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Hypercapnia occurs in ventilated infants even if tidal volume (V T ) and minute ventilation (V E ) are maintained. We hypothesised that increased physiological dead space (V d,phys ) caused decreased minute alveolar ventilation (V A ; alveolar ventilation (V A ) × respiratory rate) in well-ventilated infants with hypercapnia. We investigated the relationship between dead space and partial pressure of carbon dioxide (PaCO 2 ) and assessed V A . Intubated infants (n = 33; mean birth weight, 2257 ± 641 g; mean gestational age, 35.0 ± 3.3 weeks) were enrolled. We performed volumetric capnography (V cap ), and calculated V d,phys and V A when arterial blood sampling was necessary. PaCO 2 was positively correlated with alveolar dead space (V d,alv ) (r = 0.54, p &lt; 0.001) and V d,phys (r = 0.48, p &lt; 0.001), but not Fowler dead space (r = 0.14, p = 0.12). Normocapnia (82 measurements; 35 mmHg ≤ PaCO 2 &lt; 45 mmHg) and hypercapnia groups (57 measurements; 45 mmHg ≤ PaCO 2 ) were classified. The hypercapnia group had higher V d,phys (median 0.57 (IQR, 0.44-0.67)) than the normocapnia group (median V d,phys /V T = 0.46 (IQR, 0.37-0.58)], with no difference in V T . The hypercapnia group had lower V A (123 (IQR, 87-166) ml/kg/min) than the normocapnia group (151 (IQR, 115-180) ml/kg/min), with no difference in V E .Conclusion: Reduction of V A in well-ventilated neonates induces hypercapnia, caused by an increase in V d,phys . What is Known: • Volumetric capnography based on ventilator graphics and capnograms is a useful tool in determining physiological dead space of ventilated infants and investigating the cause of hypercapnia. What is New: • This study adds evidence that reduction in minute alveolar ventilation causes hypercapnia in ventilated neonates.

Reduction in minute alveolar ventilation causes hypercapnia in ventilated neonates with respiratory distress