How Do We Monitor Oxygenation during the Management of PPHN? Alveolar, Arterial, Mixed Venous Oxygen Tension or Peripheral Saturation?

Abstract

Oxygen is a pulmonary vasodilator and plays an important role in mediating circulatory transition from fetal to postnatal period. Oxygen tension (PO₂) in the alveolus (PAO₂) and pulmonary artery (PaO₂) are the main factors that influence hypoxic pulmonary vasoconstriction (HPV). Inability to achieve adequate pulmonary vasodilation at birth leads to persistent pulmonary hypertension of the newborn (PPHN). Supplemental oxygen therapy is the mainstay of PPHN management. However, optimal monitoring and targeting of oxygenation to achieve low pulmonary vascular resistance (PVR) and optimizing oxygen delivery to vital organs remains unknown. Noninvasive pulse oximetry measures peripheral saturations (SpO₂) and a target range of 91-95% are recommended during acute PPHN management. However, for a given SpO₂, there is wide variability in arterial PaO₂, especially with variations in hemoglobin type (HbF or HbA due to transfusions), pH and body temperature. This review evaluates the role of alveolar, preductal, postductal, mixed venous PO₂, and SpO₂ in the management of PPHN. Translational and clinical studies suggest maintaining a PaO₂ of 50-80 mmHg decreases PVR and augments pulmonary vasodilator management. Nevertheless, there are no randomized clinical trials evaluating outcomes in PPHN targeting SpO₂ or PO₂. Also, most critically ill patients have umbilical arterial catheters and postductal PaO₂ may not be an accurate assessment of oxygen delivery to vital organs or factors influencing HPV. The mixed venous oxygen tension from umbilical venous catheter blood gas may assess pulmonary arterial PO₂ and potentially predict HPV. It is crucial to conduct randomized controlled studies with different PO₂/SpO₂ target ranges for the management of PPHN and compare outcomes.

Keywords: PPHN; oxygen tension; oxygenation.

Figure 1

The primary determinant of hypoxic pulmonary vasoconstriction is the precapillary pulmonary arteriole. The oxygen tension at this site is determined by alveolar PAO₂ and pulmonary arterial PO₂. In the absence of lung disease, pulmonary venous PO₂ and alveolar PAO₂ are usually similar. In the absence of significant shunts, preductal PaO₂ is reflective of pulmonary venous PO₂. Umbilical venous PO₂ is similar to mixed venous PO₂ and pulmonary arterial PO₂ in the absence of a left-to-right atrial/ductal shunt. Oxygen delivery to the brain and heart is based on preductal PaO₂ and SpO₂. Postductal PaO₂ (from an umbilical arterial line) can be low and does not predict PVR or oxygen delivery to vital organs. Copyright Satyan Lakshminrusimha.

Figure 2

Created using data from Custer et al. [31]. Importance of alveolar hypoxia in directing lung blood flow. Neonatal lambs and adult sheep were instrumented. Each lung was intubated with a different endotracheal tube. One lung was ventilated with 100% oxygen and the other test lung with varying concentrations of oxygen mixed with nitrogen. Relative distribution of perfusion was calculated with Qp1 (blood flow to test lung) and Qp2 (blood flow to the 100% oxygen lung) using the formula shown in the figure. Lower PAO₂ had a profound effect on pulmonary vasoconstriction in newborn ovine model (red line) compared to adults (blue line).

Figure 3

A graph depicting the relationship of inspired oxygen, PVR, left pulmonary blood flow, arterial oxygenation and preductal SpO₂ is illustrated in an ovine model of meconium aspiration model with PPHN. [36] The pulmonary vascular resistance (PVR—brown cross), pulmonary blood flow (Qp—purple open circles), FiO₂ (blue circles) and PaO₂ (red squares) at different preductal saturation (SpO₂) ranges are shown. Preductal SpO₂ in high 80 s resulted in high PVR and low Qp. Preductal SpO₂ in the low−90 s was associated with increased PaO₂, increased Qp, low FiO₂ and high PVR (due to high pulmonary arterial pressure–not shown). Preductal SpO₂ in the mid−90 s was associated with FiO₂ in the 0.5 range with lowest PVR, highest Qp in this model. Increasing FiO₂ to 1.0 increased PaO₂ and SpO₂ but did not result in further increase in Qp or decrease in PVR. For detailed statistical analysis, please refer to Rawat et al. [36]. Copyright Satyan Lakshminrusimha.

Figure 4

The scatterplot between PVR and PVO₂ is shown in (A) meconium aspiration model and (B) preterm RDS model. The PVO₂ was obtained from the main pulmonary artery blood gas. The MCMC model using SAS 9.4 (NC) estimated change point. Copyright MR/PC/SL.

Figure 5

The relation between SpO₂ (y-axis) and PaO₂ (x-axis) in hypothermia and normothermia is shown. In normothermia and hypothermia, the relationship between SpO₂ and PaO₂ is altered. Targeting a preductal corrected PaO₂ of 50–80 mmHg may require preductal SpO₂ in the mid- to high 90 s during management of severe PPHN on whole body hypothermia. Copyright Satyan Lakshminrusimha.