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Biochemical shunt: where and how?

Mattia Busana, Luigi Camporota, Luciano Gattinoni
European Respiratory Review 2022 31: 220148; DOI: 10.1183/16000617.0148-2022
Mattia Busana
1Department of Anesthesiology, University Medical Center Göttingen, Göttingen, Germany
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Luigi Camporota
2Department of Adult Critical Care, Guy's and St Thomas’ NHS Foundation Trust, Health Centre for Human and Applied Physiological Sciences, London, UK
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Luciano Gattinoni
1Department of Anesthesiology, University Medical Center Göttingen, Göttingen, Germany
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  • For correspondence: gattinoniluciano@gmail.com
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Abstract

Response to Harutyunyan et al. “Hypoxaemia in the early stage of COVID-19: prevalence of physical or biochemical factors?” https://bit.ly/3K1NSKu

Reply to G. Harutyunyan and co-workers:

G. Harutyunyan and co-workers, in their reply to our correspondence, introduce the fascinating concept of “biochemical shunt” to help explain some of the gas exchange abnormalities reported in patients with early coronavirus disease 2019 (COVID-19). In brief, they assert the plausibility that the oxyhaemoglobin dissociation curve (ODC), which may be normal in the arterial and venous blood, could be altered (i.e. reduced oxygen affinity) in the pulmonary blood flowing through diseased alveolar capillaries. It is not easy for us to understand which COVID-19-related factors, or metabolites, might alter the ODC specifically in the pulmonary circulation, and to what extent they involve the lung parenchyma (partially or totally, where and why). Let us suppose, for example, that the biochemical shunt occurs in the whole parenchyma (nearly fully ventilated in early COVID-19). Let us assume that these COVID-19 patients are treated with an inspiratory oxygen fraction of 40% and they are able to maintain an arterial carbon dioxide tension (PaCO2) of 40 mmHg. The lung capillary oxygen tension (PO2), in equilibrium with alveolar PO2 (PAO2), will be around 235 mmHg (at a respiratory quotient of 0.8). Even assuming a dramatic right shift of the ODC (as may occur with a pH 7.0, a carbon dioxide tension (PCO2) of 40 mmHg, and 2,3-diphosphoglycerate of 1.6 mM, i.e. double the normal concentration), with a capillary PO2 of 235 mmHg, the haemoglobin oxygen saturation would be 99.5% [1], 99.8% [2] or 98.7% [3], depending on which equation is used. It is even more difficult to accept the biochemical shunt if the alteration to the ODC occurs only, as an example, in 50% of the lung parenchyma.

We have also some problems in conceptualising the discussion of G. Harutyunyan and co-workers about the PaCO2–end-tidal carbon dioxide tension (PETCO2) gap. Shunt or, more correctly, the venous admixture, does affect the alveolar–arterial PCO2 (PACO2–PaCO2 gap), while the PETCO2–PACO2 gap is a function of the alveolar dead space. Therefore, in the ideal gas exchanger, the PETCO2/PaCO2 ratio is an indicator of the overall gas exchange efficiency in the lung, which includes both shunt and dead space fractions [4]. A ratio of 1 would indicate the “perfect” gas exchanger, i.e. no shunt and no dead space. This is the physiological background of the paper from Lazzari et al. [5].

Finally, if we set aside the Riley's approach, more commonly used for the definition of shunt and dead space, and we refer to a continuous distribution of ventilation and perfusion and their mismatch, it is worth remembering that the ventilation–perfusion mismatch affects both oxygen and carbon dioxide exchange, which must always be considered together [6]. We remain, however, interested to learn about these local metabolic or endothelial factors that affect the ODC selectively in the alveolar capillaries, but not in the systemic blood, and their quantitative contribution to the gas exchange abnormalities seen in COVID-19.

Footnotes

  • Provenance: Invited article, peer reviewed.

  • Conflict of interest: L. Gattinoni reports the following relationships outside the submitted work: grants or contracts received from Estor; royalties or licence from SIDAM; consulting fees from Estor, SIDAM, Medtronic and General Electric; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events for General Electrics and Estor; patents planned, issued or pending for SIDAM. The remaining authors have nothing to disclose.

  • Received August 8, 2022.
  • Accepted August 12, 2022.
  • Copyright ©The authors 2022
http://creativecommons.org/licenses/by-nc/4.0/

This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions{at}ersnet.org

References

  1. ↵
    1. Kelman GR
    . Digital computer subroutine for the conversion of oxygen tension into saturation. J Appl Physiol 1966; 21: 1375–1376. doi:10.1152/jappl.1966.21.4.1375
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    1. Severinghaus JW
    . Simple, accurate equations for human blood O2 dissociation computations. J Appl Physiol Respir Environ Exerc Physiol 1979; 46: 599–602.
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    2. Swenberg ML,
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    Oxygen equilibrium curve of normal human blood and its evaluation by Adair's equation. J Biol Chem 1977; 252: 2331–2337. doi:10.1016/S0021-9258(17)40559-X
    OpenUrlAbstract/FREE Full Text
  4. ↵
    1. Bonifazi M,
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    3. Busana M, et al.
    End-tidal to arterial PCO2 ratio: a bedside meter of the overall gas exchanger performance. Intensive Care Med Exp 2021; 9: 21. doi:10.1186/s40635-021-00377-9
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  5. ↵
    1. Lazzari S,
    2. Romitti F,
    3. Busana M, et al.
    End-tidal to arterial PCO2 ratio as guide to weaning from veno-venous extra-corporeal membrane oxygenation. Am J Respir Crit Care Med 2022; in press [https://doi.org/10.1164/rccm.202201-0135OC].
  6. ↵
    1. West JB
    . Causes of and compensations for hypoxemia and hypercapnia. Compr Physiol 2011; 1: 1541–1553. doi:10.1002/cphy.c091007
    OpenUrl
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Biochemical shunt: where and how?
Mattia Busana, Luigi Camporota, Luciano Gattinoni
European Respiratory Review Sep 2022, 31 (165) 220148; DOI: 10.1183/16000617.0148-2022

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Biochemical shunt: where and how?
Mattia Busana, Luigi Camporota, Luciano Gattinoni
European Respiratory Review Sep 2022, 31 (165) 220148; DOI: 10.1183/16000617.0148-2022
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