DISCUSSION
In this study we investigated which clinical characteristics may be
associated with successful extubation following the commencement of
dexamethasone in less than 30 week GA neonates with BPD. Our analysis
show that after we adjusted for the multiple factors measured, three
factors remained as likely to be prognostically informative. These
included less mature at birth, higher MAP, and greater
FiO2 requirement.
There are very few similar studies: most involving older patient cohorts
and focus on long-term outcomes. Our study is the first looking
specifically at extubation success and the occurrence of both modifiable
and unmodifiable individual patient variables. Cuna17evaluated the outcomes of neonates with evolving BPD who were ventilator
dependent and treated with systemic dexamethasone at either 14-28 days
old vs 29-42 days old. They found that delaying dexamethasone had worse
outcomes; it is difficult to compare Cuna’s study to ours as both the
patient cohort and the primary outcomes differ, and their data do not
allow predicting successful extubation at the time of starting steroids.
A likely explanation as to why the individual variables affect
extubation success is that they either increase the risk of BPD (younger
GA) or are markers of the severity of BPD (MAP and FiO2requirement). Higher MAP and greater FiO2 requirement
will decrease the chance of successful extubation as it is these
neonates that have more severe pulmonary inflammation and require higher
tidal volumes and oxygen delivery for adequate ventilation and
oxygenation. The trends in data (both Table 2 and Table 3 - unadjusted
ORs) support this, as those not successfully extubated by day 14 had
higher MAPs (13, IQR 11-14 cm H2O) and higher average
FiO2 requirements (0.40, IQR 0.33-0.48) compared to
those successfully extubated MAP (11, range 10-12 cm
H2O) and FiO2 (0.35, range 0.30-0.39).
These neonates were also less mature at birth putting them at greater
risk of BPD. They also had a higher proportion of grade 3 or 4 CXR
changes (66% vs 32%) and higher proportion on HFOV use (41% vs 21%).
The higher proportion of neonates requiring HFOV in this study cohort is
noteworthy, given that its use is predominantly as a rescue strategy
once conventional ventilation was no longer adequate. Whilst we have
identified variables associated with failing extubation, it is important
to acknowledge which are potentially modifiable, and therefore which
factors we as clinicians, can act on to maximise the chances of
successful extubation in this high-risk population. Given the large
variability of MAP and FiO2 requirement we cannot
provide cut-off values at which they are no longer negatively predictive
of successful extubation, so clinical acumen is required. It is a
balance between the risk and benefit of staying on the ventilator to
achieve lung growth and potentially decrease FiO2 and
MAP requirements versus risking extubation failure and increasing the
number of repeated ventilation courses which we know is
detrimental.1 It would be require a randomised
controlled trial to investigate such strategies.
Another
counter-intuitive finding is that we could not demonstrate the starting
dose of dexamethasone to be associated with successful extubation.
Having said this, the retrospective nature of this observational study
means we were unable to systematically vary neither dose or duration
independent of other clinical variables. Different clinicians made these
decisions based on a variety of factors, several of which, were possibly
not recorded in our dataset. To clarify this issue we would suggest
performing a prospective study.
There
were some limitations to this study. Its retrospective nature means that
the reasoning for the timing of dexamethasone treatment is unknown.
There may also have been a confounding effect in our study related to
practice variation (across the ten-year period) in practices not related
to dexamethasone prescription including but not limited to feeding
methodology, medication types, parenteral nutrition usage, and some
subtle changes to ventilation practices. It was not possible within the
constraints of this dataset to control for these variables. The results
may also not be generalizable to other neonatal units with different
extubation practices and, given the complexity, a larger sample
collected from across multiple neonatal units may be useful.
The strengths of this study include a comparatively large sample size
and that as far as we know prescribing practices for dexamethasone
remained consistent across the duration of the study. All neonates
receiving systemic dexamethasone older than 7 days of
age.9 A potential decrease in confounding could be
inferred from the reasonable sample size of our study allowing
multivariable analysis to adjust for multiple confounding factors
including GA, weight and postnatal age.
This study has established a number of factors present at the onset of
the first course of dexamethasone are predictive of extubation success.
However further work could be done: a more comprehensive multi-centre
prospective study which would allow first, a better understanding of the
suitability and utility in deferring steroid treatment, and second, the
development of prognostic scoring models.