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Determinants of end-tidal carbon dioxide measurement reliability in neonatal ventilation: a bench lung simulation study

Pediatric Research (2026) Cite this article

Abstract

Background

End-tidal carbon dioxide (ETCO₂) monitoring is used in the neonatal intensive care unit to estimate arterial carbon dioxide as a measure of ventilation efficacy; however, lung mechanics and circuit-related factors can affect measurement reliability.

Methods

Using a bench neonatal lung simulator, we varied lung compliance (0.5–2.0 mL/cmH₂O), airway leak (0 to >45%), and apparatus dead space (5.5–9.1 mL) during pressure-controlled ventilation while alveolar carbon dioxide was held constant at 40 mmHg. Regression and receiver operating characteristic analyses were used to identify factors associated with reliable ETCO₂ measurement, defined as ETCO₂ ≥ 33.26 mmHg (≈83% of 40 mmHg).

Results

Measurement reliability improved with increasing compliance, particularly under higher leak and larger dead space. Reliable ETCO₂ measurements were best predicted by expiratory tidal volume >12.6–14.0 mL (AUC 0.927–0.931) and an expiratory tidal volume–to–dead-space ratio >1.82 (AUC 0.984).

Conclusion

Reliable end-tidal carbon dioxide measurement depends on compliance, leak, and dead space; minimizing apparatus dead space and accounting for leak are essential, especially when expiratory tidal volume is small relative to dead space.

Impact

  • This study quantifies how lung compliance, airway leak, and dead space interact to determine ETCO₂ measurement reliability during neonatal ventilation.

  • It clarifies measurement-related mechanisms that contribute to discrepancies between ETCO₂ and PaCO₂ in preterm infants.

  • These findings can guide improvements in capnography technology and more individualized ventilator management in NICU settings.

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Fig. 1: Experimental setup for the neonatal lung model simulation.
The alternative text for this image may have been generated using AI.
Fig. 2: Representative waveforms of measured ETCO₂_vent, flow, and airway pressure at different lung compliances.
The alternative text for this image may have been generated using AI.
Fig. 3: Effect of lung compliance on measured end-tidal CO₂ at the ventilator side (ETCO₂_vent) across leak ranges and added dead space conditions.
The alternative text for this image may have been generated using AI.
Fig. 4: Relationship between lung compliance and measured ETCO₂_vent across leak ranges and added dead space conditions.
The alternative text for this image may have been generated using AI.
Fig. 5: Relationship between expiratory tidal volume (TVexp) and measured ETCO₂_vent across added dead space conditions.
The alternative text for this image may have been generated using AI.
Fig. 6: Receiver operating characteristic (ROC) analysis for predicting reliable ETCO₂_vent measurement.
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Data availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank an external technical support team for assistance with equipment setup, capnography integration, and troubleshooting.

Author information

Authors and Affiliations

  1. Division of Neonatology, Fukuda Hospital, Kumamoto, Japan

    Daijiro Takahashi & Koko Goto

  2. Division of Pediatrics, Fukuda Hospital, Kumamoto, Japan

    Daijiro Takahashi & Kei Goto

Authors
  1. Daijiro Takahashi
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  2. Koko Goto
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  3. Kei Goto
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Contributions

D.T. conceptualized and designed the study, conducted experiments, analyzed data, and drafted the manuscript. K.G. (Koko Goto) contributed to data interpretation and manuscript revision. K.G. (Kei Goto) contributed to data interpretation and critically revised the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Daijiro Takahashi.

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The authors declare no competing interests.

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Takahashi, D., Goto, K. & Goto, K. Determinants of end-tidal carbon dioxide measurement reliability in neonatal ventilation: a bench lung simulation study. Pediatr Res (2026). https://doi.org/10.1038/s41390-026-05122-0

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