Perioxygenation

Body Oxygen Stores

Oxygen is carried in the blood in two forms: the greater portion is in reversible chemical combination with hemoglobin (Hb), and the smaller part is dissolved in plasma. The ability to carry large amounts of oxygen in Hb is important, because without it the amount carried in the plasma would be so small that cardiac output would need to be increased 20 times or more to yield adequate oxygen delivery. The amount of chemically bound oxygen is directly related to the concentration of Hb and how saturated the Hb is with oxygen. Arterial oxygen content (Ca o ₂ ) can be calculated from the following equation:

where

• 1.36 = estimated mass volume of oxygen that can be bound by 1 g of normal Hb

• Sa o ₂ = arterial oxyhemoglobin saturation (when fully saturated, Sa o ₂ = 100%)

• Pa o ₂ = arterial partial pressure of oxygen

• 0.003 = solubility coefficient of oxygen in human plasma

The Ca o ₂ with a Hb concentration of 15 g/dL and 100% Sa o ₂ is approximately 20 mL of oxygen per 100 dL of blood. In addition, approximately 0.3 mL of oxygen/100 dL blood is in physical solution at a normal physiologic Pa o ₂ ; this amount of dissolved oxygen normally accounts for only 1.5% of the total oxygen content, but its contribution increases when Pa o ₂ is increased (dissolved oxygen is linearly related to Pa o ₂ ). The venous oxygen content (C _V o ₂ ) can be calculated with the same formula using mixed venous oxygen tension (P _V o ₂ ) and mixed venous oxyhemoglobin saturation (S _V o ₂ ).

The pattern of uptake and release of oxygen by Hb is demonstrated by the oxyhemoglobin dissociation curve, which is a plot of Hb saturation as a function of partial pressure of oxygen (P o ₂ ). The sigmoid shape of the curve reflects the fact that the four binding sites on a given Hb molecule interact with each other. When the first site has bound a molecule of oxygen, the binding of the next site is facilitated, and so forth. The result is a curve that is steep up to a P o ₂ of 60 mm Hg and shallower thereafter, approaching 100% saturation asymptotically. At a P o ₂ of 100 mm Hg (the normal arterial value), 97% of the hemes have bound oxygen; at 40 mm Hg (a typical value for Pv o ₂ in a resting person), the saturation declines to about 75%. The shape of the oxyhemoglobin dissociation curve has important physiologic implications. The flatness of the curve above a P o ₂ of 80 mm Hg ensures a relatively constant Sa o ₂ despite wide variations in alveolar oxygen pressure. The steep portion of the curve between 20 and 60 mm Hg permits unloading of oxygen from Hb at relatively high P o ₂ values, which favors the delivery of large amounts of oxygen into the tissues by diffusion.

The oxygen-binding properties of Hb are influenced by several factors, including pH, partial pressure of carbon dioxide (P co ₂ ), and temperature. These factors cause shifts of the oxyhemoglobin dissociation curve to the right or left without changing the slope of the curve. For example, an increase in temperature or a decrease in pH, such as may occur in active tissues, decreases the affinity of Hb for oxygen and shifts the oxyhemoglobin dissociation curve to the right. As a result, a higher P o ₂ is required to achieve a given saturation, facilitating the unloading of oxygen at the tissue. To quantify the extent of a shift of the oxyhemoglobin dissociation curve, the P ₅₀ is used—that is, the P o ₂ required for 50% saturation. The P ₅₀ of normal adult Hb at 37°C and normal pH and P co ₂ is 26 to 27 mm Hg.

Despite its great importance, oxygen is a very difficult gas to store in a biologic system. In subjects breathing air, oxygen stores are small ( Table 15.1 ). ^, The relatively steep oxyhemoglobin dissociation curve and the small oxygen stores imply that factors affecting Pa o ₂ produce their full effects very quickly. This contrasts with CO ₂ , for which the large size of the stores buffers the body against rapid changes. Therefore, in a subject breathing air, a pulse oximeter probably gives an earlier indication of hypoventilation than does CO ₂ measurement. In contrast, in a subject breathing a high fraction of inspired oxygen (F io ₂ ), CO ₂ measurement gives an earlier indication of hypoventilation.

The amounts of body oxygen in the various storage sites of a person breathing air are increased with breathing an F io ₂ of 100% ( Fig. 15.2 ; see also Table 15.1 ). ^, The largest increase in oxygen stores occurs in the functional residual capacity (FRC). Storage of oxygen in the tissue is rather difficult to assess, but assuming that Henry’s law applies and that the partition coefficient for gases approximates the gas-water coefficients, breathing oxygen for 3 minutes significantly increases tissue oxygen stores.

Physiology of Apnea

During apnea in the paralyzed patient there is no diaphragmatic movement or lung expansion, and the total body oxygen consumption (V˙o ₂ ) remains fairly constant at about 230 mL/min. Consequently, Pa o ₂ decreases rapidly because of the depletion of the diminishing oxygen stores in the lungs. If the airway becomes obstructed, oxygen removal will generate a substantial and immediate negative pressure, contributing to a further decrease of Pa o ₂ . Although the Pa o ₂ falls in direct relation to the alveolar oxygen concentration (P ao ₂ ), Sa o ₂ remains 90% or more as long as Hb can be reoxygenated in the lungs. ^{, , ,} Sa o ₂ begins to decrease only after lung oxygen stores are depleted and the Pa o ₂ is lower than 60 mm Hg. It is for this reason that oximetry is not the best physiologic means, compared with Pa o ₂ , for predicting the onset of hypoxemia. However, because it detects decreases in Sa o ₂ before other clinical signs, oximetry is an invaluable clinical monitor that adds to the safety of anesthetic management. Critical oxyhemoglobin desaturation may be defined as Sa o ₂ 80% or less; for patients with Sa o ₂ 80% or less, the range in the rate of decrease is 20% to 40% per minute during apnea.

Apneic Oxygenation

The physiologic nomenclature for describing apneic oxygenation has changed several times since the phenomenon was discovered by Volhard in 1908. It has been described as “diffusion respiration” by Draper and Whitehead, as “aventilatory mass flow” by Bartlett and colleagues, and as “apneic oxygenation” by Frumin and colleagues. What all of these studies describe is oxygenation using only the difference in the rates of excretion of CO ₂ and absorption of oxygen as the driver of gaseous flow.

Mechanism

Preoxygenation followed by oxygen insufflation during subsequent apnea maintains Sa o ₂ by apneic oxygenation. ^, In the apneic adult, V˙ o ₂ averages 230 mL/min, whereas the output of CO ₂ to the alveoli is limited to about 20 mL/min, and the remaining CO ₂ production (approximately 90%) is buffered within the body tissues. The difference in gas solubility between oxygen and CO ₂ and the affinity of oxygen for Hb accounts for the difference in movement of oxygen and CO ₂ across the alveolar membrane.

Lung gas volume initially decreases because of the net negative gas exchange rate of 210 mL/min. Therefore, a pressure gradient is created between the upper airway and the alveoli, and if the airway is patent, this results in a mass movement of oxygen down the trachea into the alveoli, prolonging apnea time. Conversely, CO ₂ is not exhaled because of this mass movement of oxygen down the trachea, and the alveolar CO ₂ concentration (P aco ₂ ) shows an initial rise of about 8 to 16 mm Hg during the first minute and a subsequent fairly linear rise of about 3 mm Hg/min.

Fraioli and colleagues emphasized the importance of the ratio of FRC to body weight during apneic oxygenation and demonstrated that patients with a low FRC/body weight ratio could not tolerate apnea for more than 4 minutes, whereas those with a high FRC/body weight ratio (>53.3 ± 7 mL/kg) maintained Pa o ₂ at 90% of the control value for 15 minutes or longer. Some studies demonstrated that with a patent airway and an F io ₂ of 1.0, Sa o ₂ can be maintained at greater than 90% for up to 100 minutes with apneic oxygenation. ^,

The success of apneic oxygenation depends on airway patency to allow oxygen to move into the apneic lungs. In the presence of airway obstruction, not only does lung gas volume decrease rapidly, but intrathoracic pressure also decreases at a rate that is dependent on V˙ o ₂ and thoracic compliance, subsequently leading to a marked decrease in Pa o ₂ . When airway obstruction is relieved, rapid flow of oxygen into the lungs occurs, and with high F io ₂ , rapid reoxygenation resumes.

Apneic oxygenation can be achieved by preoxygenation followed by insufflation of oxygen through a nasopharyngeal or oropharyngeal cannula or through a needle inserted in the cricothyroid or cricotracheal membrane. This provides at least 10 minutes of adequate oxygenation in healthy apneic patients whose airways are unobstructed and therefore has many practical applications. In patients who are difficult to intubate or ventilate, pharyngeal oxygen insufflation (or tracheal insufflation, in cases of upper airway obstruction) may allow additional time for laryngoscopy and endotracheal intubation. ^{, ,} This can be advantageous in patients who have decreased oxygen reserves, such as children, pregnant women, obese patients, and patients with acute respiratory distress syndrome (ARDS). The combination of preoxygenation and apneic oxygenation can be used during bronchoscopy and can provide an otolaryngologist adequate time for glottic surgery unimpeded by the presence of an endotracheal tube (ETT) or by a patient’s respiratory movements.

The relationship between the ambient oxygen fraction and the time to development of dangerous hypoxemia (apnea time) has been investigated in a computational modeling analysis by McNamara and Hardman. As the ambient oxygen fraction increases, the onset of hypoxia is delayed irrespective of shunt fraction, and the increase in time to desaturation is very much greater with very high ambient oxygen fractions ( Fig. 15.3 ). Increasing the ambient oxygen fraction from 0.9 to 1.0 more than doubles the time to desaturation compared with increasing the ambient oxygen fraction from 0.21 to 0.9. This effect was maintained over a wide range of shunt fractions (1% to 30% of cardiac output) during apnea. These findings have significant implications for anesthetic practice, where assurance of effective apneic oxygenation involves ensuring the patency of the airway and the provision of 100% oxygen. Failure to provide 100% oxygen to the apneic patient’s open airway greatly hastens the development of hypoxemia.

Efficacy of Preoxygenation

Preoxygenation increases alveolar oxygen concentration and decreases alveolar nitrogen in a parallel fashion ( Fig. 15.4 ); it is the washout of nitrogen from the lungs that is the key to achieving preoxygenation. ^, Historically, preoxygenation and denitrogenation have been used interchangeably, although a change in focus from preoxygenation to denitrogenation has been suggested. With normal lung function, oxygen wash-in and nitrogen wash-out are exponential functions; therefore the rate of preoxygenation (or denitrogenation) is governed by the time constant (τ) of the exponential curves. This constant is the same for both the wash-in and wash-out curves and is proportional to the ratio of alveolar ventilation (V˙ a ) to FRC. Because the oxygen flow used for V˙ a is delivered via an anesthesia circuit, preoxygenation occurs in two sequential stages according to the time constant, which is the time necessary for a given flow through a container to equal the volume of the container. These are the two stages:

• 1.

  Wash-out of the anesthesia circuit by oxygen flow

• 2.

  Wash-out of the FRC by alveolar ventilation

After 1 τ, the oxygen concentration of the FRC will be increased by approximately 63% of its original value; after 2 τ, to 86%; after 3 τ, to 95%; and after 4 τ, to about 98% of its original value.

To hasten denitrogenation, it is advisable to wash out (flush) the anesthesia circuit with a high oxygen flow before applying the face mask to the patient. During preoxygenation, an oxygen flow rate that eliminates rebreathing should be used.

In summary, three steps should be followed to enhance preoxygenation: (1) the anesthesia circuit is flushed by a high oxygen flow, (2) a nonleaking face mask is used to avoid air entrainment, and (3) an oxygen flow of 5 L/min is used for tidal volume breathing (TVB), and a flow of 10 L/min is used for deep breathing.

The end points of maximal alveolar preoxygenation or denitrogenation have been defined as an end-tidal oxygen concentration (EtO ₂ ) of approximately 90% and an end-tidal nitrogen concentration (EtN ₂ ) of 5%. ^, In an adult with a normal FRC and V˙ o ₂ , an EtO ₂ of 90% or more means that the lungs contain more than 2000 mL of oxygen (8 to 10 times the V˙ o ₂ ). Because of the obligatory presence of CO ₂ and water vapor in the alveolar gas, an EtO ₂ greater than 97% cannot be easily achieved. Factors affecting the efficacy of preoxygenation include F io ₂ , duration of breathing, and the V˙ a /FRC ratio ( Box 15.1 ).

Efficiency of Preoxygenation

Preoxygenation can markedly delay arterial oxyhemoglobin desaturation during apnea. In healthy individuals breathing room air, desaturation to 70% can occur within 1 minute, whereas with adequate preoxygenation, desaturation occurs after 5 minutes. The delay in desaturation during apnea depends on the efficacy of preoxygenation, the capacity for oxygen loading, and V˙ o ₂ (see Box 15.1 ). Patients with a decreased capacity for oxygen loading (decreased FRC, Pa o ₂ , Ca o ₂ , or cardiac output) or with increased V˙ o ₂ , or both, desaturate much faster during apnea than healthy patients do. The main difference in the rate of apnea-induced oxyhemoglobin desaturation after different preoxygenation techniques is observed between Sa o ₂ levels of 100% and 99%. ^{, , ,} This range represents the flat portion of the oxyhemoglobin dissociation curve. When oxygen reserves are depleted, rapid desaturation occurs regardless of the technique of preoxygenation and is like that observed in patients breathing air.

Farmery and Roe developed a computer model describing the rate of oxyhemoglobin desaturation during apnea. This model was found to agree reasonably well with actual data from patients whose weight and degree of preoxygenation were reliably known ( Fig. 15.5 ). ^, Because it would be dangerous to obtain data on time to marked oxyhemoglobin desaturation in humans, this model is uniquely useful for analysis of oxyhemoglobin desaturation below 90%. ^, As the pre-apnea F ao ₂ is progressively decreased from 0.87 to 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, and 0.13 (F ao ₂ at room air) in a healthy 70-kg patient, the apnea time to 60% Sa o ₂ is progressively decreased from 9.9 to 9.31, 8.38, 7.30, 6.37, 5.40, 4.40, 3.55, and 2.8 minutes, respectively. ^, Fig. 15.5 shows that for a healthy 70-kg adult, a moderately ill 70-kg adult, a healthy 10-kg child, and an obese 127-kg adult, 80% Sa o ₂ is reached after 8.7, 5.5, 3.7, and 3.1 minutes, respectively, whereas 60% Sa o ₂ is reached at 9.9, 6.2, 4.23, and 3.8 minutes, respectively. ^,

Techniques for Preoxygenation

Several methods of preoxygenation are described in the scientific literature. Traditional techniques include TVB, deep breathing, and positive airway pressure ( Box 15.2 ). THRIVE can also be used for preoxygenation (see later discussion).