Hyperbaric oxygen therapy (HBO) is a popular and effective treatment for a variety of disease processes. The methods by which it exerts its effect are poorly understood at the moment, but research has shown that it is an effective main treatment for a range of conditions, as well as a useful adjunctive treatment for many more. It is defined by the Undersea and Hyperbaric Medical Society (UHMS) as "a treatment in which a patient intermittently breathes 100% oxygen while the treatment chamber is pressurised to a pressure greater than sea level." (Hampson, 1999) There have been many claims made in the last 40yrs about its use in the treatment of a wide number of diseases, but clinical evidence is only really just starting to collect confirming or disproving these.
History of hyperbaric medicine
The first hyperbaric chamber was actually built in 1662 by an English clergyman and physician called Henshaw, meaning that hyperbaric oxygen therapy has a history going back nearly 350yrs. He called his creation the 'domicilium'. It was a metal chamber that was fitted with a large pair of organ bellows, with valves placed so that air could either be compressed into the chamber or extracted from it. Increased pressures were used for the treatment of acute disease, and reduced pressures for the treatment of chronic diseases:
"In times of good health this domicilium is proposed as a good expedient to help digestion, to promote insensible respiration, to facilitate breathing and expectoration and consequently, of excellent use for prevention of most affections of the lungs."(Henshaw, 1664)
His reports of this new treatment spread far and wide, and by 1878, much knowledge had been gathered about the effects and uses of hyperbaric oxygen therapy.
Paul Bert, a French
physiologist, published his findings on the effects of hyperbaric treatment in 1878, and in 1879, the French surgeon Fontaine told of his mobile hyperbaric chamber's favourable effects on the outcome of surgery.
The father of modern-day hyperbaric medicine is thought of as Dr. Boerema, a Dutch cardiovascular surgeon, who published his findings in the 1950s on the use of HBO in surgery, particularly for congenital cyanotic disorders such as tetralogy of Fallot and transposition of the great vessels; his reasoning was that by saturating the body tissues with oxygen, he'd be able to extend the tissue survival time when clamping the major arteries. The advent of more effective cardiopulmonary bypass techniques means that HBO is no longer used for cardiac surgery; however, his discovery (with his colleague, Dr. Brummelkamp) that HBO inhibited the growth of anaerobic bacteria, and thus was an effective treatment for gas gangrene is still saving lives even today.
Physiology of hyperbaric oxygen therapy
Hyperbaric oxygen therapy describes the exposure of a patient to 100% O2 at greater than atmospheric pressure, causing saturation of the body tissue with oxygen. Its effects are mediated by the manipulation of gas laws in combination with the effects of hyperoxia on body tissues. Most of the oxygen in the body is bound to the haemoglobin found in the red cells in plasma; at atmospheric pressure, there is 97% saturation. As blood travels through the body, the haemoglobin gradually gives up its oxygen molecules, where they then dissolve into the plasma surrounding the red cells. This is where the remaining 3% of the body's oxygen is stored; dissolved in solution. This translates to the concentration of oxygen in plasma being around 5-6 ml/L. When a patient is given HBO, this figure approaches 60 ml O2 per litre of plasma. When you consider that, at rest, the tissues in the body require an average of 60ml O2 per litre of blood flow, you can see that the resting requirements are almost fulfilled without the need for using the oxygen bound to haemoglobin (Tibbles, Edelsburg, 1996). It is this effect that makes HBO a successful treatment for both severe carbon monoxide poisoning, and severe anaemia in those unable to receive a blood transfusion, such as Jehovah's Witnesses.
The three laws that should be considered when thinking about HBO are:
- Boyle's law: at a constant temperature, the pressure and volume of a gas are inversely propostional.
- Dalton's law: in a mixed gas, each element exerts a pressure proportional to its fraction of the total volume (partial pressure).
- Henry's law: the amount of gas dissolved in a liquid or tissue is proportional to the partial pressure of the gas in contact with the liquid or tissue.
Pressure is described as multiples of the atmospheric pressure at sea level (1 ATM or 'atmosphere absolute'). HBO exposes the patient to 100% O2 at 3 ATM; the net effect of the three previously stated laws means that a very high partial pressure of oxygen is delivered to the patient, which results in an increase in the amount of oxygen dissolved in the tissues of the body. This increased amount is nearly sufficient to supply the body's metabolic requirements, meaning that the venous blood entering the right atrium will be nearly 100% saturated with O2 still. This hyperoxic state has three main physiological effects.
Increased rate of O2 diffusion into tissues, caused by a larger diffusion gradient in the capillary beds. This is effect is manipulated as a treatment for diseases that cause a microvascular angiopathy (such as diabetes and radiation-induced tissue injury) by reversing the hypoxia in the tissues served by the affected vessels, and by stimulating angiogenesis; this stimulation of angiogenesis also promotes wound healing.
Arteriolar vasoconstriction in the systemic circulation stimulated by the hyperoxia causes an increase in vascular resistance, a rise in blood pressure and a fall in heart rate and cardiac output. However, the arterioles serving ischaemic tissues are not affected. HBO also inhibits the adhesion of leukocytes to ischaemic tissues, preventing the pathological vasoconstriction that results from this (Weiss, 1989). The net result of these two effects is an increase in the blood flow to the oxygen-starved tissue. Arteriolar vasoconstriction also reduces the formation of oedema, which is beneficial in the treatment of crush injuries, burns and compartment syndromes.
Inhibition of bacterial growth and multiplication, particularly anaerobic bacteria. HBO causes an increase in the number of oxygen free radicals, which oxidise bacterial proteins and lipid membranes, damage DNA, and inhibit metabolic functions. It also facilitates the oxygen-dependent peroxidase reaction of leukocytes to bacteria (Knighton et al, 1984), and improves the oxygen-dependent transport of certain antibiotics across bacterial cell walls (Mader et al, 1987). HBO has been found to be particularly effective for the Clostridial myonecrosises, such as Clostridium perfringens in gas gangrene, but is also of use in the treatment of necrotising fasciitis; there is a improvement in the systemic illness, and a reduction in the amount of tissue that needs to be surgically excised.
The Undersea and Hyperbaric Medical Society consider HBO as the main or adjunctive treatment for:
(Pitkin, Hawksley Davies, 2001)
There are many other conditions for which HBO has been touted as being a beneficial treatment, but there is a lack of published evidence of the vast majority of these. This includes multiple sclerosis, for which only one out of fourteen trials has shown any benefit for its use as a treament.
Hazards of hyperbaric oxygen therapy
As with the vast majority of treatments, HBO is not without its problems. With regards to the chambers themselves, when a patient is in a chamber receiving treatment they are less accessible in the event of an unexpected emergency; also, having an atmosphere of 100% oxygen is a significant fire hazard. There have been 50 reported deaths worldwide due to fire in the twenty years (Sheffield, Desautels, 1997), making it the most common fatal complication of HBO. The primary problem of putting a patient in an increased pressure environment is the risk of barotrauma; this is principally of the tympanic membranes, as the patient may not be well enough to perform the Valsalva manoeuvre in order to equalise the pressure in their middle ears, resulting in perforation. A prophylactic myringotomy would be appropriate in this situation. Other, general, problems can include claustrophobia, headache, fatigue and vomiting. Also, there is the risk of causing a decompression illness if extensive HBO therapy has to be given.
However, the main physiological danger in HBO is that of oxygen toxicity. This should not be a problem normally, if HBO is limited to 3 ATM with the session lasting a maximum of 120 minutes at a time. Even then, they may be some adverse effects noticed by the patient. Respiration requires oxygen, but the process results in the formation of free radicals in the form of superoxide ions, hydrogen peroxide, hydroxyl and singlet oxygen radicals; these are molecules that have an unpaired electron in their outer shell, making them highly reactive chemically. They then go on to react with their surrounding medium, in this case cell membranes, and enzyme proteins, eventually leading to the death of the cell. Normal cellular processes remove these damaging free radicals via a complex system of antioxidant defences, and a disruption of this balance leads to cellular damage. Organs vary in their sensitivity to an excess of free radicals.
The central nervous system has a very low threshold for the oxidative damage that results from HBO. This can lead to muscle twitching, nausea, visual disturbances (such as a reversible myopia), and dysphoria in the more mild instances. The more extreme manifestation is that of seizures, but these usually cause no damage and are controlled by turning off the oxygen and allowing the patient to breath normal air for 15mins or so. The other organ sensitive to free radical excess is the lung; this problem is also associated with normal general anaesthesia and intensive medicine. Initially, there is a fall in the in the vital capacity of the lungs and the patient will complain of a cough and chest discomfort. This will progress to the formation of pulmonary oedema and alveolar haemorrhage, and culminate in respiratory distress. In practice, most sessions of HBO are not long enough to cause lung toxicity damage; but it can be a significant problem for those that need long-term treatment.
There was worry for a time that HBO could increase oxygenation of malignant tumours, stimulating their growth, but evidence has so far disproved this theory. Similarly, there is no clinical evidence that HBO causes any adverse effects if given during pregnancy. The only absolute contraindication is that of a tension pneumothorax, which must be excluded before therapy is given. Treatment should be given under specialist advisement for patients with an impaired ability to equalise air spaces (middle ears, etc.) or those with cardiac disease.
References
- Bennett P, Elliott D, 1993, "The physiology and medicine of diving", 4th edition, WB Saunders
- Gill AL, Bell CNA, 2004, "Hyperbaric oxygen: its uses, mechanisms of action and outcomes", Q J Med 2004; 97: 385-395
- Hampson NB, "Hyperbaric Oxygen Therapy: 1999 Committee report", UHMS 1999
- Henshaw N, 1664, "Aero-chalinos", Dublin, Dancer
- Knighton DR, Halliday B, Hunt TK, 1984, "Oxygen as an antibiotic: the effect of inspired oxygen on infection", Arch Surg; 119:119-204
- Leach RM, Rees PJ, Wilmshurst P, 1998, "ABC of Oxygen: Hyperbaric Oxygen Therapy", BMJ; 317:1140-1143
- Mader JT, Adams KR, Couch LA, et al, 1987, "Potentiation of tobramycin by hyperbaric oxygen in experimental Pseudomonas aeruginosa osteomyelitis (asbract 1331) ", abstracts of the 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington DC, American Society for Microbiology
- Pitkin AD, Hawksley Davies NJ, 2001, "Hyperbaric oxygen therapy", BJ Anaesth. CEPD Reviews; 1(5):150-156
- Sheffield PJ, Desaultels DA, 1997, "Hyperbaric and hypobaric chamber fires: a 73yr analysis", Undersea Hyperb Med; 24:153-164
- Tibbles PM, Edelsberg JS, 1996, "Hyperbaric-Oxygen Therapy", N. England J. Med.; 334:1642-1648
- Weiss SJ, 1989, "Tissue destruction by neutrophils", N Eng J Med; 320:365-376