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Low-Dose Nitric Oxide Therapy for Persistent Pulmonary Hypertension of the Newborn. Clark RH, Kueser TJ, Marshall WW, et al. NEJM 2000; 342:469-74. This study by the Clinical Inhaled Nitric Oxide Research Group is a multicenter randomized clinical trial that was designed to determine whether low-dose NO would reduce the need for ECMO in neonates with PPHN. Eligible patients were > 34 weeks gestation, < 5 days old, and had hypoxemic respiratory failure (OI > 25). Infants randomized to receive NO were treated with 20 ppm for a maximum of 24 hours, followed by 5 ppm for up to 4 days. Results included a decreased need for ECMO in the treatment group (48 of 126 babies) versus the control group (78 of 122 babies) (p=.001). Chronic lung disease was also less frequent in the NO group than the control group ( 7% vs 20%, p=.02). There was no difference in mortality between the two groups (7% in the NO group vs 8% in the control group).
Comment. Now that its efficacy and safety have been established, the FDA has approved nitric oxide for clinical use in the treatment of PPHN. This study demonstrated that NO treatment is useful in treating PPHN, regardless of whether the underlying cause was meconium aspiration syndrome, RDS, pneumonia or isolated pulmonary hypoplasia. The one notable exception was babies with diaphragmatic hernia, in whom NO did not reduce the need for ECMO or improve outcome.
There were 3 technical points about the use of NO that deserve comment. First, there is no need to try higher doses if babies don’t respond to the initial dose of 20 ppm. Second, if babies respond to the initial dose of 20 ppm, the dose of NO can usually be reduced to 5 ppm after 4-24 hours. Third, responders can usually be weaned off NO therapy in 1-4 days. The median duration of NO therapy in this study was 44 hours.
Finally, now that the FDA has approved the use of nitric oxide in neonates with PPHN, debate continues regarding whether NICU’s should offer this therapy if they do not have ECMO available for non-responders. I feel that a minimum standard for the use of NO in NICU’s should include the close proximity of an ECMO center, and the availability of giving nitric oxide during transport.
Andrew B. Kairalla MD