Unstable SpO₂ in preterm infants: The key role of reduced ventilation to perfusion ratio

Introduction: Instability of peripheral oxyhemoglobin saturation (SpO₂) in preterm infants is correlated with late disability and is poorly understood. We hypothesised that a reduced ventilation to perfusion ratio (V_A/Q) is the key predisposing factor for SpO₂ instability. Methods: We first used a mathematical model to compare the effects of reduced V_A/Q or shunt on SaO₂ stability (SaO₂ and SpO₂ are used for model and clinical studies respectively). Stability was inferred from the slope of the SaO₂ vs. inspired oxygen pressure (P _IO₂) curve as it intersects the 21 kPa P _IO₂ line (breathing air). Then, in a tertiary neonatal intensive care unit, paired hourly readings of SpO₂ and P _IO₂ were recorded over a 24 h period in week old extremely preterm infants. We noted SpO₂ variability and used an algorithm to derive V_A/Q and shunt from the paired SpO₂ and P _IO₂ measurements. Results: Our model predicted that when V_A/Q < 0.4, a 1% change in P _IO₂ results in >8% fluctuation in SaO₂ at 21 kPa P _IO₂. In contrast, when a 20% intrapulmonary shunt was included in the model, a 1% change in P _IO₂ results in <1% fluctuation in the SaO₂. Moreover, further reducing the V_A/Q from 0.4 to 0.3 at 21 kPa P _IO₂ resulted in a 24% fall in SaO₂. All 31 preterm infants [mean gestation (±standard deviation) 26.2 (±1) week] had V_A/Q < 0.74 (normal >0.85) but only two infants had increased shunt at 1.1 (±0.5) weeks' postnatal age. Median (IQR) SpO₂ fluctuation was 8 (7)%. The greatest SpO₂ fluctuations were seen in infants with V_A/Q < 0.52 (n = 10): SpO₂ fluctuations ranged from 11%-17% at a constant P _IO₂ when V_A/Q < 0.52. Two infants had reduced V_A/Q and increased shunt (21% and 27%) which resolved into low V_A/Q after 3-6 h. Discussion: Routine monitoring of P _IO₂ and SpO₂ can be used to derive a hitherto elusive measure of V_A/Q. Predisposition to SpO₂ instability results from reduced V_A/Q rather than increased intrapulmonary shunt in preterm infants with cardiorespiratory disease. SpO₂ instability can be prevented by a small increase in P _IO₂.