Discussion
Although support for outpatient chronic diuretic use is lacking, many
preterm children with BPD are prescribed diuretics after initial
hospital discharge.(18) (19) In this study, we characterized clinical
features associated with outpatient diuretic use and timing of diuretic
weaning, in children < 32 weeks gestation with the diagnosis
of BPD. We found that children diagnosed with severe BPD in the NICU
were more likely to be on a diuretic at their first pulmonary visit
compared to those who were not. Additionally, lower birthweight and
earlier gestational age were associated with outpatient diuretic use in
children with BPD. In the outpatient setting, thiazides were the most
commonly prescribed diuretic, with most children prescribed either a
thiazide alone (46.4%) or a thiazide and a potassium sparing agent
(44.8%). Interestingly, children on a potassium sparing agent were just
as likely to be prescribed potassium supplementation as those on
non-potassium sparing diuretics. Children who were prescribed loop
diuretics or greater than two diuretics at their first outpatient
pulmonary visit were more likely to have comorbidities, including
tracheostomy, home ventilator use and pulmonary hypertension. Healthcare
providers guided diuretic weaning in the majority of patients and most
children in this study were weaned off diuretics by two years of age.
Diuretic weaning was slower in children born at an earlier gestational
age, who had comorbidities, and who were prescribed loop diuretics.
Children on public insurance also had slower diuretic weaning,
suggesting that socioeconomic barriers to weaning may exist in this
group of children. There was no difference in supplemental oxygen
weaning between those on one or no diuretic, suggesting that home use
may not be necessary in some children with BPD weaning off home
supplemental oxygen.
In our study, thiazide monotherapy or dual therapy with a thiazide and
potassium sparing agent were the most commonly prescribed diuretic(s) in
children with BPD at their first pulmonary outpatient visit. This
finding supports other studies which found that these diuretics are
commonly used in the outpatient setting to treat children with BPD.(20)
In our study we found no significant differences in gestational age,
birthweight, BPD severity, respiratory support requirements or pulmonary
hypertension diagnosis between children on thiazide monotherapy or dual
therapy with a potassium sparing agent. Furthermore, those on a
potassium sparing agent were just as likely to be on electrolyte
supplementation as those on other diuretics. Another study that examined
diuretic use in NICUs across the United States also found only modest
reductions in use of potassium chloride supplementation in infants with
BPD on thiazides plus potassium sparing agents compared to those on
thiazides alone.3 Our findings indicate that the
combination of a thiazide plus a potassium sparing agent may not provide
additional benefit over a thiazide alone, with regard to electrolyte
imbalances.
In the NICU, loop diuretics are commonly used to treat infants with
severe BPD. 2,19 Slaughter et. al., found that
furosemide was the most commonly used diuretic in the NICU, however
thiazides in the NICU were used for the longest duration of
use.19 In our study, we found that only 8.4% of
children were on a loop diuretic at their first outpatient pulmonary
visit. This finding supports a study by Bamat et. al., in which reported
use of loop diuretics at NICU discharge ranged between 13.5% and 5.1%
in children with grade 2 or 3 BPD.2 Although
infrequently used in our outpatient population of BDP children, those
prescribed loop diuretics (n=62) were more likely to be technology
dependent and to be older at NICU discharge compared to those on
non-loop diuretics (n=675). Those on loop diuretics also had a higher
likelihood of home oxygen dependency, gastric tube use and the diagnosis
of pulmonary hypertension. These children were also more likely to
require electrolyte supplementation. Our study indicates that loop
diuretics, although commonly used in the NICU, are less likely to be
prescribed in the outpatient setting in children with BPD; with their
use primarily limited to those with significant disease co-morbidities
and technology dependence. Our study also found that BPD severity in the
NICU at 36 weeks post menstrual age (PMA) did not correlate with timing
of diuretic weaning in the outpatient setting, suggesting that NICU
severity scores at 36 weeks gestation are not predictive of outpatient
diuretic weaning. Not surprisingly however, we found that slower
diuretic weaning was associated with children on home supplemental
oxygen, loop diuretics, inhaled corticosteroids and technology
dependence.
Of further interest, we found that children with BPD on public insurance
in the outpatient setting were more likely to wean slower from
diuretics, compared to children on private insurance. We previously
found that children with BPD on public insurance were more likely to
utilize acute care and have nighttime respiratory symptoms during the
first 3 years of life, suggesting that these children may be sicker as
outpatients and/or have impaired access to timely healthcare.(21) We
also previously found that children on public insurance had delayed
weaning of home supplemental oxygen compared to those on private
insurance.(22) Social determinants of health may be a major factor that
influences rate of weaning diuretics in the outpatient setting in
children with BPD, causing prolonged and possibly unneeded exposure to
diuretics. Although public insurance provides a safety net for children,
those on public insurance may also have greater challenges due to
poverty, access to care, or food insecurity. There is an ongoing need to
understand the relationship between social determinants of health and
outpatient outcomes and medication use in children with BPD.
Interestingly, in the subset of children on home supplemental oxygen we
found no difference in oxygen weaning between those on no diuretics
versus one diuretic. This suggest that children precribed one diuretic
may be unnecessarily exposed to a diuretic when weaning off home
supplemental oxygen. However, we did find that weaning of home oxygen
was slower in those children prescribed 2 or more diuretics. Our
findings suggest that children prescribed two or more diuretics and who
are on home supplemental oxygen, may either have greater lung disease
severity and/or that healthcare providers are more reluctant to wean
supplemental oxygen due to a perception of more severe lung disease.
Our study has limitations including the retrospective nature of the
study and inclusion of only two sites. However, our study included both
children both prescribed or not prescribed diuretics and those on and
off home supplemental oxygen, providing us an opportunity to study
differences in patient characteristics between these groups and to
examine diuretic weaning practices in children on or off home
supplemental oxygen. Although we noted practice variations between the
two sites, thiazides were found to be the most frequently prescribed
diuretic in the outpatient setting, in contrast to loop diuretics which
have been reported to be the most commonly prescribed diuretic in the
inpatient setting. The outpatient preference to use thiazides may
reflect the better safety profile of thiazides compared to loop
diuretics. Future prospective studies are needed to address outpatient
practice variation across diverse geographic areas and to more
comprehensively phenotype patients in the outpatient setting to further
distinguish those who may benefit most from outpatient diuretic usage.
In summary, diuretic use is common in children with BPD in the
outpatient setting. Patient characteristics are similar between those on
one or two diuretics, whereas children on loop diuretics are more likely
to be technology dependent and to have comorbidities, including
pulmonary hypertension. Interestingly, there were no differences in
weaning off home supplemental oxygen between those on one or no
diuretic. Finally, we noted that children on public insurance are more
likely to be weaned slower from diuretics in the outpatient setting.
Further studies are needed to understand how outpatient diuretic use
influences long-term respiratory outcomes in BPD and how social
determinants of health can influence diuretic weaning. Understanding
these associations will help optimize health outcomes and potentially
lessen side-effects of outpatient diuretic use in children with BPD.