Hypoxia: Assessment and Intervention

Hypoxia: Assessment and Intervention


The prevention, detection, and treatment of hypoxia must be foremost in the minds of clinicians treating cardiopulmonary patients. The ultimate goal in the management of oxygenation is the prevention of tissue hypoxia. When hypoxia is present, the goal is immediate recognition and intervention to minimize untoward effects.

There is no single, simple index or way to quickly and accurately assess tissue oxygenation. Rather, tissue oxygenation status is best assessed by systematically analyzing the various components of the oxygenation system and by evaluating related laboratory data. I have divided tissue hypoxic assessment into two phases. First, as a matter of routine, one should evaluate the three essential components of oxygen supply shown in Box 11-1. The ABCs of tissue oxygen supply are Arterial oxygenation assessment, Blood hemoglobin concentration, and Circulatory status. A deficiency in any one of these components may compromise oxygenation of the tissues.

Although evaluation of oxygen supply components is a logical starting point, in many cases, it is still difficult to conclude whether tissue hypoxia is, indeed, present. Therefore, when more definitive information is needed, the clinician may look to specific indices that suggest oxygenation failure and tissue hypoxia. Potential markers of tissue hypoxia are listed in Box 11-2. These include lactate measurement, indices of mixed venous oxygenation, oxygen uptake and utilization, and gastric mucosal acidosis.


Each of the oxygen supply variables as shown in Box 11-1 will be described in detail.

Arterial Oxygenation

There are two primary indicators of arterial oxygen supply: PaO2 and SaO2. An approximate gauge of SaO2 is often reflected by pulse oximetry and in this case may be referred to as SpO2. The student should understand that true SaO2can only be measured by CO-oximetry as described later in this chapter and Chapter 15. Nevertheless, SpO2provides a crude index of SaO2in the absence of abnormal Hb species.


PaO2 as an Index of Hypoxia

When available, the partial pressure of oxy- gen in the arterial blood (PaO2) is a logical starting point in tissue oxygenation assessment. As described in previous chapters, the degree of hypoxemia in a given individual is a simple indicator of the likelihood of hypoxia. Hypoxia is unlikely in mild hypoxemia, possible in moderate hypoxemia, and likely in severe hypoxemia. In moderate hypoxemia, development of hypoxia depends mainly on the integrity of the cardiovascular system.

These guidelines represent clinical rules of thumb. There are, of course, exceptions to every rule. It has been shown that under certain conditions, hypoxia does not occur despite the presence of severe hypoxemia.378 379 380 For example, mountain climbers at the summit of Mt. Everest had PaO2 levels below 30 mm Hg without apparent adverse consequences.378 Similarly, patients with congenital heart disease had PaO2 levels averaging 37 mm Hg without notable physiologic impairment.380 Furthermore, these patients were capable of some exercise, during which PaO2 levels decreased further to 28 mm Hg.380

Finally, despite the fact that a PaO2 of less than 20 mm Hg is generally considered to be incompatible with life, 13 of 22 patients in one study recovered without permanent physiologic impairment despite PaO2 levels of less than 21 mm Hg.379 Thus, PaO2 alone, even when extremely low, is inadequate as an index of tissue hypoxia.

Also, one must not rely too heavily on PaO2 alone because measurements in stable critically ill patients in one study varied as much as 13% from one reading to another.381 This constitutes an average variance of about 16 mm Hg in PaO2 measurements without a noticeable change in patient condition.

Prevention of Hypoxemic Hypoxia

The guidelines presented previously, notwithstanding the exceptions, represent a prudent approach to the classification of hypoxemia and the prevention of hypoxia. One must remember that in normal persons, when PaO2 decreases to about 55 mm Hg, judgment and short-term memory may be impaired, presumably due to hypoxia.382 Therefore, in all but unusual circumstances, it is unacceptable to allow moderate or severe hypoxemia (i.e., PaO2 < 60 mm Hg) to persist.382 This is true even in patients with chronic obstructive pulmonary disease (COPD), because a PaO2 of 60 mm Hg is not associated with a great risk of increasing hypercarbia.382

As described in Chapter 10, there are some circumstances (e.g., paraquat poisoning, ARDS) when moderate degrees of hypoxemia may be considered acceptable or permissive. Indeed, a rebuttal of the traditional approach to treatment of hypoxemia has been presented.696 Nevertheless, treatment of moderate hypoxemia seems prudent until clear evidence suggests otherwise.

Methods available to treat hypoxemia have been discussed in detail in Chapter 10. Although the PaO2 is a useful starting point in clinical hypoxic assessment, it is foolhardy to equate a normal PaO2 with normal tissue oxygenation. The myriad other factors that may influence O2 transport and internal respiration must also be evaluated.


SaO2 Determination

The SaO2 is the percentage of hemoglobin that is carrying oxygen in the arterial blood. It should be remembered that 98% of oxygen is carried in arterial blood combined with Hb. Regarding saturation, it is important for the clinician to note the technique that is being used to determine SaO2, because the values obtained by different techniques may vary. Saturation may be calculated via a nomogram or measured by oximetry, CO-oximetry, or pulse oximetry.

Calculated SaO2 Using a Nomogram.

Some laboratories use a nomogram to predict the SaO2, based on the PaO2 and pH.383 This calculated SaO2 does not account for factors other than the pH that may alter HbO2 affinity. Furthermore, this methodology assumes that no abnormal forms of Hb are present, such as HbCO or MetHb. Obviously, calculated SaO2 provides little more information than PaO2 and may sometimes lead to a false sense of security. Some laboratories label calculated saturation as SO2.


SaO2 may be measured more accurately via oximetry. Oximeters are two- wavelength spectrophotometers. The specific technique underlying two-wavelength oximetry is discussed in Chapter 15.

It is important to understand two essential points when SaO2 is measured with the two- wavelength method. First, when only two wavelengths are used, abnormal forms of Hb such as HbCO and MetHb cannot be detected.383 Second, SaO2 measured in this way is the percentage of HbO2 compared with the sum of HbO2 and desaturated Hb only. Because this measurement does not include abnormal forms of Hb, it is sometimes referred to as functional SaO2.383 Functional SaO2 is the percentage of HbO2 compared with the quantity of Hb capable of carrying O2. MetHb and HbCO are not capable of carrying O2; therefore, they are not specifically considered in this measurement.

Pulse oximetry, as described subsequently, is used routinely to evaluate oxygen satura- tion. Since pulse oximeters use only two wavelengths, they may likewise provide incorrect information when substantial MetHb or HbCO is present. It is imperative that we always keep these important issues in mind and do not routinely assume a normal pulse oximeter reading always indicates adequate oxygen saturation.


Functional SaO2, as described previously, is in contrast with SaO2 measurement using a CO-oximeter. As the name implies, this instrument can measure HbCO% in addition to the SaO2. Also, methemoglobin levels may be measured as a percentage of total Hb with this unit.384

In CO-oximeter measurements, all forms of Hb are included in the calculation of the total Hb concentration. Thus, with this instrument, SaO2 is the percentage of HbO2 compared with all forms of Hb (including abnormal forms of Hb). SaO2 measured in this way is sometimes referred to as fractional SaO2, which may be substantially different from functional SaO2 in certain situations.

In review, the percentage of HbO2 compared with the sum of Hb and HbO2 is called functional SaO2; the percentage of HbO2 compared with all forms of Hb is called fractional SaO2.

SaO2 as an Index of Hypoxia

SaO2 is a better indicator of arterial oxygen content than is the PaO2. Approximately 98% of blood oxygen is carried in the combined state (e.g., HbO2); therefore, SaO2 more accurately reflects the quantity of oxygen in the blood than the PaO2. Clinically, as long as SaO2 exceeds 90%, most clinicians are confident that the patient is not hypoxic. Usually a red flag is raised, however, when SaO2 falls below 90%.

Furthermore, with the advent of routine SpO2, understanding of the oxyhemoglobin curve assumes greater clinical importance. Important relationships between PO2 and SO2 must be committed to memory (i.e., PO2 of 60 mm Hg = SO2 of 90%; PO2 of 40 mm Hg = SO2 of 75%). The clinician must be able to mentally equate and interchange these two important parameters of oxygenation.

The PO2–SO2 relationships described earlier hold true given normal oxyhemoglobin affinity. A change in this relationship (e.g., PO2 = 60 mm Hg; SO2 = 80%) is indicative of a change in Hb–O2 affinity (i.e., shift in oxyhemoglobin curve) that may be clinically important to recognize. For example, in the presence of alkalemia and hypocarbia, SpO2 may remain above 90% even when PaO2 is much lower than 60 mm Hg.

There is sometimes concern that a left-shifted oxyhemoglobin dissociation curve may cause tissue hypoxia because the hemoglobin will not release oxygen to the tissues. This phenomenon alone, especially in chronic conditions, is probably unlikely to cause tissue hypoxia as a patient with a p50 of 11 mm Hg did not appear to show any evidence of hypoxia.436

Finally, the relative insensitivity of SaO2 must also be recognized. Although SaO2 is a superior index of quantitative oxygen content in the blood, it is inferior to PaO2 as a sensitive index of pulmonary deterioration, mild hypoxemia, and/or hyperoxemia. Because the normal individual has an SaO2 on the flat portion of the oxyhemoglobin dissociation curve, relatively large changes in PaO2 result in minimal or no change in SaO2.

SpO2 and Abnormal Hb Species

As described earlier, SpO2 measures functional saturation, not fractional saturation. Thus, abnormal Hb species (e.g., HbCO, MetHb) are not reflected. HbCO is recorded as HbO2 because only two wavelengths of light are being measured. This could lead to a false sense of security regarding the patient with significant levels of abnormal Hb species. If, for example, an individual has an HbCO level of 20% and a fractional HbO2 level of 70%, SpO2 will read approximately 90%.

Thus, pulse oximetry may be misleading in the patient with recent exposure to carbon monoxide. With increased methemoglobinemia, SpO2 readings tend to migrate toward 85%. As always, one cannot depend too heavily on any single technology as a replacement for thorough clinical evaluation.

Although pulse oximetry has some shortcomings as a true measure of oxygen saturation, it is useful particularly as a monitor of desaturation. In other words, when there is a fall in oxygen saturation from previous levels, it will usually be reflected. For this reason, pulse oximetry is an excellent method to monitor oxygen status on a real-time basis.

Maintenance of an Adequate SaO2

In summary, SaO2 values may vary substantially depending on the technique of measurement. The clinician must understand the method being used and its implications regarding patient management. When abnormal forms of Hb are suspected, SaO2 should always be measured by using CO-oximetry.

When fractional SaO2 is low, as determined by CO-oximetry, therapy is focused on decreasing the amount of any abnormal Hb species present in the blood and increasing blood oxygen content to satisfactory levels.

High levels of HbCO are treated with fraction of inspired oxygen (FIO2) of 1.0 and, when available, hyperbaric oxygen. The half-life of HbCO is approximately 5 hours on room air. Thus, it takes the body about 5 hours to eliminate 50% of HbCO while breathing room air. Breathing 100% O2 decreases the half-life to about 1 hour. Furthermore, the high levels of inspired oxygen maximally saturate available Hb and enhance dissolved O2 concentration. In the case of very high MetHb levels, methylene blue is often useful to accelerate the reduction of MetHb to Hb.

In most clinical situations, conventional wisdom is simply to maintain the fractional SaO2 above 90% to 92%. This usually equates to a PaO2 > 60 mm Hg. When SaO2 falls below this point, however, immediate action is usually indicated to restore SaO2 to safer levels. One must remember that below 90% saturation, SaO2 will fall precipitously with further PaO2 reductions. Although this approach has been recently challenged,696 presently it is probably best to adhere to conventional wisdom.

Blood Hemoglobin Concentration


Not only is the SaO2 important in tissue oxygenation, but the absolute quantity of hemoglobin present in the patient must be adequate to carry and deliver oxygen throughout the body. The normal red blood cell concentration (abbreviated [RBC]) is 5 million/mm3 (±700,000) for men and 4.5 million/mm3 (±500,000) for women. The normal Hb concentration (abbreviated [Hb]) is 15 g% (15 g/100 mL of blood) in men and 13 to 14 g% in women.

A reduction in the amount of circulating RBCs or Hb is termed anemia. In general, the classic criterion for an individual to be considered anemic is if [RBC] is less than 4 million/mm3 or if [Hb] is less than 12.5 g%.702 Actual normal values vary with age and sex. Anemia may greatly diminish the ability of the blood to transport oxygen because hemoglobin is responsible for approximately 98% of oxygen transport.

When blood is centrifuged or allowed to stand, it separates into two layers: (1) a layer of formed elements that includes RBCs, white blood cells (WBCs), and platelets; and (2) a layer of straw-colored fluid called plasma.The percentage of formed elements by volume is known as the hematocrit (Hct). Hematocrit is normally approximately 47% in men and approximately 42% in women. Because the RBCs make up the major portion of the hematocrit, it is also a useful indicator of anemia.

In a sense, hematocrit is a double-edged sword. If Hct is extremely low, arterial oxygen content and oxygen transport will be compromised. Conversely, when Hct is excessive, blood viscosity is increased and again, oxygen transport may be diminished due to a fall in cardiac output (Fig. 11-1). The optimal clinical Hct is likewise controversial and, in different patient populations, has been shown to be as low as 30% or as high as 45%.437

Laboratory Diagnosis of Anemia

When anemia is observed, the cause should be investigated. A thorough discussion of the various types of anemia and differential diagnosis is beyond the scope of this book; however, some fundamentals and terminology involved in anemia are reviewed.

Anemia is generally classified and diagnosed based on the characteristics of the RBCs observed and the number of immature RBCs seen. In particular, the size, shape, and amount of Hb have diagnostic significance.

Mean Corpuscular Volume

Normal RBCs are, for the most part, approximately 7 μm in diameter. Figure 11-2 shows a normal RBC film magnified 1000 times. Anisocytosis is said to exist when there are abnormal variations in cell size (Fig. 11-3). The presence of great numbers of large (>10 μm) RBCs is called macrocytosis. This condition is also seen in Figure 11-3. Conversely, the presence of great numbers of small (<5 μm) RBCs is called microcytosis (Fig. 11-4).

Cell size is measured in the clinical laboratory using the mean corpuscular volume (MCV) index. Normal MCV is 90 (±8) femptoliters (fL).388 Decreased [Hb] associated with an MCV less than 82 fL is called microcytic anemia; decreased [Hb] associated with an MCV greater than 98 fL is called macrocytic anemia.

Immature Red Blood Cells

The presence of large numbers of immature RBCs in the blood suggests that anemia may be due to acute blood loss. Under normal conditions, between 0.5% and 1.5% of RBCs are in the immature form known as reticulocytes (Fig. 11-5).389 The presence of increased reticulocytes in the blood is called reticulocytosis. Reticulocytosis leads to rapid oxygen consumption in acquired blood samples and may lower blood PaO2 if not measured promptly. Another type of immature RBC, the normoblast, is not normally found in the blood but may be observed in anemia secondary to acute blood loss. A normoblast is a nucleated RBC similar in size to a normal RBC.


Table 11-1 compares MCV and MCHC.Table 11-2 summarizes many of the terms used in describing RBCs when diagnosing anemia. Common types of anemia associated with each laboratory finding are also shown in Box 11-3.

Types of Anemia

Some of the more common types of anemia are briefly discussed here to acquaint the reader with the variety of potential anemic mechanisms (see Table 11-2). The presence of anemia means either (1) that there is a decrease in the production of RBCs or hemoglobin or (2) that RBCs or Hb is being lost or destroyed at an accelerated rate.

Decreased production may be due to a problem at the production site (i.e., bone marrow) or to a deficiency in one of the necessary constituents for RBC/Hb production. On the other hand, accelerated loss or destruction may be due to excessive rupture (hemolysis) of RBCs or to excessive blood loss.

Inadequate Hemoglobin Synthesis

The most common problem in Hb synthesis is iron deficiency. Iron supply is normally not a problem, because iron is recycled following the destruction of old RBCs. However, when iron is lost from the body, as in hemorrhage, or when additional iron is required, such as in pregnancy, it may be in short supply for Hb production.

Probably the most common cause of iron deficiency anemia is chronic blood loss. It may also be seen in infants or in mothers during pregnancy. An interesting diagnostic characteristic observed in some individuals with iron deficiency is pagophagia.438 Pagophagia is a type of “pica” or craving for unusual substances. Pagophagia is a strong craving for ice and is the most common type of pica seen in iron deficiency anemia. Pica occurs in up to 58% of patients with iron deficiency.438

In recent years, severe iron deficiency has become relatively uncommon. Nevertheless, mild iron deficiency is still far too common and can have damaging long-term consequences.439 Thus, we must continue to be vigilant in its identification and prevention.

Production of Hb may be abnormal in a genetic disorder called thalassemia. Thalassemia, also known as Cooley’s anemia or Mediterranean disease, may manifest itself in one of two forms: thalassemia major is a severe form of the disease that may be associated with severe anemia; thalassemia minor is a milder form.

Inadequate production of Hb is associated with hypochromia and the presence of small RBCs (microcytosis).

Inadequate Red Blood Cell Formation

Production of RBCs depends on an adequate supply of folic acid, vitamin B12, and the hormone erythropoietin. Folic acid is plentiful in green leafy vegetables. Alcohol, however, interferes with the metabolism of folic acid. Therefore, poor diet or alcoholism may lead to folic acid deficiency.

Vitamin B12, sometimes referred to as extrinsic factor, is normally absorbed in the stomach. This absorption is facilitated through a substance that has been labeled intrinsic factor. Individuals lacking in this intrinsic factor may develop anemia due to vitamin B12 deficiency. Anemia that develops by this mechanism is known as pernicious anemia.

Anemia is also common in chronic renal failure and is due at least in part to decreased erythropoietin. Some loss of RBCs into the urine may also occur due to increased permeability of the diseased glomerulus.

Anemia due to folic acid or vitamin B12 deficiency leads to a high number of large RBCs (i.e., macrocytosis). In addition, megaloblasts may be observed in the blood of these individuals.

Red Blood Cell Loss/Hemolysis

Immediately after acute blood loss, [RBC] may be normal. Soon after, however, fluid enters the blood from the interstitial space and thus leads to anemia.

Hemolysis is usually the result of the presence of toxins in the blood. Toxins may originate from infectious processes or may directly enter the blood, such as in poisonous snakebites. Many chemical agents may be associated with hemolysis. Finally, chronic hemolysis with acute exacerbation may occur in disorders such as sickle-cell disease (see Chapter 7) or thalassemia.

The pain rate (episodes per year) is a useful measure of the severity of sickle cell disease.440 Treatment, which has been discussed briefly in Chapter 7, may include bone marrow transplant, or more commonly, administration of pharmacological agents (e.g., hydroxyurea) aimed at increasing the amount of fetal Hb (HbF).441 Increases in HbF have an ameliorating effect on the disease and symptoms. Many of these chemotherapeutic agents, however, may cause adverse effects and drugs with less potential of side effects (e.g., butyrate) continue to be explored.441

Reticulocyte levels typically are increased in conditions associated with hemolysis or blood loss. In most long-term hemolytic anemias, reticulocytes exceed 5%.390 When evaluating the reticulocyte levels, however, one must keep in mind that reticulocytes are usually expressed as a percentage of total RBCs.

It is probably better to think in terms of the actual count of reticulocytes rather than the percentage. The normal actual count of reticulocytes is about 50,000 cells/mm3 or 1% of [RBC]. If [RBC] decreases from 5 million to 2.5 million/mm3, and the reticulocyte count remains constant (i.e., 50,000 cells), the percentage of reticulocytes would be 2%. If the actual reticulocyte count is not considered, this could be wrongly interpreted as an increase in RBC production.

The presence of normoblasts in the blood is abnormal and a sign of accelerated RBC production. Anemia secondary to the loss of RBCs is typically normocytic in laboratory analysis.

Anemia and Hypoxia

Surprisingly, mild anemia (i.e., [Hb] 10 g%) usually will not result in hypoxia. The large reserve of O2 normally present in the blood and the body’s compensatory mechanisms both tend to ensure adequate tissue oxygenation. As discussed previously, usually only about 25% of the oxygen in arterial blood is extracted by the tissues; therefore, mild anemia does not substantially affect tissue O2 supply.

Furthermore, the body responds to anemia by increasing cardiac output and increasing 2,3-diphosphoglycerate (DPG) levels. In healthy individuals, mild, acute normovolemic anemia is compensated for by increases in cardiac output up to 50%.391 Within 2 weeks the cardiac output returns to preanemic levels, with an increase in DPG accounting for the compensation. Thus, the major compensatory mechanism in acute anemia is an increased cardiac output, whereas in chronic conditions, increases in DPG prevail.

In moderate to severe anemia (i.e., [Hb] = 6 to 9 g%) hypoxia may occur, depending on the cardiac reserve and the acuteness of onset. Anemic hypoxia in all likelihood will be seen when [Hb] falls below 6 g% and the capabilities of compensatory mechanisms are exceeded.392

Blood Transfusions

Blood transfusion is the treatment of choice for severe anemia; however, this therapy may be associated with substantial risk. Some adverse effect to blood transfusion may occur in as many as 20% of recipients.442 Immune side effects are seen in approximately 3% of all transfusions.393 Typically these are mild allergic reactions, although potentially fatal hemolytic reactions are observed in approximately one of 6000 transfusions.393

In addition, anaphylactic reactions may occur, and not infrequently patients contract post-transfusion hepatitis.393 Finally, blood is a complex substance and may carry with it additional risk factors not yet clearly identified. The acquired immunodeficiency syndrome has been a painful lesson in this regard.

The ideal hematocrit and [Hb] in critically ill patients are also a matter of some controversy. Certainly, Hct need not be within the normal range in order to ensure adequate oxygenation. Optimal levels are probably somewhere between 30% and 45% depending on the individual’s particular pathology.394 437 There is some evidence to suggest that the optimal hematocrit in critically ill patients is about 33% (see Fig. 11-1), because further increases do not result in increased cellular O2 availability.395 Obviously, low Hct levels are associated with decreased ability of the blood to carry oxygen. In contrast, high Hct levels increase blood viscosity and thereby dampen cardiac output.

A [Hb] blood transfusion trigger of less than 7.0 g/dL has been recommended and is probably a useful guideline.444 Nevertheless, at high altitude, or for patients with brain injury, a much higher trigger (e.g., 10 g/dL) is probably appropriate.443

Circulatory Status

Cardiac Output

The cardiovascular system is the core of the human oxygenation system. The cardiac minute output (abbreviated image or sometimes CO) is the volume of blood ejected from the left side of the heart each minute. Cardiac output is a crucial index concerning tissue oxygenation. Cardiac output is approximately 5 L/min in normal individuals. The cardiac index (CI) relates cardiac output to body size and expresses cardiac output as liters per minute per body surface area in square meters (m2). Thus, the cardiac index should be the same in all individuals regardless of size or weight. The normal cardiac index is 3.5 ± 0.7 L/min/m2.

Clinical Assessment

Notwithstanding, in many clinical situations, cardiac output must be assessed indirectly. This assessment is accomplished through evaluation of a host of clinical signs and symptoms. Urine output, neurologic status, blood pressure, pulse, capillary refill (i.e., the speed at which color returns to the skin after it is depressed), cyanosis, and warmth of extremities all pro- vide clues about the adequacy of circulation. Although all these indicators provide useful information, they cannot replace actual measurement of cardiac output when it is in serious question.

Even when cardiac output is measured, however, complete cardiovascular assessment must include sequential evaluation of the three basic components of the cardiovascular system: (1) the pump (heart), (2) the fluid (blood), and (3) the tubules (blood vessels). The interaction of these three components determines the important cardiovascular parameters of cardiac output and arterial blood pressure. Furthermore, this chronologic assessment aids in determining the root cause of any cardiovascular disturbance.


Shock is a state of collapse of the cardiovascular system usually associated with a loss of arterial blood pressure. The signs and symptoms of shock are a result of inadequate perfusion to a particular organ or may be due to the compensatory response of the central nervous system to the shock state. The sympathetic portion of the autonomic nervous system is typically stimulated in shock, resulting in the release of epinephrine and norepinephrine. These substances, in turn, lead to an increased heart rate and constriction of peripheral blood vessels, which represents an attempt of the body to preserve cardiac output and arterial blood pressure.

< div class='tao-gold-member'>

Stay updated, free articles. Join our Telegram channel

Jul 10, 2016 | Posted by in RESPIRATORY | Comments Off on Hypoxia: Assessment and Intervention

Full access? Get Clinical Tree

Get Clinical Tree app for offline access