Outcome of oral sildenafil therapy on persistent pulmonary hypertension of the newborn at Queen Sirikit National Institute of Child Health.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a common problem in the neonates with a high mortality rate. The prevalence ranges from 0.38-0.99 per 1,000 live births at Queen Sirikit National Institute of Child Health. The survival rate has improved after the advent of high-frequency ventilation and inhaled nitric oxide. However, inhaled nitric oxide is expensive and unavailable in most neonatal centers in Thailand. Sildenafil is a phosphodiesterase inhibitor type 5 that selectively reduces pulmonary vascular resistance and hence may play a role in the treatment of PPHN. OBJECTIVE: To evaluate effectiveness and short-term side effects of oral sildenafil for infants > 36 weeks gestational age who have PPHN. MATERIAL AND METHOD: The present study was conducted between January 2006 and December 2008 in the neonatal intensive care unit (NICU) at Queen Sirikit National Institute of Child Health. All infants > or = 36 weeks gestational age who were diagnosed as PPHN by echocardiogram and had an oxygenation index > or = 20 were included in the study. Oral sildenafil was given as per study protocol with a starting dose of 0.25-0.5 mg/kg/dose. Oxygenation index (OI), oxygen saturations (SpO2), alveolar arterial oxygen gradient (A-aDO2) and mean arterial blood pressure (MAP) were monitored serially. RESULTS: A total of 40 infants were diagnosed with PPHN during this period. Eleven infants were included in the present study. The initial median OI was 31.95 (24.25-48.25). All infants received standard therapy with mechanical ventilation, sedation and inotropic drugs. OI decreased 4.6% from base line after the first hour of starting oral sildenafil and progressively decreased by 13%, 27%, 37%, 41% and 90% at 2, 4, 6, 12 and 24 hours respectively. Oral sildenafil was discontinued in one infant. It was combined with inhaled iloprost in 2 infants due to systemic hypotension and with inhaled nitric oxide in one infant due to deterioration. One infant died during the present study. CONCLUSION: Oral sildenafil may be effective in improving oxygenation in some infants with persistent pulmonary hypertension of the newborn. Systemic hypotension was a cause for concern in the present study. Further studies are needed to assess the pharmacokinetics, efficacy and long-term side effects of this drug.

A randomized trial of non-synchronized Nasopharyngeal Intermittent Mandatory Ventilation (nsNIMV) vs. Nasal Continuous Positive Airway Pressure (NCPAP) in the prevention of extubation failure in pre-term < 1,500 grams.

OBJECTIVE: To compare the rate of reintubation within 7 days after extubation and study the complications in premature infants who were randomized in the immediate postextubation period to either nsNIMV or NCPAP. MATERIAL AND METHOD: This study was conducted in the neonatal unit of Queen Sirikit National Institute of Child Health between June 1 and November 30, 2006. Intubated premature infants born at GA < or = 34 weeks or with birth weight < or = 1500 gm, ready to be extubated before 4 weeks of age were recruited. Infants were randomized to either nsNIMV or NCPAP after extubation. Non-synchronized NIMV setting was the same as ventilator setting before extubation and NCPAP pressure was set at the same mean airway pressure of pre extubation ventilator value. Extubation was performed after intravenous loading dose of aminophylline. Primary outcome measurement was reintubation within 7 days of initial extubation and the secondary outcome was possible complications such as apnea, abdominal distension, gastrointestinal (GI) perforation, necrotizing enterocolitis (NEC), sepsis and death. RESULTS: A total of 70 VLBW infants were admitted to the neonatal unit during the study period. A total of 57 infants were intubated of which 48 infants were recruited for the study; 24 were in the nsNIMV group and 24 were in the NCPAP group. Infants in the nsNIMV group had mean birth weight and body weight at the start of study less than that in the NCPAP group (984.8 +/- 218 vs. 1067 +/- 214 and 1185 +/- 219 vs. 1205 +/-191, p = 0.003, 0.02). The nsNIMV group also had a higher rate of RDS and antenatal steroid used when compared to the NCPAP group (19/24 vs. 12/24 and 17/24 vs. 8/24, p = 0.03, 0.01). The nsNIMV group had fewer males than in the NCPAP group (8/24 vs. 17/24, p = 0.01). Reintubation was similar in both groups but atelectasis and sepsis were statistically significant risk factor for reintubation in NCPAP group. There were no significant differences in treatment related complications between the two groups, with respect to incidence of apnea (41.7% in nsNIMV vs. 62.5% in NCPAP), abdominal distensions (8.3% in nsNIMVvs. 16.7% in NCPAP), NEC (4.2% in nsNIMVvs. 12.5 in NCPAP), sepsis (4.2% in nsNIMVvs. 8.3% NCPAP). No GI perforation was observed in both groups. CONCLUSION: Non-invasive mode of ventilation, both NIMV and NCPAP, for weaning ofpre-term infants from ventilator may reduce the rate of reintubation in this group. Both modes seem to be equally safe. We believe that the use of non-invasive ventilator techniques will significantly reduce neonatal morbidity in the future. Additional prospective evaluation of these approaches should be conducted in the future.