Expired CO2 levels indicate degree of lung aeration at birth

Abstract

As neonatal resuscitation critically depends upon lung aeration at birth, knowledge of the progression of this process is required to guide ongoing care. We investigated whether expired CO2 (ECO2) levels indicate the degree of lung aeration immediately after birth in two animal models and in preterm infants. Lambs were delivered by caesarean section and ventilated from birth. In lambs, ECO2 levels were significantly (p<0.0001) related to tidal volumes and CO2 clearance/breath increased exponentially when tidal volumes were greater than 6 mL/kg. Preterm (28 days of gestation; term = 32 days) rabbits were also delivered by caesarean section and lung aeration was measured using phase contrast X-ray imaging. In rabbit kittens, ECO2 levels were closely related (p<0.001) to lung volumes at end-inflation and were first detected when ∼7% of the distal lung regions were aerated. ECO2 levels in preterm infants at birth also correlated with tidal volumes. In each infant, ECO2 levels increased to >10 mmHg 28 (median) (21-36) seconds before the heart rate increased above 100 beats per minute. These data demonstrate that ECO2 levels can indicate the relative degree of lung aeration after birth and can be used to clinically assess ventilation in the immediate newborn period.

Figure 1. Expired CO₂ levels, airway pressure and tidal volumes in a newborn lamb immediately after birth.

Expired CO₂ levels (ECO₂) are demonstrated in the top panel, airway pressure in the middle panel and tidal volumes (V_T) in the bottom panel. The lamb was resuscitated with five 3 second inflations (last 4 shown) followed by tidal ventilation. The first 3 inflations yielded no ECO₂, despite achieving a V_T of 5–7 mL, whereas the 4^th and 5^th inflations produced small increases in ECO₂ levels. Subsequent inflations produced a gradual increase in both ECO₂ levels and V_T.

Figure 2. Expired CO₂ levels and tidal volumes measured in a newborn lamb during the first 18 minutes after birth.

Expired CO₂ levels (ECO₂) are demonstrated in the top panel and tidal volumes (V_T) in the bottom panel. Tidal volumes were increased at “A” and “B” by increasing the inflation pressure and then the ventilation mode was changed to volume guarantee at “C” to target a V_T of 8 mL/kg. ECO₂ levels and V_T were closely associated.

Figure 3. Relationship between expired CO₂ levels at end-expiration and tidal volumes in lambs.

Figure 4. Lung gas volumes, airway pressures and expired CO₂ levels in a ventilated newborn rabbit delivered preterm at 28 days of gestation.

Lung gas volumes are demonstrated in the top panel, airway pressures in the middle panel and expired CO₂ (ECO₂) levels in the bottom panel. Images A and B were acquired at the times indicated by the arrows. The increase in ECO₂ levels closely followed the increase in end-inflation lung volumes. All of the corresponding phase contrast X-ray images have been compiled into Movie S1.

Figure 5. Relationship between expired CO₂ levels and end-inflation lung gas volumes in ventilated newborn rabbits delivered preterm at 28 days of gestation.

All data points are mean ± SEM and the relationship was highly significant (p<0.001), with an r² value of 0.93.

Figure 6. Lung gas volumes, airway pressures and expired CO₂ levels in 4 ventilated newborn rabbits delivered preterm at 28 days of gestation.

Lung gas volumes are demonstrated in the top panel, airway pressures in the middle panel and expired CO₂ (ECO₂) levels in the bottom panel. Functional residual capacity (FRC) and end-inflation lung volumes (EILV) are indicated on the lung volume trace. Changes in ECO₂ levels closely followed changes in end-inflation lung volumes caused by altering ventilation parameters. The corresponding phase contrast X-ray images, compiled into a movie, for kitten 4 are displayed in Movie S2.

Figure 7. Airway pressure, gas flow, expired CO₂ levels and tidal volumes measured in a preterm infant during positive pressure ventilation.

This preterm infant received positive pressure ventilation that was initially applied via facemask and then followed by intubation. Before intubation, little expired CO₂ (ECO₂) could be detected, despite a good tidal volume (V_T) and no detectable facemask leak. Following intubation, ECO₂ levels rapidly increased with increasing V_T and preceded the increase in heart rate, which increased from 75 beats/min at “A” to 100 beats/min at “B”.

Figure 8. Maximum expired CO₂ levels against tidal volume in preterm infants.

A demonstrates data from all preterm infants studied (A; n = 10 infants and 517 breaths). The individual relationships between ECO₂ and V_T for each infant are displayed in (B) and (C) for clarity.