|
|
|
|
Oxygen toxicity
|
| |
|
| |
Oxygen toxicity is a condition resulting from the harmful effects of breathing molecular oxygen at elevated partial pressures. It is also known as oxygen toxicity syndrome, oxygen intoxication, hyperoxia, or the Paul Bert effect and Lorrain Smith effect, after the researchers who pioneered its discovery and description in the late 19th century. Severe oxygen toxicity can result in cell damage and death.
Discussion
Ask a question about 'Oxygen toxicity' Start a new discussion about 'Oxygen toxicity' Answer questions from other users |
Encyclopedia
Oxygen toxicity is a condition resulting from the harmful effects of breathing molecular oxygen at elevated partial pressures. It is also known as oxygen toxicity syndrome, oxygen intoxication, hyperoxia, or the Paul Bert effect and Lorrain Smith effect, after the researchers who pioneered its discovery and description in the late 19th century. Severe oxygen toxicity can result in cell damage and death. Effects are most often observed as damage to the central nervous system, lungs and eye. Oxygen toxicity is a concern for scuba divers, premature babies on supplemental oxygen, and astronauts.
The result of breathing elevated concentrations of oxygen is hyperoxia, an excess of oxygen in body tissues. Depending on the type of exposure the body is impacted in different ways. Central nervous system toxicity is caused by short exposure to high concentrations of oxygen at greater than atmospheric pressure. Pulmonary and ocular toxicity result from longer exposure to elevated oxygen levels at normal pressure. Symptoms include disorientation, breathing difficulty and vision changes. Serious incidents can cause oxidation damage to cell membranes, collapse of the alveoli in the lungs, myopia, retinal detachment, and seizures. Oxygen toxicity is treated by reducing the exposure to elevated oxygen levels. Studies show that the long term recovery from most types of oxygen toxicity is good.
Prevention of oxygen toxicity is an important precaution whenever oxygen is breathed at greater than normal partial pressures, and has led to use of protocols for avoidance of hyperoxia in such fields as diving, hyperbaric therapy, neonatal care and human spaceflight. This has resulted in oxygen toxicity seizures becoming increasingly rare, with pulmonary and ocular damage being mainly confined to the problems of managing premature infants.
Classification
The effects of oxygen toxicity are commonly classified by the organs affected.
There are three principal types of oxygen toxicity:
- Central nervous system (CNS), 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 elevated pressures of oxygen for extended periods;
- Ocular (retinopathic conditions), characterised by alterations to the eye, occurring when breathing elevated pressures of oxygen for extended periods.
Central nervous system oxygen toxicity can cause a seizure, a brief period 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 (HBOT).
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 red blood cell destruction (hemolysis), liver (hepatic) effects, heart (myocardial) damage, endocrine effects (adrenal, gonads, and thyroid), kidney (renal) damage, 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 chronic obstructive pulmonary disease (COPD). Oxygen toxicity is not associated with hyperventilation, because breathing air at atmospheric pressure always has a partial pressure of oxygen (ppO2) of and the lower limit for toxicity is more than .
Signs and symptoms
Central nervous system (CNS) oxygen toxicity manifests as symptoms such as visual changes (especially tunnel vision), ringing in the ears (tinnitus), 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). 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. In addition, many external factors, such as underwater immersion, exposure to cold, and exercise will decrease the time to onset of CNS symptoms.
Decrease of tolerance has been shown to be 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.
Pulmonary toxicity symptoms result from an inflammation of the airways leading to and within the lungs (tracheobronchitis) which appears in the upper chest region (substernal and carinal) and spreads to the remaining area of the lungs (tracheobronchial tree).
This begins as a mild tickle on inhalation and progresses into frequent coughing. If oxygen breathing is not discontinued, patients will have 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 (hyperemia of the nasal mucosa). The radiological finding from the lungs show inflammation and swelling (pulmonary edema). Pulmonary function measurements are reduced as noted by the reduction in vital capacity and change in expiratory function and lung elasticity. Tests in animals have indicated a variation in tolerance similar to that found in CNS toxicity, as well as significant variations between species. When the exposure to oxygen above is intermittent, it permits the lungs to recover and delays the onset of toxicity.
The signs of retinopathy of prematurity (ROP) are observed (via an opthalmoscope) 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
CNS toxicity
Short exposures (from minutes to a few hours) to partial pressure of oxygen above (about 8 times the atmospheric concentration) are usually associated with central nervous system (CNS) oxygen toxicity and are most likely to occur among patients undergoing hyperbaric oxygen therapy (HBOT) and divers. Since atmospheric pressure is about , CNS toxicity can only occur under hyperbaric conditions, where ambient pressure is above normal.
Divers breathing air at depths greater than 60 metres (200 feet) face a risk of an oxygen toxicity "hit" (seizure). Divers using a gas mixture enriched with oxygen (nitrox) who descend below the maximum depth allowed for the mixture can similarly suffer a CNS seizure at lesser depths.
Pulmonary toxicity
The lungs have a very large area in contact with the breathing gas and contain thin membranes with limited antioxidant defenses, making them particularly susceptible to damage by oxygen. Pulmonary toxicity occurs with prolonged exposure of 16–24 hours or more to elevated concentrations of oxygen greater than 50%. Pulmonary manifestations of oxygen toxicity are not the same for normobaric conditions as they are for hyperbaric conditions.
The risk of bronchopulmonary dysplasia ("BPD") in infants, or acute respiratory distress syndrome (ARDS) in adults, begins to increase with exposure for over 16 hours to oxygen partial pressures (ppO2) of or more.
At sea-level, 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 (normal ppO2 at sea level) and 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 oxygen fractions above 50%.
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, typically nitrogen, will prevent this effect.
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.
Ocular toxicity
Prolonged exposure to high inspired fractions of oxygen causes damage to the retina.
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.
Hyperoxia may be a contributing factor for the disorder called retrolental fibroplasia or retinopathy of prematurity (ROP) in infants.
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.
Hyperoxic myopia has occurred in closed circuit oxygen rebreather divers with prolonged exposures.
This is 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.
Mechanism
A high concentration of oxygen damages cells.
Higher than normal concentrations lead to increased levels of reactive oxygen species (ROS), and while not all mechanisms of damage are understood, the process of lipid peroxidation is known to cause damage to cell membranes.
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.
One example 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.
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).
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. Cell damage and cell death then result.
Diagnosis
Diagnosis of central nervous system (CNS) oxygen toxicity in divers prior to seizure is difficult as the symptoms of visual disturbance, ear problems, dizziness, confusion and nausea can be due to many factors common to the underwater environment such as narcosis, congestion and coldness. However, these symptoms may be helpful in diagnosing the first stages of oxygen toxicity in patients undergoing hyperbaric oxygen therapy. In either case, unless there is a prior history of epilepsy or tests indicate hypoglycemia, a seizure occurring while breathing oxygen at partial pressures greater than will be diagnosed as oxygen toxicity by exclusion.
Diagnosis of bronchopulmonary dysplasia (BPD) in new-born infants with breathing difficulties is difficult in the first few weeks. However, if the infant's breathing does not improve during this time, blood tests and x-rays may be used to confirm BPD. In addition, an echocardiogram can help to eliminate other possible causes such as congenital heart defects or pulmonary arterial hypertension.
The diagnosis of retinopathy of prematurity (ROP) in infants is typically suggested by the clinical setting. Prematurity, low birth weight and a history of oxygen exposure are the principal indicators, while no hereditary factors have been shown to yield a pattern.
Prevention
A seizure caused by central nervous system (CNS) oxygen toxicity is a deadly but entirely avoidable event while diving. The diver may experience no warning symptoms. The effects are sudden convulsions and unconsciousness, during which victims can lose their regulator and drown. One of the advantages of a full-face diving mask is to prevent losing the regulator in the event of a seizure. As there is an increased risk of CNS oxygen toxicity on deep dives, long dives and dives where oxygen-rich breathing gases are used, divers are taught to calculate a maximum operating depth for oxygen-rich breathing gases; and cylinders containing such mixtures must be clearly marked with that depth.
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. 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. For the following partial pressures of oxygen the limit is: 45 minutes at , 120 minutes at , 150 minutes at , 180 minutes at and 210 minutes at , but is impossible to predict with any reliability whether or when CNS symptoms will occur.
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.
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.
Bronchopulmonary dysplasia (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. One or two days of exposure without "oxygen breaks" are needed to cause such damage.
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 modern pure oxygen use in spacesuits, which must operate at low pressure (also historically, very high percentage oxygen and lower than normal atmospheric pressure was used in early spacecraft, for example, the Gemini and Apollo spacecraft).
In such applications as extra-vehicular activity (EVA), high-fraction oxygen is non-toxic, even at breathing mixture fractions approaching 100%, because the oxygen partial pressure is not allowed to chronically exceed .
Vitamin E and selenium were proposed and later rejected as a potential method of protection against pulmonary oxygen toxicity.
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.
Management
Treatment of seizures during oxygen therapy consists of removing the patient from oxygen, thereby dropping the partial pressure of oxygen delivered. A seizure underwater requires that the diver is brought to the surface as soon as practicable. The buddy will ensure that the victim's air supply is established and maintained, then carry out a controlled buoyant lift. The buddy will need to ensure their own safety is not compromised during the convulsive phase, but lifting an unconscious body is taught by most diver training agencies. Upon reaching the surface, emergency services should be contacted as there is a possibility of further complications requiring medical attention.
The occurrence of symptoms of bronchopulmonary dysplasia (BPD) or acute respiratory distress syndrome (ARDS) is treated by lowering the fraction of oxygen administered, along with a reduction in the periods of exposure and an increase in the break periods where normal air is supplied. Where supplemental oxygen is required for treatment of another disease (particularly in infants), a ventilator may be needed to ensure that the lung tissue remains inflated. Reductions in pressure and exposure will be made progressively and medications such as bronchodilators and pulmonary surfactants may be used.
Retinopathy of prematurity (ROP) may regress spontaneously, but should the disease progress beyond a threshold (defined as five contiguous or eight cumulative hours of stage 3 ROP), both cryosurgery and laser surgery have been shown to reduce the risk of blindness as an outcome. Where the disease has progressed further, techniques such as scleral buckling and vitrectomy surgery may assist in re-attaching the retina.
Prognosis
Although the convulsions caused by central nervous system (CNS) oxygen toxicity may lead to incidental injury to the victim, it remained uncertain for many years whether damage to the nervous system following the seizure could occur and several studies searched for evidence of such damage. An overview of these studies by Bitterman in 2004 concluded that following removal of breathing gas containing high fractions of oxygen, no long-term neurological damage from the seizure remains.
The majority of infants who have survived following an incidence of bronchopulmonary dysplasia (BPD) will eventually recover near-normal lung function, since lungs continue to grow during the first 5–7 years and the damage caused by BPD is to some extent reversible (even in adults). However, they are likely be more susceptible to respiratory infections for the rest of their lives and the severity of later infections is often greater than that in their peers.
Retinopathy of prematurity (ROP) in infants frequently regresses without intervention and eyesight may be normal in later years. Where the disease has progressed to the stages requiring surgery, the outcomes are generally good for the treatment of stage 3 ROP, but are much worse for the later stages. Although surgery is usually successful in restoring the anatomy of the eye, damage to the nervous system by the progression of the disease leads to comparatively poorer results in restoring vision. The presence of other complicating diseases also reduces the likelihood of a favourable outcome.
Epidemiology
The incidence of central nervous system (CNS) toxicity among divers has decreased since the Second World War, as protocols have developed to limit exposure and partial pressure of oxygen inspired. In 1947, Donald recommended limiting the depth breathing pure oxygen to , or a ppO2 of . This limit has been reduced until today a limit of during a recreational dive and during shallow decompression stops is accepted: oxygen toxicity has become a rare occurrence other than when caused by equipment malfunction and human error. Historically, the U.S. Navy has refined its Navy Diving Manual Tables to reduce oxygen toxicity incidents. Between 1995 and 1999, reports showed 405 surface-supported dives using the helium-oxygen tables; of these, oxygen toxicity symptoms were observed on 6 dives (1.5%). As a result, the U.S. Navy in 2000 modified the schedules and conducted field tests of 150 dives, none of which produced symptoms of oxygen toxicity. Revised tables were published in 2001.
The variability in tolerance and other variable factors such as workload have resulted in the U.S. Navy abandoning screening for oxygen tolerance. Of the 6,250 oxygen-tolerance tests performed between 1976 and 1997, only 6 episodes of oxygen toxicity were observed (0.1%).
The incidence of CNS oxygen toxicity among patients undergoing hyperbaric oxygen therapy is rare and influenced by a number of a factors: individual sensitivity and treatment protocol; and probably therapy indication and equipment used. A study by Welslau in 1996 reported 16 incidents out of a population of 107,264 patients (0.015%), while Hampson and Atik in 2003 found a rate of 0.03%. Yildiz, Ay and Qyrdedi, in a summary of 36,500 patient treatments between 1996 and 2003, reported only 3 oxygen toxicity incidents, giving a rate of 0.008%.
Bronchopulmonary dysplasia (BPD) is among the most common complications of prematurely born infants and its incidence has grown as the survival of extremely premature infants has increased. Nevertheless, the severity has decreased as better management of supplemental oxygen has resulted in the disease now being related mainly to factors other than hyperoxia.
In 1997 a summary of studies of neonatal intensive care units in industrialised countries showed that up to 60% of low birth weight babies develop retinopathy of prematurity (ROP) , which rises to 72% in extremely low birth weight babies, i.e. less than 1 kilogram (2.2 pounds) at birth. However, severe outcomes are much less frequent: for very low birth weight babies (defined as less than at birth), the incidence of blindness was found to be no more than 8%.
History
Central nervous system (CNS) toxicity was first described by Paul Bert in 1878.
He showed that oxygen was toxic to insects, arachnids, myriapods, molluscs, earthworms, fungi, germinating seeds, birds, and other animals. CNS toxicity may be referred to as the "Paul Bert effect".
Pulmonary oxygen toxicity was first described by J. Lorrain Smith in 1899 when he noted CNS toxicity and discovered in experiments in mice and birds that had no effect but of oxygen was a pulmonary irritant.
Pulmonary toxicity may be referred to as the "Lorrain Smith effect"
The first recorded human exposure was undertaken in 1910 by Bornstein when two men breathed oxygen at for 30 minutes while he went on to 48 minutes with no symptoms.
In 1912, Bornstein developed cramps in his hands and legs while breathing oxygen at for 51 minutes.
Smith then went on to show that intermittent exposure to a breathing gas with less oxygen permitted the lungs to recover and delayed the onset of pulmonary toxicity.
Behnke et al. in 1935 were the first to observe visual field contraction (tunnel vision) on dives between and .
During World War II, Donald and Yarbrough et al. performed over 2,000 experiments on oxygen toxicity to support the initial use of closed circuit oxygen rebreathers.
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".
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.
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.
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.
Retinopathy of prematurity (ROP) was not observed prior to World War II, but with the availability of supplemental oxygen in the decade following, it rapidly became one of the principal causes of infant blindness in developed countries. By 1960 the use of oxygen had become identified as a risk factor and its administration restricted. The resulting fall in ROP was accompanied by a rise in infant mortality and hypoxia-related complications. Since then, more sophisticated monitoring and diagnosis has established protocols for oxygen use which aim to balance between hypoxic conditions and problems of ROP.
Bronchopulmonary dysplasia (BPD) was first described by Northway in 1967, who outlined the conditions that would lead to the diagnosis.
This was later expanded by Bancalari and in 1988 by Shennan, who suggested the need for supplemental oxygen at 36 weeks could predict long-term outcomes.
Nevertheless, Palta et al in 1998 concluded that radiographic evidence was the most accurate predictor of long-term effects.
Bitterman et al. in 1986 and 1995 showed that darkness and caffeine will delay the onset of changes to brain electrical activity in rats.
In the years since, research on CNS toxicity has centered around methods of prevention and safe extension of tolerance.
These include topics such as circadian rhythm, drugs, age, and gender that have been shown to contribute to CNS oxygen toxicity sensitivity.
In 1988, Hamilton et al. wrote procedures for the National Oceanic and Atmospheric Administration (NOAA) to establish oxygen exposure limits for habitat operations.
Even today, models for the prediction of pulmonary oxygen toxicity do not explain all the results of exposure to high partial pressures of oxygen.
Society and culture
Recreational divers who use breathing mixtures with oxygen fractions greater than air have to be trained in the potential dangers of oxygen toxicity and how to prevent them. In order to buy nitrox, a diver has to show evidence of a nitrox qualification.
Since the late 1990s the recreational use of oxygen has been promoted by oxygen bars, where customers breathe air enriched to less than 50% oxygen. Claims have been made that this reduces stress, increases energy, and lessens the effects of hangovers and headaches, despite the lack of any scientific evidence to support them.
There are also devices on sale that offer "oxygen massage" and "oxygen detoxification" with claims of removing body toxins and reducing body fat.
The American Lung Association has stated "there is no evidence that oxygen at the low flow levels used in bars can be dangerous to a normal person's health", but the U.S. Center for Drug Evaluation and Research (CDER) cautions that people with heart or lung disease need their supplementary oxygen carefully regulated and should not use oxygen bars.
Bibliography
External links
General
The following external site is a compendium of resources:
- . - Online collection of the oxygen toxicity research
Specialised
The following external sites contain resources specific to particular topics:
- An explanation of calculations for the "Oxygen clock" with programming examples.
- . - Video of "Oxygen Toxicity" lecture by Dr. Richard Vann (free download, mp4, 86MB).
. - Wide and detailed discussion of the effects of breathing oxygen on the respiratory system.
- Concise clinical overview with extensive references.
|
| |
|
|
