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Electron shell 008 Oxygen.svg
Electron shell diagram of oxygen
Classification and external resources
ICD-10 T59.8
ICD-9-CM 987.8
MeSH D018496

Oxygen toxicity or oxygen toxicity syndrome (also known as the "Paul Bert effect" or the "Lorrain Smith effect") is severe hyperoxia caused by breathing oxygen at elevated partial pressures.[1][2][3] These above-normal concentrations of oxygen within the body can cause cell damage in two principal regions: the central nervous system (CNS), and the lungs (pulmonary).[4] Over time, it can also cause damage to the retina and may be implicated in some retinopathic conditions.[5][6]

The damage may be caused by long exposure (days) to lower concentrations of oxygen or by shorter exposure (minutes or hours) to high concentrations. Long exposures to partial pressures of oxygen above 0.5 bar (50 kPa) can result in pulmonary oxygen toxicity and are a concern for patients breathing pure oxygen for extended periods.[7][8][9] Short exposures to partial pressure of oxygen above 1.6 bar (160 kPa) are usually associated with CNS oxygen toxicity and are most likely to occur among divers and individuals undergoing hyperbaric oxygen therapy.[10][11][12]

The observed effects of CNS oxygen toxicity are seizures which consist of a brief period of rigidity, followed by convulsions and unconsciousness, which are of particular concern to divers. Pulmonary oxygen toxicity results in damage to the lungs causing pain and difficulty in breathing, while retinopathic oxygen toxicity may lead to myopia or a detached retina. These are of concern when supplementary oxygen is administered as part of a treatment, particularly to new-born infants.

Prevention of oxygen toxicity is an important precaution whenever oxygen is breathed at greater than normal partial pressures. This has led to use of protocols for avoidance of hyperoxia in such fields as diving, hyperbaric therapy and human spaceflight. Hyperventilation does not lead to hyperoxia, because oxygen toxicity never results from breathing air at atmospheric pressure.


In humans, there are several types of oxygen toxicity:[1][3]

  • Central nervous system (CNS), characterised by convulsions followed by unconsciousness, occurring under hyperbaric conditions
  • Pulmonary, characterised by difficulty in breathing and pain within the chest, occurring when breathing elevated pressures of oxygen for extended periods
  • Retinopathic, characterised by alterations to the eye, occurring when breathing elevated pressures of oxygen for extended periods

Signs and symptoms[edit]

CNS oxygen toxicity manifests as symptoms such as visual changes, ringing in the ears, nausea, twitching (especially on the face), irritability (personality changes, anxiety, confusion, etc.), and dizziness. This may be followed by a tonic-clonic seizure where intense muscle contraction occurs for several seconds followed by rapid spasms of alternate muscle relaxation and contraction producing convulsive jerking, which is followed by a period of unconsciousness (the postictal state).[1][2] The onset depends upon partial pressure of oxygen (ppO2) in the breathing gas and exposure duration but experiments have shown that there is a wide variation in exposure time before onset amongst individuals and in the same individual from day to day.[1][2][4][10][11]

Image is of pulmonary oxygen toxicity in a rat lung following long hyperbaric oxygen exposure. Histology shows alveolar edema, hyaline membranes, inflammatory cell infiltration, and septal thickening.

Early symptoms of pulmonary oxygen toxicity are breathing difficulty and pain or discomfort within the chest (substernal pain). The lungs show inflammation and swelling (pulmonary edema).[1][2]. Tests in animals have indicated a similar variation in tolerance as found in CNS toxicity.


As CNS toxicity is caused by breathing oxygen at elevated ambient pressures, patients undergoing hyperbaric oxygen therapy are at risk of suffering hyperoxic seizures.[1][12][13] For the same reason, divers breathing air at depths greater than 60 metres (200 ft) face a risk of an oxygen toxicity "hit" (seizure) as do divers breathing a gas mixture enriched with oxygen (nitrox).

The lungs have a very large area in contact with the breathing gas and contain thin membranes, making them particularly susceptible to damage by oxygen. The risk of bronchopulmonary dysplasia ("BPD") in infants, or adult respiratory distress syndrome in adults, begins to increase with exposure for over 16 hours to oxygen partial pressures of 0.5 bar (50 kPa) or more.[7][8][9] At sea-level, 0.5 bar (50 kPa) is exceeded by gas mixtures having oxygen fractions greater than 50%, while the rate of damage rises non-linearly between the 50% threshold of toxicity and the rate at 100% oxygen. Partial pressures between 0.2 bar (20 kPa) (normal at sea level) and 0.5 bar (50 kPa) are considered non-toxic but intensive care patients breathing more than 60% oxygen, and especially patients at fractions near 100% oxygen, are considered to be at particularly high risk. If the treatment continues for a lengthy period, it may begin to cause lung damage which exacerbates the original problem requiring the high-oxygen mixture. Oxygen toxicity is also a potential complication of mechanical ventilation with pure oxygen, where it is called respiratory lung syndrome. Pulmonary manifestations of oxygen toxicity are not the same for normobaric conditions as they are for hyperbaric conditions.[14] Principally, breathing 100% oxygen eventually leads to collapse of the alveoli (atelectasis), while - at same partial pressure of oxygen - the presence of significant partial pressures of inert gases will prevent this effect.[15] In the treatment of decompression sickness, divers are exposed to long periods of oxygen breathing under hyperbaric conditions. This exposure, coupled with that from the dive preceding the symptoms, can be a significant cumulative oxygen exposure and pulmonary toxicity may occur.[12]

Prolonged exposure to high inspired fractions of oxygen causes damage to the retina.[5][16][17][18] Damage to the developing eye of infants exposed to high oxygen fraction at normal pressure has a different mechanism and effect from the eye damage experienced by adult divers under hyperbaric conditions.[19][6] Hyperoxia may be a contributing factor for the disorder called retrolental fibroplasia or retinopathy of prematurity (ROP) in infants.[5][19] In preterm infants, the retina is often not fully vascularised. ROP occurs when the development of the retinal vasculature is arrested and then proceeds abnormally. Associated with the growth of these new vessels is fibrous tissue (scar tissue) that may contract to cause retinal detachment. Supplemental oxygen exposure, while a risk factor, is not the main risk factor for development of this disease. Restricting supplemental oxygen use does not necessarily reduce the rate of ROP, and may raise the risk of other hypoxia-related systemic complications.[19]

Hyperoxic myopia has occurred in closed circuit oxygen rebreather divers with prolonged exposures.[6][16][20][21] This must be due to an increase in the refractive power of the lens, since axial length and keratometry readings do not reveal a corneal or length basis for a myopic shift.[6][22]


A high concentration of oxygen damages cells.[4] Not all mechanisms of damage caused by reactive oxygen species (ROS) are known, but the process of lipid peroxidation causes damage to cell membranes.[23] ROS form as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling. However, during times of environmental stress ROS levels can increase dramatically, which can result in significant damage to cell structures. This cumulates into a situation known as oxidative stress.[4][24] One example of this is that oxygen has a propensity to react with certain metals to form the ROS superoxide, which attacks double bonds in many organic molecules, including the unsaturated fatty acid residues in cells.[25][26] High concentrations of oxygen are also known to increase the formation of free radicals which harm DNA and other structures (see nitric oxide, peroxynitrite, and trioxidane).[4][27] Normally the body has many defense systems against such injury, such as glutathione, catalase, and superoxide dismutase, but at higher concentrations of free oxygen, these systems are eventually overwhelmed, and the rate of damage to cell membranes exceeds the capacity of the systems which control or repair it.[28][29][30] Cell damage and cell death then result.



The diving cylinder contains oxygen-rich gas (36%) and is marked with maximum operating depth of 28 metres.

A seizure caused by CNS oxygen toxicity is a deadly but entirely avoidable event while diving.[31] The diver may experience no warning symptoms. The effects are sudden convulsions and unconsciousness, during which victims can lose their regulator and drown.[1][2] There is an increased risk of CNS oxygen toxicity on deep dives, long dives and dives where oxygen-rich breathing gases are used.[31] Divers are taught to calculate a maximum operating depth for oxygen-rich breathing gases.[31][32] Cylinders containing such mixtures must be clearly marked with that depth.[31][32]

In some diver training courses for these types of diving, divers are taught to plan and monitor what is called the "oxygen clock" of their dives.[31] This is a notional alarm clock, which "ticks" more quickly at increased ppO2 and is set to activate at the maximum single exposure limit recommended in the National Oceanic and Atmospheric Administration (NOAA) Diving Manual.[31][32] For the following partial pressures of oxygen the limit is: 45 minutes at 1.6 bar (160 kPa), 120 minutes at 1.5 bar (150 kPa), 150 minutes at 1.4 bar (140 kPa), 180 minutes at 1.3 bar (130 kPa) and 210 minutes at 1.2 bar (120 kPa), but is impossible to predict with any reliability whether or when CNS symptoms will occur.[1][2][33][34] Many Nitrox-capable dive computers calculate an "oxygen loading" and can track it across multiple dives. The aim is to avoid activating the alarm by reducing the ppO2 of the breathing gas or the length of time breathing gas of higher ppO2. As the ppO2 depends on the fraction of oxygen in the breathing gas and the depth of the dive, the diver obtains more time on the oxygen clock by diving at a shallower depth, by breathing a less oxygen-rich gas or by shortening the duration of exposure to oxygen-rich gases.

BPD is reversible in the early stages by use of "break periods" on lower oxygen pressures, but it may eventually result in irreversible lung injury if allowed to progress to severe damage. Usually several days of exposure without "oxygen breaks" are needed to cause such damage.

Pulmonary oxygen toxicity is an entirely avoidable event while diving. The limited duration and naturally intermittent nature of most diving makes this a relatively rare (and even then, reversible) complication for divers. Guidelines have been established that allow divers to calculate when they are at risk of pulmonary toxicity.[1][2][35][36][37][38]

In low-pressure environments oxygen toxicity may be avoided since the toxicity is caused by high oxygen partial pressure, not merely by high oxygen fraction. This is illustrated by oxygen use in spacesuits (historically, for example, the Gemini and Apollo spacecraft).[39] In such applications high-fraction oxygen is non-toxic, even at breathing mixture fractions approaching 100%, because the oxygen partial pressure is not allowed to chronically exceed 0.35 bar (35 kPa).

Vitamin E and selenium were proposed and later rejected as a potential method of protection against pulmonary oxygen toxicity.[40][41][42] There is however some experimental evidence in rats that vitamin E and selenium aid in preventing in vivo lipid peroxidation and free radical damage, and therefore prevent retinal changes following repetitive hyperbaric oxygen exposures.[43]


Treatment of seizures during oxygen therapy consists of removing the patient from oxygen, thereby dropping the partial pressure of oxygen delivered.[2]


An overview of previous studies by Bitterman in 2004 concluded that following removal of breathing gas that contains high fractions of oxygen, no long-term neurological damage from the seizure remains.[4][44]



CNS toxicity was first described by Paul Bert in 1878.[1][45][46] He showed that oxygen was toxic to insects, arachnids, myriapods, molluscs, earthworms, fungi, germinating seeds, birds, and other animals. The first recorded human exposure was undertaken in 1910 by Bornstein when two men breathed oxygen at 2.8 atm (280 kPa) for 30 minutes while he went on to 48 minutes with no symptoms.[47] In 1912, Bornstein developed cramps in his hands and legs while breathing oxygen at 2.8 atm (280 kPa) for 51 minutes.[48] Behnke et al. in 1935 were the first to observe visual field contraction (tunnel vision) on dives between 1.0 atm (100 kPa) and 4.0 atm (410 kPa).[49][50] During World War II, Donald and Yarbrough et al. performed many studies on oxygen toxicity to support the initial use of closed circuit oxygen rebreathers.[10][11][51][16] They discovered that underwater immersion, exposure to cold, and exercise would decrease the time to onset of CNS symptoms. Donald also showed a large day-to-day variability in tolerance among individuals.[10][11] In the decade following World War II, Lambertsen et al. made further discoveries on the effects of oxygen at pressure as well as methods of prevention.[52][53] Lambertsen's work showing the effect of carbon dioxide in decreasing time to onset of CNS symptoms has influenced work from current exposure guidelines to future breathing apparatus design.[31][54][32]

Naval divers in the early years of oxygen rebreather diving developed a mythology about a monster called "Oxygen Pete", who lurked in the bottom of the Admiralty Experimental Diving Unit "wet pot" (a water-filled hyperbaric chamber) to catch unwary divers. They called having an oxygen toxicity attack "getting a Pete".[55][56]

Bitterman et al. in 1986 and 1995 showed that darkness and caffeine will delay the onset of changes to brain electrical activity in rats.[57][58] In the years since, research on CNS toxicity has centered around methods of prevention and safe extension of tolerance.[59] These include topics such as circadian rhythm, drugs, age, and gender that have been shown to contribute to CNS oxygen toxicity sensitivity.[60][61][62][63]

Pulmonary oxygen toxicity was first described by Lorrain Smith in 1899 when he noted CNS toxicity and discovered in experiments in mice and birds that 0.42 atm (43 kPa) had no effect but 0.74 atm (75 kPa) of oxygen was a pulmonary irritant.[64] He went on to show that intermittent exposure permitted the lungs to recover and delayed the onset of toxicity.[64] Lambertsen et al. made further discoveries on the effects of oxygen at pressure as well as methods of prediction and prevention.[1][2][52] Their work on intermittent exposures for extension of oxygen tolerance and on a model for prediction of pulmonary oxygen toxicity based on pulmonary function are key documents in the development of operational oxygen procedures.[35][65] In 1988, Hamilton et al. wrote procedures for NOAA to establish oxygen exposure limits for habitat operations.[1][36][37][38] Models for the prediction of pulmonary oxygen toxicity do not explain all the results of exposure to high partial pressures of oxygen.[66]

Society and culture[edit]

Research directions[edit]

In other animals[edit]



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External links[edit]

[[:Category:Diving medicine]] [[:Category:Element toxicology]] [[:Category:Intensive care medicine]] [[:Category:Oxygen]] [[:Category:Pulmonology]] [[:Category:Neurobiological brain disorder]] [[da:Iltforgiftning]] [[de:Paul-Bert-Effekt]] [[es:Efecto de Paul Bert]] [[fr:Hyperoxie]] [[nl:Zuurstofvergiftiging]] [[ja:酸素中毒]] [[pl:Zatrucie tlenowe]] [[pt:Efeito Paul Bert]] [[ro:Hiperoxia]] [[ru:Кислородное отравление]]