Function	Mechanism	Clinical Manifestation
Mechanics of ventilation	Loss of lung elastic recoil; decreased chest wall compliance	↓ VC; ↑ RV; no change in TLC; ↓ expiratory flow rates
	Decreased respiratory muscle mass and strength	↓ Maximal inspiratory and expiratory force
Perfusion, ventilation, and gas exchange	Decreased uniformity of ventilation, with small airway closure during tidal breathing, especially while supine	↑ P(A-a)O₂; ↓ Pao₂; no change in Paco₂ or pH ↓ cardiac output; ↓ Co₂
	Increased physiologic deadspace	None (slightly ↑ E)
	Decreased alveolar surface area	↓ DLCO
Exercise capacity	Decreased aerobic work capacity of skeletal muscle; deconditioning	↓ Maximum o₂
	Decreased efficiency of ventilation	↑ E/L o₂
Regulation of ventilation	Decreased responsiveness of central and peripheral chemoreceptors	↓ E and P_0.1 responses to hypoxia and hypercapnia
Sleep and breathing	Decreased ventilatory drive	↑ Frequency of apneas, hypopneas, and desaturation episodes during sleep
	Decreased upper airway muscle tone	Snoring; ↑ incidence of obstructive sleep apnea
	Decreased arousal and cough reflexes	↑ Susceptibility to aspiration and pneumonia
Lung defense mechanisms	Decreased upper airway function; decreased mucociliary clearance	↑ Susceptibility to aspiration and pneumonia
	Decreased humoral and cellular immunity	↑ Susceptibility to infection; ↓ clinical response to infection

E, Expired minute ventilation; D_LCO, diffusing capacity for carbon monoxide; o₂, O₂ consumption; P_0.1, mouth occlusion pressure; Co₂, mixed venous O₂ content; P(A-a)O₂, alveolar-arterial PO₂ difference.

From Pierson DJ, Kacmarek RM: Foundations of Respiratory Care. New York, Churchill Livingstone, 1993. Churchill Livingstone

a. The lower limit of “normal” Pao₂ is decreased approximately 4 mm Hg per decade in later life.

(1) Pao₂ <60 mm Hg is always considered hypoxemia.

b. Because the lung changes with age there is a progressive increase in the alveolar-arterial O₂ partial pressure difference (Figure 34-1).

FIG. 34-1 The relationship between P(a—a)o₂ and aging. Because Pao₂ naturally decreases with age, P(a—a)o₂ increases at the rate of approximately 3 mm Hg each decade beyond 20 years.

c. Acceptable lower limits of Pao₂ for older adults can be estimated using the following formula.

< ?xml:namespace prefix = "mml" />Amount of gas in cylinder=(1.5lb)(860)2.5/L=516LDuration of the gas in minutes=516L3L/min=172minutes (1)

Pao₂ = 100.1 − (0.323 × age) mm Hg (1)

B Causes of hypoxemia (see Chapters 8 and 15)

1. True shunting

2. Ventilation/perfusion mismatch

3. Hypoventilation

4. Impaired diffusion

5. Decreased ambient O₂ tension

C Responsive versus refractory hypoxemia

1. Refractory hypoxemia is hypoxemia demonstrating a negligible increase in the Pao₂ with the application of an acceptable level of oxygen.

a. If the F_IO₂ is >0.40 to 0.50 and the Pao₂ is <60 mm Hg (Sao₂ <90%), the hypoxemia is refractory.

b. If a 0.20 increase in the F_IO₂ results in a <10-mm Hg increase in the Pao₂, the hypoxemia is refractory.

c. Refractory hypoxemia is a result of true shunting.

2. Responsive hypoxemia is hypoxemia that demonstrates a significant response to an increase in the F_IO₂.

a. A 0.20 increase in the F_IO₂ results in a >10-mm Hg increase in the Pao₂.

b. Responsive hypoxemia is a result of ventilation/perfusion inequalities.

D Clinical manifestations of hypoxemia

1. Rapid respiratory rate and/or large tidal volume (Vt)

2. Dyspnea

3. Tachycardia and hypertension

a. If cardiovascular status is poor or hypoxemia is severe, bradycardia and hypotension may result.

4. Peripheral vasoconstriction with moderate to severe hypoxemia

5. Constriction of pulmonary vascular bed leading to pulmonary hypertension

6. Development of cyanosis if hypoxemia is severe

7. Headache, restlessness

8. Confusion, disorientation, or both

9. Secondary polycythemia (with chronic hypoxemia)

IV Indications for Oxygen Therapy, Modified from AARC Clinical Practice Guidelines on Oxygen Therapy, 2002.

A Documented hypoxemia: Pao₂ is <60 mm Hg or Sao₂ is <90%

B Acute care situations in which hypoxemia is suspected

1. Severe trauma

2. Acute myocardial infarction

3. Short-term therapy (e.g., postanesthesia recovery)

V General Goals of Oxygen Therapy

A Maintain adequate tissue oxygenation and minimize cardiopulmonary work

1. Increasing alveolar Po₂ increases pressure gradient for oxygen diffusion into bloodstream. This may increase Pao₂.

2. An increase in Pao₂ may reduce stimulation of peripheral chemoreceptors and reduce work of breathing.

3. Oxygen therapy may correct hypoxemia and decrease the stimulus to increase cardiac output.

VI Hazards of Oxygen Therapy

A Retinopathy of prematurity (ROP) (see Chapter 27)

1. Occurs primarily in premature infants (<34 weeks gestation) with incomplete vascularization of the retina

a. Incidence of ROP is inversely proportional to birth weight and gestational age.

2. Increased oxygen exposure (Sao₂ 96% to 99%) is just one of many factors involved in the pathogenesis of ROP.

3. Maintaining Sao₂ ≤96% may reduce the risk of ROP.

B Oxygen toxicity

1. A series of reversible pathophysiologic inflammatory changes of lung tissue that can produce a progressive and lethal form of lung injury similar to acute respiratory distress syndrome (ARDS)

2. Free radical theory of oxygen toxicity

a. The following free radicals of oxygen can be produced at the cellular level.

(1) Hydrogen peroxide: H₂O₂

(2) Superoxide radical:

(3) Hydroxyl radical: OH·

(4) Singlet excited oxygen: ¹O₂

b. The following enzymes are important cellular defenses against oxygen free radicals.

(1) Superoxide dismutase (SOD), which converts to O₂

(2) Catalase (CAT), which converts H₂O₂ to H₂O and O₂

(3) Additional intracellular antioxidants that provide defense against oxygen free radicals include

(a) Glutathione peroxide

(b) Glutathione

(d) Cysteamine

(e) Vitamin E in lipid membrane

(f) Vitamin C (intracellular)

(g) Selenium

(h) Ceruloplasmin

(i) Transferrin

c. The quantity of oxygen free radicals depends on Pao₂. The greater the Pao₂, the greater the quantity of free radicals.

d. Effects of oxygen free radicals

(1) Inhibition of glycolysis

(2) Interference with surfactant transport and production

(3) Nucleic acid (DNA) damage

(4) Cross-linkage of DNA molecules

(5) Cell and organelle membrane disruption

(6) Enzyme inhibition

3. Pathophysiology of oxygen toxicity

a. Cellular susceptibility to hyperoxia (100% O₂)

(1) Pulmonary capillary endothelium (most susceptible)

(2) Alveolar type I epithelial cells

(3) Alveolar type II epithelial cells

(4) Alveolar type III epithelial cells (least susceptible)

b. With continued exposure to 100% O₂, type I alveolar cells are destroyed and replaced by type II cells.

c. Early or acute exudative phase is characterized by perivascular, interstitial, and intraalveolar edema with destruction and necrosis of endothelial cells. Alveolar congestion and fibrinous exudation (hyaline membrane) develop.

d. Late or chronic proliferative phase is characterized by a progressive reabsorption of the exudate and a thickening of the alveolar septa.

e. Clinical manifestations

(1) Tracheobronchitis

(2) Cough

(3) Substernal pain

(4) Nausea and vomiting

(5) Anorexia

(6) Paresthesia

(7) Refractory hypoxemia

(8) Diffuse patchy bilateral infiltrates

(9) Alveolar atelectasis

(10) Decreased compliance

4. Susceptibility and risk factors associated with the development of oxygen toxicity

a. The balance between oxidant and antioxidant activity determines the severity of tissue injury.

b. Exposure to F_IO₂ levels >0.40 for lengthy periods

c. Previous development of severe acute pulmonary disease, which decreases the risk of toxicity. The acute disease is believed to induce the production of SOD and glutathione, thus reducing the oxygen free radical levels.

5. Prevention: Judicious use of oxygen therapy. Use only enough to maintain adequate tissue oxygenation.

a. When possible limit exposure to 100% oxygen to <24 hours. Decrease to level maintaining acceptable Pao₂ >60 mm Hg as soon as possible.

6. Treatment: Appropriate use of positive end-expiratory pressure therapy, diuretics, and fluids while reducing the F_IO₂ as soon as possible.

C Oxygen-induced hypoventilation

1. This is infrequently observed in patients with chronic CO₂ retention or central nervous system depression (see Chapter 20).

2. The increased Pao₂ decreases or eliminates the hypoxic drive, inducing greater levels of hypoventilation. Although rare it can be potentially life threatening.

3. Intermittent use of oxygen therapy may cause arterial Po₂ to decrease below pretreatment levels.

4. If oxygen is indicated it should never be withheld because of the risk of ventilatory depression.

D Absorption atelectasis (Figure 34-2)

FIG. 34-2 Schematic representation of primary mechanisms causing denitrogenation absorption atelectasis. Top drawings represent the alveolar-capillary units shortly after administration of 100% inspired oxygen. White circles represent oxygen molecules that have increased in concentration in both units. A and B, The ablation of alveolar hypoxia in unit A results in loss of vasoconstriction with considerably increased blood flow. The increased blood flow to this still poorly ventilated alveolus results in significantly increased oxygen extraction, which results in decreased gas volume. Black circles represent nitrogen, which is rapidly depleted from all units secondary to the fact that inspired nitrogen concentration is now zero. Initially more nitrogen leaves the blood and the body via unit B because it is better ventilated. However, as the blood Pn₂ level progressively decreases, nitrogen will start to leave alveolus A via the blood. This results in further loss of gas volume from alveolus A because it remains poorly ventilated but well perfused. Thus nitrogen is depleted from all units within 5 to 15 minutes. The bottom drawing represents the final steady state in which increased oxygen and nitrogen extraction has caused the alveolus to collapse. Thus a poorly ventilated, poorly perfused unit A becomes a nonventilated, poorly perfused unit after administration of 100% inspired oxygen.

1. Nitrogen is metabolically inactive and constitutes 80% of alveolar gas. Nitrogen is essential to maintain alveolar stability.

2. Administration of high F_IO₂ (>0.50) washes out nitrogen.

3. In poorly ventilated alveoli more oxygen is removed per unit time by the perfused blood than can be replaced by normal ventilation.

4. This results in a decrease in alveolar size.

5. As alveoli reach their critical volume, collapse and atelectasis occur.

6. This commonly occurs in patients with low Vt or poor distribution of ventilation because of partial airway obstruction.

VII Oxygen Delivery Systems

A Delivery systems generally are divided into two categories: high flow and low flow (Table 34-2).

TABLE 34-2

Classification of Oxygen Delivery System

Low-flow systems	Cannula
	Simple mask
	Partial rebreathing mask
	Nonrebreathing mask^*
High-flow systems^†	Venturi masks
	Aerosol systems
	Large-volume humidifier systems