Mechanisms underlying rapid arterial hypoxaemia during apnea in the preterm infant

Apnea, defined as cessation of breathing, is one of the most common clinical problems in neonatal intensive care, occurring in virtually all preterm infants. Given the brain and growth impairment that accompanies apnea and arterial desaturation (blood oxygen lack), the primary motivation for the studies carried out in this thesis was to explain the strikingly rapid desaturation that develops during cyclic apnea in preterm infants, where oxygen levels are halved in just 6-7 seconds. The first objective was to develop a mathematical model of the preterm infant. Use of this model showed that elevated metabolic oxygen consumption accelerates desaturation throughout apnea. By contrast, each other factor has a specialised impact: low ventilation causes an early onset of desaturation but thereafter has little impact; reduced lung volume, red-blood cell content and cardiac output accelerate desaturation rate in the early phase of arterial desaturation, and finally, only whole body oxygen capacity (blood volume and red-blood cell content) determines the desaturation in the late phase of apnea when desaturation becomes life threatening. Further development of the model to describe non-ideal gas exchange in the forms of diffusion limitation and ventilation-perfusion mismatch, revealed that these factors unexpectedly have little impact on desaturation rate, causing an earlier onset of desaturation but not a faster peak desaturation rate. Finally, in a combined modelling and experimental lamb study, the thesis shows that a first apnea causes venous desaturation that persists into a second apnea; consequently a transient surge in lung-to-blood oxygen transfer during the second apnea rapidly depletes lung oxygen stores and in turn yields rapid desaturation. This finding establishes that severe desaturation inevitably occurs during a sequence of brief apneas and may provide a pathophysiological explanation for the neurocognitive and cardiovascular consequences of breathing disorders that manifest cyclic recurrent apnea.