Discussion:
Understanding the capacity of critical body organs to compensate for
short periods of hypoxemia is important to individualize the acceptable
SpO2 and crRTO for sick preterm infants. The degree of
this compensation is largely dependent upon the ability of the cerebral
vasculature to autoregulate blood flow and thus buffer brain
oxygenation, and there is a gap in literature regarding mechanisms of
compensation in infants with HRF(12,13). In this study we assessed
patterns of CAR in preterm infants with HRF through graded stepwise
reduction of FiO2, aiming to test the concordance
between SpO2 and crRTO which represents integrity of
autoregulation(26–28). Monitoring oxygen by pulse oximetry has several
limitations, including different calibration between different devices,
and the SpO2 on the monitor is a calibrated mean between
2 standard deviations, this might increase the chances of hyperoxia with
higher delivered FiO2(29,30). Autoregulatory mechanism
is induced by a local vasodilator effect through local release of nitric
oxide from red blood cells when there is decrease of oxygen delivery,
and augments blood flow to buffer low delivery of oxygen; this serves as
the initial brain rescue step in hypoxemia (13,31). In some preterm
infant this CAR might be impaired as a consequence of prematurity or
severity of sickness, and it is almost absent for early postnatal
transition period in very premature infants and increased oxygen
extraction is the main compensatory mechanism with impaired or
compromised autoregulation (32,33). Infants with intact CAR (group 1)
had low FOE, reasoning in reverse, we infer that maintenance of a normal
crRTO and a low FOE signifies that CAR is still able to compensate for
desaturations. Where FOE maintained or decreases as SpO2decreases (as in figure 1B), it means that the brain tissue does not
need to increase oxygen extraction to compensate for the decreased
hemoglobin oxygen saturation, as CAR is compensating by increasing the
volume of brain blood flow(20). In infants with impaired CAR (group 2)
linear fluctuations of both SpO2 and crRTO trigger mirror image
fluctuations of FOE, and increased FOE will immediately maintain
cerebral oxygen demands (figure 2B), while SpO2, crRTO
and HR are positively correlated. This concordance may represent
sensitivity of SA node and chemoreceptors to brief hypoxemic episodes.
We speculate that mild tachycardia during desaturations signifies intact
autoregulation, but bradycardia represents failure of the sinoatrial
node to continue firing at a physiologic rate due to energy compromise
secondary to hypoxia. The strong positive correlation between
SpO2 and HR in infants in group 2 signifies impaired CAR
at the SA node level resulting in frequent bradycardia, which would also
contributing to compromise of cerebral blood flow and oxygen
delivery(16). Understanding the safe ranges of FiO2 at
which SpO2 and crRTO are acceptable is considered
helpful to individualize titration of inspired oxygen, aiming to avoid
either cerebral hypoxia or hyperoxia(29). We utilized this approach to
titrate FiO2 only in group 1 infants with intact CAR, in
whom we were able to wean FiO2 significantly and this is
after teaching the nurses on how to wean oxygen according to both SpO2
and crRTO simultaneously. This oxygen titration approach was avoided in
infants with a group 2 pattern of impaired autoregulation and arterial
saturation-dependent oxygen delivery, this new physiologic approach was
approved by our patient care committee as a standard of care.
This is the first study to our knowledge reporting CAR in preterm
infants with HRF. The strength of our study is the development of a
practical bedside application with direct clinically relevance to
management of HRF. The main limitation is the retrospective design of
the study, absence of long term follow up, and the small sample size,
although this report can be considered as a quality assessment of the
approved patient care protocol. The methods used here also cannot
distinguish a FOE decrease due to a primary impairment of tissue oxygen
utilization; however, infants studied were medically stable and
non-septic, rendering toxic impairment of oxygen uptake unlikely.