Oxygen therapy


Arterial blood normally has a Po2 of about 95 mmHg and nearly 100% saturated with oxygen.

As red blood cells pass from an arterioles through its capillary bed to its vein oxygen is released to respiring cells.

At a venous PO2 of 40 mmHg, the oxygen saturation is about 80%: thus approximately 20% of oxygen in the blood is unloaded.

With anemia and higher red cell 2,3 BPG levels,  about 30% of oxygen can be unloaded.

In an individual with a hemoglobin in 15 g/dL the oxygen carrying capacity of blood is 20 mL of oxygen per deciliter and in traversing the arterioles and capillary bed, approximately 20% of the oxygen will be unloaded – approximately 4 mL per deciliter of blood.

Essential for treatment of acute and chronic respiratory failure, supportive therapy for general anesthesia and most surgical procedures, and in adjunctive therapy in patients with sepsis, trauma, or heart failure.

Studies of long-term oxygen therapy in patients with COPD and severe hypoxemia have revealed 4.5 patients need to be treated with long-term oxygen therapy to save one life during five years.

There is approximately 1500 ml of O2 in the tissues, of which about 370 ml is in the lungs and about 280 ml in blood.

The  inspiratory flow rate at the nares of an adult usually exceeds 12 liters per minute, and can exceed 30 liters a minute for someone with mild respiratory distress. 

Traditional oxygen therapy is limited to six liters per minute, does not begin to approach the inspiratory demand of an adult, and therefore the oxygen is diluted with room air during inspiration.

Home oxygen is provided by three systems: oxygen concentrator, compressed oxygen cylinder, and liquid oxygen.

All three systems can supply an oxygen concentration of 90% or more to the patient.

Home oxygen risks include hypercapnia, mucosal irritation, retinopathy, pulmonary toxicity, oxygen toxicity and burn injuries.

Home oxygen therapy comes in second place, after hospitalizations,  as the most expensive healthcare expenditure associated with COPD.

Oxygen toxicity includes retinal hyperplasia in premature infants, and lung injury from hyperoxia associated with ventilator associated lung injury.

Excessive oxygen supplementation and resulting hyperoxia promotes resorption atelectasis and free radical formation leading to oxidative damage to tissues, endothelial dysfunction, and other deleterious manifestations.

Burn injuries with oxygen therapy are related to exposure to lighted tobacco products.

Patients with COPD and normal resting PaO2 experiencing desaturation during sleep or physical activity treated with oxygen do not have improvements in survival compared to controls.

Patients with a PaO2 56-65 mmHg provided supplemental oxygen do not have improved survival compared to controls.

There is no difference in survival between patients with COPD with the resting PaO2 of 56-69 mmHg who receive nocturnal oxygen compared to a control group.

Oximetry may help identify patients with chronic hypoxemia, those that will benefit from long-term oxygen therapy.
Sleep related oxygen desaturation occurs often in patients with COPD that do not qualify for long-term oxygen therapy: alveolar hypoventilation, particularly during REM and ventilation-perfusion mismatch are likely mechanisms.
These factors are considered as an indication for prescribing nocturnal oxygen because of progressive COPD leads to stages of severe hypoxemia, right heart failure, and death from the severity of the saturation occurring during sleep.
In an underpowered trial there was no indication that nocturnal oxygen had a positive or negative effect on survival or progression to long-term oxygen therapy in patients with COPD (Lacasse Y).

High-flow oxygen therapy through a nasal cannula occurs when heated and humidified oxygen is delivered to the nose at high flow rates.

Studies suggest a lower risk of intubation but not mortality with the use of high flow nasal oxygen when compared with standard oxygen therapy.

High flow rates generate low levels of positive pressure in the upper airways.

High flow nasal oxygen administers heated humidified oxygen to large bore nasal cannula, typically between 30 and 60 L per minute.

The fraction of inspired oxygen can be adjusted by changing the fraction of oxygen in the driving gas.

The high flow rates may decrease physiological dead space by flushing CO2 from the upper airway and decreasing work of breathing.

High flow nasal oxygen therapy allows a constant FiO2 during peak inspiratory flow and confers benefits such as a low level of continuous positive airway pressure with increase in expiratory lung volume and reduced work of breathing, partly through intrinsic positive and expiration pressure compensation and dead space washout.

High flow oxygen therapy may decrease need for endotracheal intubation and risk of escalation of therapy in patients with acute hypoxemic respiratory failure, but may have no effect on mortality rates.

Nasal high-flow oxygen therapy utilize is warmed, humidified oxygen and high flow rate of 1-60 L per minute with a linear relationship between air flow and airway pressures as well as lung impedance. 

Nasal high-flow therapy provides positive end-expiratory pressure that may decrease the work of breathing, especially in patients with acute upper airway obstruction, unlike a face mask or nasal prongs.

Nasal high-flow therapy is more comfortable than a facemask or nasal prongs.


High flow oxygen therapy inspired gas is warmed and humidified, improving patient comfort and possibly reducing airway inflammation, leading to improve respiratory secretion drainage.

High flow oxygen therapy after extubation has clinical benefits in specific groups of people such as preterm infants, and patients undergoing cardiac surgery.

High-flow therapy after planned extubation decreases reintubation rate in the general population of critical patients (Hernandez G).

In The LOCO2 trial of mechanically ventilated adults with acute respiratory distress syndrome low oxygen targets lead to harm, with no difference in 28 day mortality but a higher incidence of mesenteric ischemic events in the conservative oxygen therapy group.

In the HOT-ICU trial of similar patients to above there was no difference in mortality or adverse events at 90 days, in contrast to the above study.

Among critically ill adults receiving mechanical ventilation, the number of ventilator free days did not differ among groups in which goal of 90%, 94%, or 98% were reached (Semler M).

In acute respiratory failure high-flow oxygen results in better comfort and oxygenation than standard oxygen therapy delivered through a face mask.

Among children who were acutely ill, requiring noninvasive respiratory support in a pediatric critical care unit, high flow nasal cannula oxygen met the criterion for non-inferiority compared with continuous positive airway pressure therapy for time to liberation from respiratory support.

Facemask noninvasive ventilation is associated with a lower rate of overall overall mortality and endotracheal intubation when compared with standard oxygen therapy for patients with acute hypoxemic respiratory failure who have COPD and/or congestive heart failure.

In critically ill patients high-flow therapy during the acute phase of respiratory failure improves oxygenation, survival, comfort, and ease of respiratory secretions drainage.

The routine use of oxygen therapy in patients with acute myocardial infarction with normal oxygen saturation levels shows no benefit on meta-analysis studies.

Administering oxygen therapy to patients with COPD reduces the risk of developing dementia.

Toxicity attributable to oxygen supplementation is categorized into local and systemic effects.

Local effects include absorptive atelectasis from displacement of alveolar nitrogen by high oxygen concentrations.

High inspired oxygen leads to excess reactive oxygen species, which can cause oxidative injury leading to poor mucocilliary clearance, surfactant impairment, airway irritation, and alterations in the microbial flora of the airways.

Systemic effects of excess oxygen are reached when the partial pressure of arterial oxygen threshold exceeds 100 mmHg, at which point oxyhemoglobin saturation is nearly complete and dissolved oxygen increases.

The administration of supplemental oxygen is a cornerstone of care in the intensive care unit (ICU).

The use of oxygen is to avoid hypoxemia in patients with, or at risk for, impaired pulmonary gas exchange. 

It is typically administered with an upward titration of the fraction of inspired oxygen (Fio2) to achieve a high level of arterial oxygen saturation.

There is less attention on avoidance of excess use.

An elevated level of the partial pressure of arterial oxygen increases the production of toxic reactive oxygen species, which can cause injury, especially in the lungs, retinae, and central nervous system.


In the presence of increased oxygen tension or an exaggerated stimulus such as toxins or physiological stress, ROS production increases and outstrips anti-oxidant capacity.


Under the circumstances oxidative stress occurs, with inflammation, cell damage, and cell death.

ROS superoxide anionsCan activate nitric oxide and PaO2 exceeds 150 mmHg and  can induce vasoconstriction in the coronary, retinal and cerebrovascular beds

High Fio2 values in patients with poorly ventilated alveolar-capillary units can also lead to absorption atelectasis.

Liberal oxygen use is associated with increased mortality in observational studies.

A large observational study involving 36,307 critically ill patients from 50 intensive care units reported a U-shaped relationship between PaO2 and in-hospital mortality.

In a single-center randomized trial of the use of a conservative oxygen strategy and a liberal oxygen strategy; the trial had been stopped prematurely as conservative therapy had lower mortality than those who received usual care (11.6% vs. 20.2%).( Girardis).

1000 adults in the ICU who were receiving mechanical ventilation underwent randomization to conservative-oxygen therapy or usual care.

Correcting abnormal physiology to normal levels may often lead to harm, and a less is more approached targeting physiological goals might result in a more favorable risk/benefit trade-off for many interventions.

There was no significant difference in the primary outcome of the number of ventilator-free days (21.3 vs. 22.1 days) or in mortality.

Barrot et al. report the results of the LOCO2 (Liberal Oxygenation versus Conservative Oxygenation in Acute Respiratory Distress Syndrome) trial: the trial was stopped prematurely owing to concerns about the safety of the conservative strategy and futility.

Among critically ill patients, targeting oxygenation to a low normal range compared with a high-normal range does not result in statistically significant reduction in organ dysfunction.

The primary outcome of mortality at 28 days was 34.3% in the conservative-oxygen group and 26.5% in the liberal-oxygen group; mortality at 90 days was 44.4% and 30.4%, respectively.

In the above study there  were episodes of mesenteric ischemia, all in the conservative-oxygen group.

Despite preliminary evidence supporting conservative oxygen use, ICU-ROX did not show a benefit, and the LOCO2 trial suggested potential harm.

Among adult patients with acute hypoxemic respiratory failure in the ICU, lower oxidation target not result in lower mortality than a higher target at 70 days.

Critically ill patients often have heterogeneous organ injury with heterogeneous regional perfusion abnormalities.

Systemic oxygenation could help some tissue beds and harm others, with variable net effects on the patients outcomes.

Avoiding excess oxygen by not administering supplemental oxygen when the Spo2 is 96% or greater and not starting supplemental oxygen when the Spo2 is 92% or 93% are recent guidelines.

Reports suggest that there are harms attributable to hyperoxia or hyperoxemia crisis series of acute care conditions.

In patients with cardiac arrest and hypoxic ischemic cephalopathy patients with hyperoxemia of a PaO2 of greater than 300 mmHg and increase risk of in-hospital mortality of 63% versus 45% of the normoxia group and 57% for the hypoxia group.

In the above study mechanism of death was attributed to worsening secondary brain injury doing to increased oxygen stress or ROS formation.

The prevention or reversal of hypoxia can be life-saving, but excessive oxygen supplementation and resulting hyperoxia promotes resorption atelectasis and free radical formation leading to oxidative damage to tissues, endothelial dysfunction, and other negative effects.

In the AVORID trial patient with ST-elevation myocardial infarction were assigned to receive supplemental oxygen compared with ambient air: the group that received liberal oxygen administration had larger myocardial infarction size at six months and higher frequency of recurrent myocardial infarction.

In theOxygen-ICU trial and theHyper S2S trial, both demonstrated higher mortality with higher oxygen targets or higher oxygen delivery.

In  a single center trial of 434 patients in a ICU population compared oxygen titration to a partial pressure of oxygen saturation of 70 to 100 mmHg versus up to 150 mmHg and found that the lower oxygen goals reduced mortality.

Multiple other studies however showed no benefit from lower oxygen targets.

A third trimester pregnancy trial showed that maternal hyperoxia led to a decline in cardiac index that was more pronounced than it was among non-pregnant study patients.

Unrestricted oxygen in preterm infants leads to retinal hyperplasia.

High fraction inspired oxygen during general anesthesia for adults undergoing surgery was found not to reduce surgical site infections.

Liberal oxygen therapy benefit is the bactericidal property associated with increased ROS formation through oxidative killing of bacteria.

A metaanalysis showed no benefits from higher inspired oxygen of .80 FiO2 versus 0.3-0.3 5 Fio2 in patients undergoing general anesthesia for a reduction in surgical site infections.

Is a randomized trial patients in the ICU treated with the PAO2 target of 70-100 mmHg had a lower mortality than those who were treated with a PAo2 target of up to 150 mmHg.

A PO2 target of up to 55-80 mmHg is often referred to as a standard of care in patients with acute respiratory distress syndrome: Lower oxygenation targets may be preferable in acutely ill adults.

In  adult ICU patients with COVID-19 and severe hypoxemia, targeting a PAO2 of 60 mmHg resulted in more days alive without life support in 90 days and targeting a PAO2 of 90 mmHg.(Covid Trial Group).

In a randomized trial involving patients undergoing mechanical ventilation in the ICU it was found that targeting the peripheral oxygen saturation at 88-92%, as compared with the value of 96% of above, was feasible without evident harm.

Oxygen may be beneficial in wound infections for which oxygen tissue tensions may be reduced compared with normal tissues,

In septic shock liberal oxygen increased mortality in hyperoxia group.

Individual differences are present in the adaptive response to hypoxemia: hyperoxemia important for the treatment of carbon monoxide poisoning or necrotizing skin infections, while the exposure to higher PaO2 levels in ischemia/reperfusion injury such as in cardiac arrest, myocardial infarction, or stroke, is associated with worse outcomes.

The use of helmet noninvasive ventilation is associated with decreased risk of intubation and mortality compared with other modalities in patients with acute hypoxemic respiratory failure.

The helmet interface decreases air leaks compared with a face mask interface, decreased air leaks may allow for more effective delivery of high levels of positive end expiratory pressure, potentially increasing alveolar  recruitment and decreasing respiratory effort.

Helmet noninvasive ventilation has a more effective seal than facemasks, more effective delivery of positive end expiratory pressure, greater tolerance, and less work of breathing.










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