Hyperoxia | |
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Specialty | Emergency Medicine |
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Hyperoxia is the state of being exposed to high levels of oxygen; it may refer to organisms, cells and tissues that are experiencing excessive oxygenation, [1] or to an abnormally high oxygen concentration in an environment (e.g. a body of water).
In medicine, it refers to excessive oxygen in the lungs or other body tissues, and results from raised alveolar oxygen partial pressure ― that is, alveolar oxygen partial pressure greater than that due to breathing air at normal (sea level) atmospheric pressure. This can be caused by breathing air at a pressure above normal or by breathing other gas mixtures with a high oxygen fraction, high ambient pressure or both.
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 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, while hypoxia refers to a state in which oxygen supply is insufficient.[ citation needed ]
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. [2]
Associated with hyperoxia is an increased level of reactive oxygen species (ROS), which are chemically reactive molecules 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 antioxidants to combat reactive molecules, but the protective antioxidant defenses can become depleted by abundant reactive oxygen species, resulting in oxidation of the tissues and organs. [1]
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. [3]
The supplementation of oxygen can lead to oxygen toxicity, 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. [4]
Temporary exposure to high partial pressures of oxygen at greater than atmospheric pressure can lead to CNS toxicity. 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 suggest 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. [4]
Prolonged exposure to higher oxygen levels at atmospheric pressure can lead to pulmonary and ocular toxicity. Symptoms of oxygen toxicity may include disorientation, respiratory problems, myopia, or accelerated development of cataracts. 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. 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, and shortness of breath. If exposure is continued, a fatality may result due to the lack of oxygen. [4]
The supplementation of oxygen has been a common procedure of pre-hospital treatment for many years. Hyperoxia often occurs in controlled medical environments where high concentrations of oxygen are administered, such as during mechanical ventilation or oxygen therapy in intensive care units. The highest risk of hyperoxia is in hyperbaric oxygen therapy, 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. [5] In such settings, it is crucial to regularly monitor PaO2 levels to prevent hyperoxia and its associated complications. [6]
An additional cause of hyperoxia is related to underwater diving with breathing apparatus. Divers breath a mixture of gases 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 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 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. [7]
Oxygen rebreathers 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.
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 ROS caused by hyperoxia. These ROS react with biological tissues and may damage proteins, lipids, and nucleic acids. Antioxidants that normally protect tissues can be overwhelmed by higher levels of ROS, thereby causing oxidative stress. [1]
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. The maximum benefit of oxygen availability is a balance between necessity and toxicity along a continuum. [1]
Cumulative oxygen dose is determined by a combination of exposure time, ambient pressure, and the 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. This is known as low-pressure oxygen poisoning, pulmonary toxicity, or the Lorrain Smith effect. This form of exposure leads to lung airway congestion, pulmonary edema, and atelectasis 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 becomes 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 due to the hemoglobin-oxygen buffer system, with relatively little oxygen 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. [1]
Hyperoxia has also been linked to cellular damage through the induction of apoptosis and necrosis. The overproduction of ROS can disrupt cellular signaling pathways, lead to mitochondrial dysfunction, and trigger inflammatory responses. These effects contribute to the pathogenesis of diseases such as acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). In the central nervous system, high levels of oxygen can cause seizures, which are a significant risk in hyperbaric oxygen therapy if not carefully monitored. [2] Besides, hyperoxia can result in vasoconstriction, particularly affecting cerebral and coronary circulation, potentially leading to adverse outcomes, including increased mortality in critically ill patients. [8]
Further research is ongoing to better understand the long-term impacts of hyperoxia on various organs and systems, as well as to optimize oxygen therapy protocols to minimize these risks while ensuring effective treatment for hypoxic conditions. [2]
Hyperoxia is primarily diagnosed by measuring the partial pressure of oxygen (PaO2) in arterial blood. This method is more accurate than non-invasive measures like the Oxygen Reserve Index (ORI) and oxygen saturation (SpO2), which have shown limited diagnostic accuracy for detecting hyperoxia, particularly in critically ill patients. [9]
The primary diagnostic method for hyperoxia involves measuring the partial pressure of oxygen in arterial blood through arterial blood gas (ABG) analysis. This approach is considered the gold standard for diagnosing hyperoxia, as it accurately assesses PaO2 levels. Normally, PaO2 ranges from 75 to 100 mmHg, with hyperoxia generally being recognized when PaO2 exceeds 100 mmHg.
In addition to PaO2 measurement, non-invasive methods such as the Oxygen Reserve Index (ORI) and oxygen saturation (SpO2) are also used, though their effectiveness is limited. The ORI, despite being non-invasive, has a low correlation with PaO2 and is therefore unreliable for diagnosing hyperoxia. Studies have shown that ORI's ability to detect PaO2 levels greater than 100 mmHg is limited, as indicated by an area under the receiver operating characteristic curve (AUROC) of only 0.567. [9] Similarly, SpO2 measured via pulse oximetry is useful for monitoring oxygen levels, but its diagnostic utility for hyperoxia is constrained because SpO2 readings are capped at 100%. This makes SpO2 more effective for detecting hypoxia rather than hyperoxia.
The management of hyperoxia primarily involves titrating oxygen therapy to avoid excessive oxygen levels while ensuring adequate tissue oxygenation. Clinical guidelines recommend maintaining arterial oxygen saturation (SpO2) within a target range of 88-95% to prevent both hypoxemia and hyperoxemia.
Emerging evidence suggests that prolonged exposure to high oxygen levels, even when clinically indicated, can lead to cellular injury due to oxidative stress. Hyperoxia-induced lung injury, neurological effects, and disruptions in systemic circulation have been observed in certain cases, particularly in patients with preexisting conditions. These risks highlight the importance of constant vigilance in managing oxygen levels, especially in critical care.
Antioxidant therapy may be employed to mitigate the harmful effects of ROS generated during hyperoxia. Additionally, careful monitoring and adjustment of mechanical ventilation settings are crucial in critical care settings to balance oxygen delivery and minimize the risk of oxygen toxicity. Recent studies emphasize the importance of individualized oxygen therapy, considering the patient’s specific clinical condition and response to treatment. [10]
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 or full-face mask protects the airway much more than a demand valve 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 surface orientated diving 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 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, 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.
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Hyperbaric medicine is the medical use of oxygen at a higher pressure level than our atmosphere. [12] Hyperbaric medicine is also known as hyperbaric oxygen therapy. The air we normally breathe is composed of 21 percent oxygen. Hyperbaric treatments utilise 100 percent oxygenated air to treat many conditions. [13]
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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. [2] While adhering to regulations and recommended levels, oxygen levels can be individualised and tailored to the patient's conditions to reduce the risk of hyperoxia. [10]
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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. Long-term oxygen therapy (LTOT) is the treatment proven to improve survival in chronic obstructive pulmonary disease (COPD) patients with chronic respiratory failure. It also appears to reduce the number of hospitalizations, increase effort capacity, and improve health-related quality of life. [14]
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Epidemiologically, hyperoxia primarily centers on its prevalence in clinical settings where patients receive supplemental oxygen, such as intensive care units, neonatal wards, and while receiving anesthesia. It is frequently observed in populations with conditions like COPD, ARDS, and cardiac arrest, where oxygen therapy is routine. Though it is essential for treatment, prolonged exposure to high oxygen levels can lead to harmful oxidative stress, which could potentially lead to complications such as lung damage, retinopathy in neonates, and poor, or worsened neurological outcomes. The occurrence of hyperoxia varies across healthcare systems depending on the rigor of oxygen monitoring and management practices.
Nitrox refers to any gas mixture composed of nitrogen and oxygen that contains less than 78% nitrogen. In the usual application, underwater diving, nitrox is normally distinguished from air and handled differently. The most common use of nitrox mixtures containing oxygen in higher proportions than atmospheric air is in scuba diving, where the reduced partial pressure of nitrogen is advantageous in reducing nitrogen uptake in the body's tissues, thereby extending the practicable underwater dive time by reducing the decompression requirement, or reducing the risk of decompression sickness. The two most common recreational diving nitrox mixes are 32% and 36% oxygen, which have maximum operating depths of about 110 feet and 95 feet (29 meters respectively.
Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level. Hypoxia may be classified as either generalized, affecting the whole body, or local, affecting a region of the body. Although hypoxia is often a pathological condition, variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise.
Decompression sickness is a medical condition caused by dissolved gases emerging from solution as bubbles inside the body tissues during decompression. DCS most commonly occurs during or soon after a decompression ascent from underwater diving, but can also result from other causes of depressurisation, such as emerging from a caisson, decompression from saturation, flying in an unpressurised aircraft at high altitude, and extravehicular activity from spacecraft. DCS and arterial gas embolism are collectively referred to as decompression illness.
Hyperbaric medicine is medical treatment in which an increase in barometric pressure over ambient pressure is employed increasing the partial pressures of all gases present in the ambient atmosphere. The immediate effects include reducing the size of gas embolisms and raising the partial pressures of all gases present according to Henry's law. Currently, there are two types of hyperbaric medicine depending on the gases compressed, hyperbaric air and hyperbaric oxygen.
An air embolism, also known as a gas embolism, is a blood vessel blockage caused by one or more bubbles of air or other gas in the circulatory system. Air can be introduced into the circulation during surgical procedures, lung over-expansion injury, decompression, and a few other causes. In flora, air embolisms may also occur in the xylem of vascular plants, especially when suffering from water stress.
A breathing gas is a mixture of gaseous chemical elements and compounds used for respiration. Air is the most common and only natural breathing gas, but other mixtures of gases, or pure oxygen, are also used in breathing equipment and enclosed habitats. Oxygen is the essential component for any breathing gas. Breathing gases for hyperbaric use have been developed to improve on the performance of ordinary air by reducing the risk of decompression sickness, reducing the duration of decompression, reducing nitrogen narcosis or allowing safer deep diving.
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, 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, and those undergoing hyperbaric oxygen therapy.
Barotrauma is physical damage to body tissues caused by a difference in pressure between a gas space inside, or in contact with, the body and the surrounding gas or liquid. The initial damage is usually due to over-stretching the tissues in tension or shear, either directly by an expansion of the gas in the closed space or by pressure difference hydrostatically transmitted through the tissue. Tissue rupture may be complicated by the introduction of gas into the local tissue or circulation through the initial trauma site, which can cause blockage of circulation at distant sites or interfere with the normal function of an organ by its presence. The term is usually applied when the gas volume involved already exists prior to decompression. Barotrauma can occur during both compression and decompression events.
Oxygen therapy, also referred to as supplemental oxygen, is the use of oxygen as medical treatment. Supplemental oxygen can also refer to the use of oxygen enriched air at altitude. Acute indications for therapy include hypoxemia, carbon monoxide toxicity and cluster headache. It may also be prophylactically given to maintain blood oxygen levels during the induction of anesthesia. Oxygen therapy is often useful in chronic hypoxemia caused by conditions such as severe COPD or cystic fibrosis. Oxygen can be delivered via nasal cannula, face mask, or endotracheal intubation at normal atmospheric pressure, or in a hyperbaric chamber. It can also be given through bypassing the airway, such as in ECMO therapy.
Generalized hypoxia is a medical condition in which the tissues of the body are deprived of the necessary levels of oxygen due to an insufficient supply of oxygen, which may be due to the composition or pressure of the breathing gas, decreased lung ventilation, or respiratory disease, any of which may cause a lower than normal oxygen content in the arterial blood, and consequently a reduced supply of oxygen to all tissues perfused by the arterial blood. This usage is in contradistinction to localized hypoxia, in which only an associated group of tissues, usually with a common blood supply, are affected, usually due to an insufficient or reduced blood supply to those tissues. Generalized hypoxia is also used as a synonym for hypoxic hypoxia This is not to be confused with hypoxemia, which refers to low levels of oxygen in the blood, although the two conditions often occur simultaneously, since a decrease in blood oxygen typically corresponds to a decrease in oxygen in the surrounding tissue. However, hypoxia may be present without hypoxemia, and vice versa, as in the case of infarction. Several other classes of medical hypoxia exist.
Diving medicine, also called undersea and hyperbaric medicine (UHB), is the diagnosis, treatment and prevention of conditions caused by humans entering the undersea environment. It includes the effects on the body of pressure on gases, the diagnosis and treatment of conditions caused by marine hazards and how aspects of a diver's fitness to dive affect the diver's safety. Diving medical practitioners are also expected to be competent in the examination of divers and potential divers to determine fitness to dive.
Diving disorders, or diving related medical conditions, are conditions associated with underwater diving, and include both conditions unique to underwater diving, and those that also occur during other activities. This second group further divides conditions caused by exposure to ambient pressures significantly different from surface atmospheric pressure, and a range of conditions caused by general environment and equipment associated with diving activities.
Freediving blackout, breath-hold blackout, or apnea blackout is a class of hypoxic blackout, a loss of consciousness caused by cerebral hypoxia towards the end of a breath-hold dive, when the swimmer does not necessarily experience an urgent need to breathe and has no other obvious medical condition that might have caused it. It can be provoked by hyperventilating just before a dive, or as a consequence of the pressure reduction on ascent, or a combination of these. Victims are often established practitioners of breath-hold diving, are fit, strong swimmers and have not experienced problems before. Blackout may also be referred to as a syncope or fainting.
Smoke inhalation is the breathing in of harmful fumes through the respiratory tract. This can cause smoke inhalation injury which is damage to the respiratory tract caused by chemical and/or heat exposure, as well as possible systemic toxicity after smoke inhalation. Smoke inhalation can occur from fires of various sources such as residential, vehicle, and wildfires. Morbidity and mortality rates in fire victims with burns are increased in those with smoke inhalation injury. Victims of smoke inhalation injury can present with cough, difficulty breathing, low oxygen saturation, smoke debris and/or burns on the face. Smoke inhalation injury can affect the upper respiratory tract, usually due to heat exposure, or the lower respiratory tract, usually due to exposure to toxic fumes. Initial treatment includes taking the victim away from the fire and smoke, giving 100% oxygen at a high flow through a face mask, and checking the victim for injuries to the body. Treatment for smoke inhalation injury is largely supportive, with varying degrees of consensus on benefits of specific treatments.
Latent hypoxia is a condition where the oxygen content of the lungs and arterial blood is sufficient to maintain consciousness at a raised ambient pressure, but not when the pressure is reduced to normal atmospheric pressure. It usually occurs when a diver at depth has a lung gas and blood oxygen concentration that is sufficient to support consciousness at the pressure at that depth, but would be insufficient at surface pressure. This problem is associated with freediving blackout and the presence of hypoxic breathing gas mixtures in underwater breathing apparatus, particularly in diving rebreathers.
Hyperbaric nursing is a nursing specialty involved in the care of patients receiving hyperbaric oxygen therapy. The National Board of Diving and Hyperbaric Medical Technology offers certification in hyperbaric nursing as a Certified Hyperbaric Registered Nurse (CHRN). The professional nursing organization for hyperbaric nursing is the Baromedical Nurses Association.
The physiology of decompression is the aspect of physiology which is affected by exposure to large changes in ambient pressure. It involves a complex interaction of gas solubility, partial pressures and concentration gradients, diffusion, bulk transport and bubble mechanics in living tissues. Gas is breathed at ambient pressure, and some of this gas dissolves into the blood and other fluids. Inert gas continues to be taken up until the gas dissolved in the tissues is in a state of equilibrium with the gas in the lungs, or the ambient pressure is reduced until the inert gases dissolved in the tissues are at a higher concentration than the equilibrium state, and start diffusing out again.
Human physiology of underwater diving is the physiological influences of the underwater environment on the human diver, and adaptations to operating underwater, both during breath-hold dives and while breathing at ambient pressure from a suitable breathing gas supply. It, therefore, includes the range of physiological effects generally limited to human ambient pressure divers either freediving or using underwater breathing apparatus. Several factors influence the diver, including immersion, exposure to the water, the limitations of breath-hold endurance, variations in ambient pressure, the effects of breathing gases at raised ambient pressure, effects caused by the use of breathing apparatus, and sensory impairment. All of these may affect diver performance and safety.
A built-in breathing system is a source of breathing gas installed in a confined space where an alternative to the ambient gas may be required for medical treatment, emergency use, or to minimise a hazard. They are found in diving chambers, hyperbaric treatment chambers, and submarines.
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