Гипероксия: причины, последствия и токсичность кислорода.

Exposure of tissues to abnormally high concentrations of oxygen. Hyperoxia occurs when cells, tissues and organs are exposed to an excess supply of oxygen (O2) or higher than normal partial pressure of oxygen. 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 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, 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.

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. 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. An additional cause of hyperoxia is related to underwater diving 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 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. 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 reactive oxygen species (ROS) caused by hyperoxia. These ROS react with biological tissues, and may damage proteins, lipids, and nucleic acids. Antioxidants normally protecting the tissues can be overwhelmed by higher levels of ROS, thereby causing oxidative stress. The use of non invasive measures like the Oxygen Reserve Index (ORI) and oxygen saturation (SpO2) have shown limited diagnostic accuracy for detecting hyperoxia in critically ill patients.

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 (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 and perfusion. 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.

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 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, 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.

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.