Introduction:
Since many preterm infants have impaired lung function, oxygen is one of
the most common therapies in neonatal medicine(1). However, preterm
infants are also particularly sensitive to the harmful effects of
oxygen(2,3). Highly reactive free oxygen radicals cause cellular
injury(4). Preterm infants are not adequately protected from such direct
biochemical oxidative stress(3,5–7). Oxygen saturation, blood flow and
hemoglobin are the three main components of oxygen delivery, and relying
solely on arterial oxygen saturation may not adequately monitor tissue
exposure to either hypoxia or hyperoxia(8–10). What is the optimal
target arterial oxygen saturation as measured by pulse oximetry
(SpO2) in infants with hypoxemic respiratory failure
(HRF) in the neonatal intensive care unit (NICU), is still an unanswered
question(3,5,11). Despite many recent large-scale studies, it is unclear
if either low or high target oxygen saturation is safe, provides
adequate organ oxygen delivery, and at the same time limits oxygen
toxicity and accumulation of reactive oxygen species(3). Accepting lower
oxygen saturation targets in infants with acute lung injury may limit
toxic oxygen exposure, and enable weaning of inspired oxygen over a
shorter period of time(5). However the outcome using this approach is
dependent upon the ability of the organs to autoregulate blood
flow(12,13). Cerebral autoregulation is defined as the interaction
between locally released nitric oxide from red blood cells (RBCs), and
the vasodilator ability of the arterioles in tissues, in order to
protect oxygen delivery during active tissue metabolism and maintain
oxygen saturation of the brain during hypoxemic episodes, in a setting
of acceptable hemoglobin, carbon dioxide (CO2) and
normal cerebral blood flow (12,14,15). In preterm infants, we do not
know if CAR can adequately protect the brain during even brief periods
of desaturation or intermittent hypoxemia(16). Our group has developed
an integrated approach set-up to provide us with the novel ability to
longitudinally measure cerebral autoregulation in real time, in infants
undergoing cerebral oxygen and hemodynamics monitoring(17–19). Although
it is standard of practice in modern neonatal intensive care units to
monitor SpO2 via pulse oximetry, a limited number of
units (including our unit) use near infrared spectroscopy (NIRS) to
monitor tissue oxygenation, and there is insufficient evidence that
either mild desaturations or hypoxemia impact cerebral autoregulation.
Understanding the temporal relationship between desaturation and
cerebral blood flow autoregulation should lead to individualized safer
weaning of oxygen while maintaining the integrity of CAR(18,20,21).
We hypothesized that CAR can compensate for short periods of hypoxemia
or desaturation in preterm infants with normal hemodynamics and
hemoglobin, thus maintaining brain oxygen tension, and this compensatory
role of CAR can be clinically recognized as low SpO2 below target limits
but crRTO is maintained without change.