Version May 2024
INTRODUCTION — Inspired oxygen from the environment moves across the alveolar-capillary membrane into the blood. Most of the oxygen binds to hemoglobin in red blood cells, although a small amount dissolves into the plasma. The oxygen is then transported from the lungs to the peripheral tissues, where it is removed from the blood and used to fuel aerobic cellular metabolism. This process can be conceptualized as three steps: oxygenation, oxygen delivery, and oxygen consumption. In this topic review, oxygen delivery and consumption are reviewed. Oxygenation is discussed separately. (See "Measures of oxygenation and mechanisms of hypoxemia".)
DEFINITIONS
Oxygen content — The arterial oxygen content (CaO2) is the amount of oxygen bound to hemoglobin plus the amount of oxygen dissolved in arterial blood:
CaO2 (mL O2/dL) = (1.34 x hemoglobin concentration x SaO2) + (0.0031 x PaO2)
where SaO2 is the arterial oxyhemoglobin saturation and PaO2 is the arterial oxygen tension. In dyshemoglobinemias, the oxygen content is calculated with the same equation, although the saturations (and therefore the oxygen content) will be different for a specific PaO2 [1]. Normal CaO2 is approximately 20 mL O2/dL.
Similarly, the mixed venous blood oxygen content (CvO2) is the amount of oxygen bound to hemoglobin plus the amount of oxygen dissolved in mixed venous blood:
CvO2 (mL O2/dL) = (1.34 x hemoglobin concentration x SvO2) + (0.0031 x PvO2)
where SvO2 is the mixed venous oxyhemoglobin saturation and PvO2 is the mixed venous oxygen tension. Normal CvO2 is approximately 15 mL O2/dL. Mixed venous blood is drawn from the right atrium. Peripheral venous blood should not be substituted because it tends to overestimate venous oxygen content.
Oxygen delivery — Oxygen delivery (DO2) is the rate at which oxygen is transported from the lungs to the microcirculation:
DO2 (mL/min) = Q x CaO2
where Q is the cardiac output. Normal DO2 is approximately 1000 mL/min. Normal DO2 is approximately 500 mL/min/m2 if cardiac index is substituted for cardiac output.
Realize, cardiac output can be measured by thermodilution using a pulmonary artery catheter, or calculated using the Fick equation:
Q (L/min) = Oxygen consumption ÷ (10 x arteriovenous oxygen difference)
where oxygen consumption is either measured by respirometry (discussed below) or estimated using a nomogram, and the arteriovenous (AV) oxygen difference is calculated:
AV oxygen difference (mL O2/dL) = CaO2 - CvO2
Oxygen consumption — Oxygen consumption (VO2) is the rate at which oxygen is removed from the blood for use by the tissues. It can be measured directly or calculated. Both approaches assume that all unused oxygen passes from the arterial to the venous circulation.
Direct measurement of VO2 is performed by respirometry. During respirometry, the patient breathes through a chamber that receives continuous air flow. Measurement of the oxygen depleted from the chamber, as well as the carbon dioxide and water vapor produced in the chamber, is used to determine VO2. Respirometry can be used in mechanically ventilated patients, but the accuracy of direct measurement of VO2 diminishes at high oxygen concentrations (eg, >80 percent) [2-7]. Normal VO2 in a conscious, resting person is approximately 250 mL O2/min.
Calculation of VO2 can be performed by rearranging the Fick equation:
VO2 (mL O2/min) = Q x (CaO2 - CvO2)
When calculating VO2, cardiac output should be measured and not calculated from the Fick equation or a mathematical coupling error may be introduced.
Oxygen extraction — Oxygen extraction is the slope of the relationship between oxygen delivery (DO2) and oxygen consumption (VO2). It is most commonly expressed as the oxygen extraction ratio, which is the proportion of arterial oxygen that is removed from the blood as it passes through the microcirculation:
O2 Extraction Ratio = (CaO2 - CvO2)/CaO2
Normal O2 extraction ratios range from 0.25 to 0.3.
NORMAL PHYSIOLOGY — Under normal circumstances:
●Oxygen consumption (VO2) is proportional to oxygen delivery (DO2) and oxygen extraction
●DO2 and oxygen extraction are inversely proportional to one another
At rest, VO2 remains constant over a wide range of oxygen delivery (DO2) because changes in DO2 are balanced by reciprocal changes in oxygen extraction (figure 1). VO2 decreases if DO2 declines to such a degree that it cannot be balanced by increasing oxygen extraction. The threshold value of DO2 below which VO2 will fall is called the "critical DO2" (figure 2).
When metabolic demand increases (eg, exercise, pregnancy), VO2 also increases because more oxygen is required to maintain aerobic cellular metabolism. This is normally achieved by increasing both DO2 and oxygen extraction [8,9]. VO2 is disproportionately impacted by the increased oxygen extraction, with the increased DO2 contributing little [10]. Enhanced extraction of oxygen is probably mediated at the capillary level [8]. Studies suggest dysregulation of peripheral extraction may play an important role in limiting exercise capacity in some disorders such as heart failure with preserved ejection fraction [11]
ABNORMALITIES OF OXYGEN DELIVERY AND DEMAND — Decreased oxygen delivery or increased metabolic demand are common sequelae of medical illness.
Decreased oxygen delivery — Oxygen delivery (DO2) will decrease if cardiac output falls or arterial oxygen content (CaO2) declines.
●Cardiac output can decrease due to cardiac disease or hypovolemia.
●CaO2 can decrease due to anemia or poor oxygenation. The latter can be caused by lung disease (eg, ventilation-perfusion mismatch, diffusion limitation), a right-to-left shunt, diminished inspired oxygen, or hypoventilation. (See "Measures of oxygenation and mechanisms of hypoxemia".)
In the setting of diminished DO2, maintenance of a normal oxygen consumption (VO2) can be accomplished by a compensatory increase in oxygen extraction [12]. If increased oxygen extraction is insufficient to maintain VO2, cardiac output will increase in an effort to improve DO2. VO2 will fall if these actions are insufficient and DO2 is below the critical DO2 [13].
Increased metabolic demand — Metabolic demand is elevated in critically ill patients (eg, acute respiratory distress syndrome, sepsis, or septic shock) [3,6,14-21]. VO2 increases because more oxygen is required to maintain aerobic cellular metabolism. In critically ill patients, VO2 elevation may be disproportionately accomplished by increasing the DO2. This is different from healthy individuals in whom VO2 elevation is disproportionately accomplished by increasing the oxygen extraction, with DO2 contributing little [10]. Whether such a difference exists between healthy and critically ill individuals is controversial:
●Proponents believe that VO2 is disproportionately affected by DO2 because oxygen extraction is impaired during critical illness. Supporting this hypothesis, lactic acidosis is often present despite increased DO2 [22,23]. In other words, anaerobic metabolism is required despite an increased supply of oxygen. Ineffective oxygen extraction may be due to poor oxygen uptake or poor utilization by the cells [15].
●Opponents argue that both VO2 and DO2 were calculated in most of the studies that suggest that DO2 has a disproportionate impact on VO2 during critical illness [24]. This could introduce mathematical coupling errors, which would falsely increase the strength of the relationship between VO2 and DO2. In addition, VO2 was not disproportionately affected by DO2 in the few studies that directly measured VO2 [3,25-28].
We believe that the relationship between DO2 and VO2 in critically ill patients is similar to that in healthy patients during increased metabolic demand (eg, exercise, pregnancy). In other words, we believe that increased oxygen extraction, and not increased DO2, has the greatest impact on increasing the VO2 in critically ill patients. We base this belief on the following:
●Numerous studies have evaluated the impact of augmenting DO2 on VO2 with conflicting results [3,7,9,25-44]. Methods of augmenting DO2 have included inotropic agents, saline loading, and vasodilators to improve cardiac output, as well as red blood cell transfusions to increase arterial oxygen content (CaO2). Regardless of the intervention, DO2 and VO2 were strongly correlated when VO2 and DO2 were both calculated, but not when VO2 was directly measured.
●A few studies have evaluated the impact of augmenting DO2 and patient-centered outcomes, such as survival, organ failure, length of ICU stay, and length of hospitalization [35,37-39,45-51]. While some of the studies found an improvement in morbidity or mortality, others found no effect or potential harm. Those that demonstrated improvement had significant methodologic problems, such as baseline differences between the treatment and control groups, and failure to use an intention-to-treat analysis.
Taken together, we believe there are insufficient data to warrant the routine augmentation of DO2 in critically ill patients if there is no evidence of ongoing tissue hypoxia.
SUMMARY AND RECOMMENDATIONS
●Definitions – Inspired oxygen from the environment moves across the alveolar-capillary membrane into the blood and is then transported to the peripheral tissues. There, it is removed from the blood and used to fuel aerobic cellular metabolism. This process can be conceptualized as three steps: oxygenation, oxygen delivery, and oxygen consumption. (See 'Introduction' above.)
•The arterial oxygen content (CaO2) is the amount of oxygen bound to hemoglobin plus the amount of oxygen dissolved in arterial blood, while the mixed venous blood oxygen content (CvO2) is the amount of oxygen bound to hemoglobin plus the amount of oxygen dissolved in mixed venous blood. (See 'Oxygen content' above.)
•Oxygen delivery (DO2) is the rate at which oxygen is transported from the lungs to the microcirculation, oxygen consumption (VO2) is the rate at which oxygen is removed from the blood for use by the tissues, and oxygen extraction is the proportion of arterial oxygen that is removed from the blood as it passes through the microcirculation. (See 'Oxygen delivery' above and 'Oxygen consumption' above and 'Oxygen extraction' above.)
●Normal physiology – VO2 normally remains constant over a wide range of DO2 because changes in DO2 are balanced by reciprocal changes in oxygen extraction. VO2 will decrease only if DO2 declines to such a degree that it cannot be balanced by increasing oxygen extraction. VO2 increases when metabolic demand increases (eg, exercise, pregnancy). This is disproportionately accomplished by increasing the oxygen extraction, with DO2 contributing little(See 'Normal physiology' above.)
●Abnormalities of oxygen delivery and consumption – Decreased oxygen delivery or increased metabolic demand are common sequelae of medical illness.
•When DO2 is decreased (eg, heart failure), a compensatory increase in oxygen extraction may allow VO2 to remain normal. If increased oxygen extraction is insufficient to maintain VO2, cardiac output will increase in an effort to improve DO2. VO2 will fall if these compensatory mechanisms are inadequate. (See 'Decreased oxygen delivery' above.)
•When metabolic demand increases (eg, sepsis), VO2 also increases. This may be disproportionately accomplished by increasing the DO2, rather than enhancing the oxygen extraction. In critically ill patients in whom there is no evidence of ongoing tissue hypoxia, we do not routinely augment DO2. (See 'Increased metabolic demand' above.)
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