Methods of measuring ventilation-perfusion mismatch

This chapter is most relevant to Section F6(ix) from the 2017 CICM Primary Syllabus, which expects the exam candidates to be able to "outline the methods used to measure ventilation-perfusion mismatch".  Though V/Q matching has been explored in multiple past papers, the methods of measuring it have never appeared, and one might be forgiven for skipping this topic entirely. The salient points are included in the grey box; everything else is essentially SEO-killing ballast.

In summary:

There is no single best article to give as the "one true reference" for this issue.  For the MIGET method, the best article would probably be the retrospective by its creator (Wagner, 2008) but one would have to pay Springer 35 Euros for it. The Riley three-compartment model is well described by Riley and Cournard (1949. For different modalities of tomographic and radionuclide V/Q imaging, one really needs to scour the internet and look for individual articles, a substantial effort which will probably go unrewarded by primary exam marks. 

Multiple Inert Gas Elimination Technique (MIGET)

Wagner Saltzman and West (1974) described this technique for the first time, and then published dozens of papers on the results of using it in different circumstances, producing countless graphs with which junior anaesthesia and ICU trainees have subsequently been tortured. Wagner wrote a review of this same technique in 2008, from the elevated vantage point of an extremely long and illustrious career. It is called MIGET, the Multiple Inert Gas Elimination Technique. For the purposes of understanding V/Q mismatch and even for the purpose of the CICM Part One exam (well known for its cruelty) it is not essential to know this in any great detail. It will suffice to describe it in the following point-form way:

• Several gases are prepared, which have different blood solubility.
  • In order of most to least soluble, they usually are:
    • Acetone (most soluble)
    • Ethane
    • Cyclopropane
    • Enflurane
    • Ether
    • Sulphur hexafluoride (least soluble)
  • Saline or dextrose with these dissolved gases in it is infused into the subject.
  • Then:
    • Gas levels in the arterial  blood are measured
    • Gas levels in the mixed venous blood are also measured
  • For each gas, the ratio of arterial to mixed venous partial pressure can therefore be determined.
    • This ratio falls as V/Q rises (i.e. as perfusion decreases, more inert gas gets left in the blood)  
  • For each gas, the blood:gas partition coefficient is already known (λ, the ratio of concentrations of the gas in blood and alveolar gas, at equilibrium)
  • From the arteriovenous concentration ratio and the known blood:gas partition coefficient, the distribution of V/Q ratios can be determined by searching for the distribution of blood flow and ventilation that best fits (according to the least-squares principle), the measured retention of that  particular gas
  • Multiple gases are required (i.e. you  can't just rely on one gas):
    • A gas of a given coefficient (λ) is best suited to interrogate alveoli where the V/Q ratio approximates λ:
    • For alveoli with a V/Q ratio 10 times greater than the λ, most of the gas wll be retained in the blood
    • For alveoli with a V/Q 10 times smaller than λ, virtually all of the gas will be washed out into exhaled air.
    •  Thus, multiple gases need to be used so that a large range of V/Q ratios can be interrogated

Using this technique, Wagner and coworkers were able to measure all of the curves described in the chapter on the effects of V/Q mismatch on gas exchange. 

Three-compartment model (Riley method)

It is named after Riley because Riley and Cournard (1949) were the first to publish and popularise this approach, even though it probably originated with Fenn Rahh and Otis in 1946.  In essence, its genius rests in being able to take the bell curve of V/Q scatter and average it in a way that the lung is seen to consist of only three units:

• a unit consisting purely of ideally V/Q matched alveoli (V/Q = 1.0),
• a unit consisting purely of "true" shunt (V/Q = 0)
• a unit consisting purely of dead space ( V/Q = ∞)

Because gas exchange can only occur in the ideally matched unit, all changes in arterial and alveolar gas mixtures are due to events taking place in this unit. Thus, the only measurement you really need to make is alveolar O₂, alveolar CO₂, arterial O₂ and arterial CO₂. From these, it is possible to determine:

• The magnitude of shunt (as a fraction of cardiac output)
• The magnitude of dead space (as a fraction of tidal volume)

Shunt and dead space are discussed in greater detail elsewhere.

Imaging techniques

Various useful imaging techniques can be used to determine V/Q ratio. The basic premise here appears to be the use of tracer. It is relatively easy to determine the perfusion of the lung (just give them some sort of IV tracer) and the main challenge appears to be finding some way of imaging the gas inside the lungs while still allowing the patient to breathe normally and comfortably (i.e. ideally the presence of that gas should still allow enough air into the lungs to permit normal gas exchange).

These methods are mentioned in Nunn's (Ch.8, p. 129 of the 8th edition) and are therefore fair game for the examiners:

• MRI
  • Using gadolinium as an IV contrast to image the lung vessels
  • Using a tracer gas (eg. oxygen,  ³He or ¹²⁹Xe) one can image the gas in the lungs
• SPECT
  • The regional distribution of blood flow and ventilation is therefore possible to calculate, and one is able to view the relationship graphically (i.e. areas of poor V/Q matching can be determined by visually inspecting the scan results)
  • The regional distribution of these radionuclides is measured by a camera which detects gamma rays with their specific spectra, and rejecting photons which come from specific angles
  • Perfusion is measured using intravenous infusion of ^99mTc-labeled macroaggregated albumin
  • Ventilation is measured using ¹³³Xe
  • A good reference is the EANM set of guidelines from 2009
• PET
  • The advantage of PET is a much higher sensitivity than SPECT, leading to improved image quality
  • Essentially the same technique as SPECT but with the use of positron-emitter isotopes (eg.¹³N₂), instead of gamma-ray emitters (Melo et al, 2003)