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PEDIATRICS Vol. 108 No. 4 October 2001, pp. 949-955
Received Sep 18, 2000; accepted Jan 31, 2001.
From the * University of California, San Diego Medical Center,
San Diego, California; and Objective. There is little
information on the response to very low doses of inhaled nitric oxide
(iNO) in hypoxic near-term infants. The potential toxicities of iNO are
dose related; thus, the ability to use lower doses safely and
effectively may be advantageous. We hypothesized that there is no
difference in the acute improvement in oxygenation between treatment
with inhaled nitric oxide at 1 to 2 parts per million (ppm) or 10 to 20 ppm.
Methods. We randomized near-term and term infants with
hypoxic respiratory failure with oxygenation indices (OIs) of Results. Thirty minutes after the study gas was initiated,
PaO2 increased significantly overall in the
low-dose (90.7 ± 41 torr to 166.8 ± 95.6 torr) and
high-dose (76.2 ± 32.7 torr to 198.7 ± 142.8 torr) groups;
the maximal increase was seen in the infants who initially were treated
with 10 ppm. The OI also decreased significantly overall and also was
significant in the high-dose group (21.0 ± 13.7 to 11.4 ± 10.4; low-dose: 18.3 ± 7.1 to 13.2 ± 12.3). There was a
nonsignificant fall of PaCO2 with iNO treatment (low dose 35 ± 7.3 to 30 ± 8.5 torr vs high dose 35.2 ± 9.9 to 32.4 ± 10.7 torr). A sustained response (ie,
maintaining a PaO2 and OI gain greater than
20% for the duration of the study gas administration) was greater in
the high-dose group (53.3% vs 30.0%). In addition, dose increases
were required more often in the low-dose group than in the high-dose
group (80.0% vs 57.1%). Among patients who did not respond to the
initial iNO dose, 100.0% and 83.3% responded at higher doses of iNO
for the low- and high-dose groups, respectively. There were no
differences for death, need for extracorporeal membrane oxygenation, or
other outcomes between the groups.
Conclusions. We did not find any significant difference in
response to low- versus high-dose iNO. An initial exposure to low-dose
iNO does not compromise the response to higher doses if required and
may result in less toxicity.
Royal Victoria Hospital, Montreal,
Quebec, Canada.
10 and
PaO2 <100 on 2 separate blood gases taken at
least 30 minutes apart. Infants with congenital diaphragmatic hernia
were excluded. After parental consent was obtained, patients were
randomized to receive a starting nitric oxide (iNO) dose of either 1 to
2 ppm (low-dose group, n = 15) or 10 to 20 ppm
(high-dose group, n = 21). The response to iNO was
assessed according to the increase in arterial
PaO2 and decrease in OI 30 to 60 minutes after
exposure to the initial starting concentration. A response of <10%
increase on PaO2 and a <10% decrease in OI
resulted in a doubling of iNO within the dose range protocol (1, 2, 4, and 8 ppm for the low-dose group; 10, 20, 40, and 80 ppm for the
high-dose group).
This article has been cited by other articles:
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  M. Beghetti, C. Sparling, P. N. Cox, D. Stephens, and I. Adatia Inhaled NO inhibits platelet aggregation and elevates plasma but not intraplatelet cGMP in healthy human volunteers Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H637 - H642. [Abstract] [Full Text] [PDF]
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