The uses of hyperbaric medicine are growing every day.
Hyperbaric oxygenation involves the delivery of 100 percent oxygen at inspiratory pressures (Pio2) above atmospheric pressure. This can be accomplished in a hyperbaric chamber that allows one patient to be treated at any given time (a monoplace chamber) or in a chamber that allows for more than one patient to be treated at once (a multiplace chamber). No matter which type of chamber is used, the effects of the hyperoxic state are identical. The sole difference lies in the type of gas that is used to pressurize the chamber.
In a monoplace chamber, the patient breathes 100 percent oxygen from the ambient environment at pressures of up to 3 atmospheres absolute (ATA). In a multiplace chamber, the patient breathes air from the ambient environment at pressures of up to 6 ATA and periodically breathes oxygen, through a hood, at a pressure identical to that of the ambient environment. The oxygen is delivered through the hood under hyperbaric conditions. To attain the same amount of total oxygen exposure, patients are required to remain in a multiplace chamber for longer periods of time than in a monoplace chamber (because of the difference in Pio2).
There are two basic effects of hyperbaric oxygenation: its mechanical effect and the effect of an increased Po2. The mechanical effect is predominantly important in reducing gas-bubble size, but it also plays a role in oxygen solubility and in carbon dioxide transport.
Mechanical Effects of Hyperbaric Oxygen
Any collection of gas, whether in a body cavity or in a bubble, is subject to physical change based on ambient pressure. Boyle’s law states that volume is inversely related to pressure. Therefore, if pressure is increased, any given volume will decrease in a progressive manner. This gas law explains the mechanical effect of bubble-size reduction. The largest amount of bubble reduction takes place early in pressurization, with subsequent amounts of reduction decreasing as the pressure increases.
Barotrauma can occur, however, when ambient pressure is increased. Barotrauma can affect any gas-filled cavity. It can result in middle-ear distress syndrome, sinus-cavity squeezing, lung squeezing, or pneumothorax. Each of these barotrauma effects produces pain and, in the case of lung squeezing and pneumothorax, significant hemodynamic compromise.
Gaseous distention of the bowel can be decompressed in the hyperbaric environment, and the pain associated with this distention can also be significantly decreased. In fact, if a patient with bowel distention breathes oxygen over a 2-hour period at 2 ATA, bowel gas will decrease 50 percent.1 When a person has decompression sickness or air-gas embolism, nitrogen-filled bubbles enter the circulation. These bubbles may lodge in a joint space, perineural space, or (in the case of air-gas embolism) a large vessel, causing distal ischemia or anoxia. If this occurs in the central circulation, it can result in hemodynamic or central nervous system compromise. The mechanical effect of bubble reduction can reverse this process. When a gas bubble is exposed to 6 ATA of pressure, its volume decreases 84 percent.2
The mean extraction rate of oxygen in the body is 6 vol percent when a person is exposed to oxygen under hyperbaric conditions (2.8 ATA), the Pao2 approaches 2,000 mm Hg. Since oxygen content is equal to dissolved plus bound oxygen, and dissolved oxygen is equal to Pao2 x 0.003 (0.3 percent total oxygen content), 2,000 mm Hg x 0.003 is equal to 6 vol percent oxygen. This means that the oxygen carried in the plasma is enough to meet the needs of the body. Because of this, the hemoglobin of even venous blood is fully saturated. This has led to the use of hyperbaric oxygenation in the massive anemia of acute blood loss and in patients who have religious beliefs that do not allow emergency transfusion. Boerema et al3 showed, in an animal model, that they could support a massively anemic subject using only dissolved oxygen in plasma. Because the venous blood is fully saturated with oxygen, this can block the circulation’s ability to remove carbon dioxide effectively. Carbon dioxide diffuses much more rapidly than oxygen, however, and the bicarbonate buffering system is adequate under most circumstances, so this decrease in carbon dioxide transport rarely causes a clinical problem. There is only a mild shift of pH to the acidic side. In a patient who already requires the bicarbonate buffering system in order to maintain a normal pH (for example, a chronic carbon dioxide retainer), the ability to maintain normality may be impaired by venous saturation.
Effects of Elevated Po2
Blood flow is reduced to hyperoxic tissues. Several investigators have looked at the effect of oxygen on the vasculature. Bird and Telfer4 looked at limb circulation during hyperbaric (2.4-ATA) oxygen breathing with 100 percent oxygen and found a 20 percent reduction in flow based on vasoconstriction, but felt that the available oxygen dissolved in plasma compensated for this effect. Ohta et all5 found that exposure to 100 percent oxygen at 2 ATA resulted in a decrease in cerebral blood flow as Po2 increased. As the pressure was raised above 2 ATA, the cerebral blood flow decreased further, only to return to normal when the patient went back to 1 ATA. This was felt to be a direct effect of oxygen on the cerebral blood flow’s regulatory system.
When a subject is exposed to hyperbaric oxygenation, cardiac output decreases up to 35 percent and the left ventricular stroke work index decreases up to 30 percent. This is accompanied by an afterload increase of 30 percent to 60 percent.6 Some concerns have been raised about treating decompression sickness in light of these decreases in blood flow and of the change in tone of the vasculature. Since the nitrogen in a bubble is returned to its soluble state when the bubble is reduced in size under pressure, a decrease in blood flow may hinder the gas from exiting the body. Thus far, however, there have been no reports suggesting that decreased perfusion is a problem in nitrogen elimination.
Since hyperbaric oxygen has been shown to decrease blood flow in hyperoxic tissue, there was a concern that this effect might also occur in hypoxic tissues, thus rendering them still more hypoxic. In 1988, Hammarlund et al7 investigated dermal circulation using Doppler flow studies. They found vasoconstriction and decreased flow in the skin in response to oxygen. They also studied a patient with a chronic ischemic leg ulcer. This patient had a decrease in flow at his fingertip, as would be expected, but they saw no change in blood flow at the level of the wound. After treatment with hyperbaric oxygenation, the flow in the area around the wound showed a decrease when exposed to oxygen, just as the fingertip did initially. It is this ability to regulate blood flow that allows hyperbaric oxygen therapy to be useful in wound care. Poorly healing wounds that are ischemic require increased blood flow in order to oxygenate the area better and to improve white blood cell function, as well as to increase collagen turnover. All of these factors help to heal the wound. Once wound healing takes place, the oxygen-dependent flow characteristics then go back to normal.
Collagen is required for appropriate wound healing. In order for fibroblasts to release collagen, they must have an adequate supply of oxygen. Ischemic, poorly healing wounds lack adequate levels of oxygen. When the wound is exposed to the hyperoxic state, that oxygen becomes available and the fibroblasts synthesize and release collagen. The tensile strength of a wound is also an oxygen-dependent process. Without adequate levels of oxygen, the tensile strength of any healing wound is markedly depressed, compromising surface continuity. During the healing process, the empty space within the healing wound requires adequate oxygen to allow for approximation of the wound’s edges.
Another important effect of the elevated Po2 produced by hyperbaric oxygenation is the decrease seen in lipid peroxidation. Lipid peroxidation is thought to be the result of transient ischemic-hypoxic injury. It may also result from noxious or pharmacological effects. Although lipid peroxidation is oxygen dependent, hyperbaric-oxygen–induced hyperoxia has a paradoxical effect on it. When there is an associated oxidative defect, as seen in ischemia-reperfusion injury, hyperbarically induced hyperoxia can lessen the injury caused by lipid peroxidation.
Thom8 showed that carbon monoxide poisoning resulted in lipid peroxidation and ischemia-reperfusion injury. These can cause significant neurological and neuropsychiatric deficits in carbon-monoxide–poisoned animals and humans. By exposing subjects to hyperbarically induced hyperoxia, lipid peroxidation and ischemia-reperfusion injury can be prevented.
Hyperoxia can result in numerous changes to blood cells. It may cause an increase in the ability of red blood cells to deform; this may help them pass through capillaries and narrowed blood vessels. Hyperoxia also causes a decrease in platelet aggregation. This, coupled with the change in shape of red blood cells, can result in a significant alteration in blood flow through diseased blood vessels.9,10 Neutrophils require oxygen for microbial killing. Once the white blood cell phagocytizes a bacterium, there is an oxidative burst that is highly oxygen dependent. The burst requires the conversion of oxygen to free radicals (superoxide dismutase, peroxide, and hydroxyl radicals). The production of these free radicals is directly proportionate to the amount of available oxygen.11
Angiogenesis is the process of new capillary formation. This requires four steps: endothelial cell migration, cell division, capillary endothelial cell enzyme production, and basement membrane matrix production. These are all oxygen-dependent activities, and all become more active in the hyperoxic state.12
Although animal studies have suggested that there is a suppression of the immune response when there is hyperoxia, this has never been proven in human studies. In addition, there have been no studies suggesting that there is an increase in autoimmune function associated with hyperoxia. In fact, one study13 looked at the effects of standard hyperbaric exposure and found no increase or decrease in immune response.
It is the effects of hyperoxia that have led to the successful use of hyperbaric oxygenation for certain illnesses. The indications for use of hyperbaric oxygen therapy can be divided into groups of illnesses that benefit from one or more of these effects. The most important fact to remember is that although the hyperoxic state can lead to several therapeutic effects, there is a fine line separating therapeutic hyperoxia and oxygen toxicity. In considering the use of hyperbaric oxygenation for wound healing, several hyperoxic effects are important. The first is the enhancement of white blood cell function through hyperoxia, along with greater support of the oxidative burst. There is also improved blood flow to hypoxic tissue, creating better oxygen delivery and increasing the production and deposition of collagen. In addition to increasing blood flow in hypoxic tissue, the hyperoxic state also results in angiogenesis, which increases the capillary bed and thereby increases blood flow to the wound.
Current research is focusing on the effects of carbon monoxide on lipid peroxidation. The ability to decrease lipid peroxidation and protect against the effects of oxygen free radicals is important. It may explain why many patients poisoned with carbon monoxide have a better outcome when they are treated with hyperbaric oxygenation.8 There is a randomized study in progress using group sequential design; this study is expected to be completed in approximately 1 year (personal communication: Weaver LK, LDS Hospital, Salt Lake City, May 20, 1998). In addition, the body’s ability to function using dissolved oxygen (not bound oxygen) is another benefit of using hyperbaric oxygenation to treat patients with carbon monoxide poisoning.
Angiogenesis is the main reason that hyperbaric oxygenation is useful in the treatment of osteoradionecrosis. Radiation-induced injury to the bone results in ischemic tissue and a paucity of blood vessels. Through hyperbaric oxygenation, this tissue slowly becomes vascularized; this allows better oxygenation, followed by better wound healing.12 For this reason, hyperbaric oxygenation has become a major part of the treatment of osteoradionecrosis.
In looking at the mechanical effects of hyperbaric oxygenation, the reason that it is an important part of the treatment of air-gas embolism (and the main treatment for decompression sickness) quickly becomes apparent. The mechanical effect of hyperoxia on carbon dioxide transport obviously can become an adverse effect if not carefully watched, however. The ability to meet the body’s daily oxygen requirements using only dissolved oxygen opens an entire new area in which hyperbaric oxygenation can be important.
Craig S. Conoscenti, MD, is chief of hyperbaric medicine and senior attending physician, pulmonary and critical care medicine, at Norwalk (Conn) Hospital.
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