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Hyperoxia occurs when cells, tissues and organs are exposed to an excess supply of
oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...
(O2) or higher than normal
partial pressure In a mixture of gases, each constituent gas has a partial pressure which is the notional pressure of that constituent gas as if it alone occupied the entire volume of the original mixture at the same temperature. The total pressure of an ideal gas ...
of oxygen. In
medicine Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pract ...
, it refers to excessive oxygen in the
lungs The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of th ...
or other body tissues, which can be caused by breathing air at pressures greater than normal
atmospheric pressure Atmospheric pressure, also known as barometric pressure (after the barometer), is the pressure within the atmosphere of Earth. The standard atmosphere (symbol: atm) is a unit of pressure defined as , which is equivalent to 1013.25 millibars, 7 ...
, or breathing gas mixtures whenever the alveolar oxygen partial pressure is greater than that due to breathing air at normal atmospheric pressure, which can be a consequence of high oxygen fraction, high ambient pressure or a combination of ambient pressure and oxygen fraction resulting in an oxygen partial pressure significantly higher than that of sea level air. The body is tolerant of some deviation from normal inspired oxygen partial pressure, but a sufficiently elevated level of hyperoxia can lead to
oxygen toxicity Oxygen toxicity is a condition resulting from the harmful effects of breathing molecular oxygen () at increased partial pressures. Severe cases can result in cell damage and death, with effects most often seen in the central nervous system, lu ...
over time, with the mechanism related to the partial pressure, and the severity related to the dose. Hyperoxia is the opposite of hypoxia; hyperoxia refers to a state in which oxygen supply to the tissues is excessive, and hypoxia refers to a state in which oxygen supply is insufficient. Supplementary oxygen administration is widely used in emergency and intensive care medicine and can be life-saving in critical conditions, but too much can be harmful and affects a variety of pathophysiological processes. Reactive oxygen species are known problematic by-products of hyperoxia which have an important role in cell signaling pathways. There are a wide range of effects, but when the homeostatic balance is disturbed, reactive oxygen species tend to cause a cycle of tissue injury, with inflammation, cell damage, and cell death. In the environment, hyperoxia refers to an abnormally high oxygen concentration in a body of water or other habitat.


Signs and symptoms

Associated with hyperoxia is an increased level of
reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...
(ROS), which are chemically reactive
molecule A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...
s containing oxygen. These oxygen containing molecules can damage lipids, proteins, and nucleic acids, and react with surrounding biological tissues. The human body has naturally occurring
antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
s to combat reactive molecules, but the protective antioxidant defenses can become depleted by abundant reactive oxygen species, resulting in
oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
of the tissues and organs. The symptoms produced from breathing high concentrations of oxygen for extended periods have been studied in a variety of animals, such as frogs, turtles, pigeons, mice, rats, guinea pigs, cats, dogs and monkeys. The majority of these studies reported the occurrence of irritation, congestion and edema of the lungs, and even death following prolonged exposures.


Oxygen toxicity

The supplementation of oxygen can lead to
oxygen toxicity Oxygen toxicity is a condition resulting from the harmful effects of breathing molecular oxygen () at increased partial pressures. Severe cases can result in cell damage and death, with effects most often seen in the central nervous system, lu ...
, also known as oxygen toxicity syndrome, oxygen intoxication, and oxygen poisoning. There are two main types of oxygen toxicity: central nervous system (CNS) toxicity, and pulmonary and ocular toxicity. Temporary exposure to high partial pressures of oxygen at greater than atmospheric pressure can lead to central nervous system toxicity (CNS). An early but serious sign of CNS oxygen toxicity is a grand-mal seizure, also known as a generalized tonic-clonic seizure. This type of seizure consists of a loss of consciousness and violent muscle contractions. Signs and symptoms of oxygen toxicity are usually prevalent, but there are no standard warning signs that a seizure is about to ensue. The convulsion caused by oxygen toxicity does not lead to hypoxia, a side effect common to most seizures, because the body has an excess amount of oxygen when the convulsion begins. The seizures can lead to drowning, however, if the convulsion is suffered by a diver still in the water. Prolonged exposure to higher oxygen levels at atmospheric pressure can lead to
pulmonary The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of th ...
and
ocular Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and con ...
toxicity. Symptoms of oxygen toxicity may include disorientation, respiratory problems,
myopia Near-sightedness, also known as myopia and short-sightedness, is an eye disease where light focuses in front of, instead of on, the retina. As a result, distant objects appear blurry while close objects appear normal. Other symptoms may include ...
, or accelerated development of
cataract A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble w ...
s. Prolonged exposure to higher than normal partial pressures of oxygen can result in oxidative damage to cell membranes. Signs of pulmonary (lung) oxygen toxicity begin with slight irritation in the
trachea The trachea, also known as the windpipe, is a Cartilage, cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all air-breathing animals with lungs. The trachea extends ...
. A mild cough usually ensues, followed by greater irritation and a worse cough until breathing becomes quite painful and the cough becomes uncontrollable. If supplementation of oxygen is continued, the individual will notice tightness in the chest, difficulty breathing, shortness of breath, and if exposure is continued, fatality due to lack of oxygen.


Cause

Oxygen supplied at greater than atmospheric pressure has been known to damage plants, animals, and aerobic bacteria such as
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
. The damaging effects vary depending on the specimen used, its age, physiological state, and diet. Evidence indicates that hyperoxia may be harmful, but robust data from interventional studies is limited. The supplementation of oxygen has been a common procedure of pre-hospital treatment for many years. Guidelines include cautions about
chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...
(COPD). These guidelines stress the use of 28% oxygen masks and caution the dangers of hyperoxia. Long-term use of supplemental oxygen improves survival in patients with COPD, but can lead to lung injury. An additional cause of hyperoxia is related to
underwater diving Underwater diving, as a human activity, is the practice of descending below the water's surface to interact with the environment. It is also often referred to as diving, an ambiguous term with several possible meanings, depending on context ...
with breathing apparatus. Divers breath a mixture of gasses which must include oxygen, and the partial pressure of oxygen in any given gas mixture will increase with depth. Atmospheric air becomes hyperoxic during the dive, and a hyperoxic gas mixture known as
nitrox Nitrox refers to any breathing gas, gas mixture composed (excepting trace gases) of nitrogen and oxygen. This includes atmospheric air, which is approximately 78% nitrogen, 21% oxygen, and 1% other gases, primarily argon. In the usual applicatio ...
is used to reduce the risk of decompression sickness by substituting oxygen for part of the nitrogen content. Breathing nitrox can lead to
oxygen toxicity Oxygen toxicity is a condition resulting from the harmful effects of breathing molecular oxygen () at increased partial pressures. Severe cases can result in cell damage and death, with effects most often seen in the central nervous system, lu ...
due to the high partial pressure of oxygen if used too deep or for too long. Protocols for the safe use of raised oxygen partial pressure in diving are well established and used routinely by recreational scuba divers, military combat divers and professional saturation divers alike. The highest risk of hyperoxia is in
hyperbaric oxygen therapy Hyperbaric medicine is medical treatment in which an ambient pressure greater than sea level atmospheric pressure is a necessary component. The treatment comprises hyperbaric oxygen therapy (HBOT), the medical use of oxygen at an ambient pressure ...
, where it is a high probability side effect of the treatment for more serious conditions, and is considered an acceptable risk as it can be managed effectively without apparent long term effects. Oxygen
rebreather A rebreather is a breathing apparatus that absorbs the carbon dioxide of a user's breathing, exhaled breath to permit the rebreathing (recycling) of the substantially unused oxygen content, and unused inert content when present, of each breath. ...
s are also used for normobaric routine work and emergency response in non-breatheable atmospheres, or in circumstances where the suitability of the ambient gas for breathing is unknown or may change without warning, such as firefighting, underground rescue, and work in confined spaces. Supplemental oxygen is also used for high altitude exposures in aviation and mountaineering. In all these cases, the maximum concentration is naturally limited by the ambient pressure, but the lower limit is usually more difficult to control, and the immediate consequences of hypoxia are generally more serious that the immediate consequences of hyperoxia, so there is a tendency to provide a larger margin for error for hypoxia, and the user is exposed to hyperoxic conditions for much of the time.


Mechanism

Supplementary oxygen is an effective and widely available treatment for hypoxemia and hypoxia associated with many pathological processes, but other pathophysiological processes are associated with increased levels of
reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...
(ROS) caused by hyperoxia. These ROS react with biological tissues, and may damage
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s,
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
s, and
nucleic acid Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main cl ...
s.
Antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
s normally protecting the tissues can be overwhelmed by higher levels of ROS, thereby causing
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...
. Alveolar and alveolar capillary epithelial cells are vulnerable to injuries caused by oxygen free radicals due to hyperoxia. In acute lung injuries of this type, hyperpermeability of the pulmonary microvasculature allows plasma leakage, causing pulmonary edema and abnormalities in coagulation and fibrin deposition. Surfactant production can be impaired. Maximum benefit of oxygen availability is a balance between necessity and toxicity along a continuum. Cumulative oxygen dose is determined by a combination of exposure time, ambient pressure and oxygen fraction of the inhaled gas. The latter two factors can be combined as the partial pressure of inhaled oxygen in the alveoli. Partial pressures of inhaled oxygen exceeding 0.6 bar (FIO2 >0.6 at normal atmospheric pressure), administered for extended periods in the order of days, are toxic to the lungs, which is known as low pressure oxygen poisoning, pulmonary toxicity, or the Lorraine Smith effect. This form of exposure leads to lung airway congestion, pulmonary edema and
atelectasis Atelectasis is the collapse or closure of a lung resulting in reduced or absent gas exchange. It is usually unilateral, affecting part or all of one lung. It is a condition where the alveoli are deflated down to little or no volume, as distinct ...
caused by damage to the linings of the bronchi and alveoli. Fluid accumulation in the lungs causes a feeling of shortness of breath, a burning sensation is felt in the throat and chest, and breathing is painful. At normal atmospheric pressures the effect is mainly confined to the lungs as they are directly exposed to the high concentration of oxygen, which is not distributed throughout the body as transport is limited by the hemoglobin-oxygen buffer system, and relatively little oxygen is carried in solution in the plasma. At higher ambient pressures, and higher oxygen partial pressures, where a larger amount of oxygen is carried in solution, toxic effects on the central nervous system manifest over a much shorter exposure time. This is known as high pressure oxygen poisoning, or the Paul Bert effect.


Diagnosis

Diagnodis is generally simplified by a known history of exposure to intentionally raised concentrations of oxygen. There are few circumstances where a person would be unaware of exposure to higher than normal oxygen dosage.


Treatment

Oxygen supplementation is used to treat tissue hypoxia and to relieve arterial hypoxemia. High concentrations of oxygen are often given to patients with chronic obstructive pulmonary disease (COPD) or
acute lung injury Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin colo ...
(ALI). Supplementing oxygen is known to cause tissue damage, with toxicity increasing with the increase of oxygen concentrations and exposure pressures. Unfortunately, the supplementation of oxygen is necessary if an individual is not able to obtain sufficient oxygen through
respiration Respiration may refer to: Biology * Cellular respiration, the process in which nutrients are converted into useful energy in a cell ** Anaerobic respiration, cellular respiration without oxygen ** Maintenance respiration, the amount of cellul ...
and
perfusion Perfusion is the passage of fluid through the circulatory system or lymphatic system to an organ or a tissue, usually referring to the delivery of blood to a capillary bed in tissue. Perfusion is measured as the rate at which blood is deliver ...
. To decrease the chances of hyperoxia, the therapist should use the lowest concentration of oxygen required by an individual. There are no known alternatives to oxygen supplementation.


Prevention


Diving

Divers can be at risk from both central nervous system and pulmonary oxygen toxicity, and the risks have been well researched. Protocols have been developed which impose limits on oxygen partial pressure in the breathing gas which expose the diver to acceptable overall risks, bearing in mind that convulsions and loss of consciousness underwater on scuba equipment often lead to death by drowning. Diving with surface supplied gas using a
helmet A helmet is a form of protective gear worn to protect the head. More specifically, a helmet complements the skull in protecting the human brain. Ceremonial or symbolic helmets (e.g., a policeman's helmet in the United Kingdom) without protect ...
or
full-face mask A full-face diving mask is a type of diving mask that seals the whole of the diver's face from the water and contains a mouthpiece, demand valve or constant flow gas supply that provides the diver with breathing gas. The full face mask ha ...
protects the
airway The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa. Air is breathed in through the nose to th ...
much more than a
demand valve A diving regulator is a pressure regulator that controls the pressure of breathing gas for diving. The most commonly recognised application is to reduce pressurized breathing gas to ambient pressure and deliver it to the diver, but there are als ...
held by the teeth, and in some circumstances slightly higher partial pressures and a slightly higher risk of oxygen toxicity may be acceptable. There is a trade-off between risk from longer decompression obligations which keep the diver in the water longer, versus oxygen toxicity. In the exposure time is usually insufficient to develop symptoms of pulmonary toxicity, and the intervals between dives are usually long enough for recovery, so oxygen partial pressure (PO2) is commonly selected to maximise no-stop time or minimise decompression time as in-water decompression in cold water tends to be stressful to the diver. In
saturation diving Saturation diving is diving for periods long enough to bring all tissues into equilibrium with the partial pressures of the inert components of the breathing gas used. It is a diving mode that reduces the number of decompressions divers working ...
, where the diver will be breathing the gas mixture under pressure for periods in the order of weeks to a month, the PO2 must be kept low enough to avoid pulmonary toxicity, and allow downward excursions from storage pressure, while being high enough to allow for possible contingencies involving temporary reduction of pressure, during which it is highly desirable that the affected divers remain conscious and are able to perform necessary tasks to minimise the consequences, and to allow for upwards excursions without requiring a gas switch. A partial pressure of around 0.4 bar has been found to satisfy these conditions.


Hyperbaric medicine


Critical care and emergency medicine

Supplemental oxygen is one of the most commonly used treatments for critical illness and is routinely used in treatment in acute shock and other emergency medicine, but the optimum dosage is seldom obvious, and during mechanical ventilation, anesthesia, and resuscitation supply usually exceeds physiological requirements, to avoid a deficit. The resulting excess to requirements can be detrimental, but usually less so than an overall hypoxic state. Careful titration of the oxygen supply while monitoring oxygenation can allow sufficient tissue oxygenation without hyperoxic harm.


Long term oxygen therapy

At atmospheric pressure there is no risk of acute oxygen toxicity, but the possibility of pulmonary toxicity exists, and hyperoxia can exacerbate some of the conditions for which supplementary oxygen provision is otherwise beneficial.


Prognosis


Epidemiology


See also

* * * * *


References

{{Underwater diving, divmed Oxygen Respiratory diseases Diving medicine