**3. Physiological basis, efficiency, and productivity**

After rapid sequence induction, spontaneous ventilation reinitiation does not occur rapidly after an unsuccessful intubation procedure and saturation falls below 90% in 11% of patients [10]. Administration of succinylcholine (0.56 and 1 mg/kg) after induction with propofol (2 mg/kg) and fentanyl (μg/kg) has increased desaturation risk and apnea duration compared to placebo [11]. In a pharmacodynamic study with succinylcholine (0.3–1 mg/kg), it found that the intubation conditions were excellent at doses above 0.5 mg/kg, but the delay in resumption of spontaneous breathing rose from 4.0 to 6.16 minutes after administration of 0.6 and 1 mg.kg−1, respectively [12]. Reversal of deep neuromuscular block (induced by high-dose rocuronium) with sugammadex (16 mg/kg) used for rapid sequence induction is significantly faster than spontaneous recovery of succinylcholine (6.2 ± 1.8 versus 10.9 ± 2.4 minutes) [13]. Reversal with sugammadex following rapid sequence induction with rocuronium allows earlier restoration of spontaneous respiration compared to succinylcholine (216 versus 406 seconds) [14]. Thus, the choice of the rocuronium would increase the margin of safety for a resumption of spontaneous ventilation after a rapid sequence

Desaturation attacks occur frequently in children, with 4–10% during induction and 20% during tracheal intubation [15]. Desaturation occurs faster if the child is younger [16, 17] and apnea duration in predesaturation has a linear relationship with the age of the patient. The low weight of the child increases the frequency of severe arterial desaturation. It is suggested

noted that upper respiratory tract infection increased desaturation risk during induction [15]. The number of important factors effect the time from the onset of apnea to the development

FRC is the most important oxygen storage in the body. The larger the FRC, the longer apnea times can be preceded before the critical hypoxia develops. Alveolar oxygen fraction (FAO<sup>2</sup>

of the lungs (290 mL) will be consumed within 1 minute. This explains why you can expect a critical hypoxia after 1-minute apnea. Reduced FRC patients (lung disease, kyphoscoliosis,

ticularly recommended in patients at risk for apneic arterial oxyhemoglobin desaturation. The success of preoxygenation to delay the onset of desaturation has been known for many years [19–21]. Preoxygenation during anesthesia induction is highly recommended in cases of desaturation prior to airway safety with endotracheal intubation. In situations where manual ventilation is not desired, such as patients with aspiration risk, preoxygenation has become

is around 13% in air breathing. For an adult with normal FRC and VO<sup>2</sup>

pregnancy, and obesity) reach critical hypoxia much faster.

may be the safe apnea limit during induction of pediatric anesthesia [18]. It was

before anesthesia induction and tracheal intubation is par-

)

, the oxygen content

induction.

26 Tracheal Intubation

that 95% SpO<sup>2</sup>

of critical hypoxemia.

*2.3.1.2. Preoxygenation*

Preoxygenation using a high FiO<sup>2</sup>

*2.3.1.1. Functional residual capacity (FRC)*

*2.3.1. Desaturation in pediatrics*

Preoxygenation increases the body O2 stores, the main increase occurring in the functional residual capacity. Accurate quantification of the increases in the O<sup>2</sup> volume in various body tissues is difficult, but the estimated increases are notable when assuming that the partition coefficient for gases approximates the gas-water coefficients (**Table 1**, **Figure 1**) [2, 34].

The effectivity of preoxygenation is assessed by efficacy and efficiency. Efficacy indices include FAO<sup>2</sup> increase, decreases in alveolar nitrogen fraction (FAN<sup>2</sup> ), and increase in PaO2 [35–42]. The efficiency of preoxygenation is assessed by the decrease in oxyhemoglobin desaturation (SpO<sup>2</sup> ) during apnea [10, 43, 44]. Preoxygenation increases FAO<sup>2</sup> and decreases FAN<sup>2</sup> (**Figure 2**) [45].

The key to achieve maximum preoxygenation is the excretion of alveolar nitrogen (N<sup>2</sup> ). The terms preoxygenation and denitrogenation have been used synonymously to describe the


**Table 1.** Body O2 stores (in mL) during room air and 100% O<sup>2</sup> breathing [34].

**Figure 1.** Variation in the volume of O<sup>2</sup> stored in the functional residual capacity (□), blood (▲), tissue (○), and whole body (◼) with the duration of preoxygenation [2].

after-tidal N<sup>2</sup>

by O2 flow

alveolar ventilation [32].

**Table 2.** Stages of preoxygenation.

ide (CO<sup>2</sup>

tain >2000 mL of O<sup>2</sup>

1 Washout of anesthesia circuit

tion gases, and the high O2

expected lower end-tidal CO<sup>2</sup>

• Inspired oxygen concentration

the following equation:

Efficacy

Efficiency

• VA/FRC ratio

consumption)

concentration of 5% (EtN<sup>2</sup>

easily. Many factors affect efficacy and efficiency (**Table 3**).

Factors affecting the efficacy of preoxygenation are FiO<sup>2</sup>

, which is 8–10 times the VO<sup>2</sup>

**Stage Description Determinant of** *t* **Recommendation**

rate

2 Washout of FRC by VA FRC/VA Use of O<sup>2</sup>

Size of circuit/O<sup>2</sup>

flow

FRC, functional residual capacity; t, time required for flow through a container (volume) to equal its capacity; and VA,

alveolar ventilation/functional residual capacity ratio. Failure to achieve a FiO<sup>2</sup>

concentration (EtCO<sup>2</sup>

FAO<sup>2</sup> = 0.693 × Functional residual capacity/Volume of alveolar ventilation.

1.0 depends on the height of the ozone beneath the face mask, the rebreathing of exhala-

affected by the duration of the aeration, the breathing technique, and the amount of fresh gas flow [50]. Bearded patients, toothless patients, elderly patients with sagging cheeks, facial mask use at the wrong size, and presence of gastric tubes (nasogastric) are common factors

volume respiration can achieve an EtO2 > 90% target level within 3–5 minutes. The half-time

• Systemic oxygen supply versus demand balance (arterial oxygen content, cardiac output, whole body oxygen

) and water vapor in the alveolar air, it is thought that EtO2 > 94% cannot be obtained

dispersion of resuscitation bubbles [45, 48, 49]. FiO<sup>2</sup>

) and EtO2

fraction following each unit change in FiO<sup>2</sup>

residual capacity and oxygen consumption (VO2

that cause air entrapment and a lower FiO<sup>2</sup>

for the exponential change in the FAO<sup>2</sup>

of leaks in the anesthetic cycle [26]. With a FiO<sup>2</sup>

• Presence of leak anesthetic system used level of FGF

• Oxygen volume in lungs (alveolar oxygen tension, FRC)

**Table 3.** Factors affecting the efficacy and efficiency of preoxygenation.

• Type of breathing (tidal volume or deep breathing) and duration of breathing

FGF, fresh gas flow; FRC, functional residual capacity; and VA, alveolar ventilation [32].

) [2, 35]. In an adult subject with a normal functional

Washout of circuit by high O<sup>2</sup>

Pathophysiology of Apnea, Hypoxia, and Preoxygenation

face mask

), an EtO2 > 90% implies that the lungs con-

[26, 46]. Due to the presence of carbon diox-

. The lack of a normal capnography wave and

close to 1.0, most healthy adults with tidal

, duration of preoxygenation, and

flow rate that eliminates rebreathing

http://dx.doi.org/10.5772/intechopen.76851

should warn of the presence

of close to

flow before placing

29

may also be

is given by

**Figure 2.** Comparison of mean end-tidal O<sup>2</sup> and N<sup>2</sup> concentration obtained at 30 second intervals during 5-minute period of spontaneous tidal volume oxygenation using the circle absorber and Nasoral systems in 20 volunteers. Data are mean ± SD [45].

same process. In a normal lung function case, filling with O<sup>2</sup> and discharging of N<sup>2</sup> are exponential functions and are controlled by the time constant (t) of the exponential curves. This constant is proportional to the ratio of alveolar ventilation to functional residual capacity. Since preoxygenation prior to anesthetic induction is typically carried out using a semiclosed circular absorber cycle, the washout of the circuit must also be considered using the time constant of the circuit, which is the time required for flow through a container (volume) to equal its capacity. Thus, there are two stages of preoxygenation (**Table 2**) [32]: washing the vessel with O2 flow and washing FRC by alveolar ventilation.

After 1 t, O<sup>2</sup> at functional residual capacity is 63%; 2 t, then 86%; 3 t, then 95%; and after 4 t, an increase of about 98% is observed. The endpoints of maximum preoxygenation and denitrogenation were defined as an end-tidal O<sup>2</sup> concentration (EtO2 ) of about 90% and an


FRC, functional residual capacity; t, time required for flow through a container (volume) to equal its capacity; and VA, alveolar ventilation [32].

**Table 2.** Stages of preoxygenation.

after-tidal N<sup>2</sup> concentration of 5% (EtN<sup>2</sup> ) [2, 35]. In an adult subject with a normal functional residual capacity and oxygen consumption (VO2 ), an EtO2 > 90% implies that the lungs contain >2000 mL of O<sup>2</sup> , which is 8–10 times the VO<sup>2</sup> [26, 46]. Due to the presence of carbon dioxide (CO<sup>2</sup> ) and water vapor in the alveolar air, it is thought that EtO2 > 94% cannot be obtained easily. Many factors affect efficacy and efficiency (**Table 3**).

Factors affecting the efficacy of preoxygenation are FiO<sup>2</sup> , duration of preoxygenation, and alveolar ventilation/functional residual capacity ratio. Failure to achieve a FiO<sup>2</sup> of close to 1.0 depends on the height of the ozone beneath the face mask, the rebreathing of exhalation gases, and the high O2 dispersion of resuscitation bubbles [45, 48, 49]. FiO<sup>2</sup> may also be affected by the duration of the aeration, the breathing technique, and the amount of fresh gas flow [50]. Bearded patients, toothless patients, elderly patients with sagging cheeks, facial mask use at the wrong size, and presence of gastric tubes (nasogastric) are common factors that cause air entrapment and a lower FiO<sup>2</sup> . The lack of a normal capnography wave and expected lower end-tidal CO<sup>2</sup> concentration (EtCO<sup>2</sup> ) and EtO2 should warn of the presence of leaks in the anesthetic cycle [26]. With a FiO<sup>2</sup> close to 1.0, most healthy adults with tidal volume respiration can achieve an EtO2 > 90% target level within 3–5 minutes. The half-time for the exponential change in the FAO<sup>2</sup> fraction following each unit change in FiO<sup>2</sup> is given by the following equation:

FAO<sup>2</sup> = 0.693 × Functional residual capacity/Volume of alveolar ventilation.

Efficacy

same process. In a normal lung function case, filling with O<sup>2</sup>

and N<sup>2</sup>

flow and washing FRC by alveolar ventilation.

denitrogenation were defined as an end-tidal O<sup>2</sup>

with O2

After 1 t, O<sup>2</sup>

mean ± SD [45].

**Figure 1.** Variation in the volume of O<sup>2</sup>

28 Tracheal Intubation

**Figure 2.** Comparison of mean end-tidal O<sup>2</sup>

body (◼) with the duration of preoxygenation [2].

nential functions and are controlled by the time constant (t) of the exponential curves. This constant is proportional to the ratio of alveolar ventilation to functional residual capacity. Since preoxygenation prior to anesthetic induction is typically carried out using a semiclosed circular absorber cycle, the washout of the circuit must also be considered using the time constant of the circuit, which is the time required for flow through a container (volume) to equal its capacity. Thus, there are two stages of preoxygenation (**Table 2**) [32]: washing the vessel

of spontaneous tidal volume oxygenation using the circle absorber and Nasoral systems in 20 volunteers. Data are

4 t, an increase of about 98% is observed. The endpoints of maximum preoxygenation and

at functional residual capacity is 63%; 2 t, then 86%; 3 t, then 95%; and after

concentration (EtO2

stored in the functional residual capacity (□), blood (▲), tissue (○), and whole

and discharging of N<sup>2</sup>

concentration obtained at 30 second intervals during 5-minute period

are expo-

) of about 90% and an


Efficiency


```
FGF, fresh gas flow; FRC, functional residual capacity; and VA, alveolar ventilation [32].
```
**Table 3.** Factors affecting the efficacy and efficiency of preoxygenation.

With a functional residual capacity of 2.5 L, the half-times are 26 seconds when alveolar ventilation = 4 L/minutes and 13 seconds when alveolar ventilation = 8 L/minutes [26]. These findings indicate that hyperventilation can reduce the time required to increase the O<sup>2</sup> stores in the lungs, which provides the basis for using deep breathing as an alternative to tidal volume breathing [41, 42, 51, 52].

activating the O2

system "by-pass" during inspiration; 4 or 5 forced breaths of pure O<sup>2</sup>

Eight deep breaths at a constant oxygen flow of 10 mL/min in a 60-second period create a simple method for preoxygenation. This technique results in an average arterial oxygen pressure of 369 ± 69 mmHg, which is not significantly different from the value achieved by 3 minutes of tidal volume breathing at an oxygen flow of 5 L per minute [42]. It has been argued that the

preinduction hyperventilation was used as preoxygenation technique or normal respiration

In healthy volunteers, PSV has been shown to improve preoxygenation quality by two mechanisms: accelerate nitrogen excretion and provide better contact between mask and

volume breathing [50]. Due to the breathing properties of the circulator system, the minute ventilation during deep breathing can exceed the FGF, causing a reincrease in N<sup>2</sup>

gases during tidal volume breathing is insignificant, and thus increasing FGF by 5–10 L

All investigations have demonstrated that preoxygenation markedly delays arterial oxyhemoglobin desaturation during apnea. [26, 36, 38, 43]. The extent of this delay in desaturation

content, or cardiac output) or those with an increased VO2

Farmery and Roe developed and validated a computer model describing the rate of oxyhemoglobin desaturation during apnea [62]. The model is particularly useful for analyzing oxyhemoglobin desaturation values below 90%. These values are dangerous to allow in human

of 1.0) to 0.13 (air), the apnea time to 60% SaO<sup>2</sup>

globin desaturation more rapidly during apnea than healthy patients [26, 43].

of oxyhemoglobin dissociation curve. In a healthy 70 kg patient, when FaO<sup>2</sup>

O PSV/PEEP (94 ± 4%) [61]. Increasing fresh gas flow (FGF) between 5 and 10 L

. However, regeneration of N<sup>2</sup>

transport (decreased functional residual capacity,

found to be as efficient as conventional preoxygenation assessed on the FeO<sup>2</sup>

tion for 2 minutes) prevents postapneic hypercapnia. Postintubation PaCO<sup>2</sup>

face. In a study of healthy volunteers, the mean expired fraction of O<sup>2</sup>

during deep breathing does not provide a significant increase in FiO<sup>2</sup>

utes of preoxygenation was higher (p < 0.001) with 4 cmH<sup>2</sup>

[50].

depends on the efficacy of preoxygenation, the capacity for O<sup>2</sup>

subjects because below 90%, there will be a steep decline of PaO<sup>2</sup>

these results were not verified when using PaO<sup>2</sup>

ventilation in pure oxygen (397 ± 48 mmHg) [59].

voluntary hyperventilation technique (1 minute in FiO<sup>2</sup>

maneuvers, it is observed that PaO2

*3.1.3. Deep breathing method*

was used for 3 minutes [60].

has minimal effect on FiO<sup>2</sup>

, arterial O2

decreased from 0.87 (FiO<sup>2</sup>

9.9 to 2.8 minutes (**Figure 3**) [43].

6 cmH<sup>2</sup>

PaO2

*3.1.4. Pressure-assisted ventilation (PSV)*

the exhalation gases and therefore lower FiO<sup>2</sup>

Patients with a decreased capacity for O<sup>2</sup>

were

31

[58]. However,

was similar when

) after 3 min-

in exhalation

in

[47].

value during tidal

develop oxyhemo-

is progressively

is decreased from

due to the sigmoid shape

for comparison. After four vital capacity

Pathophysiology of Apnea, Hypoxia, and Preoxygenation

http://dx.doi.org/10.5772/intechopen.76851

followed by voluntary hyperventila-

(FeO<sup>2</sup>

loading, and the VO2

O (94 ± 3%) PSV/PEEP and

(293 ± 86 mmHg) is lower compared to after spontaneous

#### **3.1. Preoxygenation techniques**

Equipment especially face mask should be adapted and it should fit the patient. Mask and stylistic mismatch between the patient's face (mask improper length, beards, or mustaches asset) can prevent the complete closure and lead to failure [35]. The mask must be applied securely on the face of the patient; 20% dilution of O<sup>2</sup> by ambient air occurs when the mask is not tightly applied and 40% dilution occurs when it is held close to the face. The mask should be applied firmly to the patient's face; when the mask is not fully seated, dilution of up to 20% with ambient air in O2 and 40% dilution when held close to the face appear [53]. The circle system with fresh gas flow (5 L/minutes) is used as the standard for comparison in anesthesia studies evaluating the effectiveness of different circuits because it allows higher inspiratory flow rates. Some open circuit systems (Bain or Magill) have been shown to be much less efficient [54]. Before preoxygenation, the circuit and reservoir must be filled with O<sup>2</sup> . Three preoxygenation techniques are used: spontaneous breathing at FiO<sup>2</sup> of 1 for 2–5 minutes, the "four vital capacities" method, and deep breaths.

#### *3.1.1. Spontaneous breathing at FiO2 of 1*

This preoxygenation technique, first proposed by Hamilton in 1955, is still the reference standard: 3 -minute spontaneous breathing at FiO<sup>2</sup> of 1 level. In patients with normal lung function, this leads to denitrogenation with FAO<sup>2</sup> approaching 95%. Denitrogenation is effective from the first minute of preoxygenation; however, delay these effects with a rapid decline in the fugitive FiO<sup>2</sup> on the run [55]. Although pure O<sup>2</sup> breathing for longer than 1 minute seems it may have little SpO<sup>2</sup> or denitrogenation benefit, it has positive effect on apnea duration before desaturation [51]. In experiments with healthy subjects, the duration of the apnea can be as long as 10 minutes after the 3-minute classic preoxygenation. The apnea time can be increased by an additional 2 minutes by application of positive pressure during the preoxygenation and by ventilation to the mask after induction [56].

#### *3.1.2. Vital capacity maneuvers*

The four vital capacity method is used in cases where the patient cannot cooperate, and the duration of apnea without desaturation is shorter after four capacity maneuvers than with spontaneous breathing. Technical requirements are responsible for the limitations of this technic: bag capacity, inspiratory flow, and room gas inspiration. These problems are partially solved with an additional 2-liter bag and a non-rebreathing ambu valve. Vital capacity maneuver begins with forced expiration to optimize FeO<sup>2</sup> increase [57]. To be fully effective, the inspiratory O2 flow should be greater than the peak inspiratory flow, which is attained by activating the O2 system "by-pass" during inspiration; 4 or 5 forced breaths of pure O<sup>2</sup> were found to be as efficient as conventional preoxygenation assessed on the FeO<sup>2</sup> [58]. However, these results were not verified when using PaO<sup>2</sup> for comparison. After four vital capacity maneuvers, it is observed that PaO2 (293 ± 86 mmHg) is lower compared to after spontaneous ventilation in pure oxygen (397 ± 48 mmHg) [59].

#### *3.1.3. Deep breathing method*

With a functional residual capacity of 2.5 L, the half-times are 26 seconds when alveolar ventilation = 4 L/minutes and 13 seconds when alveolar ventilation = 8 L/minutes [26]. These find-

the lungs, which provides the basis for using deep breathing as an alternative to tidal volume

Equipment especially face mask should be adapted and it should fit the patient. Mask and stylistic mismatch between the patient's face (mask improper length, beards, or mustaches asset) can prevent the complete closure and lead to failure [35]. The mask must be applied

not tightly applied and 40% dilution occurs when it is held close to the face. The mask should be applied firmly to the patient's face; when the mask is not fully seated, dilution of up to 20%

system with fresh gas flow (5 L/minutes) is used as the standard for comparison in anesthesia studies evaluating the effectiveness of different circuits because it allows higher inspiratory flow rates. Some open circuit systems (Bain or Magill) have been shown to be much less

This preoxygenation technique, first proposed by Hamilton in 1955, is still the reference stan-

from the first minute of preoxygenation; however, delay these effects with a rapid decline in

desaturation [51]. In experiments with healthy subjects, the duration of the apnea can be as long as 10 minutes after the 3-minute classic preoxygenation. The apnea time can be increased by an additional 2 minutes by application of positive pressure during the preoxygenation and

The four vital capacity method is used in cases where the patient cannot cooperate, and the duration of apnea without desaturation is shorter after four capacity maneuvers than with spontaneous breathing. Technical requirements are responsible for the limitations of this technic: bag capacity, inspiratory flow, and room gas inspiration. These problems are partially solved with an additional 2-liter bag and a non-rebreathing ambu valve. Vital capacity

efficient [54]. Before preoxygenation, the circuit and reservoir must be filled with O<sup>2</sup>

preoxygenation techniques are used: spontaneous breathing at FiO<sup>2</sup>

on the run [55]. Although pure O<sup>2</sup>

 *of 1*

and 40% dilution when held close to the face appear [53]. The circle

or denitrogenation benefit, it has positive effect on apnea duration before

flow should be greater than the peak inspiratory flow, which is attained by

stores in

. Three

of 1 for 2–5 minutes, the

by ambient air occurs when the mask is

of 1 level. In patients with normal lung func-

approaching 95%. Denitrogenation is effective

breathing for longer than 1 minute seems it

increase [57]. To be fully effective,

ings indicate that hyperventilation can reduce the time required to increase the O<sup>2</sup>

breathing [41, 42, 51, 52].

30 Tracheal Intubation

with ambient air in O2

the fugitive FiO<sup>2</sup>

may have little SpO<sup>2</sup>

the inspiratory O2

*3.1.2. Vital capacity maneuvers*

**3.1. Preoxygenation techniques**

securely on the face of the patient; 20% dilution of O<sup>2</sup>

"four vital capacities" method, and deep breaths.

dard: 3 -minute spontaneous breathing at FiO<sup>2</sup>

tion, this leads to denitrogenation with FAO<sup>2</sup>

by ventilation to the mask after induction [56].

maneuver begins with forced expiration to optimize FeO<sup>2</sup>

*3.1.1. Spontaneous breathing at FiO2*

Eight deep breaths at a constant oxygen flow of 10 mL/min in a 60-second period create a simple method for preoxygenation. This technique results in an average arterial oxygen pressure of 369 ± 69 mmHg, which is not significantly different from the value achieved by 3 minutes of tidal volume breathing at an oxygen flow of 5 L per minute [42]. It has been argued that the voluntary hyperventilation technique (1 minute in FiO<sup>2</sup> followed by voluntary hyperventilation for 2 minutes) prevents postapneic hypercapnia. Postintubation PaCO<sup>2</sup> was similar when preinduction hyperventilation was used as preoxygenation technique or normal respiration was used for 3 minutes [60].

#### *3.1.4. Pressure-assisted ventilation (PSV)*

In healthy volunteers, PSV has been shown to improve preoxygenation quality by two mechanisms: accelerate nitrogen excretion and provide better contact between mask and face. In a study of healthy volunteers, the mean expired fraction of O<sup>2</sup> (FeO<sup>2</sup> ) after 3 minutes of preoxygenation was higher (p < 0.001) with 4 cmH<sup>2</sup> O (94 ± 3%) PSV/PEEP and 6 cmH<sup>2</sup> O PSV/PEEP (94 ± 4%) [61]. Increasing fresh gas flow (FGF) between 5 and 10 L during deep breathing does not provide a significant increase in FiO<sup>2</sup> value during tidal volume breathing [50]. Due to the breathing properties of the circulator system, the minute ventilation during deep breathing can exceed the FGF, causing a reincrease in N<sup>2</sup> in the exhalation gases and therefore lower FiO<sup>2</sup> . However, regeneration of N<sup>2</sup> in exhalation gases during tidal volume breathing is insignificant, and thus increasing FGF by 5–10 L has minimal effect on FiO<sup>2</sup> [50].

All investigations have demonstrated that preoxygenation markedly delays arterial oxyhemoglobin desaturation during apnea. [26, 36, 38, 43]. The extent of this delay in desaturation depends on the efficacy of preoxygenation, the capacity for O<sup>2</sup> loading, and the VO2 [47]. Patients with a decreased capacity for O<sup>2</sup> transport (decreased functional residual capacity, PaO2 , arterial O2 content, or cardiac output) or those with an increased VO2 develop oxyhemoglobin desaturation more rapidly during apnea than healthy patients [26, 43].

Farmery and Roe developed and validated a computer model describing the rate of oxyhemoglobin desaturation during apnea [62]. The model is particularly useful for analyzing oxyhemoglobin desaturation values below 90%. These values are dangerous to allow in human subjects because below 90%, there will be a steep decline of PaO<sup>2</sup> due to the sigmoid shape of oxyhemoglobin dissociation curve. In a healthy 70 kg patient, when FaO<sup>2</sup> is progressively decreased from 0.87 (FiO<sup>2</sup> of 1.0) to 0.13 (air), the apnea time to 60% SaO<sup>2</sup> is decreased from 9.9 to 2.8 minutes (**Figure 3**) [43].

*3.2.2. Morbid obesity patients*

a markedly reduced FRC.

in increased FeO<sup>2</sup>

Postintubation PaO2

*3.2.3. Pediatric patients*

90% when breathing at FiO<sup>2</sup>

required to reach a SpO<sup>2</sup>

3 minutes, the time required for SaO<sup>2</sup>

bidly obese patients (BMI > 40 kg/m<sup>2</sup>

ing spontaneous ventilation in pure O2

pressure breathing combined with 5 cmH<sup>2</sup>

morbid obese patients (BMI > 50 kg/m<sup>2</sup>

after preoxygenation, the mean time to reach 90% of SaO<sup>2</sup>

[70]. Continuous positive airway pressure (CPAP) (7.5 cmH<sup>2</sup>

Studies have demonstrated that following preoxygenation with tidal volume breathing for

was 6 minutes, while in morbid obese patients it was 2.7 minutes [69]. Rapid oxyhemoglobin desaturation during apnea in morbidly obese patients was attributed to an increased VO<sup>2</sup>

Spontaneous respiration and effectiveness of eight deep breaths as preoxygenation method

(240 and 203 seconds CPAP versus zero end expiratory pressure, respectively) [71]. PaO2 improved significantly after intubation when PEEP and PSV applied together after CPAP [72]. PSV improves preoxygenation quality, possibly by increasing alveolar circulation in obese

(185.3 ± 46.1 versus 221 ± 41.5 s) [74]. When combined with recruitment maneuvers, PSV activity has statistical significance in terms of arterial oxygenation [75]. In morbidly obese

the control group (23.8 ± 8.8 kPa) (p < 0.001). Lower oxygen saturation was lower in the control

The supine position reduces the functional residual capacity due to the upward displacement of the diaphragm. It has been shown that placement of severe obese patients in the 25° up position during preoxygenation prolongs the desaturation time [77]. Some anesthetists may prefer awake fiberoptic intubation instead of rapid sequence induction/intubation in morbid and super

Respiratory physiology of young children is age-specific. The inhibition of intercostal tone with general anesthesia is responsible for the reduction in FRC. Hypoxia occurs more rap-

to be 96.5 seconds in children less than 6 months of age, 160.4 seconds in 2–5 year olds, and 382.4 seconds in 11–18 year olds [80]. In children younger than 6 months, even shorter apnea time limits, on the order of 70–90 seconds have been reported [16]. The duration of apnea

is extended for 1–2 minutes, but no benefit was found by extension past 3 minutes [18].

Children exhibit a delay of approximately 80–90 seconds before reaching FeO<sup>2</sup>

of 1 and after muscle paralysis, the duration of apnea before the SpO<sup>2</sup>

(96.9 ± 1.3% versus 94.1 ± 2.0%) and acceleration of nitrogen elimination

was significantly higher in the CPAP/PSV group (32.2 ± 4.1 kPa) than in

are similar in obese patients with previous apnea before reaching 95% of FeO<sup>2</sup>

patients [73]. Compared to 5 minutes of spontaneous ventilation with FiO<sup>2</sup>

patients, preoxygenation resulted in better oxygenation compared to 5 cmH<sup>2</sup>

group (median 98%, range, 83–99%) than the CPAP/PSV group.

idly in children due to higher VA/FRC ratio, higher O<sup>2</sup>

to fall to 90% during apnea is markedly reduced in mor-

Pathophysiology of Apnea, Hypoxia, and Preoxygenation

http://dx.doi.org/10.5772/intechopen.76851

) compared with nonobese patients [67, 68]. During apnea

was observed not to improve the duration of apnea

O PSV and prevented desaturation episodes [76].

), especially when they have associated problems [78].

of 1 level [79]. After a period of at least 2 minutes breathing at FiO<sup>2</sup>

of 98, 95, or 90% is significantly increased when the preoxygenation

consumption and lower O2

in normal body weight patients

O versus Mapleson circuit) dur-

and

33

and SpO2

of 1, PSV results

O CPAP neutral

reserves.

values close to

reaches 90% is found

**Figure 3.** Arterial oxyhemoglobin saturation (SpO<sup>2</sup> ) versus time of apnea in an obese adult, a 10 kg child with low functional residual capacity and high ventilation, and a moderately ill adult compared with a healthy adult. FaO<sup>2</sup> indicates fractional alveolar oxygen concentration; VE, expired volume [43].

Regardless of the technique used, the goal is to reach the end of maximal preoxygenation, which can easily be measured by most anesthesia monitors.

#### **3.2. Preoxygenation for high-risk patient population**

#### *3.2.1. Pregnant patients*

Rapid sequence induction/intubation is often used in pregnancies given general anesthesia and preoxygenation is important in these patients. Maximum preoxygenation can be achieved faster in pregnant women than in nonpregnant women due to higher alveolar ventilation and lower functional residual capacity [37, 63]. However, oxyhemoglobin desaturation in pregnant women during apnea develops more rapidly because they are associated with a limited O2 volume and increased VO2 in their less functional residual capacities. During the apnea, the time required for SaO<sup>2</sup> to fall to 95% was 173 seconds for pregnant women and 243 seconds for women who were not pregnant in the supine position [64].

Using the 45° head up position causes an increase in the desaturation duration in nonpregnant women, but it is not seen in pregnant women. The size of the uterus may prevent the descent of the diaphragm and may not allow the expected increase in functional residual capacity in the head-up position [64]. Four deep breathing techniques in pregnant women are below the 3-minute tidal volume breathing technique and should not be used except in emergencies [65]. Increased minute ventilation in pregnant women requires the use of an O<sup>2</sup> flow of 10 L/minutes during preoxygenation [66].

#### *3.2.2. Morbid obesity patients*

Studies have demonstrated that following preoxygenation with tidal volume breathing for 3 minutes, the time required for SaO<sup>2</sup> to fall to 90% during apnea is markedly reduced in morbidly obese patients (BMI > 40 kg/m<sup>2</sup> ) compared with nonobese patients [67, 68]. During apnea after preoxygenation, the mean time to reach 90% of SaO<sup>2</sup> in normal body weight patients was 6 minutes, while in morbid obese patients it was 2.7 minutes [69]. Rapid oxyhemoglobin desaturation during apnea in morbidly obese patients was attributed to an increased VO<sup>2</sup> and a markedly reduced FRC.

Spontaneous respiration and effectiveness of eight deep breaths as preoxygenation method are similar in obese patients with previous apnea before reaching 95% of FeO<sup>2</sup> and SpO2 [70]. Continuous positive airway pressure (CPAP) (7.5 cmH<sup>2</sup> O versus Mapleson circuit) during spontaneous ventilation in pure O2 was observed not to improve the duration of apnea (240 and 203 seconds CPAP versus zero end expiratory pressure, respectively) [71]. PaO2 improved significantly after intubation when PEEP and PSV applied together after CPAP [72]. PSV improves preoxygenation quality, possibly by increasing alveolar circulation in obese patients [73]. Compared to 5 minutes of spontaneous ventilation with FiO<sup>2</sup> of 1, PSV results in increased FeO<sup>2</sup> (96.9 ± 1.3% versus 94.1 ± 2.0%) and acceleration of nitrogen elimination (185.3 ± 46.1 versus 221 ± 41.5 s) [74]. When combined with recruitment maneuvers, PSV activity has statistical significance in terms of arterial oxygenation [75]. In morbidly obese patients, preoxygenation resulted in better oxygenation compared to 5 cmH<sup>2</sup> O CPAP neutral pressure breathing combined with 5 cmH<sup>2</sup> O PSV and prevented desaturation episodes [76]. Postintubation PaO2 was significantly higher in the CPAP/PSV group (32.2 ± 4.1 kPa) than in the control group (23.8 ± 8.8 kPa) (p < 0.001). Lower oxygen saturation was lower in the control group (median 98%, range, 83–99%) than the CPAP/PSV group.

The supine position reduces the functional residual capacity due to the upward displacement of the diaphragm. It has been shown that placement of severe obese patients in the 25° up position during preoxygenation prolongs the desaturation time [77]. Some anesthetists may prefer awake fiberoptic intubation instead of rapid sequence induction/intubation in morbid and super morbid obese patients (BMI > 50 kg/m<sup>2</sup> ), especially when they have associated problems [78].

#### *3.2.3. Pediatric patients*

Regardless of the technique used, the goal is to reach the end of maximal preoxygenation,

functional residual capacity and high ventilation, and a moderately ill adult compared with a healthy adult. FaO<sup>2</sup>

Rapid sequence induction/intubation is often used in pregnancies given general anesthesia and preoxygenation is important in these patients. Maximum preoxygenation can be achieved faster in pregnant women than in nonpregnant women due to higher alveolar ventilation and lower functional residual capacity [37, 63]. However, oxyhemoglobin desaturation in pregnant women during apnea develops more rapidly because they are

volume and increased VO2

for pregnant women and 243 seconds for women who were not pregnant in the supine

Using the 45° head up position causes an increase in the desaturation duration in nonpregnant women, but it is not seen in pregnant women. The size of the uterus may prevent the descent of the diaphragm and may not allow the expected increase in functional residual capacity in the head-up position [64]. Four deep breathing techniques in pregnant women are below the 3-minute tidal volume breathing technique and should not be used except in emergencies [65]. Increased minute ventilation in pregnant women requires the use of an O<sup>2</sup>

in their less functional residual

) versus time of apnea in an obese adult, a 10 kg child with low

to fall to 95% was 173 seconds

which can easily be measured by most anesthesia monitors.

indicates fractional alveolar oxygen concentration; VE, expired volume [43].

capacities. During the apnea, the time required for SaO<sup>2</sup>

flow of 10 L/minutes during preoxygenation [66].

**3.2. Preoxygenation for high-risk patient population**

**Figure 3.** Arterial oxyhemoglobin saturation (SpO<sup>2</sup>

*3.2.1. Pregnant patients*

32 Tracheal Intubation

associated with a limited O2

position [64].

Respiratory physiology of young children is age-specific. The inhibition of intercostal tone with general anesthesia is responsible for the reduction in FRC. Hypoxia occurs more rapidly in children due to higher VA/FRC ratio, higher O<sup>2</sup> consumption and lower O2 reserves. Children exhibit a delay of approximately 80–90 seconds before reaching FeO<sup>2</sup> values close to 90% when breathing at FiO<sup>2</sup> of 1 level [79]. After a period of at least 2 minutes breathing at FiO<sup>2</sup> of 1 and after muscle paralysis, the duration of apnea before the SpO<sup>2</sup> reaches 90% is found to be 96.5 seconds in children less than 6 months of age, 160.4 seconds in 2–5 year olds, and 382.4 seconds in 11–18 year olds [80]. In children younger than 6 months, even shorter apnea time limits, on the order of 70–90 seconds have been reported [16]. The duration of apnea required to reach a SpO<sup>2</sup> of 98, 95, or 90% is significantly increased when the preoxygenation is extended for 1–2 minutes, but no benefit was found by extension past 3 minutes [18].

Studies have shown that maximal preoxygenation (EtO2 = 90%) can be achieved in children faster than in adults [79, 81]. With tidal volume respiration, almost all children can reach 90% EtO2 within 100 seconds, whereas it can be reached within 30 seconds by deep breathing [79, 81]. However, since children have a lower functional residual capacity and a higher VO<sup>2</sup> than adults, they may be at a greater risk of developing hypoxia when interruption of O<sup>2</sup> transport occurs, such as during apnea or airway obstruction [82–84]. In a comparison of three groups of children who breathed O2 (FlO<sup>2</sup> = 1.0) with tidal volume breathing for 1, 2, and 3 minutes before apnea, the time needed for SaO<sup>2</sup> to decrease from 100 to 95% and then to 90% during apnea was least in those who breathed O2 for 1 minute and there was no difference between those who breathed O2 for 2 and 3 minutes [85]. Based on these findings, 2 minutes of preoxygenation with tidal volume respiration seems to be sufficient to provide a maximum benefit and a safe apnea period [85]. The advantage of preoxygenation is greater in a larger child than in a baby. For example, in an 8-year-old child, the duration of the apnea-safe period may be extended to 5 minutes or longer with preoxygenation, whereas the duration is 0.47 minutes without preoxygenation [86]. The smaller the child, the faster the start of desaturation [80, 83, 84]. After the onset of apnea, most infants reach 90% SpO<sup>2</sup> within 70–90 seconds (despite preoxygenation) and this time may be shorter in the presence of upper respiratory tract infection [16, 87]. Pediatric anesthesiologists expressed concern about the use of the "adult" version of the rapid sequence induction/intubation technique in children [88]. Concerns include the safe duration of apnea and the potential for airway obstruction induced by cricoid compression. A modified version of the rapid sequence induction/intubation technique appears to be more appropriate for children with emphasis on full muscle relaxation and gentle manual ventilation using high O<sup>2</sup> concentration with adequate anesthesia depth without cricoid pressure before intubation [89].

*3.2.6. Patients in high altitude*

High altitude does not shift inhaled O<sup>2</sup>

*3.3.1. Apneic diffusion oxygenation*

adults, VO2

the O2

rapid O2

the SpO2

lowing O2

the gradual rise of PaCO<sup>2</sup>

and securing the airway [106, 107].

FiO<sup>2</sup>

obstructed. If CO<sup>2</sup>

Although the drop in PaO<sup>2</sup>

**3.3. Techniques to improve preoxygenation**

21 mL/min [32]. The remaining 90% (or more) of CO<sup>2</sup>

stores in the lungs are exhausted, and PaO2

decreases with respect to lung compliance and VO2

hemoglobin desaturation obtained by FiO<sup>2</sup>

's raising from 0.21 to 0.9 (**Figure 4**) [105].

cannot be excreted, PaCO<sup>2</sup>

in a decrease partial alveolar pressure and arterial PO2

decreases exponentially. Patients at high altitudes may need longer lasting preoxygenation.

Following preoxygenation, "apneic diffusion oxygenation" is an effective maneuver that prolongs the safe duration of apnea [32, 98–102]. The physiological basis of this maneuver is: In

enters the lung by diffusion, provided that the lung volume initially decreases by 209 mL/min and forms a pressure gradient between the upper airway and the alveoli, and the airway is not

apnea followed by a linear increase of about 3 mmHg/min [103]. The advantage of apneic diffusion oxygenation depends on reaching the maximum preoxygenation before apnea, remaining open in the respiratory tract, and is on the presence of high FRC relative to body weight.

<80%, the saturation reduction rate is approximately 30%/min. In the presence of an airway obstruction, the volume of gas in the lungs decreases rapidly and the intrathoracic pressure

studies have shown that through an open air pathway, apneic diffusion oxygenation can keep

increase can cause a fairly disproportionate delay in hemoglobin desaturation. The delay in

Apneic diffusion oxygenation can be achieved with maximum face mask preoxygenation fol-

a needle inserted into the cricothyroid membrane. In healthy patients with a healthy airway, this technique can provide adequate oxygenation for at least 10 minutes. Although oxygenation can be maintained for a longer period of time, a limiting factor of apneic oxygenation is

The CPAP usage in the preoxygenation delayed the desaturation period by mechanical ventilation using positive end expiratory pressure (PEEP) for 5 minutes before removing the mask

*3.3.2. Continuous positive airway pressure (CPAP) and positive expiratory pressure (PEEP)*

insufflation to 15 L/minutes via a nasopharyngeal or an oropharyngeal cannula or

, SpO2

averages are 230 mL/min during apnea, whereas CO<sup>2</sup>

is directly related to PaO2

flow begins in the lungs and preoxygenation with high FiO<sup>2</sup>

value above 90% for up to 100 minutes [99, 100]. When FiO<sup>2</sup>

during apnea [103].

as the hemoglobin is oxygenated again in the lungs [46, 99, 100, 104]. SpO2

concentration but reduced barometric pressure causes

Pathophysiology of Apnea, Hypoxia, and Preoxygenation

[97]. As altitude increases, PaO<sup>2</sup>

http://dx.doi.org/10.5772/intechopen.76851

35

delivery to alveoles is only

is buffered in body tissues. As a result, O<sup>2</sup>

remains greater than 90% as long

. When airway obstruction is relieved, a

decreases only after

improves [46]. Some

is at a high level, a small

becomes

increases to 8–16 mmHg for the first minute of

falls below 60 mmHg. When SpO<sup>2</sup>

's raising from 0.9 to 1.0 was above that obtained by

#### *3.2.4. Elderly patients*

Old age is associated with significant structural and physiological changes in the respiratory system [90, 91]. The changes also include a reduction in elastic recoil with weakened respiratory muscles and parenchymal changes in the lungs. Lung volumes are reduced by increased closure volume, which causes ventilation-perfusion mismatch, reduced pulmonary reserve, and impaired oxygen uptake in the lung. While basal VO2 declines with aging, impaired O2 intake creates a faster desaturation during apnea under anesthesia [91]. In elderly patients, tidal volume breathing of 3 minutes or longer has been shown to be more effective than four deep breathing techniques [92, 93].

#### *3.2.5. Patients with lung diseases*

Severe pulmonary disease is associated with decreased FRC, increased ventilation-perfusion incompatibility, and increased VO2 , which can reduce the safety margin. Anesthesia has been shown to cause further deterioration of gas exchange in patients with chronic obstructive pulmonary disease [94]. As well as in aspiration, even short ventilation interruptions can cause desaturation. Besides, atelectasis is not a consequence, presumably the chronic hyperinflation of the lungs resists volume decline and collapse [95]. For maximum preoxygenation in these patients, 5 minutes or more may be needed with tidal volume breathing [96].

#### *3.2.6. Patients in high altitude*

Studies have shown that maximal preoxygenation (EtO2 = 90%) can be achieved in children faster than in adults [79, 81]. With tidal volume respiration, almost all children can reach 90%

such as during apnea or airway obstruction [82–84]. In a comparison of three groups of children

 for 2 and 3 minutes [85]. Based on these findings, 2 minutes of preoxygenation with tidal volume respiration seems to be sufficient to provide a maximum benefit and a safe apnea period [85]. The advantage of preoxygenation is greater in a larger child than in a baby. For example, in an 8-year-old child, the duration of the apnea-safe period may be extended to 5 minutes or longer with preoxygenation, whereas the duration is 0.47 minutes without preoxygenation [86]. The smaller the child, the faster the start of desaturation [80, 83, 84]. After the onset of apnea,

be shorter in the presence of upper respiratory tract infection [16, 87]. Pediatric anesthesiologists expressed concern about the use of the "adult" version of the rapid sequence induction/intubation technique in children [88]. Concerns include the safe duration of apnea and the potential for airway obstruction induced by cricoid compression. A modified version of the rapid sequence induction/intubation technique appears to be more appropriate for children with emphasis on

Old age is associated with significant structural and physiological changes in the respiratory system [90, 91]. The changes also include a reduction in elastic recoil with weakened respiratory muscles and parenchymal changes in the lungs. Lung volumes are reduced by increased closure volume, which causes ventilation-perfusion mismatch, reduced pulmonary reserve,

intake creates a faster desaturation during apnea under anesthesia [91]. In elderly patients, tidal volume breathing of 3 minutes or longer has been shown to be more effective than four

Severe pulmonary disease is associated with decreased FRC, increased ventilation-perfusion

shown to cause further deterioration of gas exchange in patients with chronic obstructive pulmonary disease [94]. As well as in aspiration, even short ventilation interruptions can cause desaturation. Besides, atelectasis is not a consequence, presumably the chronic hyperinflation of the lungs resists volume decline and collapse [95]. For maximum preoxygenation in these

patients, 5 minutes or more may be needed with tidal volume breathing [96].

However, since children have a lower functional residual capacity and a higher VO<sup>2</sup>

they may be at a greater risk of developing hypoxia when interruption of O<sup>2</sup>

full muscle relaxation and gentle manual ventilation using high O<sup>2</sup>

anesthesia depth without cricoid pressure before intubation [89].

and impaired oxygen uptake in the lung. While basal VO2

within 100 seconds, whereas it can be reached within 30 seconds by deep breathing [79, 81].

(FlO<sup>2</sup> = 1.0) with tidal volume breathing for 1, 2, and 3 minutes before apnea,

to decrease from 100 to 95% and then to 90% during apnea was least

for 1 minute and there was no difference between those who breathed

within 70–90 seconds (despite preoxygenation) and this time may

than adults,

transport occurs,

concentration with adequate

declines with aging, impaired O2

, which can reduce the safety margin. Anesthesia has been

EtO2

34 Tracheal Intubation

O2

who breathed O2

the time needed for SaO<sup>2</sup>

in those who breathed O2

most infants reach 90% SpO<sup>2</sup>

*3.2.4. Elderly patients*

deep breathing techniques [92, 93].

incompatibility, and increased VO2

*3.2.5. Patients with lung diseases*

High altitude does not shift inhaled O<sup>2</sup> concentration but reduced barometric pressure causes in a decrease partial alveolar pressure and arterial PO2 [97]. As altitude increases, PaO<sup>2</sup> decreases exponentially. Patients at high altitudes may need longer lasting preoxygenation.

#### **3.3. Techniques to improve preoxygenation**

#### *3.3.1. Apneic diffusion oxygenation*

Following preoxygenation, "apneic diffusion oxygenation" is an effective maneuver that prolongs the safe duration of apnea [32, 98–102]. The physiological basis of this maneuver is: In adults, VO2 averages are 230 mL/min during apnea, whereas CO<sup>2</sup> delivery to alveoles is only 21 mL/min [32]. The remaining 90% (or more) of CO<sup>2</sup> is buffered in body tissues. As a result, O<sup>2</sup> enters the lung by diffusion, provided that the lung volume initially decreases by 209 mL/min and forms a pressure gradient between the upper airway and the alveoli, and the airway is not obstructed. If CO<sup>2</sup> cannot be excreted, PaCO<sup>2</sup> increases to 8–16 mmHg for the first minute of apnea followed by a linear increase of about 3 mmHg/min [103]. The advantage of apneic diffusion oxygenation depends on reaching the maximum preoxygenation before apnea, remaining open in the respiratory tract, and is on the presence of high FRC relative to body weight. Although the drop in PaO<sup>2</sup> is directly related to PaO2 , SpO2 remains greater than 90% as long as the hemoglobin is oxygenated again in the lungs [46, 99, 100, 104]. SpO2 decreases only after the O2 stores in the lungs are exhausted, and PaO2 falls below 60 mmHg. When SpO<sup>2</sup> becomes <80%, the saturation reduction rate is approximately 30%/min. In the presence of an airway obstruction, the volume of gas in the lungs decreases rapidly and the intrathoracic pressure decreases with respect to lung compliance and VO2 . When airway obstruction is relieved, a rapid O2 flow begins in the lungs and preoxygenation with high FiO<sup>2</sup> improves [46]. Some studies have shown that through an open air pathway, apneic diffusion oxygenation can keep the SpO2 value above 90% for up to 100 minutes [99, 100]. When FiO<sup>2</sup> is at a high level, a small increase can cause a fairly disproportionate delay in hemoglobin desaturation. The delay in hemoglobin desaturation obtained by FiO<sup>2</sup> 's raising from 0.9 to 1.0 was above that obtained by FiO<sup>2</sup> 's raising from 0.21 to 0.9 (**Figure 4**) [105].

Apneic diffusion oxygenation can be achieved with maximum face mask preoxygenation following O2 insufflation to 15 L/minutes via a nasopharyngeal or an oropharyngeal cannula or a needle inserted into the cricothyroid membrane. In healthy patients with a healthy airway, this technique can provide adequate oxygenation for at least 10 minutes. Although oxygenation can be maintained for a longer period of time, a limiting factor of apneic oxygenation is the gradual rise of PaCO<sup>2</sup> during apnea [103].

#### *3.3.2. Continuous positive airway pressure (CPAP) and positive expiratory pressure (PEEP)*

The CPAP usage in the preoxygenation delayed the desaturation period by mechanical ventilation using positive end expiratory pressure (PEEP) for 5 minutes before removing the mask and securing the airway [106, 107].

of the endothelin and K<sup>+</sup>

accompanies high O2

about 20% in cerebral O<sup>2</sup>

cerebral O2

amount of CO<sup>2</sup>

oxygen fraction FiO<sup>2</sup>

open air [126]. Increasing the FiO<sup>2</sup>

nism in the PaCO<sup>2</sup>

channels sensitive to ATP [118, 119]. It is well known that high O2

consumption and decreased neuronal activity [122]. The reduction in

consumption is thought to be due to the fact that reactive oxygen radicals damage

that

37

pass-

is more water soluble

dissociation

affinity for blood is

[121]. The decline mecha-

and hydrogen ion concentration,

inhalation, the CO<sup>2</sup>

Pathophysiology of Apnea, Hypoxia, and Preoxygenation

http://dx.doi.org/10.5772/intechopen.76851

during breathing. The volume of CO<sup>2</sup>

produced per minute (about 20 mL) reaches

inhalation may reduce cerebral blood flow due to vasoconstriction [120–123]. It has been proposed that this effect may be because, at least in part, of the associated decrease in PaCO<sup>2</sup>

which stimulate respiration that causes cerebral vasoconstriction with a decrease in PaCO<sup>2</sup> [122, 123]. Researchers assessed the effect of hyperoxia on cerebral oxygen consumption using a functional magnetic resonance technique and found that hyperoxia caused a reduction of

lipids and proteins and reduce enzyme activity in the oxidative metabolic pathways. Studies in animal models have shown that hyperoxia causes vasoconstriction and causes a decrease in blood circulation in the peripheral vascular beds, including the kidney and gastrointestinal tract [120, 124, 125]. However, it is doubtful that changes in peripheral vascular beds will have any significant clinical effect during preoxygenation. So far, cardiovascular findings do not

and CO<sup>2</sup>

entering the alveoli is very low. The reason is that CO<sup>2</sup>

ing from the pulmonary circulation to the alveolar space is 80% of the oxygen volume moving in the reverse direction. This changes radically at the onset of apnea. During apnea, the rate of oxygen extraction from the alveoli remains at 250 mL/min without being affected. The

the alveolar space. The remaining 90% remain molten in the textures. Therefore, the volume of gas in the lungs decreases rapidly during apnea, and if the airway becomes clogged, intrathoracic pressure decreases due to oxygen consumption and thoracic compliance. The closed airway apex begins with an intrathoracic pressure equal to or slightly greater than the ambient pressure. Oxygen uptake causes by an almost subatmospheric intrathoracic pressure. During long-standing apnea, the intrathoracic pressure may be much lower than the environmental pressure, and the alveolar partial pressure of oxygen is significantly dangerously reduced. An open airway will allow oxygen to spread to the apneic lung. Providing an open airway and exposing 100% oxygen creates "apneic mass movement oxygenation," which has been shown to provide oxygen saturation for up to 100 minutes in animal and simulated human studies. If the denitrogenesis of the alveolar space is as complete as possible and a tight compliance mask is used, this passive diffusion of oxygen is more effective. It is important to provide a very high

fraction applied to the respiratory tract from 90 to 100% doubles critical hypoxia time with

effect on the critical hypoxia time. In a patient with an apnea, 100% oxygen administration to the patent airway will delay the onset of critical hypoxia, but this approach will not reverse the

in order to extend the safety time of the apnea; increasing the oxygen

applied to the airway from 21 to 90% has a much greater

is increased by 100% O<sup>2</sup>

breathing rather than to a direct effect of O<sup>2</sup>

curve for blood changes (Christiansen-Douglas-Haldane effect), thus CO<sup>2</sup>

is that: When PaO2

reduced. This causes an increase in the cerebral tissue PCO<sup>2</sup>

provide any justification for limiting the use of preoxygenation.

**4. Maintenance of a patent airway**

There is a dynamical balance between O2

than oxygen. For this reason, only 10% of the CO<sup>2</sup>

**Figure 4.** The time (duration of apnea) required to reach 50% SaO<sup>2</sup> with an open airway exposed to various ambient O2 fractions [105].

#### *3.3.3. Noninvasive bilevel positive airway pressure (BİPAP)*

BiPAP combines pressure-assisted ventilation (PSV) and CPAP advantages and keeps the lungs open during the respiratory cycle. BiPAP has been used during preoxygenation to decrease intrapulmonary shunting and to increase the margin of safety during apnea in morbidly obese patients [108]. This technique is also used to reduce postoperative pulmonary dysfunction and to treat patients with respiratory insufficiency from various etiologies [109].

#### *3.3.4. Transnasal humidified rapid insufflation ventilatory exchange (THRIVE)*

THRIVE is a new technique that is available for use in critically ill patients and in patients with difficult airways. The technique combines the benefits of apneic oxygenation and CPAP with a reduction in CO<sup>2</sup> levels through gaseous mixing and flushing of the dead space [110]. THRIVE is used as standard with a nasal, high flow oxygen delivery system, as sold in the market. The THRIVE technique has been shown to significantly prolong the period of apnea safety while avoiding CO<sup>2</sup> increase [111].

#### **3.4. Potential risks of the preoxygenation**


It causes a decrease in heart rate and cardiac output. Systemic vascular resistance and arterial blood pressure increase [112–114]. These changes are detected by chemoreceptors or baroreceptors. Direct coronary vasoconstrictor effect of hyperoxia is due to oxidative inactivation of nitric oxide and other vasodilators released by vasculature [115–117]; it reaches up to collapse of the endothelin and K<sup>+</sup> channels sensitive to ATP [118, 119]. It is well known that high O2 inhalation may reduce cerebral blood flow due to vasoconstriction [120–123]. It has been proposed that this effect may be because, at least in part, of the associated decrease in PaCO<sup>2</sup> that accompanies high O2 breathing rather than to a direct effect of O<sup>2</sup> [121]. The decline mechanism in the PaCO<sup>2</sup> is that: When PaO2 is increased by 100% O<sup>2</sup> inhalation, the CO<sup>2</sup> dissociation curve for blood changes (Christiansen-Douglas-Haldane effect), thus CO<sup>2</sup> affinity for blood is reduced. This causes an increase in the cerebral tissue PCO<sup>2</sup> and hydrogen ion concentration, which stimulate respiration that causes cerebral vasoconstriction with a decrease in PaCO<sup>2</sup> [122, 123]. Researchers assessed the effect of hyperoxia on cerebral oxygen consumption using a functional magnetic resonance technique and found that hyperoxia caused a reduction of about 20% in cerebral O<sup>2</sup> consumption and decreased neuronal activity [122]. The reduction in cerebral O2 consumption is thought to be due to the fact that reactive oxygen radicals damage lipids and proteins and reduce enzyme activity in the oxidative metabolic pathways. Studies in animal models have shown that hyperoxia causes vasoconstriction and causes a decrease in blood circulation in the peripheral vascular beds, including the kidney and gastrointestinal tract [120, 124, 125]. However, it is doubtful that changes in peripheral vascular beds will have any significant clinical effect during preoxygenation. So far, cardiovascular findings do not provide any justification for limiting the use of preoxygenation.

## **4. Maintenance of a patent airway**

*3.3.3. Noninvasive bilevel positive airway pressure (BİPAP)*

**Figure 4.** The time (duration of apnea) required to reach 50% SaO<sup>2</sup>

with a reduction in CO<sup>2</sup>

fractions [105].

36 Tracheal Intubation

safety while avoiding CO<sup>2</sup>

• Absorption atelectasis.

**3.4. Potential risks of the preoxygenation**

• Production of reactive oxygen radicals.

• Cardio-cerebrovascular responses.

• Delay in the diagnosis of the esophageal intubation.

*3.3.4. Transnasal humidified rapid insufflation ventilatory exchange (THRIVE)*

increase [111].

BiPAP combines pressure-assisted ventilation (PSV) and CPAP advantages and keeps the lungs open during the respiratory cycle. BiPAP has been used during preoxygenation to decrease intrapulmonary shunting and to increase the margin of safety during apnea in morbidly obese patients [108]. This technique is also used to reduce postoperative pulmonary dysfunction and to treat patients with respiratory insufficiency from various etiologies [109].

THRIVE is a new technique that is available for use in critically ill patients and in patients with difficult airways. The technique combines the benefits of apneic oxygenation and CPAP

THRIVE is used as standard with a nasal, high flow oxygen delivery system, as sold in the market. The THRIVE technique has been shown to significantly prolong the period of apnea

It causes a decrease in heart rate and cardiac output. Systemic vascular resistance and arterial blood pressure increase [112–114]. These changes are detected by chemoreceptors or baroreceptors. Direct coronary vasoconstrictor effect of hyperoxia is due to oxidative inactivation of nitric oxide and other vasodilators released by vasculature [115–117]; it reaches up to collapse

levels through gaseous mixing and flushing of the dead space [110].

with an open airway exposed to various ambient O2

There is a dynamical balance between O2 and CO<sup>2</sup> during breathing. The volume of CO<sup>2</sup> passing from the pulmonary circulation to the alveolar space is 80% of the oxygen volume moving in the reverse direction. This changes radically at the onset of apnea. During apnea, the rate of oxygen extraction from the alveoli remains at 250 mL/min without being affected. The amount of CO<sup>2</sup> entering the alveoli is very low. The reason is that CO<sup>2</sup> is more water soluble than oxygen. For this reason, only 10% of the CO<sup>2</sup> produced per minute (about 20 mL) reaches the alveolar space. The remaining 90% remain molten in the textures. Therefore, the volume of gas in the lungs decreases rapidly during apnea, and if the airway becomes clogged, intrathoracic pressure decreases due to oxygen consumption and thoracic compliance. The closed airway apex begins with an intrathoracic pressure equal to or slightly greater than the ambient pressure. Oxygen uptake causes by an almost subatmospheric intrathoracic pressure. During long-standing apnea, the intrathoracic pressure may be much lower than the environmental pressure, and the alveolar partial pressure of oxygen is significantly dangerously reduced. An open airway will allow oxygen to spread to the apneic lung. Providing an open airway and exposing 100% oxygen creates "apneic mass movement oxygenation," which has been shown to provide oxygen saturation for up to 100 minutes in animal and simulated human studies. If the denitrogenesis of the alveolar space is as complete as possible and a tight compliance mask is used, this passive diffusion of oxygen is more effective. It is important to provide a very high oxygen fraction FiO<sup>2</sup> in order to extend the safety time of the apnea; increasing the oxygen fraction applied to the respiratory tract from 90 to 100% doubles critical hypoxia time with open air [126]. Increasing the FiO<sup>2</sup> applied to the airway from 21 to 90% has a much greater effect on the critical hypoxia time. In a patient with an apnea, 100% oxygen administration to the patent airway will delay the onset of critical hypoxia, but this approach will not reverse the hypoxemia that is currently developing. Moreover, after a while, it does not prevent continuous development of hypercapnia, which is life threatening and acidosis related to hypercapnia.

sustain oxygen homeostasis is crucial for survival of all vertebrate species. For the O<sup>2</sup>

**8.2. Physiological responses to hypoxia**

pulmonary ventilation and perfusion to optimize O<sup>2</sup>

*8.2.1. Systemic responses*

smooth muscle cells.

several of the various K<sup>+</sup>

muscle cells (**Figure 5B**) [129].

muscle cells and (B) peripheral smooth muscle cells [129].

intrinsically O2

*8.2.2. Vascular smooth muscle cells*

use of O<sup>2</sup>

tation, correct forming of complex platform such as entry (lungs), transport vehicles (erythrocytes), motorways and secondary roads (vasculature), and repulsive force (heart) during development and regulations in organism entry form the basis for oxygen homeostasis.

Hypoxia and hyperoxia are detected by specialized chemoreceptor cells. In cases where the

on the direct response of the neuroepithelial bodies present in the airway to the specialized chemoreceptor cells, such as arterial circulation carotid bodies, and the hypoxia of vascular

While the peripheral vein are enlarged in response to low oxygen, the veins in the pulmonary vein narrows in order to achieve ventilation-perfusion matching by removing blood from areas where ventilation is worse [127]. Hypoxic pulmonary vasoconstriction is a rapid response in the pulmonary arteries and venules. It is abundant in small resistance arteries. Pulmonary vein is an intrinsic feature of the vein smooth muscles and begins with the inhibition of one or

depolarization activates voltage-gated Ca+2 channels, and activation of the channels increases

the effects of hypoxic pulmonary vasoconstriction, it does not known that whether they are

cially indicated in coronary and cerebral vessels. Hypoxic vasodilation is mediated in part by K-ATP channels opened in response to hypoxia-induced ATP reduction in vascular smooth

**Figure 5.** Schematic representation of the response of vascular smooth muscle cells to hypoxia. (A) Pulmonary smooth

the systolic calcium level and leads to myocyte constriction (**Figure 5A**). While K<sup>+</sup>


is another rapid response that increases blood perfusion in O<sup>2</sup>

is impaired, chemoreceptor systems rapidly change blood circulation as well as

channels that regulate the membrane potential [128]. The resulting

delivery to tissues. This process is based

Pathophysiology of Apnea, Hypoxia, and Preoxygenation

http://dx.doi.org/10.5772/intechopen.76851

presen-

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channels are

receptor. Hypoxic vasodilatation

