A dose response study of inhaled nitric oxide in hypoxic respiratory failure in preterm infants.
BACKGROUND
Inhaled nitric oxide (iNO) is used widely in newborn infants with hypoxic respiratory failure, despite the known and theoretical toxicity of iNO, and a relative lack of information about appropriate doses.


OBJECTIVE
To determine whether a dose-response relationship existed for iNO in preterm infants.


METHODS
A four-period, four-dose, cross-over design was used with iNO given for 15 min in a randomised sequence in concentrations of 5, 10, 20 and 40 parts per million (ppm), with a minimum 5 min wash-out period. Data on ventilatory, blood gas and other physiological measurements were recorded before and at the end of each period. The relationship of clinical response with iNO dose and period was analysed using multivariate regression.


METHODS
Infants with gestational age < 34 weeks and < 28 days postnatal age with hypoxic respiratory failure were recruited.


METHODS
A clinically significant dose-response was defined as a rise in the post-ductal arterial oxygen tension (PaO(2)) of at least 3 kPa.


RESULTS
Thirteen infants were recruited. At trial entry, ten were < 3 days of age; 11 were being treated with high frequency oscillatory ventilation; median (inter-quartile range) gestational age 27 (25-29) weeks; birthweight 983 (765-1120) g; oxygenation index 27.1 (21.8-28.8). Six infants (46%) showed a clinically significant response. After adjusting for period and patient effect, no evidence for an overall dose effect was identified (likelihood ratio test, p=0.34).


CONCLUSIONS
No evidence of a dose-response relationship with iNO was found in this study of very preterm infants with respiratory failure.
Ahluwalia
J
J
Neonatal Intensive Care Unit, Addenbrookes Hospital, Cambridge, U.K. jag.ahluwalia@addenbrookes.nhs.uk
Tooley
J
J
Cheema
I
I
Sweet
D G
DG
Curley
A E
AE
Halliday
H L
HL
Field
D
D
Al'malik
H
H
Annamalai
S
S
Midgley
P
P
Hardy
P
P
Tomlin
K
K
Elbourne
D
D
D000280:Administration, Inhalation; D001784:Blood Gas Analysis; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology*; D008297:Male; D015999:Multivariate Analysis; D009569:Nitric Oxide / Q000008:administration & dosage*; D010100:Oxygen / Q000097:blood; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy* / Q000503:physiopathology; D012131:Respiratory Insufficiency / Q000188:drug therapy* / Q000503:physiopathology
D009569:Nitric Oxide; D010100:Oxygen