• The blood oxygen-carrying capacity is the milliliters of oxygen present in 1 deciliter of blood.
• In blood, oxygen can exist in 2 forms: Dissolved and attached to hemoglobin. Hemoglobin is the primary transporter of oxygen in mammals.
• In the event of decreased oxygen delivery, the blood provides a limited cushion against hypoxia.

• Oxygen is necessary for aerobic metabolism and cell integrity. However, despite its absolute necessity, the body only has minimal storage capacity (unlike glucose). When apneic, oxygen stores are limited to the oxygen in the lungs (FRC) and the blood; both of which are unable to sustain life beyond a few minutes.
• In a healthy adult at rest, oxygen consumption is ~200–250 mL O₂/min and oxygen delivery is ~950–1,150 mL O₂/min. Thus, ~25% of the arterial oxygen is used every minute, and the deoxygenated blood returning to the lungs has ~75% saturation (mixed venous oxygen saturation) (1).
• Hemoglobin provides the most efficient means of carrying and transporting blood. At full oxygen saturation, 1 g of hemoglobin in 1 dL of blood is capable of carrying 1.34 mL of O₂. Thus, Hgb × 1.34 × SaO₂ determines the milliliters of oxygen bound to hemoglobin in 1 dL of blood. Oxygen bound to hemoglobin does not exert partial pressure.
• Oxygen is poorly soluble in blood with a coefficient of 0.003 milliliters of oxygen per deciliter of plasma per millimeter of mercury oxygen. Hence, a patient breathing room air with an approximate PaO₂ of 100 mm Hg has 0.3 mL of oxygen dissolved in 1 dL of blood.
• Oxygen–hemoglobin (O₂–Hgb) dissociation curve: PaO₂ on the x-axis, and SaO₂ on the y-axis. As PaO₂ increases, SaO₂ increases. The curve is not linear, but sigmoid in shape. This represents hemoglobin's desire to be fully bound or fully dissociated from oxygen; it is unstable in intermediate states. This characteristic facilitates its physiologic function; at the lungs, hemoglobin will fully saturate and at the tissue level, it will easily dissociate and unload to oxygenate the tissues.
• Assuming normal hemoglobin moieties and conditions, the PaO₂ is in equilibrium with oxyhemoglobin and dissolved oxygen. for example, a PaO₂ of 100 mm Hg has an SpO₂ of 98% and 0.3 mL O₂/dL of blood. A PaO₂ of 500 mm Hg has an SpO₂ of 100% and 1.5 mL O₂/dL of blood.

• Hemoglobin is an iron-containing protein that is composed of 4 polypeptide chains or subunits. The iron-containing heme group of each polypeptide reversibly binds up to 4 molecules of oxygen (2).
• The adult hemoglobin (HbA) molecule is made of 2 globin and 2 globin subunits.
• The binding of the first oxygen molecule to hemoglobin induces conformational changes in the structure of the hemoglobin that allows the binding of other molecules of oxygen more readily. At normal resting conditions, 25% of the oxygen bound to hemoglobin is extracted by the tissues (equivalent to a partial pressure of 40 mm Hg).
• Fetal hemoglobin (HbF), on the other hand, has 2 and 2 subunits that possess a strong affinity for oxygen. The fetus is exposed to much lower oxygen pressures from the placenta; ~21% of the level found in the adult lung (1).

• Low oxygen-carrying capacity is the result of a low PaO₂, low hemoglobin, impaired oxygen-to-hemoglobin binding, or an increased oxygen demand/consumption.
  • Low PaO₂: Hypoxic mixture (low inspired oxygen), hypoventilation, V/Q mismatching, shunting, impaired diffusion
  • Low hemoglobin: Chronic or acute anemia
  • Impaired oxygen-to-hemoglobin binding: Abnormal hemoglobins (fetal, thalassemia, sickle cell disease), carboxyhemoglobin, cyanhemoglobin, methemoglobin, sulfhemoglobin
  • Increased oxygen demand/consumption: Hyperthermia, hyperthyroidism, sepsis, pregnancy, vigorous exercise
• Acute anemia: The initial hemodynamic response is a fall in systemic vascular resistance (SVR) that is partly due to the decrease in blood viscosity and in part, the result of nitric oxide-mediated vasodilation. The decrease in SVR reduces blood pressure and causes a baroreceptor-mediated neurohormonal activation, identical to that seen in patients with severe low-output heart failure. Eventually, sympathetic and renin–angiotensin–aldosterone activity cause peripheral vasoconstriction and decrease in renal blood flow and glomerular filtration rate. Kidneys retain salt and water (3).
• Chronic anemia results in hemodynamic and non-hemodynamic (erythropoiesis) compensatory responses to enhance oxygen-carrying capacity (2,4).
  • Hemodynamic responses are complex and involve a vasodilation-mediated high-output state with neurohormonal activation (as described above in acute anemia). The high-output state initially helps to increase oxygen transport. However, compensatory mechanisms have deleterious long-term consequences and could contribute to anemia's role as an independent risk factor for adverse outcomes.
  • Non hemodynamic responses: Increased levels of 2,3-diphosphoglycerate (2,3-DPG) shift the O₂–Hgb dissociation curve to the right. This is the least energy-consuming mechanism to support increased oxygen delivery to the tissues (lacks significant increase in cardiac output). Erythropoiesis also serves to increase red blood cell production.
• In elevated altitudes, ventilation and heart rate are elevated with a minimum reduction in stroke volume. In addition, plasma volume is reduced over 24–48 hours to improve the oxygen-carrying capacity of the blood. Prolonged sojourn at altitudes is compensated for with enhanced erythropoiesis and a larger hemoglobin mass, allowing for a partial or full restoration of the blood volume and arterial oxygen content.

• General anesthesia causes a 15% reduction in metabolic rate and a subsequent decrease in oxygen requirement. Artificial ventilation further decreases the oxygen requirement by 6% with the removal of the work of breathing. Anesthetic agents, however, do not affect the transport of oxygen by hemoglobin or its solubility in blood.
• The increased utilization of oxygen when metabolic rate is increased (postoperative shivering, malignant hyperthermia, etc.) leads to a decrease in PaO₂ which activates normal protective responses to hypoxia (aortic and carotid chemoreceptors, sympathetic nervous system) to increase cardiac output. However, these protective responses are usually reduced by anesthetic drugs intraoperatively, and can extend into the postoperative period.
• Blood transfusion: It remains the clinician's responsibility to determine the transfusion "trigger" for an individual patient based on multiple elements that determine the demand for the delivery of oxygen and the physiological reserve. The decision should be based on the premise that the oxygen-carrying capacity is increased to prevent oxygen consumption from exceeding oxygen delivery. Additionally, the following should be considered:
  • Theoretically, the oxygen-carrying benefit of red blood cells should hasten recovery from respiratory failure, and transfusion would therefore be expected to shorten the duration of mechanical ventilation. However, evidence to the contrary has been reported.
  • Storage of packed red blood cells (pRBCs) is associated with a decline in 2,3-DPG that leads to a subsequent left shift of the O₂–Hgb dissociation curve. Therefore, while transfusion increases the patient's hemoglobin, it results in a less efficient oxygen delivery when compared to the native hemoglobin at that same hematocrit. 2,3-DPG levels return to normal over 12–24 hours.
  • The need to restore blood viscosity may precede the need to restore oxygen-carrying capacity during hemodilution or anemic conditions. A minimum level of blood viscosity appears to be necessary for generating shear stress and stimulating the release of vasoregulatory factors such as nitric oxide and prostacyclin (3).
  • Studies in subpopulations (renal failure, Jehovah's Witnesses, military casualties) have shown that considerably greater amounts of anemia than was previously believed can be well tolerated.
  • Patients that are unable to increase their cardiac output (coronary artery disease, prior/acute myocardial infarction, beta-adrenergic blockade, decreased SVR such as sepsis or post-cardiopulmonary bypass) or have impaired oxygenation (pulmonary disease, high altitude) have limited compensatory responses to hypoxia.
• Isovolemic hemodilution to hemoglobin levels of 5 g/dL in normal volunteers is well tolerated. A robust cardiovascular response manifested by increases in heart rate and stroke volume leads to compensation.
• Blood substitutes are being investigated to increase oxygen-carrying capacity. At this time, there are no available products for clinical use.

• Oxygen content = [(Hgb × 1.39 × SaO₂) + (PaO₂ × 0.003)]. Units are as follows: Hgb is in g/dL; 1.39 is mLO₂/dL; SaO₂ is % (0.01) but no units (5).
• Oxygen arterial content (CaO₂) = [(Hgb × 1.39 × SaO₂) + (PaO₂ × 0.003)] (5).
• Oxygen venous content (CvO₂) = [(Hgb × 1.39 × SvO₂) + (PvO₂ × 0.003)]. If obtained at the pulmonary artery (PAC), it is a representation of the true mixed venous oxygen (5).
• Oxygen delivery (DO₂) (mL/min) = cardiac output (CO) × blood oxygen content

Oxygen–hemoglobin dissociation curve

Left shift (affinity)*	Right shift (affinity)*
[H+] (pH)	[H+] (pH)
2,3-DPG	2,3-DPG
temperature	temperature
Fetal hemoglobin (HbF); P50 = 19 mm Hg	Pregnancy; P50 = 31 mm Hg
Dyshemoglobins (MetHb, COHb)	Hemoglobinopathies (thalassemia, sickle cell hemoglobin), SulfHb
Tobacco use	Chronic anemia
	Volatile anesthetics

*Affinity of Hgb for O₂ holds tightly to O₂; *Affinity of Hgb for O₂ released at the tissue level.

• Blood Substitutes
• Isovolemic Hemodilution
• Mixed Venous Oxygen Saturation

Onyi Onuoha , MD, MPH

Nina Singh-Radcliff , MD