DISCUSSION
The use of LUS in studying respiratory function of preterm infants has
been well established. It has been used to predict the need for
surfactant administration and/or respiratory
support.17-20 Using LUS to diagnose neonates with
pulmonary edema has been shown to be more sensitive and with greater
negative predictive value than X-rays.21 Similarly,
LUS showed good positive predictive value in the assessment of the early
risk for BPD in ELGANs.22 Surprisingly, despite the
controversy, LUS has not been systematically used in the evaluation of
diuretic effect in premature infants diagnosed with BPD. Recently, a
very small study used LUS to evaluate a heterogeneous group (4/18
neonates had PDA) of preterm neonates with pulmonary edema treated with
diuretics. The study showed lower LUS scores in the group of diuretic
responders compared to non-responders. However, this pilot study
enrolled neonates quite early in life, with diuretics being administered
at a mean of 31 days of life. The study concluded that responders were
treated with diuretics for much shorter periods and ultimately developed
less severe BPD.23
We found that diuretic therapy was associated with significant decrease
in pulmonary edema, FiO2 requirement, and respiratory flow support
compared to the control group by day 3. FiO2 requirements were not
different between the diuretic and control groups on day 6, either
because they were both low and approaching the room air target on day 6,
or because clinicians preferentially weaned respiratory flow support
before FiO2 in the diuretic group. It is also possible that infants
developed tolerance to diuretics after prolonged
use.24,25 In the diuretic group, 46% of infants were
treated with diuretics for a duration of 7-10 days, and 3.6% of them
had a rebound increase in need for FiO2 or respiratory flow support upon
cessation of diuretic therapy. Our findings are consistent with previous
studies showing that diuretics can improve O2 requirements and
respiratory mechanics in infants.26 Although, there is
only limited previous data on the use of pulmonary edema scores in
neonates, the correlation of decreasing scores with decreasing
respiratory support parameters in our subjects supports their validity.
A recent retrospective longitudinal cohort study confirmed the
long-established association between chronic diuretic use and
electrolyte disturbances requiring electrolyte supplementation,
especially in infants treated with thiazides.27 In our
study group, 25% of infants had to be supplemented with either NaCl
and/or KCl. This common side effect together with other concerns related
to diuretic use such as ototoxicity, metabolic bone disease, and
nephrocalcinosis underline the importance of careful evaluation of the
need for diuretics in infants with CLD.
Our study has several limitations. The specific indications for
diuretics in BPD are unclear, and thresholds for treatment were
heterogeneous in our cohort, based on clinical experience and
preference. In addition, infants in the diuretic group received several
distinct regimens based on clinician preference, and the study was not
adequately powered to compare them. It is also important to note that,
while diuretics have short-term beneficial effects on respiratory
function, they have not been associated with a decrease in long-term
outcomes or length of hospital stay.28 We could not
evaluate the length of the hospital stay in our study because several
infants from the control group eventually were later treated with
diuretics.