seven neonates were enrolled before developing the need for iNO. In these neonates, OI improved significantly by 4 hours after initiation of sildenafil infusion (24.6 to 14.7; P = .009); 6 neonates completed treatment without the need for iNO or ECMO. Conclusions IV sildenafil was well tolerated, and acute and sustained improvements in oxygenation were noted in those neonates who received the higher infusion doses.
Objective To assess the ability of vasopressin to stabilize hemodynamics in infants with systemic hypotension secondary to congenital diaphragmatic hernia (CDH). Study design A retrospective chart ...review was performed to identify 13 patients with CDH treated with vasopressin for refractory hypotension to assess the effect of vasopressin on pulmonary and systemic hemodynamics and gas exchange in this setting. Data collected included demographics, respiratory support, inotropic agents, pulmonary and systemic hemodynamics, urine output, and serum and urine sodium levels during vasopressin therapy. Results Vasopressin therapy increased mean arterial pressure and decreased pulmonary/systemic pressure ratio, heart rate, and fraction of inspired oxygen. In 6 of 13 patients, extracorporeal membrane oxygenation therapy was no longer indicated after treatment with vasopressin. Improvement in left ventricular function and oxygenation index after vasopressin initiation was associated with a decreased need for extracorporeal membrane oxygenation therapy. Prolonged vasopressin treatment was associated with hyponatremia, increased urine output, and increased urine sodium. Conclusions Vasopressin stabilized systemic hemodynamics without adverse effects on pulmonary hemodynamics in a subset of infants with CDH. Our results suggest a potential role for vasopressin therapy in patients with CDH with catecholamine-resistant refractory hypotension.
Objective To assess the efficacy and safety of early, noninvasive inhaled nitric oxide (iNO) therapy in premature newborns who do not require mechanical ventilation. Study design We performed a ...multicenter randomized trial including 124 premature newborns who required noninvasive supplemental oxygen within the first 72 hours after birth. Newborns were stratified into 3 different groups by birth weight (500-749, 750-999, 1000-1250 g) prior to randomization to iNO (10 ppm) or placebo gas (controls) until 30 weeks postmenstrual age. The primary outcome was a composite of death or bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age. Secondary outcomes included the need for and duration of mechanical ventilation, severity of BPD, and safety outcomes. Results There was no difference in the incidence of death or BPD in the iNO and placebo groups (42% vs 40%, P = .86, relative risk = 1.06, 0.7-1.6). BPD severity was not different between the treatment groups. There were no differences between the groups in the need for mechanical ventilation (22% vs 23%; P = .89), duration of mechanical ventilation (9.7 vs 8.4 days; P = .27), or safety outcomes including severe intracranial hemorrhage (3.4% vs 6.2%, P = .68). Conclusions We found that iNO delivered noninvasively to premature infants who have not progressed to early respiratory failure is a safe treatment, but does not decrease the incidence or severity of BPD, reduce the need for mechanical ventilation, or alter the clinical course.
Objective To assess whether the combination of early inhaled nitric oxide (iNO) therapy and vitamin A supplementation lowers the incidence of bronchopulmonary dysplasia (BPD) in premature newborns ...with respiratory failure. Study design A total of 793 mechanically ventilated infants (birth weight 500-1250 g) were randomized (after stratification by birth weight) to receive placebo or iNO (5 ppm) for 21 days or until extubation (500-749, 750-999, or 1000-1250 g). A total of 398 newborns received iNO, and of these, 118 (30%) received vitamin A according to their enrollment center. We compared patients who received iNO + vitamin A with those who received iNO alone. The primary outcome was a composite of death or BPD at 36 weeks postconceptual age. Results BPD was reduced in infants who received iNO + vitamin A for the 750-999 g birth weight group compared with iNO alone ( P = .01). This group also showed a reduction in the combined outcome of BPD + death compared with iNO alone ( P = .01). The use of vitamin A did not change the risk for BPD in the placebo group. Overall, the use of vitamin A was low (229 of 793 patients, or 29%). Combined therapy improved Bayley Scales of Infant Development II Mental and Psychomotor Developmental Index scores at 1 year compared with infants treated solely with iNO for the 500-749 g birth weight group. Conclusions In this retrospective analysis of the nonrandomized use of vitamin A, combined iNO + vitamin A therapy in preterm infants with birth weight 750-999 g reduced the incidence of BPD and BPD + death and improved neurocognitive outcomes at 1 year in the 500-749 g birth weight group.
Objective To determine the incidence and risk factors for readmission to the intensive care unit (ICU) among preterm infants who required mechanical ventilation at birth. Study design We studied ...preterm newborns (birth weight 500-1250 g) who required mechanical ventilation at birth and were enrolled in a multicenter trial of inhaled nitric oxide therapy. Patients were assessed up to 4.5 years of age via annual in-person evaluations and structured telephone interviews. Univariate and multivariable analyses of baseline and birth hospitalization predictors of ICU readmission were performed. Results Of 512 subjects providing follow-up data, 58% were readmitted to the hospital (51% of these had multiple readmissions, averaging 3.9 readmissions per subject), 19% were readmitted to an ICU, and 12% required additional mechanical ventilation support. In univariate analyses, ICU readmission was more common among male subjects (OR 2.01; 95% CI 1.27-3.18), infants with grade 3-4 intracranial hemorrhage (OR 2.13; 95% CI 1.23-3.69), increasing duration of birth hospitalization (OR 1.01 per day; 95% CI 1.00-1.02), and prolonged oxygen therapy (OR 1.01 per day; 95% CI 1.00-1.01). In the first year after birth hospitalization, children readmitted to an ICU incurred greater health care costs (median $69 700 vs $30 200 for subjects admitted to the ward and $9600 for subjects never admitted). Conclusions Small preterm infants who were mechanically ventilated at birth have substantial risk for readmission to an ICU and late mechanical ventilation, require extensive health care resources, and incur high treatment costs.
A newborn with persistent pulmonary hypertension (PH) unresponsive to conventional therapies was found to be homozygous for a mutation in the gene encoding adenosine triphosphate binding cassette ...protein, member A3 (ABCA3). Most causes of PH respond to lung recruitment, inhaled nitric oxide, and hemodynamic support. When PH is prolonged and does not respond to standard therapies, genetic causes of surfactant abnormalities should be considered in the differential diagnosis.
Newborns with congenital diaphragmatic hernia frequently have catecholamine-unresponsive systemic hypotension and respiratory failure. We found that adrenal insufficiency frequently complicates the ...clinical course of infants with congenital diaphragmatic hernia and was associated with increased severity of illness.
PDF