Question 17

Pass rate: 16%

Highest mark: ?

Outline the advantages  and limitations of the A-a gradient and PaO2/FiO2 ratio as indices of pulmonary oxygen transfer. (You may tabulate your answer)

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College Answer

A-a gradient

PaO2/FiO2 ratio


a) Bedside index,

b) easily calculated,

c) may allow the distinction between hypoventilation (normal gradient) and V/Q mismatch (raised gradient) as causes of hypoxemia

a) Bedside index

b) Easily calculated

c) Input variable in lung injury scores


FiO2 dependent,
Age dependent

Varies with lung pathophysiology

a) Cannot distinguish
between hypoventilation and V/Q mismatch

b) P/F ratio unreliable unless FiO2 > 0.5 or PaO2 < 100

c) Not reliable in COPD because of V/Q mismatch

d) Barometric pressure dependent


The tabulated college answer is comprehensive. Essentialy, the two indices differ slightly. Both assess the gradient of oxygen exchange. A-a gradient gives one some sort of impression of whether hypoventilation or diffusion are to blame for one's hypoxia. The PaO2/FiO2 ratio does not tell you anything about the diffusion, but is useful as a risk stratification tool for comparing the severities of hypoxic states. A-a gradient will change with age, and becomes confused by shunts. P/F ratio is also confused by shunts, and only works while the atmospheric pressure is normal (it breaks down at altitude and in hyperbaric oxygen chambers) A more detailed discussion of tension-based indices of oxygenation is carried out elsewhere. There, a table of indices is available, which closely resembles the college answer, and I reproduce it below to simplify revision.

Additionally, this whole thing seems heavily based on Chapter 18 from Oh's Manual ("Monitoring oxygenation") by Thomas J Morgan and Balasubramanian Venkatesh, where precisely this question is answered on pages 148-149.

Indices of Pulmonary Oxygen Transfer: Advantages and Limitations





Oxygen saturation

Measured directly by infrared interferometry
  • real-time monitoring
  • Non-invasive
  • requires no special expertise
  • Invasive
  • requires arterial access expertise
  • requires blood gas analyser
  • confounded by collection error, eg. bubbles in the syringe
  • Measurement delay exists


Measured directly by Clark electrode
  • accurate impression of oxygenation
  • not confounded by dyshemoglobins
  • allows accurate calculation of hemoglobin saturation
  • confused by dyshemoglobins
  • does not reflect level of oxygenation in hyperoxic patients
  • not a direct measurement of hemoglobin saturation - instead, uses a signal intensity and a look-up table derived from empirical data
  • no absolute method for calibration exists - only empirical data collected from hypoxic volunteers
  • unreliable in severely hypoxic patients
  • unreliable in poorly perfused patients
  • unreliable in arrhythmia
  • positional
  • unreliable in confused patients, confounded by mostion artifact

A-a gradient

Alveolar gas equation

  • Simple
  • Minimally invasive
  • May distinguish alveolar hypoventilation from all other causes of hypoxia
  • Required by APACHE II, III and IV
  • The magnitude of the A-a gradient is highly dependent on FiO2, especially in the presence of a large shunt
  • Age dependent (increases with age)
  • Non-specific - influenced by numerous factors

PaO2/FiO2 ratio

Divison of alveolar tension by inspired O2 fraction

  • Simple
  • Minimally invasive
  • Required by APACHE IV
  • Used in severity stratification of ARDS
  • Cannot distinguish between alveolar hypoventilation and other causes of hypoxia
  • Makes no attempt to incorporate changes in PaCO2
  • Unreliable unless FiO2 > 0.5 or PaO2 < 100
  • Not reliable in COPD because of V/Q mismatch
  • Barometric pressure dependent
a/A ratio

Arterial pO2 divided by alveolar pO2.

  • Reasonably simple
  • Minimally invasive
  • May distinguish alveolar hypoventilation from all other causes of hypoxia
  • Independent of FiO2 changes
  • Age dependent (increases with age)
  • Non-specific - influenced by numerous factors
  • Oxygen tension based index;
Respiratory index

A-a gradient divided by the PaO2

  • Reasonably simple
  • Minimally invasive
  • May distinguish alveolar hypoventilation from all other causes of hypoxia
  • Independent of FiO2 changes
  • No addiitonal advantages over the a/A ratio
  • Not commonly used; difficult to relate findings to management decision criteria or compare them to published studies.
Estimated shunt fraction (Fshunt)

Shunt equation

(using a CaO2-CVO2difference of around 30-50ml/L)

  • Oxygen content rather than oxygen tension based index
  • Minimally invasive- does not require mixed venous sampling
  • Independent of FiO2 and PaCO2changes
  • Assigned CaO2-CVO2 difference can be completely incorrect in critical illness, completely invalidating the calculations.
Measured intrapulmonary shunt

Shunt equation

  • Gold standard of shunt assesment
  • Empiric measurement; accounts for unpredictable influences on shunt.
  • Maximally invasive (requires PA catheter)
  • Requires mixed venous sampling
  • Complex calculations involved

Other questions in this paper

Other questions in this topic


Hess, D., and C. Maxwell. "Which is the best index of oxygenation: P (Aa) o2, Pao2/Pao2, or Pao2/Fio2." Respir Care 30 (1985): 961-963.

Chapter 18 from Oh's Manual ("Monitoring oxygenation") by Thomas J Morgan and Balasubramanian Venkatesh (p. 148-149)

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.

Hahn, C. E. W. "Editorial I KISS and indices of pulmonary oxygen transfer."British journal of anaesthesia 86.4 (2001): 465-466.

Zander R, Mertzlufft F, eds. The Oxygen Status of Arterial Blood. Würzburg, Germany: Bonitas‐Bauer, 1991

Nirmalan, M., et al. "Effect of changes in arterial‐mixed venous oxygen content difference (C (a–v̄) O2) on indices of pulmonary oxygen transfer in a model ARDS lung†,††." British journal of anaesthesia 86.4 (2001): 477-485.

LAGHI, FRANCO, et al. "Respiratory index/pulmonary shunt relationship: Quantification of severity and prognosis in the post-traumatic adult respiratory distress syndrome." Critical care medicine 17.11 (1989): 1121-1128.

Zetterström, H. "Assessment of the efficiency of pulmonary oxygenation. The choice of oxygenation index." Acta anaesthesiologica scandinavica 32.7 (1988): 579-584.

Liliethal JL, Riley RL, Prommel DD, et al: "An experimental analysis in man of the oxygen pressure gradient from alveolar air to arterial blood" Am J Physiol 1946; 147:199-216

Gilbert, R., and J. F. Keighley. "The arterial-alveolar oxygen tension ratio. An index of gas exchange applicable to varying inspired oxygen concentrations."The American review of respiratory disease 109.1 (1974): 142.

Viale, JEAN-PAUL, et al. "Arterial-alveolar oxygen partial pressure ratio: a theoretical reappraisal." Critical care medicine 14.2 (1986): 153-154.