Hyperbaric Oxygen Therapy

Hyperbaric oxygen therapy - technical


Hyperbaric oxygen therapy (HBOT) is the use of oxygen at increased atmospheric pressure. The history of hyperbaric oxygen therapy can be traced back to the late seventeenth century, when Henshaw treated patients in a pressurized chamber. Initially, patients were treated with pressurized air. In 1955, the modern era of hyperbaric oxygen therapy was born.

Today, patients are treated in either monoplace chambers or multiplace chambers. The pressurized oxygen exerts its effects by several different mechanisms, including creating a diffusion gradient for inert gases, oxygenating ischemic tissues, limiting reperfusion injuries, inactivating certain toxins, and supporting angiogenesis and leukocyte function.

There are 13 indications for which scientific evidence supports the use of hyperbaric oxygen therapy: arterial gas embolism; decompression sickness; carbon monoxide poisoning; clostridial myonecrosis; crush injuries, compartment syndrome, and other acute ischemias; enhancement of healing in selected problem wounds; exceptional blood loss anemia; intra-cranial abscess; necrotizing soft tissue infections; refractory osteomyelitis; delayed radiation injury; preservation of skin grafts and flaps; and thermal burns.


Using hyperbaric therapy for treatment of multiple disorders dates back to 1662, when Reverend Henshaw used a pressurized chamber for therapeutic purposes. In 1889, a British engineer, Ernest Moir, became the first person to treat decompression sickness (DCS) with recompression. When he took over as the super-intendent of the Hudson River tunnel project, workers had a 25% mortality rate from DCS. After he installed a recompression chamber at the work site, the mortality rate from DCS declined to 1.7%.

In 1955, Ite Boerema, from the University of Amsterdam, performed an experiment using hyperbaric oxygen to keep exsanguinated pigs alive by the oxygen dissolved in plasma alone. At the same time, W H Brummelkamp at the University of Amsterdam discovered that hyperbaric oxygen could be used to inhibit anaerobic infections. In Scotland, studies suggested that hyperbaric oxygen was beneficial in the treatment of carbon monoxide poisoning in humans. There are 13 indications for the use of hyperbaric oxygen therapy (HBOT) which are backed by scientific evidence.

HBOT consists of treating a patient with 100% oxygen at pressures above 1.4 atm absolute (4m of seawater) in a hyperbaric chamber. The oxygen is delivered to the patient by inhalation. There are two types of chambers in which patients are treated: monoplace and multiplace. They (Figure 1) are used to treat a single patient. They are pressurized with oxygen or air, and attendants do not have to go into the chamber with the patient. Mono-place chambers are less expensive than multiplace chambers, and they require less operating space.

Multiplace chambers (Figure 2) are larger and used to treat multiple patients simultaneously. These chambers are pressurized with air, and oxygen is delivered to the patients via plastic hoods or face masks. Multiplace chambers have the advantage of treating multiple patients at a single time. Also, critically ill patients can be treated with a nurse and other support personnel in the chamber.

Hyperbaric oxygenation has two primary mechanisms of action that are the basis of its use: the mechanical effect and the effect of an increased partial pressure of oxygen. The mechanical effects of pressure shrink gas bubbles and gas-filled spaces in the body following Boyle’s law (volume is inversely proportional to absolute pressure).

There are multiple other physiologic effects that supernormal partial pressures of oxygen exert on the body. These benefits include angiogenesis, fibroblast growth and collagen production, improved osteoclast function, enhanced removal of carbon monoxide (CO) from hemoglobin, inhibition of a-toxin production in clostridial myonecrosis, improved leukocyte killing, decreased neutrophil adherence to capillary walls, increased production of superoxide dismutase, and vasoconstriction in normal vessels. These effects are the physiologic rationale for the use of HBOT in the conditions discussed next.

Indications for Hyperbaric Oxygen Therapy

Gas Embolism

A gas embolism occurs from any number of mechanisms, including mechanical ventilation, penetrating chest trauma, chest tube placement, bronchoscopy, and pulmonary barotrauma from scuba diving. Gas bubbles enter the arteries or veins and cause a number of different symptoms, including loss of consciousness, altered mental status, focal neurological deficits, hypotension, pulmonary edema, or cardiac arrhythmias including cardiac arrest. A patient who exhibits neurologic symptoms or cardiac symptoms from a gas embolism should be treated with HBOT.

First, HBOT exerts a mechanical effect on bubble size with recompression. As the pressure in the chamber increases, the bubble size will decrease. Second, the increased amount of oxygen in the blood creates a diffusion gradient to help further reduce the size of the bubbles. Third, HBOT inhibits neutrophil adherence to capillary walls, reducing the inflammatory response caused by damage to the endothelium from the presence of a gas bubble. Finally, the increased oxygen carried by the plasma may help oxygenate partially ischemic tissues.

Decompression Sickness

Decompression sickness (DCS) encompasses a myriad of syndromes caused by bubbles of inert gas that are generated from rapid decompression during ascent from diving, flying, or in a hyperbaric or hypobaric chamber. When these bubbles occur in large enough numbers to cause pain or impede normal organ function, symptoms of DCS arise. As with gas embolism, the treatment for DCS is HBOT. The mechanism of action of HBOT is the same as for gas embolism.

Carbon Monoxide Poisoning

Carbon monoxide (CO) is a colorless, odorless, and tasteless gas that is a leading cause of injury and death from poisoning worldwide. Patients who suffer from CO poisoning can present with tachycardia, tachypnea, chest pain, headache, altered mental status, seizures, amnesia, or peripheral neuropathy. Laboratory abnormalities include elevated carboxyhemoglobin levels and a metabolic acidosis. There are five randomized clinical trials in the literature using HBOT in patients with CO poisoning.

Although there have been contradictory results from these studies, the best was done by Weaver and coworkers and was published in 2002. This study showed a statistically significant reduction in neuropsychological sequelae in patients treated with HBOT. Patients with evidence of metabolic acidosis, ischemic chest pain and/or electrocardiographic evidence of ischemia, abnormal psychometric testing, history of unconsciousness, carboxyhemoglobin level greater than 15% in a pregnant patient (because of increased binding of CO to fetal hemoglobin), or a carboxyhemoglobin level greater than 40% should be treated with HBOT.

HBOT benefits the CO-poisoned patient by decreasing the half-life of carboxyhemoglobin from more than 300 minutes breathing room air to 23 minutes breathing 100% oxygen at 3 atm absolute (ATA). The half-life of carboxyhemoglobin remains 90 minutes if breathing 100% oxygen at sea level. Also, CO has been shown to inhibit cellular oxidative metabolism by binding to cytochrome c oxidase. HBOT at 3 ATA has been shown to expedite the dissociation of CO from cytochrome c oxidase, thereby allowing the process of oxidative phosphorylation to return to normal. Other benefits of HBOT in CO poisoning are the prevention of lipid peroxidation of the cell membrane and prevention of the adherence of neutrophils to the vascular endothelium by inhibiting the b2 integrin system.

Clostridial Myonecrosis

Clostridial myonecrosis is a severe, life-threatening infection caused by anaerobic, spore-forming, grampositive, encapsulated bacilli of the genus Clostridium. These infections are rapidly progressive and treatment involves the combined use of surgery, antibiotics, and HBOT. HBOT has been shown to be bacteriostatic to clostridia in vivo and in vitro by the formation of oxygen free radicals. The clostridia organisms have no free radical-degrading enzymes, such as superoxide dismutases, catalases, and peroxidases, thereby making them susceptible to the oxygen free radicals produced during HBOT. Also, it has been shown that oxygen tensions of 250mmHg, which can be achieved on 100% oxygen at 3 ATA, inhibit the production of a-toxin, which is one of the main hemolytic and tissue-necrotizing toxins produced by the clostridial organisms.

Necrotizing Soft Tissue Infections

Necrotizing soft tissue infections are an increasing problem in current medical practice. These infections are caused by aerobic or anaerobic bacteria, but most commonly they are caused by mixed bacterial flora. Often, hosts are immunocompromised, contributing to the rapid spread of the infection. Necrotizing infections are hypoxic and an occlusive endarteritis caused by the infection contributes to the wound hypoxia. There are a limited number of neutrophils at the wound site due to intravascular sequestration of the polymorphonuclear leukocytes (PMNs).

The PMNs that are present function poorly due to hypoxia and a decreased oxidation–reduction potential (Eh) from the accumulation of metabolic products from the aerobic organisms. HBOT is recommended as an adjunct to surgical debridement and antibiotics. With HBOT, there is increased tissue oxygenation, which inhibits anaerobic bacteria growth by direct toxic mechanisms and by improving the Eh as well. Also, with improved tissue oxygenation, PMN function improves. Patients are treated twice a day until the infection is controlled and then daily until no further debridement is required.

Crush Injury and Other Acute Traumatic Peripheral Ischemias

Traumatic injury causes a wound with damaged blood vessels. Tissue ischemia and a hypoxic wound environment can then ensue. This hypoxic wound environment causes increasing edema, which contributes to a vicious cycle of wound ischemia and edema. Several surgical and orthopedic conditions have this pathophysiology: crush injuries, compartment syndromes, threatened grafts and flaps, threatened replantations, burns, and frostbitten extremities.

As such, HBOT is used as an adjunct for the treatment of these conditions. Initially, HBOT will provide oxygen to hypoxic tissues. PMN function is improved, fibroblast migration and proliferation improve, collagen is laid down, and neovascularization proceeds because tissue oxygen tensions are increased due to HBOT. Another benefit of HBOT is edema reduction. Hyperoxygenation during HBOT causes vasoconstriction, which has been shown to reduce blood flow by 20%. Venous outflow continues unabated, so there is an overall edema reduction.

Oxygen delivery to tissues is unaffected by vasoconstriction because of the hyperoxygenation from HBOT. Finally, HBOT limits the reperfusion injury by preventing lipid peroxidation of the cell membrane; antagonizing the b2 integrin system, thereby inhibiting the sequestration of neutrophils to the vascular endothelium; and providing additional oxygen for reperfused tissues to generate scavengers such as superoxide dismutase, catalase, peroxidase, and glutathione.

Enhancement of Healing in Selected Problem Wounds

Problem wounds can result in significant morbidity and mortality, and they represent an increasing burden on the healthcare system as the population ages. Diabetic ulcers are an example of problem wounds that are difficult to heal by conventional methods. These wounds are hypoxic due to the small vessel disease caused by diabetes. Since wound healing has been shown to be oxygen-dependent, these hypoxic wounds heal, if at all, at a much slower rate. The processes that contribute to wound healing, such as fibroblast replication, collagen placement, angiogenesis, intracellular leukocyte bacterial destruction, and infection resistance, are all reliant upon oxygen. This is why hypoxic wounds may not heal. HBOT increases tissue oxygenation, thereby reversing the effects of the hypoxic wound environment.

Exceptional Anemia

Occasionally, a profoundly anemic patient will be unable to be transfused with packed red blood cells either because of religious objections or because the patient cannot be cross-matched. If the patient’s hemoglobin is so low that oxygen delivery is insufficient to offset the basic metabolic demands of the body, then oxygen debt will accumulate. As oxygen debt increases, signs of end-organ failure develop. HBOT is a method that repays the accumulated oxygen debt. The patient can be treated with frequent HBO treatments until blood becomes available or the patient produces sufficient hemoglobin.

Intracranial Abscesses

Intracranial abscesses encompass several disorders: cerebral abscess, subdural empyema, and epidural empyema. HBOT is recommended as an adjunct to antibiotics and surgical debridement. Benefits of HBOT in these disorders include high concentrations of oxygen in brain tissue that inhibit the mainly anaerobic organisms that cause intracranial abscesses, decreased edema around the abscess site by mechanisms mentioned previously, and improved leukocyte function.

Refractory Osteomyelitis

Patients suffering from refractory osteomyelitis (i.e., osteomyelitis that does not respond or reoccurs after appropriate antibiotics and surgical debridement) usually have systemic problems or local wound factors that inhibit their ability to heal these infections. HBOT is an adjunct to systemic antibiotics and surgical debridement. The benefits of HBOT include enhancement of osteogenesis by improving the oxygen- dependent osteoclast function of removing necrotic bone.

Additionally, PMNs destroy bacteria by improved oxidative killing when oxygen tensions in the infected bone are raised to normal or supernormal levels. Studies have also shown that aminoglycoside transport across the bacteria cell wall is oxygendependent. HBOT improves aminoglycoside efficacy in hypoxic wound environments by improving delivery of the antibiotic across the bacterial cell wall. Finally, HBOT reduces tissue edema, limits the inflammatory response, and promotes neovascularization and wound healing, as described previously.

Delayed Radiation Injuries

Delayed radiation injury leads to progressive endarteritis that results in tissue hypoxia and secondary fibrosis. Once the oxygen demand of the tissues outstrips oxygen supply, tissue breakdown occurs. The most common delayed radiation injuries that benefit from HBOT are prevention of osteoradionecrosis of the mandible in patients requiring dental work following radiation to the oropharynx, treatment of radiation cystitis, and treatment of radiation proctitis. HBOT promotes angiogenesis, which leads to increased cellularity in irradiated tissues. Studies have shown that HBOT can return to radiated tissue 80% of the capillary density of nonradiated tissue.

Contraindications and Side Effects

Hyperbaric oxygen therapy is very safe and there are few contraindications to therapy. The major absolute contraindication to HBOT is an untreated pneumothorax because it could progress to a tension pneumothorax during the ascent phase of a treatment when gas volume will expand due to the decrease in barometric pressure.

Relative contraindications include pregnancy because of unknown risks to the fetus, chronic sinusitis because of the risk of sinus barotrauma, emphysema with CO2 retention because these patients may lose their stimulus to breath, high fever because this can predispose the patient to seizures from oxygen toxicity, a history of spontaneous pneumothorax because of the risk of recurrent pneumothorax, a seizure disorder because of the risk of oxygen-induced seizures, or a history of middle ear surgery because otic barotrauma could damage the repaired structures.

Several medications are contraindicated in HBOT, including doxorubicin due to cardiac toxicity, bleomycin due to pulmonary toxicity, cis-platinum due to problems with wound healing, disulfiram, and sulfamylon.

The most common side effect of HBOT is barotrauma of the middle ear. This occurs in 2% of patients and is a result of eustachian tube dysfunction or an inability to properly perform the Valsalva maneuver. Disruption of the round window is a rare consequence of HBOT and results from a forceful Valsalva maneuver.

Sinus squeeze is another form of barotrauma that results from the expansion of trapped gases in the sinuses on ascent. Another side effect of treatment is a temporary refractive change. These changes typically occur after numerous treatments and consist of progressive myopia. It is theorized that the changes are due to oxygen uptake by the lens. Claustrophobia may result from the patient being treated in a relatively small enclosed space. These symptoms can be treated with anxiolytics.

Oxygen toxicity causes effects in the central nervous system (CNS) and pulmonary systems. The manifestation of CNS oxygen toxicity is seizures.

Oxygen toxicity seizures have an incidence of 1 in 10,000 treatments at 2.4 ATA.

Pulmonary oxygen toxicity is another possible side effect. The symptoms are substernal chest pain, dry cough, and a decrease in vital capacity.

Finally, there is a theoretical risk of pneumothorax and arterial gas embolism if the patient were to have trapping of gas in his or her lungs or if the patient held his or her breath during ascent.

Further Reading

Boerema I, Meijne NG, Brummelkamp WH, et al. (1960) Life without blood. A study of the influence of high atmospheric pressure and hypothermia on dilution of the blood. Journal of Cardiovascular Surgery 1: 133–146.

Brummelkamp WH (1965) Considerations on hyperbaric oxygen therapy at three atmospheres absolute for clostridial infections type welchii. Annals of the New York Academy of Sciences 117: 688–699.

Feldmeier JJ (ed.) (2003) Hyperbaric Oxygen 2003: Indications and Results. The Hyperbaric Oxygen Therapy Committee Report. Kensington MD: Undersea and Hyperbaric Medical Society.

Kindwall EP and Whelan HT (eds.) (2002) Hyperbaric Medicine Practice, 2nd rev. edn. Flagstaff AZ: Best.

Marx RE, Ehler WJ, Tayapongsak P, and Pierce LW (1990) Relationship of oxygen dose to angiogenesis induction in irradiated tissue. American Journal of Surgery 160: 519–524.

Marx RE, Johnson RP, and Kline SN (1985) Prevention of osteoradionecrosis: a randomized prospective clinical trial of hyperbaric oxygen versus penicillin. Journal of the American Dental Association 111: 49–54.

Moon RE (1997) Treatment of decompression sickness and arterial gas embolism. In: Bove AA (ed.) Diving Medicine, 3rd edn., pp. 184–204. Philadelphia: Saunders.

Thom SR (1993) Functional inhibition of leukocyte beta-2 integrins by hyperbaric oxygen in carbon monoxide mediated brain injury in rats. Toxicology and Applied Pharmacology 123: 248–256.

Weaver LK, Hopkins RO, Chan KJ, et al. (2002) Hyperbaric oxygen for acute carbon monoxide poisoning. New England Journal of Medicine 347: 1057–1067.

Zamboni WA, Roth AC, Russell RC, et al. (1989) The effect of acute hyperbaric oxygen therapy on axial pattern skin flap survival when administered during and after total ischemia. Journal of Reconstructive Microsurgery 5: 343–347.

Zamboni WA, Wong H, Stephenson L, et al. (1997) Evaluation of hyperbaric oxygen for diabetic wounds: prospective study. Undersea Hyperbaric Medicine 24: 175–179.