oxygen toxicity oxygen toxicity oxygen toxicity is a condition resulting from the harmful effects of breathing molecular oxygen (o2) at increased partial pressures. severe cases can result in cell damage and death, with effects most often seen in the central nervous system, lungs, and eyes. historically, the central nervous system condition was called the paul bert effect, and the pulmonary condition the lorrain smith effect, after the researchers who pioneered the discoveries and descriptions in the late 19th century. oxygen toxicity is a concern for underwater divers, those on high concentrations of supplemental oxygen (particularly premature babies), and those undergoing hyperbaric oxygen therapy. oxygen toxicityother namesoxygen toxicity syndrome, oxygen intoxication, oxygen poisoningin 1942–43 the uk government carried out extensive testing for oxygen toxicity in divers. the chamber is pressurised with air to 3.7 bar. the subject in the centre is breathing 100% oxygen from a mask.specialtyemergency medicine the result of breathing increased partial pressures of oxygen is hyperoxia, an excess of oxygen in body tissues. the body is affected in different ways depending on the type of exposure. central nervous system toxicity is caused by short exposure to high partial pressures of oxygen at greater than atmospheric pressure. pulmonary and ocular toxicity result from longer exposure to increased oxygen levels at normal pressure. symptoms may include disorientation, breathing problems, and vision changes such as myopia. prolonged exposure to above-normal oxygen partial pressures, or shorter exposures to very high partial pressures, can cause oxidative damage to cell membranes, collapse of the alveoli in the lungs, retinal detachment, and seizures. oxygen toxicity is managed by reducing the exposure to increased oxygen levels. studies show that, in the long term, a robust recovery from most types of oxygen toxicity is possible. protocols for avoidance of the effects of hyperoxia exist in fields where oxygen is breathed at higher-than-normal partial pressures, including underwater diving using compressed breathing gases, hyperbaric medicine, neonatal care and human spaceflight. these protocols have resulted in the increasing rarity of seizures due to oxygen toxicity, with pulmonary and ocular damage being largely confined to the problems of managing premature infants. in recent years, oxygen has become available for recreational use in oxygen bars. the us food and drug administration has warned those who have conditions such as heart or lung disease not to use oxygen bars. scuba divers use breathing gases containing up to 100% oxygen, and should have specific training in using such gases. classification breathing air with high oxygen pressure can lead to several adverse effects. the effects of oxygen toxicity may be classified by the organs affected, producing three principal forms: central nervous system, characterised by convulsions followed by unconsciousness, occurring under hyperbaric conditions; pulmonary (lungs), characterised by difficulty in breathing and pain within the chest, occurring when breathing increased pressures of oxygen for extended periods; ocular (retinopathic conditions), characterised by alterations to the eyes, occurring when breathing increased pressures of oxygen for extended periods. central nervous system oxygen toxicity can cause seizures, brief periods of rigidity followed by convulsions and unconsciousness, and is of concern to divers who encounter greater than atmospheric pressures. pulmonary oxygen toxicity results in damage to the lungs, causing pain and difficulty in breathing. oxidative damage to the eye may lead to myopia or partial detachment of the retina. pulmonary and ocular damage are most likely to occur when supplemental oxygen is administered as part of a treatment, particularly to newborn infants, but are also a concern during hyperbaric oxygen therapy. oxidative damage may occur in any cell in the body but the effects on the three most susceptible organs will be the primary concern. it may also be implicated in damage to red blood cells (haemolysis), the liver, heart, endocrine glands (adrenal glands, gonads, and thyroid), or kidneys, and general damage to cells. in unusual circumstances, effects on other tissues may be observed: it is suspected that during spaceflight, high oxygen concentrations may contribute to bone damage. hyperoxia can also indirectly cause carbon dioxide narcosis in patients with lung ailments such as chronic obstructive pulmonary disease or with central respiratory depression. hyperventilation of atmospheric air at atmospheric pressures does not cause oxygen toxicity, because sea-level air has a partial pressure of oxygen of 0.21 bar (21 kpa) whereas toxicity does not occur below 0.3 bar (30 kpa). signs and symptoms oxygen poisoning at 90 feet (27 m) in the dry in 36 subjects in order of performance exposure (mins.) num. of subjects symptoms 96 1 prolonged dazzle; severe spasmodic vomiting 60–69 3 severe lip-twitching; euphoria; nausea and vertigo; arm twitch 50–55 4 severe lip-twitching; dazzle; blubbering of lips; fell asleep; dazed 31–35 4 nausea, vertigo, lip-twitching; convulsed 21–30 6 convulsed; drowsiness; severe lip-twitching; epigastric aura; twitch l arm; amnesia 16–20 8 convulsed; vertigo and severe lip twitching; epigastric aura; spasmodic respiration; 11–15 4 inspiratory predominance; lip-twitching and syncope; nausea and confusion 6–10 6 dazed and lip-twitching; paraesthesiae; vertigo; "diaphragmatic spasm"; severe nausea central nervous system central nervous system oxygen toxicity manifests as symptoms such as visual changes (especially tunnel vision), ringing in the ears (tinnitus), nausea, twitching (especially of the face), behavioural changes (irritability, anxiety, confusion), and dizziness. this may be followed by a tonic–clonic seizure consisting of two phases: intense muscle contraction occurs for several seconds (tonic phase); followed by rapid spasms of alternate muscle relaxation and contraction producing convulsive jerking (clonic phase). the seizure ends with a period of unconsciousness (the postictal state). the onset of seizure depends upon the partial pressure of oxygen in the breathing gas and exposure duration. however, exposure time before onset is unpredictable, as tests have shown a wide variation, both amongst individuals, and in the same individual from day to day. in addition, many external factors, such as underwater immersion, exposure to cold, and exercise will decrease the time to onset of central nervous system symptoms. decrease of tolerance is closely linked to retention of carbon dioxide. other factors, such as darkness and caffeine, increase tolerance in test animals, but these effects have not been proven in humans. lungs exposure to oxygen pressures greater than 0.5 bar, such as during diving, oxygen prebreathing prior to flight, or hyperbatic therapy is associated with the onset of pulmonary toxicity symptoms. pulmonary toxicity symptoms result from an inflammation that starts in the airways leading to the lungs and then spreads into the lungs (tracheobronchial tree). the symptoms appear in the upper chest region (substernal and carinal regions). this begins as a mild tickle on inhalation and progresses to frequent coughing. if breathing increased partial pressures of oxygen continues, subjects experience a mild burning on inhalation along with uncontrollable coughing and occasional shortness of breath (dyspnea). physical findings related to pulmonary toxicity have included bubbling sounds heard through a stethoscope (bubbling rales), fever, and increased blood flow to the lining of the nose (hyperaemia of the nasal mucosa).initially, there is an exudative phase that results in pulmonary oedema. an increase in the width of the interstitial space may be seen in histological examination. x-rays of the lungs show little change in the short term, but extended exposure leads to increasing diffuse shadowing throughout both lungs. pulmonary function measurements are reduced, as indicated by a reduction in the amount of air that the lungs can hold (vital capacity) and changes in expiratory function and lung elasticity. lung diffusing capacity decreases leading eventually to hypoxaemia. tests in animals have indicated a variation in tolerance similar to that found in central nervous system toxicity, as well as significant variations between species. when the exposure to oxygen above 0.5 bar (50 kpa) is intermittent, it permits the lungs to recover and delays the onset of toxicity. a similar progression is common to all mammalian species. if death from hypoxaemia has not occurred after exposure for several days a proliferative phase occurs, developing a chronic thickening of the alveolar membrane and a decrement in lung diffusing capacity. these changes are mostly reversible on return to normoxia, but the time required for complete recovery is not known. eyes in premature babies, signs of damage to the eye (retinopathy of prematurity, or rop) are observed via an ophthalmoscope as a demarcation between the vascularised and non-vascularised regions of an infant's retina. the degree of this demarcation is used to designate four stages: (i) the demarcation is a line; (ii) the demarcation becomes a ridge; (iii) growth of new blood vessels occurs around the ridge; (iv) the retina begins to detach from the inner wall of the eye (choroid). causes oxygen toxicity is caused by hyperoxia, exposure to oxygen at partial pressures greater than those to which the body is normally exposed. this occurs in three principal settings: underwater diving, hyperbaric oxygen therapy, and the provision of supplemental oxygen, in critical care, and for long term treatment of chronic disorders, and particularly to premature infants. in each case, the risk factors are markedly different. under normal or reduced ambient pressures, the effects of hyperoxia are initially restricted to the lungs, which are directly exposed, but after prolonged exposure or at hyperbaric pressures, other organs can be at risk. at normal partial pressures of inhaled oxygen, most of the oxygen transported in the blood is carried by haemoglobin, but the amount of dissolved oxygen will increase at partial pressures of arterial oxygen exceeding 100 millimetres of mercury (0.13 bar), when oxyhemoglobin saturation is nearly complete. at higher concentrations the effects of hyperoxia are more widespread in the body tissues beyond the lungs. central nervous system toxicity exposures, from minutes to a few hours, to partial pressures of oxygen above about 1.6 bars (160 kpa)—about eight times normal atmospheric partial pressure—are usually associated with central nervous system oxygen toxicity and are most likely to occur among patients undergoing hyperbaric oxygen therapy and divers. since sea level atmospheric pressure is about 1 bar (100 kpa), central nervous system toxicity can only occur under hyperbaric conditions, where ambient pressure is above normal. divers breathing air at depths beyond 60 m (200 ft) face an increasing risk of an oxygen toxicity "hit" (seizure). divers breathing a gas mixture enriched with oxygen, such as nitrox, similarly increase the risk of a seizure at shallower depths, should they descend below the maximum operating depth accepted for the mixture. cns toxicity is aggravated by a high partial pressure of carbon dioxide, stress, fatigue and cold, all of which are much more likely in diving than in hyperbaric therapy. lung toxicity the curves show typical decrement in lung vital capacity when breathing oxygen. lambertsen concluded in 1987 that 0.5 bar (50 kpa) could be tolerated indefinitely. the lungs and the remainder of the respiratory tract are exposed to the highest concentration of oxygen in the human body and are therefore the first organs to show toxicity. pulmonary toxicity occurs only with exposure to partial pressures of oxygen greater than 0.5 bar (50 kpa), corresponding to an oxygen fraction of 50% at normal atmospheric pressure. the earliest signs of pulmonary toxicity begin with evidence of tracheobronchitis, or inflammation of the upper airways, after an asymptomatic period between 4 and 22 hours at greater than 95% oxygen, with some studies suggesting symptoms usually begin after approximately 14 hours at this level of oxygen. at partial pressures of oxygen of 2 to 3 bar (200 to 300 kpa)—100% oxygen at 2 to 3 times atmospheric pressure—these symptoms may begin as early as 3 hours into exposure to oxygen. experiments on rats breathing oxygen at pressures between 1 and 3 bars (100 and 300 kpa) suggest that pulmonary manifestations of oxygen toxicity may not be the same for normobaric conditions as they are for hyperbaric conditions. evidence of decline in lung function as measured by pulmonary function testing can occur as quickly as 24 hours of continuous exposure to 100% oxygen, with evidence of diffuse alveolar damage and the onset of acute respiratory distress syndrome usually occurring after 48 hours on 100% oxygen. breathing 100% oxygen also eventually leads to collapse of the alveoli (atelectasis), while—at the same partial pressure of oxygen—the presence of significant partial pressures of inert gases, typically nitrogen, will prevent this effect. preterm newborns are known to be at higher risk for bronchopulmonary dysplasia with extended exposure to high concentrations of oxygen. other groups at higher risk for oxygen toxicity are patients