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.