# The concepts of venous admixture and shunt

This chapter is most relevant to Section F6(v) from the 2023 CICM Primary Syllabus, which expects the exam candidates to be able to "explain the concept of shunt", and to Section F6(vi), which asks them to "explain venous admixture, its relationship to shunt and ventilation-perfusion
(V/Q) mismatch".
This specific matter has appeared in Question 6 from the second paper of 2009. The fact that it has only appeared once should not discourage exam candidates from becoming familiar with the topic, as it is fairly fundamental. If one's eyes glaze over from the discussion of the difference between venous admixture and shunt, then at the very least the Berggren equation should be firmly understood and committed to memory, because it is fair game for future questions and viva stations.

In summary:

• Shunt is the blood which enters the systemic arterial circulation without participating in gas exchange
• Venous admixture is that amount of mixed venous blood which would have to be added to ideal pulmonary end-capillary blood to explain the observed  difference between pulmonary end-capillary PO2 and arterial PO2
• Shunt fraction is the calculated ratio of venous admixture to total cardiac output
• The shunt equation, otherwise known as the Berggren equation, is used to calculate the shunt fraction:
Qs/Qt = (CcO2 - CaO2) / (CcO2 - CvO2)
where
Qs/Qt = shunt fraction (shunt flow divided by total cardiac output)
CcO2 = pulmonary end-capillary O2 content, same as alveolar O2 content
CaO2 = arterial O2 content
CvO2 = mixed venous O2 content
• Sources of venous admixture include:
• "True" intrapulmonary shunt, blood which passes through lung regions where V/Q = 0
• V/Q scatter, blood which passes through lung regions where V/Q < 1.0
• Thebesian veins, which contribute myocardial venous blood with low oxygen content
• Bronchial veins,  which drain the bronchial walls
• Intracardiac right-to-left shunts
• Normal shunt fraction in healthy adults breathing room air is said to be close to 0% (probably 0.4-1%)
• Normal venous admixture is usually about 3% of the cardiac output.

The most detailed explanation of these concepts can be found in "Understanding the meaning of the shunt fraction calculation" by Cruz & Metting (1987), but this article is not freely available, and by virtue of being comprehensive may be unreasonable for last-minute revision. A better reference is probably Bigeleisen (2001), which is not only a free article, but also one which was written with the express intention of explaining these concepts to people who are then expected to teach others.

## The relationship of venous admixture to shunt

What is "shunt"? An authoritative-sounding document from the 1970s ("Glossary on respiration and gas exchange", Hughes et al, 1973) defines it as :

"Vascular connection between circulatory pathways so that venous blood is diverted into vessels containing arterialized blood"

So, that's clearly not the sort of shunt we are talking about here. For respiratory physiology,Wests' (p.68 of the 10th edition) defines shunt as:

"blood that enters the arterial system without going through ventilated areas of the lung"

West does not try to make a distinction between venous admixture and shunt, but in other textbooks (Nunn's and Levitzky included) the two terms are made distinct. In the 8th edition of Nunn's (p. 123), venous admixture is defined as:

"the degree of admixture of mixed venous blood with pulmonary endcapillary blood that would be required to produce the observed difference between the arterial and the pulmonary end-capillary PO2 (usually taken to equal ideal alveolar PO2)"

Thus, "venous admixture" is the calculated estimate of how much hypoxic blood would be required to produce the measured arterial oxygen results, for a given cardiac output. It is a volume of deoxygenated blood from the venous circulation which appears to have bypassed the lungs, not participating in any gas exchange.

So... How is this different to shunt? Well. The two terms are often used interchangeably. For the editors of Nunn's, the confusion in students must have been viewed as having such magnitude as to warrant a brief subsection on the nomenclature, at the end of which the authors admitted that, even though the two concepts are distinct, "venous admixture is ...often loosely termed shunt".

However, venous admixture is not shunt. It is a calculated volume which appears to have bypassed the pulmonary gas exchange surface.  It is the product of the shunt equation, which assumes that there are only two kinds of alveoli (perfectly ventilated and perfectly collapsed).  "True" intrapulmonary shunt, in contrast, is the volume of venous blood which actually bypassed the aerated alveoli, and returned deoxygenated blood to the left heart via the pulmonary circulation. "True" shunt does not integrate the contribution of Thebesian veins and alveolar regions with V/Q ratios between 0 and 1.0, or any other added sources of extra venous blood contributing to the systemic circulation (like intracardiac right-to-left shunts) and therefore the calculated venous admixture volume will usually be larger.

Thus, venous admixture does not accurately estimate the volume of true intrapulmonary shunt, nor does it help to determine exactly where that extra venous blood is coming from. The very term "venous admixture" implies that there is some known amount of hypoxic venous blood which gets mixed with the arterial circulation, but in actual fact, there is no such thing; you never quite know how much shunt blood volume there is, or how hypoxic that blood is. Instead, one calculates a certain fraction of the cardiac output which consists of that blood. This is a completely reasonable shortcut, because it is actually impossible to measure "true" shunt, as practically one can never separate the fraction of blood coming from truly unventilated lung units (V/Q =0) from blood which comes from merely incompletely ventilated units (V/Q < 1.0). For this reason, we resort to using venous admixture as a surrogate for shunt, and report it as "shunt fraction", or Fshunt.

## Types of shunt and venous admixture

A classification system seems to exist for shunt, which tends to vary across textbooks (whereas some, eg. West's, abandon the whole idea of classifying things). Not only are the categories different, but the same nominal category may have different meanings to different authors. For example, here is a comparison of Nunn's and Levitzky:

 From Nunn's, 8th edition From Levitzky, 7th edition Anatomical shunt: Physiological shunt Bronchial veins Thebesian veins "True" shunt Intracardiac shunt "Virtual" shunt Pathological anatomical shunt  V/Q scatter  Physiological shunt Physiological shunts Physiological anatomical shunt  Bronchial veins Thebesian veins Pathological anatomical shunt Intracardiac shunt Intrapulmonary shunt Absolute intrapulmonary shunt ("true" shunt) "Shunt-like states": V/Q scatter, i.e. V/Q < 0 From Basic Physiology for Anaesthetists by Chambers et al (2015) Physiological shunt: Anatomical shunt Bronchial veins Thebesian veins Functional shunt V/Q scatter Pathological shunt: Intracardiac shunt Pulmonary AVM Intrapulmonary shunt (true shunt)

These are only a few of the possible taxonomies. Judging by the lack of literature references, these were not composed by the work of some sort of scientific body, but rather concocted by each textbook author independently. As such, it is impossible to say which of them is "better". The exam candidates are invited to choose a system and stick with it.

Without trying to justify any of the existing classification systems or trying to invent a new one, the following list of shunts and shuntish admixtures is offered in an unordered state.

### Different sources of venous admixture

• "True" shunt through useless lung: blood passing through a diseased pneumonic lung (or one which has collapsed), with V/Q ratio of 0 (i.e. no V, all Q). This blood will exchange no gas.
• "V/Q scatter": Lung regions which have a V/Q ratio less than 1 will have inefficient gas exchange, and will return pulmonary venous blood which is incompletely oxygenated. As the name suggests, the oxygen content of such blood will be available in a wide range, from blood which closely resembles mixed venous, to blood which is only slightly deoxygenated. The category of anatomical shunt for some reason excludes this form of venous admixture.
• Thebesian veins, otherwise known as venae cordis minimae, are tiny valveless veins in the walls of the four cardiac chambers. Their contribution to blood flow is piddling - examination of anaesthetised subjects has suggested that thebesian vein flow contributes 0.12% to 0.43% of the total aortic flow. However, the oxygen content within these veins is probably very low, and the impact on the A-a difference is not trivial.
• Bronchial veins contribute probably no more than 1% of total cardiac output. This is blood which leaves the aorta, nourishes the bronchial wall, and then rejoins the central circulation by draining into the pulmonary veins. According to Nunn's , in patients with bronchiectasis or COPD this contribution could be considerable - as much as 10% of the cardiac output.
• Congenital heart disease with right-to-left shunting is a possibility that should be mentioned, as it allows the right heart to eject into the left circulation, bypassing the lungs.
• Intrapulmonary arteriovenous connection, such as an AVM or fistula, would do exactly the same thing as the intracardiac shunt
• Intrapulmonary sources of poorly oxygenated blood, such as blood draining from the anoxic depths of a lung tumour, or portopulmonary shunts in liver disease, can deliver very oxygen-poor blood to the pulmonary venous circulation
• Virtual shunt is virtual in the sense that it may not actually exist. When one's measurement of shunt is performed without a mixed venous blood sample, the resulting shunt is referred to as virtual. As far as one can tell, this terminology is unique to works published by, or about, Nunn (see Lawler & Nunn, 1984). According to the original authors, this is  "the shunt which would explain the relationship between arterial PO2 and inspired oxygen concentration if the arterial-to-mixed venous oxygen concentration difference was 5 vol %".

## The magnitude of a normal shunt fraction

In Question 6 from the second paper of 2009, CICM examiners seem to have expected some statement of a "normal" shunt fraction or venous admixture value. In summary, this is far from clear.

For shunt proper, different sources quote very different fractions. For example, Smeenck et al (1997) explored this in a group of patients undergoing a 100% oxygen text prior to cardiac surgery, and calculated a shunt fraction of 10%. This group, of course, cannot be considered normal or healthy, as they were all awaiting cardiac surgery.  Ming et al (2014) used a shunt fraction of 5% as the normal range cut-off for their study evaluating the 100% oxygen test. Sarkar et al (2017) report 2-3% in their review, but do not quote a source. Probably the most authoritative reference on this subject is Wagner et al (1974), who used MIGET to evaluate healthy volunteers. These subjects had essentially no shunt with normal room air, and a mean shunt of around 3.2% while breathing 100% FiO2 (or up to 10.7% in the case of one subject), which the investigators attributed to denitrogenation atelectasis.

Venous admixture, as measured in normal subjects breathing room air, is usually about 3%. This value comes from Said & Banerjee (1963).

## References

Bigeleisen, Paul E. "Models of venous admixture." Advances in physiology education 25.3 (2001): 159-166.

Cruz, Julio C., and Patricia J. Metting. "Understanding the meaning of the shunt fraction calculation." Journal of clinical monitoring 3.2 (1987): 124-134.

Berggren SM. The oxygen deficit of arterial blood caused by nonventilating parts of the lung. Acta Physiol Scand 1942; 4:Suppl 11:1-92

Hughes, R. L. Clode M, Edwards RH, Goodwin TJ, and Jones NL. "Glossary on respiration and gas exchange" American Journal of Physiology: 34:4, 336-347.

Fenn, Wallace O., Hermann Rahn, and Arthur B. Otis. "A theoretical study of the composition of the alveolar air at altitude." American Journal of Physiology--Legacy Content 146.5 (1946): 637-653.

Curran-Everett, Douglas. "A classic learning opportunity from Fenn, Rahn, and Otis (1946): the alveolar gas equation." Advances in physiology education 30.2 (2006): 58-62.

Rice, Todd W., et al. "Comparison of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio in patients with acute lung injury or ARDS." CHEST Journal 132.2 (2007): 410-417.

Hess, D., and C. Maxwell. "Which is the best index of oxygenation: P (Aa) O2, PaO2/PAO2, or PaO2/FIO2?." Respiratory Care 30.11 (1985): 961-963. - this is not available even as an abstract; Respiratory Care dont seem to care about online back-issues beyond 2003.

Cane, Roy D., et al. "Unreliability of oxygen tension-based indices in reflecting intrapulmonary shunting in critically ill patients." Critical care medicine 16.12 (1988): 1243-1245.

Wandrup, J. H. "Quantifying pulmonary oxygen transfer deficits in critically ill patients." Acta Anaesthesiologica Scandinavica 39.s107 (1995): 37-44.

Araos, Joaquin D., et al. "Use of the oxygen content–based index, Fshunt, as an indicator of pulmonary venous admixture at various inspired oxygen fractions in anesthetized sheep." American journal of veterinary research 73.12 (2012): 2013-2020.

SIGGAARD‐ANDERSEN, Ole, and Ivar H. Gøthgen. "Oxygen and acid‐base parameters of arterial and mixed venous blood, relevant versus redundant."Acta Anaesthesiologica Scandinavica 39.s107 (1995): 21-27.

Aboab, Jerome, et al. "Relation between PaO2/FIO2 ratio and FIO2: a mathematical description." Applied Physiology in Intensive Care Medicine. Springer Berlin Heidelberg, 2006. 41-44.

Sven M. Berggren. "The Oxygen Deficit of Arterial Blood Caused by Non-ventilating Parts of the Lung" 1942; Volume 11 of Acta Physiologica Scandinavica: 4; Supplementum 11. -again, this does not seem to be available anywhere as a full text, which is upsetting because this seminal work is worth preserving.

Forsgren, P., S. Jakobson, and J. Modig. "True shunt in relation to venous admixture in an experimental porcine model of early ARDS." Acta anaesthesiologica Scandinavica 33.8 (1989): 621-628.

Lawler, P. G. P., and J. F. Nunn. "A reassessment of the validity of the iso-shunt graph." British journal of anaesthesia 56.12 (1984): 1325-1335.

Smeenk, F. W., et al. "Effects of four different methods of sampling arterial blood and storage time on gas tensions and shunt calculation in the 100% oxygen test." European Respiratory Journal 10.4 (1997): 910-913.

Ming, Damien KY, et al. "The ‘anatomic shunt test’in clinical practice; contemporary description of test and in-service evaluation." Thorax 69.8 (2014): 773-775.

Hopkins, Susan R., and Peter D. Wagner. The Multiple Inert Gas Elimination Technique (MIGET). Springer US, 2017.

Sarkar, Malay, N. Niranjan, and P. K. Banyal. "Mechanisms of hypoxemia." Lung India: official organ of Indian Chest Society 34.1 (2017): 47.

Wagner, Peter D., et al. "Continuous distributions of ventilation-perfusion ratios in normal subjects breathing air and 100% O 2." The Journal of clinical investigation 54.1 (1974): 54-68.

Said, Sami I., and Chandra M. Banerjee. "Venous admixture to the pulmonary circulation in human subjects breathing 100 per cent oxygen." The Journal of clinical investigation 42.4 (1963): 507-515.