Supplemental oxygen is valuable in many clinical situations, but its excessive or
inappropriate use can be deleterious.
Thus, consider the following when prescribing oxygen long term oxygen therapy:
Proper determination of need
Determining the oxygen flow rate for each condition (i.e., the required flow rate may be
different during sleep, exercise and sedentary wakefulness)
Selection of a qualified durable medical equipment supplier
Completion of the Certification of Medical Necessity (CMN)
Reassessment for prescription renewal and/or modification
Patient education and training
Hyperoxia is poorly defined, but probably exists whenever oxygen tension exceeds 21
percent of atmospheric pressure.
It appears to produce cellular injury through:
increased production of reactive oxygen species, such as the superoxide anion,
the hydroxyl radical, and hydrogen peroxide. When the production of these
reactive species increases and/or the cell's antioxidant defenses are depleted,
oxygen radicals can react with and impair the function of essential intracellular
macromolecules, enzyme inactivation and lipid peroxidation. resulting in cell
Oxygen free radicals may also promote a deleterious inflammatory response,
leading to secondary tissue damage and/or apoptosis.
Lung tissue is exposed to the highest concentrations of oxygen in the body, placing cells
that line the tracheobronchial tree and alveoli at the greatest risk for hyperoxic
Hyperoxia may also increase susceptibility to mucous plugging, atelectasis, and
secondary infection by impairing both mucociliary clearance and the bactericidal capacity
of immune cells
1. pulmonary complications
2. extra-pulmonary complications
High fractions of inspired oxygen (FiO2) have been associated with several pulmonary
High concentrations of supplemental oxygen cause washout of alveolar nitrogen (ie, oxygen
replaces nitrogen in the alveolus). This may cause absorptive atelectasis if oxygen diffuses from
the alveoli to the capillaries faster than it is replenished by inhaled oxygen (diffusion faster than
replenishment). Theoretically more likely in e.g.
high rate of oxygen uptake, due to an increased in metabolic demand
Once well established, absorptive atelectasis is not rapidly reversed by a reduction of
FiO2 to maintenance levels, emphasizing the desirability of rapid titration of FiO2 to the
lowest fraction necessary to maintain an SaO2 >90 percent
Accentuation of hypercapnia
Hyperoxic hypercarbia describes the phenomenon of increased PaCO2 associated with
increases in FiO2 in individuals with chronic compensated respiratory acidosis. In
general, the increased hypercapnia does not lead to CO2 narcosis and respiratory failure,
because the relative rise in PaCO2 is small and these patients are acclimatized to their
higher baseline level of PaCO2.
substernal heaviness, pleuritic chest pain, cough, and dyspnea within 24 hours of
breathing pure oxygen (adult study subjects)
combination of tracheobronchitis and absorptive atelectasis.
Erythema and edema of large airways can be observed bronchoscopically in most
patients treated with a FiO2 of 0.9 for six hours and are thought to reflect hyperoxic
Bronchopulmonary dysplasia (BPD), a disease seen in neonates following recovery from
neonatal respiratory distress syndrome, has been attributed to the effects of mechanical
ventilation and oxygen toxicity in the immature lung. BPD is characterized by:
epithelial hyperplasia and squamous metaplasia in the large airways, thickened alveolar
walls, and peribronchial and interstitial fibrosis. Infants with BPD generally suffer
respiratory distress and require supplemental oxygen for up to six months.
The preterm lung is especially vulnerable to injury because of its structural and
functional immaturity. Lungs in preterm infants have poorly developed airway
supporting structures, surfactant deficiency, decreased compliance,
underdeveloped antioxidant mechanisms, and inadequate fluid clearance,
compared to term infants.
Preterm infants may have inadequate antioxidant defenses because of nutrient
deficiencies or immature enzyme development.
Determining the magnitude of parenchymal injury due solely to oxygen therapy in humans is
problematic because confounders are usually present .e.g.
ARDS who are sustained on mechanical ventilation, and may be due to progression of
the underlying process that produced ARDS,
development of ventilator-associated pneumonia,
ventilator-induced lung injury secondary to mechanical forces, or DAD from the toxic
effects of oxygen.
Potentiation by drugs e.g.
Patients ( adult study subjects) who receive bleomycin appear to be more susceptible to diffuse
alveolar damage following oxygen exposure. The typical presentation of combined
bleomycin/oxygen toxicity involves a patient with testicular cancer or Hodgkin's disease who, after
receiving bleomycin, requires supplemental oxygen due to aspiration, pneumonia, or general
anesthesia. Following oxygen administration, the patient develops subacute worsening of bilateral
alveolar infiltrates with increasing dyspnea, nonproductive cough, and decreasing lung
Lung injury associated with amiodarone or external beam radiation may involve oxygen radicals
in its pathogenesis, and also may predispose individuals to hyperoxic complications.
The retinopathy of prematurity (previously called retrolental fibroplasia) has been
attributed to the toxic effects of oxygen.
Definition: developmental vascular proliferative disorder that occurs in the retina
of preterm infants with incomplete retinal vascularization
Retinal vascularization begins at 15 to 18 weeks gestation. Retinal blood vessels
extend out from the optic disc (where the optic nerve enters the eye) and grow
peripherally. Vascularization in the nasal retina is complete at approximately 36
weeks. Vascular development usually is complete in the temporal retina by 40
weeks, although maturation may be delayed until 8 to 12 weeks after term birth
Pathogenesis of ROP:
1. An initial injury caused by factors such as hypotension, hypoxia, or
hyperoxia, with free radical formation, injures newly developing blood
vessels and disrupts normal angiogenesis-. Following this disruption,
vessels either resume normal growth or new vessels grow abnormally
out from the retina into the vitreous. Increased permeability of these
abnormal new vessels can result in retinal edema and hemorrhage.
Abnormal fibrovascular tissue may develop and later contract, producing
traction on the retina. In some severe cases, this results in retinal
distortion or even detachment
Central nervous system
symptoms, including generalized tonic-clonic seizures, have been reported
secondary to hyperoxia but are unusual in the absence of hyperbaric therapy.
Increased oxygen tension can lead to local coronary vasoconstriction, and
microscopic foci of myocardial necrosis have been observed in animal models.
Reductions in stroke volume and cardiac output, relative bradycardia, and an
increase in systemic vascular resistance may ensue, but the clinical relevance of
hyperoxia-related hemodynamic effects remains unclear
There is no single threshold of FiO2 defining a safe upper limit for prevention of oxygen toxicity.
Factors that are difficult to quantify, such as the adequacy of a given patient's antioxidant
defenses, probably also play a role in determining individual susceptibility
Reduction of FiO2 —
Reducing the FiO2 to the lowest tolerable limit is a good principle for all patients, in
particular those likely to be at risk of hyperoxia-induced lung injury because of a
prolonged duration of oxygen therapy or prior therapy with bleomycin.
In practical terms, oxygen should be administered to achieve a PaO2 of 60 to 65 mmHg
(SaO2 approximately 90 percent).
Retinopathy of prematurity