Oxygen, Helium, and Nitric Oxide Therapy
I General Characteristics of Oxygen
E Density at standard temperature and pressure: 1.43 g/L
F Boiling point at 1 atm: ° C (—297.4° F)
G Melting point at 1 atm: −216.6° C (—361.1° F)
H Critical temperature: −118.4° C (—181.1° F)
I Critical pressure: 736.9 pounds per square inch absolute (psia)
J Triple point: −218.7° C (—361.89° F) at 0.2321 psia
K Forms oxides with all elements except inert gases
L Constitutes approximately 20.95% of atmosphere
M Used at the cellular level as the final electron acceptor in electron transport chain located in mitochondria of cell
II Hypoxia: Inadequate Quantities of Oxygen at the Tissue Level
A Decreased carrying capacity of blood for oxygen (anemic hypoxia)
B Decreased cardiac output, resulting in increased systemic transit time (stagnant hypoxia)
C Inability of tissue to use available oxygen (histotoxic hypoxia)
D Decrease in diffusion of oxygen across alveolar capillary membrane (hypoxemic hypoxia)
III Hypoxemia: Inadequate Quantities of Oxygen in the Blood
1. Normal: Pao2 80 to 100 mm Hg
2. Mild hypoxemia: Pao2 <80 mm Hg
3. Severe hypoxemia: Pao2 <60 mm Hg
4. The lower level of acceptable Pao2 decreases with age because the normal aging process of the lung affects respiratory functions (Table 34-1).
TABLE 34-1
Changes in Respiratory Function with Aging
| 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; ↓ C o2 |
| 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 P0.1 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; DLCO, diffusing capacity for carbon monoxide; 
o2, O2 consumption; P0.1, mouth occlusion pressure; C
o2, 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.
b. Because the lung changes with age there is a progressive increase in the alveolar-arterial O2 partial pressure difference (Figure 34-1).
c. Acceptable lower limits of Pao2 for older adults can be estimated using the following formula.
B Causes of hypoxemia (see Chapters 8 and 15)
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 FIO2 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 FIO2 results in a <10-mm Hg increase in the Pao2, the hypoxemia is refractory.
2. Responsive hypoxemia is hypoxemia that demonstrates a significant response to an increase in the FIO2.
D Clinical manifestations of hypoxemia
1. Rapid respiratory rate and/or large tidal volume (Vt)
3. Tachycardia and hypertension
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
IV Indications for Oxygen Therapy, Modified from AARC Clinical Practice Guidelines on Oxygen Therapy, 2002.
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.
A Retinopathy of prematurity (ROP) (see Chapter 27)
1. Occurs primarily in premature infants (<34 weeks gestation) with incomplete vascularization of the retina
2. Increased oxygen exposure (Sao2 96% to 99%) is just one of many factors involved in the pathogenesis of ROP.
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.
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
c. The quantity of oxygen free radicals depends on Pao2. The greater the Pao2, the greater the quantity of free radicals.
3. Pathophysiology of oxygen toxicity
a. Cellular susceptibility to hyperoxia (100% O2)
(1) Pulmonary capillary endothelium (most susceptible)
(2) Alveolar type I epithelial cells
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.
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 FIO2 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 FIO2 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)
1. Nitrogen is metabolically inactive and constitutes 80% of alveolar gas. Nitrogen is essential to maintain alveolar stability.
2. Administration of high FIO2 (>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.
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 |
*The disposable nonrebreathing mask is not tight fitting; thus entrainment of room air normally occurs.
†For a system to be considered high flow, it must provide ≥40 L/min flow.
1. The patient’s entire inspired gas volume is consistently and predictably delivered by the system.
2. To maintain a consistent FIO2 the apparatus flow must exceed the peak inspiratory flow of the patient.
3. Peak inspiratory flows are difficult to measure but may be approximated by delivering a total flow at least four times the patient’s measured minute volume (Ve).
a. Normal peak inspiratory flows are approximately four times the patient’s measured Ve.
b. This flow usually will provide adequate volume in the face of a changing ventilatory pattern.
