NeoNotes
Journal Club
Andrew
B. Kairalla MD, Editor
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Nitric Oxide for Preemies
Inhaled Nitric Oxide in Premature Infants with the Respiratory Distress Syndrome. Schreiber MD, Gin-Mestan K, Marks JD, et al. N Engl J Med 349 : 2099 – 2107.
Background: Inhaled nitric oxide improves gas exchange, decreases pulmonary vascular lability, and reduces pulmonary inflammation. We hypothesized that the use of inhaled nitric oxide would decrease the incidence of chronic lung disease and death in premature infants with the respiratory distress syndrome.
Methods: We conducted a randomized, double-blind, placebo-controlled study of the effect of inhaled nitric oxide during the first week of life on the incidence of chronic lung disease and death in premature infants (less than 34 weeks' gestation) who were undergoing mechanical ventilation for the respiratory distress syndrome. Infants were randomly assigned to receive inhaled nitric oxide (10 ppm on day 1, followed by 5 ppm for six days) or inhaled oxygen placebo for seven days. We further randomly assigned the infants in each group to receive intermittent mandatory or high-frequency oscillatory ventilation.
Results: A total of 207 premature infants were enrolled. In the group given inhaled nitric oxide, 51 infants (48.6 percent) died or had chronic lung disease, as compared with 65 infants (63.7 percent) in the placebo group (relative risk, 0.76; 95 percent confidence interval, 0.60 to 0.97; P=0.03). There was no significant difference between the nitric oxide and placebo groups in the overall incidence of intraventricular hemorrhage and periventricular leukomalacia (33.3 percent and 38.2 percent, respectively), but the group given inhaled nitric oxide had a lower incidence of severe intraventricular hemorrhage and periventricular leukomalacia (12.4 percent vs. 23.5 percent; relative risk, 0.53; 95 percent confidence interval, 0.28 to 0.98; P=0.04). The type of ventilation had no significant effect on the outcome.
Conclusions: The use of inhaled nitric oxide in premature infants with the respiratory distress syndrome decreases the incidence of chronic lung disease and death.
Comments: The results of this study are both exciting and perplexing. We now have good data from a randomized controlled trial that suggests that we can reduce the incidence of death or chronic lung disease in ventilated premature infants by treating them with nitric oxide during the first week of life. Furthermore, it looks promising that this treatment may also reduce their risk of severe brain injury, though long-term follow up data on neuro-developmental outcomes are badly needed. I’m concerned that the cost of treating all ventilated preterm infants with this drug (currently about $12,000 / patient in the United States) would be astronomical. A cost / benefit analysis looking at potential savings in length of stay or cost of care would be helpful. If you are considering a more selective approach to the use of nitric oxide in premature infants, be aware that improvement in the primary outcome could only be demonstrated in babies with mild lung disease at birth (OI < 6.94). Selectively treating only your sicker premature infants with nitric oxide is not likely to be beneficial. ABK.
Date: 05 Dec 2003
Time: 07:21:28
I agree with Dr. Kairalla except that many centers use Nitric on select
patients and DO have good results. I guess I feel that if it will help one baby
escape CLD or IVH complications ,in the long run it is worth it . EMS
UserName: Erin Sewell
Institution: Baptist Hospital
telephone: 786-596-4672
email: erins@baptisthealth.net
Date: 04 Dec 2003
Time: 21:18:38
There was a much higher rate of early sepsis in the placebo group. Although
overall no statistical diff in GA/BW between two groups, # of <1000g babies was
significantly higher in placebo group. Could this have led to higher rate of
death/CLD in the Placebo group?
Comment Not Signed
Date: 06 Dec 2003
Time: 07:52:29
I haven't read the whole article to see the break up on B.W. but don't you
think that mortality or BPD reaching near 50% for those on Nitric Oxide and 60%
for those on placebo in premies of 34 (THIRTY FOUR) WEEKS or less is
astronomical?
UserName: Felix A. Estrada, M.D.
Institution: Parkway Regional Medical Center
telephone: 305-654-5612
email: felixaestradamd@pol.net
Date: 09 Dec 2003
Time: 19:17:30
Whoa everyone!!! Before you get on this bandwagon... please wait for the
results of the NICHD Neonatal Networks multicenter trial on iNO in Preemies. It
was stopped very early due to a poor outcome variable being statistically
significant on the first interim review. This was a much much larger trial, and
much better done than the one published here. They have not announced the
reason for the stoppage yet, but... stay tuned!
David L. Weisoly, D.O.
Institution: UT-Houston Med School - Chief Neonatal Fellow
email:
David.L.Weisoly@uth.tmc.edu
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