- Email: [email protected]
Hyperbaric medicine part I: theory and practice
Current Anaesthesia & Critical Care (2001) 12, 114d120 ^ 2001 Harcourt Publishers Ltd doi:10.1054/cacc.2001.0306, available online at http://www.idealibrary.com on
MEDICINE
Hyperbaric medicine part I: theory and practice P. J. Shirley and J. A. S. Ross Department of Anaesthesia, Intensive Care and Hyperbaric Medicine, Grampian University Hospitals Trust, Foresterhill, Aberdeen AB25 2ZN, UK
KEYWORDS oxygenation; hyperbaric; decompression sickness; hyperoxia; poisoning; carbon monoxide; pressure therapy
Summary Hyperbaric therapy has been recognized as a therapeutic treatment for over 100 years. Hyperbaric oxygen was first used to treat disease processes over 50 years ago. The relationship between volume and pressure incorporated in Boyle’s law and the supersaturation of tissues by oxygen under pressure form the basis of hyperbaric oxygen therapy. Although having many advantages, there are potentially serious side-effects including barotrauma, oxygen toxicity, visual disturbances and psychological problems, particularly claustrophobia. Many indications have been proposed but the evidence for some is scanty. Contraindications include certain respiratory conditions e.g. pneumothorax, high fevers, pregnancy, a history of seizures, optic neuritis, middle ear pathology and treatment with certain chemotherapeutic agents. It is also not suitable for patients who may be agitated or unco-operative and these individuals often require treatment under general anaesthesia. ^ 2001 Harcourt Publishers Ltd
INTRODUCTION The therapeutic use of hyperbaric oxygen was recognized as early as 1873 by Dr Paul Bert when he noted that the malaise afflicting French tunnel workers was cured by recompression.1 In fact it was underground tunnel workers who formed the basis of early epidemiological studies into recompression treatment and in the UK this was documented by Leonard Hill.2 These workers constructed bridge footings underwater in stone-lined chambers from which water was kept by pressure pumps. When these caisson workers left the construction site, dissolved nitrogen would nucleate in the joints of the back and extremities, the pain causing them to walk in a bent-over posture, hence the ‘bends.’ These symptoms were noted to resolve with immediate re-pressurization. Although oxygen had been isolated in 1775 by Priestley (‘dephlogisticated air’) and its medical benefits noted from an early stage, it was excluded from hyperbaric chambers due to its toxic effects under pressure. Hyperbaric oxygen was first used to treat decompression sickness in 1937 by Behnke and Shaw.3
Correspondence to: JASR. Dept. of Environmental and Occupational Medicine, Liberty Safe Work Research Centre, Fosterhill Road, Aberdeen, AB25 22P. Fax: 01224 662990; E-mail: [email protected]
The intensification of work into hyperbaric physiology increased markedly with its military applications for divers and aircrew during the Second World War. Post war, the clinical applications of hyperbaric oxygen therapy (HBO) attracted interest. Its use in cardiac surgery and the provision of hyperbaric operating rooms were the focus of much research. However the development of cardiopulmonary bypass to support surgical advances drew attention away from HBO therapy.4 During the 1950s the value of HBO therapy to enhance the effects of radiotherapy for malignancy were investigated.5 In 1960 the Medical Research Council (MRC) funded trials into the efficacy of HBO in various clinical settings including radiotherapy, carbon monoxide poisoning and in the treatment of gas gangrene.6 This article reviews the physical and biological basis of HBO therapy and focuses on the treatment of the commonly encountered emergency conditions.
THE PHYSIOLOGY OF PRESSURE One standard atmosphere (1ATA) has a number of equivalent pressures depending on the units employed: 1 ATA"760 mmHg"1.013 bar The bar is often used as the unit of measure: 1 bar"100 kPa"750 mmHg
HYPERBARIC MEDICINE PART I: THEORY AND PRACTICE
These differences may seem subtle but can be of great importance when exposing individual patients to the stress of compression therapy. HBO therapy involves the use of oxygen under pressure greater than that found on the surface of the earth at sea level. Only a limited amount of oxygen is dissolved in blood at normal atmospheric pressure but under hyperbaric conditions it is possible to dissolve sufficient oxygen to meet the usual requirements of the body. In such cases oxyhaemoglobin will pass from the arterial to the venous side unaltered because the oxygen dissolved in solution will be more readily utilized than that bound to haemoglobin. The five gas laws form the physical basis on which the physiological principles of hyperbaric medicine exert their effect.7
Boyle’s law The volume of a fixed mass of gas will vary inversely with the pressure, as long as the temperature is kept constant. P1V1"P2V2
Dalton’s law The pressure exerted by a mixture of gases is equal to the sums of the pressures of the individual gases. PT"PA#PB#PC#2#PN
115
Charle’s law The volume of a fixed mass of gas is proportional to its temperature. VaT
General gas law This combines the above four laws into one formula. P1V1/T1"P2V2/T2 We are subjected to 1 atmosphere pressure at the earth’s surface with an increase of one atmosphere with each 10 m of depth in salt water (Table 1). Conversely pressure decreases with altitude, although the relationship is non-linear. It must also be stressed that as barometric pressure increases, the density of the gas breathed also increases. The effect of increasing density on resting ventilation is negligible within the range of 1.5d2 ATA that is usually employed in hyperbaric chambers. However, with physical exertion in patients with decreased respiratory reserves or respiratory obstruction, increased density may lead to severe gas flow problems. The physiological effects of hyperoxia may be significant (Table 2). The theoretical benefits of using oxygen under pressure therefore range from the purely physical with a reduction in bubble size and the displacement of nitrogen to the biochemical with an enhancement of the function of polymorphs and free radical production. This is not without a degree of risk, however.
COMPLICATIONS AND SIDE-EFFECTS OF HBO THERAPY
Henry’s law The amount of gas dissolved in a liquid at a set temperature depends on both the partial pressure and the solubility coefficient of the gas. Amount of gas dissolved"Solubility;P
Barotrauma9 This usually manifests itself during descent in patients who are unable to equalize their middle ear pressures and treatment must be aborted immediately. Extreme
Table 1 Pressure/volume relationships
Air Sea
Depth (Salt water m)
Gauge pressure (atmospheres)
Absolute pressure (atmospheres)
Gas volume
0 10 20 30 40 50
0 1 2 3 4 5
1 2 3 4 5 6
100% 50% 33% 25% 20% 17%
CURRENT ANAESTHESIA & CRITICAL CARE
116
Table 2 The physiological effects of hyperoxia8 Oxygen transport and metabolism: Inactivation of normal role of haemoglobin in O2 and CO2 transport Respiratory system: Suppression of carotid and aortic bodies and depressed respiration Washout of N2 and increased susceptibility to alveolar collapse Cardiovascular system: Bradycardia Decreased cardiac output and decreased cerebral blood flow
Gastrointestinal upset Air swallowing at depth and subsequent expansion on ascent can cause discomfort.
Claustrophobia This can be a problem, requiring anxiolysis pretreatment if severe. Major problems associated with HBO therapy are rare and the side-effect rate is within acceptable limits (approximately 17% suffer some ear discomfort; 3.8% have otological barotrauma). A high level of vigilance needs to be maintained for more serious complications.11 This obviously requires a high degree of competency in the attendants who are in the chamber with the patient.
Peripheral vessels: Vasoconstriction of peripheral vessels and those in brain, kidneys and eyes Increased total peripheral resistance
INDICATIONS FOR HYPERBARIC OXYGEN THERAPY
Metabolic and biochemical: Increase of CO2 and H# ions with decreased pH in tissues Inhibition of cellular respiration Inhibition of enzyme activity Increase in free radical production
The formation of the European Committee for Hyperbaric Medicine (ECHM) and the Undersea and Hyperbaric Medical Society (UHMS) in the USA has lead to consensus amongst clinicians about the therapeutic uses of HBO therapy. European guidelines as defined by the ECHM12 are as follows:
Acute indications for HBO cases may cause rupture of the tympanic membrane and if any doubts are present pretreatment, then an ear, nose and throat specialist referral is warranted. Similar problems are seen in patients with blocked sinuses where pressure cannot be equalized.
Oxygen toxicity10 This may occur acutely as central nervous system toxicity with involuntary twitching, leading to grand mal seizure activity. It is rare using current treatment tables but has been observed with pressures as low as 2 ATA and is much more common in cases of carbon monoxide poisoning. Cumulative toxicity can occur with exposure to 100% oxygen at less than 1 ATA for prolonged periods or with 6 h continuous exposure at 2 ATA. Initial effects are of dull retro-sternal pain and a dry cough which worsens with continued exposure. This may be exacerbated if high-dose oxygen is required between treatments where it may manifest as involuntary muscular twitching.
Visual disturbance Reversible deterioration of vision occurs in all patients when treatment continues over long periods.
E E E E E E E E E E
Decompression illness Carbon monoxide intoxication Arterial gas embolism Gas gangrene Serious mixed infections of soft tissue including diabetic gangrene Crush injuries with compartment syndrome Burns with and without smoke inhalation Post-anoxic encephalopathy Sudden deafness Serious vascular visual pathologies
Chronic indications for HBO E E E E E
Chronic ischaemic ulcers Radiation tissue damage Chronic refractory osteomyelitis As an aid to survival of skin flaps and free skin grafts Bone healing
Three levels of priority have been defined by the ECHM by consensus (Table 3). (a) Type I recommendation. Situations where the transport to a hyperbaric facility is strongly recommended because it is recognized that HBO positively affects the prognosis for survival, i.e. the patient is
HYPERBARIC MEDICINE PART I: THEORY AND PRACTICE
Table 3 Priority for HBO treatment of medical conditions as defined by ECHM TYPE I Acute:
Chronic: TYPE II Acute:
Chronic:
TYPE III Acute:
Chronic:
Decompression illness Carbon monoxide poisoning (major) Gas embolism Anaerobic or mixed bacterial necrotizing soft tissue infection Radionecrotic lesions
Acute soft tissue ischaemia Sudden deafness Ischaemic lesions (without surgically treatable arterial lesions) Osteomyelitis
Carbon monoxide poisoning (minor) Re-perfusion injury Post-anoxic encephalopathy Burns Ophthalmological ischaemia Radionecrosis of intestine or spinal cord
117
recommended treatments do not reach a level I, level of evidence as defined by the US Agency for Health Care policy and research.13
US guidelines as issued by the UHMS14 E E E E E E E E E E E E E
Air or gas embolism Carbon monoxide poisoning Clostridial myositis and myonecrosis (gas gangrene) Crush injury, compartment syndrome and other acute traumatic ischaemias Decompression sickness Enhancement of healing in selected problem wounds Exceptional blood loss (anaemia) Intracranial abscess Necrotizing soft tissue infections Osteomyelitis (refractory) Delayed radiation injury (Soft tissue and bony necrosis) Skin grafts and flaps (compromized) Thermal burns
Whatever the consensus is regarding treatment, hyperbaric chambers are used for a variety of conditions, a significant proportion of which fall outside the current guidelines (Table 4).
CONTRA-INDICATIONS FOR HBO THERAPY transported to the nearest hyperbaric facility as soon as possible. (b) Type II recommendation. Situations where the transport to a hyperbaric facility is recommended because it is recognized that HBO constitutes an important part of the treatment of the condition, even if it does not influence the prognosis for survival but is important in the prevention of serious disorders. Transport to a hyperbaric facility should be made unless this represents a danger to the patient’s life. (c) Type III recommendation. Situations where the transfer to a hyperbaric facility is optional because HBO is regarded as an additional treatment modality which can improve clinical results. It is worth emphasizing at this point that the standard of care given in hyperbaric medicine should be as good as that given elsewhere. Put simply, if a hyperbaric unit does not have the ability to look after critically ill patients then it should not be accepting them for treatment. Moreover the standard of care must be appropriate during transport to the hyperbaric facility, especially if referred from another hospital. Due to the lack of randomized controlled trials in hyperbaric medicine most of the currently
Absolute contra-indications16 Several agents used for adjuvant chemotherapy may cause cardiac toxicity under pressure and a gap of one week is recommended between stopping these drugs and HBO therapy. These include bleomycin, doxorubicin, cisplatinum and disulfiram.
Relative contra-indications (i) Chest pathology Pneumothorax can be a serious problem for those undergoing hyperbaric treatment. A pocket of trapped gas in the pleura will decrease in volume on compression and reexpand on surfacing during a cycle of HBO therapy. A 1.8 l pneumothorax at 20 metres below sea level is potentially 6 l at sea level, a life threatening event. Care must be taken therefore with patients who give a history of chest trauma and if any doubts exist then a chest drain must be placed before HBO is contemplated. Patients who have emphysema with carbon dioxide retention are at risk for several reasons. Those relying on a hypoxic drive to ventilation may become apnoeic whilst receiving HBO. Moreover gas trapping and lung rupture may be a real risk if bullous disease is present. It
CURRENT ANAESTHESIA & CRITICAL CARE
118
Table 4 Treatment of patients in British Hyperbaric Association Chambers in 199715 Number of patients Decompression illness CO poisoning Gas embolism (non-diving) Soft tissue infections Post-radiotherapy Other ECHM/UHMS indications Research Other indications Totals
Percentage
349 352 0 32 112
25.4 25.6 0 2.3 8.2
271 37 221
19.7 2.7 16.1
1374
100
caution should be exercized when considering the pregnant patient for HBO.
(vii) History of seizures Increasing baseline medication prior to HBO therapy has been advocated due to the potential of the treatment to lower the seizure threshold.
(viii) Agitated or violent patients Any patient who may be a danger to themselves or to the operators may need to undergo treatment under sedation or anaesthesia.
(ix) Optic neuritis There have been incidences of deterioration of sight and even blindness in patients with a history of optic neuritis.
must also be remembered that if patients have lung disease severe enough to prevent adequate oxygen transfer into the blood stream then it is questionable whether HBO therapy is indicated. Serious consideration should be given to the risk/benefit aspects in this patient group and this includes those with smoke inhalation and significant pneumonitis.
(ii) Asthma Hyper-reactivity of small airways may lead to air-trapping and pulmonary barotrauma on ascent. Each case must be considered individually and carefully.
(iii) Upper respiratory tract infections Difficulties in clearing ears and sinuses may make this a relative contra-indication.
(iv) Viral infections There has been concern that viral infections may be worsened after HBO. The evidence for this is inconclusive and each case must be considered individually.
(v) High fevers A body temperature greater than 38.53C can lower the seizure threshold due to oxygen toxicity. If therapy is deemed urgent an attempt to lower core temperature with antipyretics can be made.
(vi) Pregnancy Previous fears about problems during pregnancy and HBO seem to have been ill-founded. Nevertheless
(x) History of middle ear surgery or disorders An inability to equalise middle-ear pressure represents a contra-indication to undergoing HBO therapy. An ENT review for grommet placement, prior to treatment may be indicated.
TREATMENT REGIMES FOR SELECTED CONDITIONS Decompression sickness Decompression sickness (DCS) is one form of dysbarism. Dysbarism is a general term applied to all pathological changes attributed to altered environmental pressure. As mentioned previously, DCS was first described in caisson workers and even now goes under various names, depending on the presentation. These presentations include the ‘bends’ (joint pains), the ‘staggers’ (vestibular symptoms), the ‘chokes’ (pulmonary symptoms) and the ‘hits’ (spinal cord symptoms) (Table 5). The underlying pathology results from a rapid reduction in environmental pressure and super-saturation of gases dissolved in tissues. Haldane classified DCS into three categories in 1907.17 It is now recognized that decompression sickness and gas embolism when taken together form the group of conditions under the umbrella of ‘decompression illness.’ (DCI). Risk factors have been isolated for DCI following air diving. Obesity (nitrogen is five times more soluble in fat than in water), high serum cholesterol, heavy exercise at depth, a prolonged stay under pressure followed by rapid decompression and a patent foramen ovale are all known to increase susceptibility. Those who fly after diving (i.e.
HYPERBARIC MEDICINE PART I: THEORY AND PRACTICE
Table 5 Signs and symptoms of Decompression Sickness (DCS) Type I DCS Limb and joint pains (‘bends’) Skin rash Type II DCS Neurological: (1) Cerebral visual disturbance aphasia hemiplegia memory loss convulsions coma (2) Spinal (‘hits’) sensory disturbance in extremities paraesthesias numbness weakness difficulty in walking bladder dysfunction paraplegia or quadriplegia (3) Vestibular (‘staggers’) nystagmus vertigo Pulmonary (‘chokes’): Dyspnoea Hyperventilation Chest pain Acute lung injury Cardiac Tachycardia Arrythmias
entering a hypobaric environment) place themselves at high risk of developing symptoms. The objectives of treatment are to get a DCI victim transferred to a hyperbaric treatment facility as soon as possible. Recompression treatment has the aims of reducing bubble volume, re-distributing and re-dissolving gas and reducing tissue oedema and hypoxia. Initial treatment consists of early administration of supplemental oxygen and rehydration. Plasma leakage is a feature and can lead to marked increases in haematocrit and haemoglobin which are associated with a poor overall outcome in DCI. Even if symptoms clear and neurological examination is normal at ground level recompression therapy is still required. DCI is a condition which frequently waxes and wanes with periods of relapse and improvement. Serious symptoms that persist at ground level require 100% O2, aggressive hydration and hyperbaric treatment using US Navy tables 5 or 6.18 Treatment on deeper dive
119
tables with helium and oxygen mixtures are becoming more popular for treating DCI. Hydration with intravenous fluids should avoid those containing dextrose as theoretically this may worsen any spinal cord and cerebral oedema. Recently researchers have adapted a clinical scoring system calculated from five clinical variables to predict the outcome following DCI. These variables are defined as repetitive dives, clinical course before HBO therapy, objective sensory deficit, motor impairment and urinary disturbance. This may prove to be useful when considering the number of treatments of HBO therapy which may be appropriate for an individual patient.19,20
Cerebral arterial gas embolism Air in the venous or arterial system can cause cerebral air embolism, leading to severe neurological deficits. Sudden decompression and pulmonary barotrauma in divers is one cause but air can also enter the circulation following trauma to the head, neck or chest and during medical procedures where invasive monitoring is in place. The clinical manifestations are usually neurological or cardiovascular but vary according to patient posture, route of entry and the size of bubbles. These bubbles may cause unconsciousness, convulsions, paresis, nausea and vertigo, visual disturbance, headache, cerebrovascular accidents and if lodged in the coronary circulation, lead to myocardial infarction,12 all of which are features of DCI. One generally accepted treatment is immediate compression to 6 ATA air for a period of 30 minutes followed by ascent to 2.8 ATA in oxygen. The reasoning behind this approach is to initially reduce bubble size thereby decreasing the inflammatory effect of the blood : bubble interface. At 6 ATA the bubble volume is reduced to 17% of its original size and the surface area reduced to 30%. The 100% oxygen counteracts the ischaemic and hypoxic effect of the vascular occlusion. One hundred per cent oxygen also improves the diffusion of nitrogen from the bubble. Vasoconstriction induced by HBO inhibits the redistribution of the embolus throughout the circulation. Most divers are aware of the symptoms associated with DCI and may have a level of medical knowledge on the subject, exceeding that of the occasional practitioner. This awareness usually extends to knowledge of the closest availability of hyperbaric facilities.
Carbon monoxide poisoning Oxygen inhalation to speed the dissociation of carbon monoxide from the haemoglobin molecule is the cornerstone of treatment, having been established by Pace in 1950.22 HBO hastens carboxyhaemoglobin (COHb) dissociation beyond the rate achievable by
120
Table 6 Clinical Indications for HBO therapy in CO poisoning26 Neurological abnormality (including hearing and gait assessment) Cognitive impairment, personality change Chest pain, abnormal ECG or raised cardiac enzymes Pregnancy History of sustained loss of consciousness Inability to assess adequately (e.g. concurrent drug overdose)
breathing 100% oxygen at sea level.23 Morbidity amongst survivors of carbon monoxide poisoning is varied but often involves delayed neurological sequelae. It is these delayed symptoms which HBO is also thought to improve. The half-life of COHb in air at 1 ATA is 5 h and 20 min; breathing 100% oxygen at 1 ATA it is 1h and 20 min; breathing 100% oxygen at 3 ATA it is 23 min. One of the difficulties of carbon monoxide poisoning is the lack of correlation of blood levels with symptoms. A blood COHb of greater than 10% is generally regarded as significant, greater than 30% is considered serious. However, clinical manifestations should be the primary consideration and COHb the secondary consideration when assessing the degree of poisoning (Table 6). The objectives of treatment are twofold, firstly to rapidly dissociate the carbon monoxide from haemoglobin and restore oxygen carrying capacity and secondly to attempt to reduce the long-term neurological sequelae. The immediate priority for treatment therefore consists of resuscitation and support with airway control, 100% oxygen and non-glucose containing IV fluids. Onward transfer to a hyperbaric chamber is the next priority where a full neurological and cardiorespiratory examination can be carried out. A minimental state examination is carried out if the patient is awake. Treatment regimes vary but have failed to reach a consensus. Recent work comparing HBO at 2.8 ATA with 100% O2 at 1 ATA claims to show worse long-term outcomes in the HBO group.24 However, this has been questioned as it goes against the weight of evidence over the previous 30 years and too many variables were present in the study to make it conclusive Furthermore, many of the so-called symptoms of carbon monoxide poisoning may have been due to oxygen toxicity related to the treatment tables used. Recent studies have pointed towards evidence that treatment of carbon monoxide poisoning with HBO therapy reduces longterm neurological deficit.27
REFERENCES 1. Jacobsen J H, Morsch J C H, Rendell-Baker L. The historical perspective of hyperbaric therapy. Ann N Y Acad Sci 1965; 117: 651d670.
CURRENT ANAESTHESIA & CRITICAL CARE 2. Hill L E. Caisson Sickness and the Physiology of Compressed Air Working. London: Edward Arnold, 1912. 3. Behnke A R, Shaw L A. Use of hyperbaric oxygen in treatment of compressed air illness. Nav Med Bull 1937; 35: 1d12. 4. Bernard W F, Tank E S. The effect of oxygen inhalation at 3.0 to 3.6 atmospheres absolute upon children with cyanotic congenital heart disease. Surgery 1963; 54: 203. 5. Churchill-Davidson I, Sanger C, Thomlinson R H. High-pressure oxygen and radiotherapy. Lancet 1955; 1: 1091d1095. 6. Sheridan R L, Shank E S. Hyperbaric oxygen treatment: a brief overview of a controversial topic. J Trauma 1999; 47: 426d435. 7. Spira A. Diving and marine medicine review. Part I: Diving physics and physiology. J Travel Med 1999; 6: 32d34. 8. Jain K K, Fischer B. In: Oxygen in Physiology and Medicine Springfield, USA: Thomas 1989. 9. Bennett M. Handbook of Diving and Hyperbaric Medicine. Prince of Wales Hospital; South Eastern Sydney Area Health Service, 1996. 10. Clark JM. Oxygen toxicity. In: Bennett P, Elliot D (eds). The Physiology and Medicine of Diving. London: WB Saunders Ltd 1993; 493. 11. Plafki C, Peters P, Almeling M, Welslau W, Busch R. Complications and side effects of hyperbaric oxygen therapy. Aviat Space Environ Med 2000; 71: 119d124. 12. Wattel F, Mathieu D (eds) Reports and Recommendations of 1st European Consensus Conference on Hyperbaric Medicine, 1994. 13. US Department of Health and Human Services, Public Health Service, Agency Health Care Policy and Research. Acute pain management: operative or medical procedures and trauma. 1992 Agency for Health Care Policy and Research Publications, Rockville, MD. 14. Hyperbaric oxygen therapy; a committee report. Undersea and Hyperbaric Medical Society. Maryland 1996. 15. Ross J A S (ed) British Hyperbaric Association. Register of member chambers 1998. University of Aberdeen, 1998 16. Kindwall E P. Contraindications and side-effects to hyperbaric oxygen treatment. In: Kindwall E P (ed). Hyperbaric Medicine Practice. Arizona: Best Publishing, 1995. 17. Haldane J S. Admiralty Report on Deep Water Diving 1907; HMSO: CN 1549. 18. Moon R E, Sheffield P J. Guidelines for treatment of decompression sickness. Aviat Space Environ Med 1997; 68: 234d243. 19. Boussuges A, Thirion X, Blanc P et al. Neurological decompression illness: a gravity score. Undersea Hyperbaric Med 1996; 23: 151d155. 20. Pitkin A D, Benton P J, Broome J R. Outcome after treatment of neurological decompression sickness is predicted by a published clinical scoring system. Aviat Space Environ Med 1999; 70: 517d521. 21. Spira A. Diving and marine medicine review part II: diving diseases. J Travel Med 1999; 6: 180d198. 22. Pace N, Strajman E, Walker E L. Acceleration of carbon monoxide elimination in man by high pressure oxygen. Science 1950; 111: 652d654. 23. Smith G, Ledingham I M, Sharp G R et al. Treatment of coal-gas poisoning with oxygen at 2 atmospheres pressure. Lancet 1962; 1: 816d818. 24. Scheinkestel C D, Bailey M, Myles P S et al. Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial. Med J Aust 1999; 170: 203d210. 25. Moon R, DeLong E. Hyperbaric oxygen for carbon monoxide poisoning. Med J Aust 1999; 170: 197d199. 26. Pitkin A D, Broome J R, Salmon J. Hyperbaric oxygen therapy in intensive care. Part II: carbon monoxide poisoning. Br J Intens Care 1999; Nov/Dec: 189d195. 27. Hawkins M, Harrison J, Charters P. Severe carbon monoxide poisoning: outcome after hyperbaric oxygen therapy. Br J Anaesth 2000; 84: 584d586.
MEDICINE
Hyperbaric medicine part I: theory and practice P. J. Shirley and J. A. S. Ross Department of Anaesthesia, Intensive Care and Hyperbaric Medicine, Grampian University Hospitals Trust, Foresterhill, Aberdeen AB25 2ZN, UK
KEYWORDS oxygenation; hyperbaric; decompression sickness; hyperoxia; poisoning; carbon monoxide; pressure therapy
Summary Hyperbaric therapy has been recognized as a therapeutic treatment for over 100 years. Hyperbaric oxygen was first used to treat disease processes over 50 years ago. The relationship between volume and pressure incorporated in Boyle’s law and the supersaturation of tissues by oxygen under pressure form the basis of hyperbaric oxygen therapy. Although having many advantages, there are potentially serious side-effects including barotrauma, oxygen toxicity, visual disturbances and psychological problems, particularly claustrophobia. Many indications have been proposed but the evidence for some is scanty. Contraindications include certain respiratory conditions e.g. pneumothorax, high fevers, pregnancy, a history of seizures, optic neuritis, middle ear pathology and treatment with certain chemotherapeutic agents. It is also not suitable for patients who may be agitated or unco-operative and these individuals often require treatment under general anaesthesia. ^ 2001 Harcourt Publishers Ltd
INTRODUCTION The therapeutic use of hyperbaric oxygen was recognized as early as 1873 by Dr Paul Bert when he noted that the malaise afflicting French tunnel workers was cured by recompression.1 In fact it was underground tunnel workers who formed the basis of early epidemiological studies into recompression treatment and in the UK this was documented by Leonard Hill.2 These workers constructed bridge footings underwater in stone-lined chambers from which water was kept by pressure pumps. When these caisson workers left the construction site, dissolved nitrogen would nucleate in the joints of the back and extremities, the pain causing them to walk in a bent-over posture, hence the ‘bends.’ These symptoms were noted to resolve with immediate re-pressurization. Although oxygen had been isolated in 1775 by Priestley (‘dephlogisticated air’) and its medical benefits noted from an early stage, it was excluded from hyperbaric chambers due to its toxic effects under pressure. Hyperbaric oxygen was first used to treat decompression sickness in 1937 by Behnke and Shaw.3
Correspondence to: JASR. Dept. of Environmental and Occupational Medicine, Liberty Safe Work Research Centre, Fosterhill Road, Aberdeen, AB25 22P. Fax: 01224 662990; E-mail: [email protected]
The intensification of work into hyperbaric physiology increased markedly with its military applications for divers and aircrew during the Second World War. Post war, the clinical applications of hyperbaric oxygen therapy (HBO) attracted interest. Its use in cardiac surgery and the provision of hyperbaric operating rooms were the focus of much research. However the development of cardiopulmonary bypass to support surgical advances drew attention away from HBO therapy.4 During the 1950s the value of HBO therapy to enhance the effects of radiotherapy for malignancy were investigated.5 In 1960 the Medical Research Council (MRC) funded trials into the efficacy of HBO in various clinical settings including radiotherapy, carbon monoxide poisoning and in the treatment of gas gangrene.6 This article reviews the physical and biological basis of HBO therapy and focuses on the treatment of the commonly encountered emergency conditions.
THE PHYSIOLOGY OF PRESSURE One standard atmosphere (1ATA) has a number of equivalent pressures depending on the units employed: 1 ATA"760 mmHg"1.013 bar The bar is often used as the unit of measure: 1 bar"100 kPa"750 mmHg
HYPERBARIC MEDICINE PART I: THEORY AND PRACTICE
These differences may seem subtle but can be of great importance when exposing individual patients to the stress of compression therapy. HBO therapy involves the use of oxygen under pressure greater than that found on the surface of the earth at sea level. Only a limited amount of oxygen is dissolved in blood at normal atmospheric pressure but under hyperbaric conditions it is possible to dissolve sufficient oxygen to meet the usual requirements of the body. In such cases oxyhaemoglobin will pass from the arterial to the venous side unaltered because the oxygen dissolved in solution will be more readily utilized than that bound to haemoglobin. The five gas laws form the physical basis on which the physiological principles of hyperbaric medicine exert their effect.7
Boyle’s law The volume of a fixed mass of gas will vary inversely with the pressure, as long as the temperature is kept constant. P1V1"P2V2
Dalton’s law The pressure exerted by a mixture of gases is equal to the sums of the pressures of the individual gases. PT"PA#PB#PC#2#PN
115
Charle’s law The volume of a fixed mass of gas is proportional to its temperature. VaT
General gas law This combines the above four laws into one formula. P1V1/T1"P2V2/T2 We are subjected to 1 atmosphere pressure at the earth’s surface with an increase of one atmosphere with each 10 m of depth in salt water (Table 1). Conversely pressure decreases with altitude, although the relationship is non-linear. It must also be stressed that as barometric pressure increases, the density of the gas breathed also increases. The effect of increasing density on resting ventilation is negligible within the range of 1.5d2 ATA that is usually employed in hyperbaric chambers. However, with physical exertion in patients with decreased respiratory reserves or respiratory obstruction, increased density may lead to severe gas flow problems. The physiological effects of hyperoxia may be significant (Table 2). The theoretical benefits of using oxygen under pressure therefore range from the purely physical with a reduction in bubble size and the displacement of nitrogen to the biochemical with an enhancement of the function of polymorphs and free radical production. This is not without a degree of risk, however.
COMPLICATIONS AND SIDE-EFFECTS OF HBO THERAPY
Henry’s law The amount of gas dissolved in a liquid at a set temperature depends on both the partial pressure and the solubility coefficient of the gas. Amount of gas dissolved"Solubility;P
Barotrauma9 This usually manifests itself during descent in patients who are unable to equalize their middle ear pressures and treatment must be aborted immediately. Extreme
Table 1 Pressure/volume relationships
Air Sea
Depth (Salt water m)
Gauge pressure (atmospheres)
Absolute pressure (atmospheres)
Gas volume
0 10 20 30 40 50
0 1 2 3 4 5
1 2 3 4 5 6
100% 50% 33% 25% 20% 17%
CURRENT ANAESTHESIA & CRITICAL CARE
116
Table 2 The physiological effects of hyperoxia8 Oxygen transport and metabolism: Inactivation of normal role of haemoglobin in O2 and CO2 transport Respiratory system: Suppression of carotid and aortic bodies and depressed respiration Washout of N2 and increased susceptibility to alveolar collapse Cardiovascular system: Bradycardia Decreased cardiac output and decreased cerebral blood flow
Gastrointestinal upset Air swallowing at depth and subsequent expansion on ascent can cause discomfort.
Claustrophobia This can be a problem, requiring anxiolysis pretreatment if severe. Major problems associated with HBO therapy are rare and the side-effect rate is within acceptable limits (approximately 17% suffer some ear discomfort; 3.8% have otological barotrauma). A high level of vigilance needs to be maintained for more serious complications.11 This obviously requires a high degree of competency in the attendants who are in the chamber with the patient.
Peripheral vessels: Vasoconstriction of peripheral vessels and those in brain, kidneys and eyes Increased total peripheral resistance
INDICATIONS FOR HYPERBARIC OXYGEN THERAPY
Metabolic and biochemical: Increase of CO2 and H# ions with decreased pH in tissues Inhibition of cellular respiration Inhibition of enzyme activity Increase in free radical production
The formation of the European Committee for Hyperbaric Medicine (ECHM) and the Undersea and Hyperbaric Medical Society (UHMS) in the USA has lead to consensus amongst clinicians about the therapeutic uses of HBO therapy. European guidelines as defined by the ECHM12 are as follows:
Acute indications for HBO cases may cause rupture of the tympanic membrane and if any doubts are present pretreatment, then an ear, nose and throat specialist referral is warranted. Similar problems are seen in patients with blocked sinuses where pressure cannot be equalized.
Oxygen toxicity10 This may occur acutely as central nervous system toxicity with involuntary twitching, leading to grand mal seizure activity. It is rare using current treatment tables but has been observed with pressures as low as 2 ATA and is much more common in cases of carbon monoxide poisoning. Cumulative toxicity can occur with exposure to 100% oxygen at less than 1 ATA for prolonged periods or with 6 h continuous exposure at 2 ATA. Initial effects are of dull retro-sternal pain and a dry cough which worsens with continued exposure. This may be exacerbated if high-dose oxygen is required between treatments where it may manifest as involuntary muscular twitching.
Visual disturbance Reversible deterioration of vision occurs in all patients when treatment continues over long periods.
E E E E E E E E E E
Decompression illness Carbon monoxide intoxication Arterial gas embolism Gas gangrene Serious mixed infections of soft tissue including diabetic gangrene Crush injuries with compartment syndrome Burns with and without smoke inhalation Post-anoxic encephalopathy Sudden deafness Serious vascular visual pathologies
Chronic indications for HBO E E E E E
Chronic ischaemic ulcers Radiation tissue damage Chronic refractory osteomyelitis As an aid to survival of skin flaps and free skin grafts Bone healing
Three levels of priority have been defined by the ECHM by consensus (Table 3). (a) Type I recommendation. Situations where the transport to a hyperbaric facility is strongly recommended because it is recognized that HBO positively affects the prognosis for survival, i.e. the patient is
HYPERBARIC MEDICINE PART I: THEORY AND PRACTICE
Table 3 Priority for HBO treatment of medical conditions as defined by ECHM TYPE I Acute:
Chronic: TYPE II Acute:
Chronic:
TYPE III Acute:
Chronic:
Decompression illness Carbon monoxide poisoning (major) Gas embolism Anaerobic or mixed bacterial necrotizing soft tissue infection Radionecrotic lesions
Acute soft tissue ischaemia Sudden deafness Ischaemic lesions (without surgically treatable arterial lesions) Osteomyelitis
Carbon monoxide poisoning (minor) Re-perfusion injury Post-anoxic encephalopathy Burns Ophthalmological ischaemia Radionecrosis of intestine or spinal cord
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recommended treatments do not reach a level I, level of evidence as defined by the US Agency for Health Care policy and research.13
US guidelines as issued by the UHMS14 E E E E E E E E E E E E E
Air or gas embolism Carbon monoxide poisoning Clostridial myositis and myonecrosis (gas gangrene) Crush injury, compartment syndrome and other acute traumatic ischaemias Decompression sickness Enhancement of healing in selected problem wounds Exceptional blood loss (anaemia) Intracranial abscess Necrotizing soft tissue infections Osteomyelitis (refractory) Delayed radiation injury (Soft tissue and bony necrosis) Skin grafts and flaps (compromized) Thermal burns
Whatever the consensus is regarding treatment, hyperbaric chambers are used for a variety of conditions, a significant proportion of which fall outside the current guidelines (Table 4).
CONTRA-INDICATIONS FOR HBO THERAPY transported to the nearest hyperbaric facility as soon as possible. (b) Type II recommendation. Situations where the transport to a hyperbaric facility is recommended because it is recognized that HBO constitutes an important part of the treatment of the condition, even if it does not influence the prognosis for survival but is important in the prevention of serious disorders. Transport to a hyperbaric facility should be made unless this represents a danger to the patient’s life. (c) Type III recommendation. Situations where the transfer to a hyperbaric facility is optional because HBO is regarded as an additional treatment modality which can improve clinical results. It is worth emphasizing at this point that the standard of care given in hyperbaric medicine should be as good as that given elsewhere. Put simply, if a hyperbaric unit does not have the ability to look after critically ill patients then it should not be accepting them for treatment. Moreover the standard of care must be appropriate during transport to the hyperbaric facility, especially if referred from another hospital. Due to the lack of randomized controlled trials in hyperbaric medicine most of the currently
Absolute contra-indications16 Several agents used for adjuvant chemotherapy may cause cardiac toxicity under pressure and a gap of one week is recommended between stopping these drugs and HBO therapy. These include bleomycin, doxorubicin, cisplatinum and disulfiram.
Relative contra-indications (i) Chest pathology Pneumothorax can be a serious problem for those undergoing hyperbaric treatment. A pocket of trapped gas in the pleura will decrease in volume on compression and reexpand on surfacing during a cycle of HBO therapy. A 1.8 l pneumothorax at 20 metres below sea level is potentially 6 l at sea level, a life threatening event. Care must be taken therefore with patients who give a history of chest trauma and if any doubts exist then a chest drain must be placed before HBO is contemplated. Patients who have emphysema with carbon dioxide retention are at risk for several reasons. Those relying on a hypoxic drive to ventilation may become apnoeic whilst receiving HBO. Moreover gas trapping and lung rupture may be a real risk if bullous disease is present. It
CURRENT ANAESTHESIA & CRITICAL CARE
118
Table 4 Treatment of patients in British Hyperbaric Association Chambers in 199715 Number of patients Decompression illness CO poisoning Gas embolism (non-diving) Soft tissue infections Post-radiotherapy Other ECHM/UHMS indications Research Other indications Totals
Percentage
349 352 0 32 112
25.4 25.6 0 2.3 8.2
271 37 221
19.7 2.7 16.1
1374
100
caution should be exercized when considering the pregnant patient for HBO.
(vii) History of seizures Increasing baseline medication prior to HBO therapy has been advocated due to the potential of the treatment to lower the seizure threshold.
(viii) Agitated or violent patients Any patient who may be a danger to themselves or to the operators may need to undergo treatment under sedation or anaesthesia.
(ix) Optic neuritis There have been incidences of deterioration of sight and even blindness in patients with a history of optic neuritis.
must also be remembered that if patients have lung disease severe enough to prevent adequate oxygen transfer into the blood stream then it is questionable whether HBO therapy is indicated. Serious consideration should be given to the risk/benefit aspects in this patient group and this includes those with smoke inhalation and significant pneumonitis.
(ii) Asthma Hyper-reactivity of small airways may lead to air-trapping and pulmonary barotrauma on ascent. Each case must be considered individually and carefully.
(iii) Upper respiratory tract infections Difficulties in clearing ears and sinuses may make this a relative contra-indication.
(iv) Viral infections There has been concern that viral infections may be worsened after HBO. The evidence for this is inconclusive and each case must be considered individually.
(v) High fevers A body temperature greater than 38.53C can lower the seizure threshold due to oxygen toxicity. If therapy is deemed urgent an attempt to lower core temperature with antipyretics can be made.
(vi) Pregnancy Previous fears about problems during pregnancy and HBO seem to have been ill-founded. Nevertheless
(x) History of middle ear surgery or disorders An inability to equalise middle-ear pressure represents a contra-indication to undergoing HBO therapy. An ENT review for grommet placement, prior to treatment may be indicated.
TREATMENT REGIMES FOR SELECTED CONDITIONS Decompression sickness Decompression sickness (DCS) is one form of dysbarism. Dysbarism is a general term applied to all pathological changes attributed to altered environmental pressure. As mentioned previously, DCS was first described in caisson workers and even now goes under various names, depending on the presentation. These presentations include the ‘bends’ (joint pains), the ‘staggers’ (vestibular symptoms), the ‘chokes’ (pulmonary symptoms) and the ‘hits’ (spinal cord symptoms) (Table 5). The underlying pathology results from a rapid reduction in environmental pressure and super-saturation of gases dissolved in tissues. Haldane classified DCS into three categories in 1907.17 It is now recognized that decompression sickness and gas embolism when taken together form the group of conditions under the umbrella of ‘decompression illness.’ (DCI). Risk factors have been isolated for DCI following air diving. Obesity (nitrogen is five times more soluble in fat than in water), high serum cholesterol, heavy exercise at depth, a prolonged stay under pressure followed by rapid decompression and a patent foramen ovale are all known to increase susceptibility. Those who fly after diving (i.e.
HYPERBARIC MEDICINE PART I: THEORY AND PRACTICE
Table 5 Signs and symptoms of Decompression Sickness (DCS) Type I DCS Limb and joint pains (‘bends’) Skin rash Type II DCS Neurological: (1) Cerebral visual disturbance aphasia hemiplegia memory loss convulsions coma (2) Spinal (‘hits’) sensory disturbance in extremities paraesthesias numbness weakness difficulty in walking bladder dysfunction paraplegia or quadriplegia (3) Vestibular (‘staggers’) nystagmus vertigo Pulmonary (‘chokes’): Dyspnoea Hyperventilation Chest pain Acute lung injury Cardiac Tachycardia Arrythmias
entering a hypobaric environment) place themselves at high risk of developing symptoms. The objectives of treatment are to get a DCI victim transferred to a hyperbaric treatment facility as soon as possible. Recompression treatment has the aims of reducing bubble volume, re-distributing and re-dissolving gas and reducing tissue oedema and hypoxia. Initial treatment consists of early administration of supplemental oxygen and rehydration. Plasma leakage is a feature and can lead to marked increases in haematocrit and haemoglobin which are associated with a poor overall outcome in DCI. Even if symptoms clear and neurological examination is normal at ground level recompression therapy is still required. DCI is a condition which frequently waxes and wanes with periods of relapse and improvement. Serious symptoms that persist at ground level require 100% O2, aggressive hydration and hyperbaric treatment using US Navy tables 5 or 6.18 Treatment on deeper dive
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tables with helium and oxygen mixtures are becoming more popular for treating DCI. Hydration with intravenous fluids should avoid those containing dextrose as theoretically this may worsen any spinal cord and cerebral oedema. Recently researchers have adapted a clinical scoring system calculated from five clinical variables to predict the outcome following DCI. These variables are defined as repetitive dives, clinical course before HBO therapy, objective sensory deficit, motor impairment and urinary disturbance. This may prove to be useful when considering the number of treatments of HBO therapy which may be appropriate for an individual patient.19,20
Cerebral arterial gas embolism Air in the venous or arterial system can cause cerebral air embolism, leading to severe neurological deficits. Sudden decompression and pulmonary barotrauma in divers is one cause but air can also enter the circulation following trauma to the head, neck or chest and during medical procedures where invasive monitoring is in place. The clinical manifestations are usually neurological or cardiovascular but vary according to patient posture, route of entry and the size of bubbles. These bubbles may cause unconsciousness, convulsions, paresis, nausea and vertigo, visual disturbance, headache, cerebrovascular accidents and if lodged in the coronary circulation, lead to myocardial infarction,12 all of which are features of DCI. One generally accepted treatment is immediate compression to 6 ATA air for a period of 30 minutes followed by ascent to 2.8 ATA in oxygen. The reasoning behind this approach is to initially reduce bubble size thereby decreasing the inflammatory effect of the blood : bubble interface. At 6 ATA the bubble volume is reduced to 17% of its original size and the surface area reduced to 30%. The 100% oxygen counteracts the ischaemic and hypoxic effect of the vascular occlusion. One hundred per cent oxygen also improves the diffusion of nitrogen from the bubble. Vasoconstriction induced by HBO inhibits the redistribution of the embolus throughout the circulation. Most divers are aware of the symptoms associated with DCI and may have a level of medical knowledge on the subject, exceeding that of the occasional practitioner. This awareness usually extends to knowledge of the closest availability of hyperbaric facilities.
Carbon monoxide poisoning Oxygen inhalation to speed the dissociation of carbon monoxide from the haemoglobin molecule is the cornerstone of treatment, having been established by Pace in 1950.22 HBO hastens carboxyhaemoglobin (COHb) dissociation beyond the rate achievable by
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Table 6 Clinical Indications for HBO therapy in CO poisoning26 Neurological abnormality (including hearing and gait assessment) Cognitive impairment, personality change Chest pain, abnormal ECG or raised cardiac enzymes Pregnancy History of sustained loss of consciousness Inability to assess adequately (e.g. concurrent drug overdose)
breathing 100% oxygen at sea level.23 Morbidity amongst survivors of carbon monoxide poisoning is varied but often involves delayed neurological sequelae. It is these delayed symptoms which HBO is also thought to improve. The half-life of COHb in air at 1 ATA is 5 h and 20 min; breathing 100% oxygen at 1 ATA it is 1h and 20 min; breathing 100% oxygen at 3 ATA it is 23 min. One of the difficulties of carbon monoxide poisoning is the lack of correlation of blood levels with symptoms. A blood COHb of greater than 10% is generally regarded as significant, greater than 30% is considered serious. However, clinical manifestations should be the primary consideration and COHb the secondary consideration when assessing the degree of poisoning (Table 6). The objectives of treatment are twofold, firstly to rapidly dissociate the carbon monoxide from haemoglobin and restore oxygen carrying capacity and secondly to attempt to reduce the long-term neurological sequelae. The immediate priority for treatment therefore consists of resuscitation and support with airway control, 100% oxygen and non-glucose containing IV fluids. Onward transfer to a hyperbaric chamber is the next priority where a full neurological and cardiorespiratory examination can be carried out. A minimental state examination is carried out if the patient is awake. Treatment regimes vary but have failed to reach a consensus. Recent work comparing HBO at 2.8 ATA with 100% O2 at 1 ATA claims to show worse long-term outcomes in the HBO group.24 However, this has been questioned as it goes against the weight of evidence over the previous 30 years and too many variables were present in the study to make it conclusive Furthermore, many of the so-called symptoms of carbon monoxide poisoning may have been due to oxygen toxicity related to the treatment tables used. Recent studies have pointed towards evidence that treatment of carbon monoxide poisoning with HBO therapy reduces longterm neurological deficit.27
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CURRENT ANAESTHESIA & CRITICAL CARE 2. Hill L E. Caisson Sickness and the Physiology of Compressed Air Working. London: Edward Arnold, 1912. 3. Behnke A R, Shaw L A. Use of hyperbaric oxygen in treatment of compressed air illness. Nav Med Bull 1937; 35: 1d12. 4. Bernard W F, Tank E S. The effect of oxygen inhalation at 3.0 to 3.6 atmospheres absolute upon children with cyanotic congenital heart disease. Surgery 1963; 54: 203. 5. Churchill-Davidson I, Sanger C, Thomlinson R H. High-pressure oxygen and radiotherapy. Lancet 1955; 1: 1091d1095. 6. Sheridan R L, Shank E S. Hyperbaric oxygen treatment: a brief overview of a controversial topic. J Trauma 1999; 47: 426d435. 7. Spira A. Diving and marine medicine review. Part I: Diving physics and physiology. J Travel Med 1999; 6: 32d34. 8. Jain K K, Fischer B. In: Oxygen in Physiology and Medicine Springfield, USA: Thomas 1989. 9. Bennett M. Handbook of Diving and Hyperbaric Medicine. Prince of Wales Hospital; South Eastern Sydney Area Health Service, 1996. 10. Clark JM. Oxygen toxicity. In: Bennett P, Elliot D (eds). The Physiology and Medicine of Diving. London: WB Saunders Ltd 1993; 493. 11. Plafki C, Peters P, Almeling M, Welslau W, Busch R. Complications and side effects of hyperbaric oxygen therapy. Aviat Space Environ Med 2000; 71: 119d124. 12. Wattel F, Mathieu D (eds) Reports and Recommendations of 1st European Consensus Conference on Hyperbaric Medicine, 1994. 13. US Department of Health and Human Services, Public Health Service, Agency Health Care Policy and Research. Acute pain management: operative or medical procedures and trauma. 1992 Agency for Health Care Policy and Research Publications, Rockville, MD. 14. Hyperbaric oxygen therapy; a committee report. Undersea and Hyperbaric Medical Society. Maryland 1996. 15. Ross J A S (ed) British Hyperbaric Association. Register of member chambers 1998. University of Aberdeen, 1998 16. Kindwall E P. Contraindications and side-effects to hyperbaric oxygen treatment. In: Kindwall E P (ed). Hyperbaric Medicine Practice. Arizona: Best Publishing, 1995. 17. Haldane J S. Admiralty Report on Deep Water Diving 1907; HMSO: CN 1549. 18. Moon R E, Sheffield P J. Guidelines for treatment of decompression sickness. Aviat Space Environ Med 1997; 68: 234d243. 19. Boussuges A, Thirion X, Blanc P et al. Neurological decompression illness: a gravity score. Undersea Hyperbaric Med 1996; 23: 151d155. 20. Pitkin A D, Benton P J, Broome J R. Outcome after treatment of neurological decompression sickness is predicted by a published clinical scoring system. Aviat Space Environ Med 1999; 70: 517d521. 21. Spira A. Diving and marine medicine review part II: diving diseases. J Travel Med 1999; 6: 180d198. 22. Pace N, Strajman E, Walker E L. Acceleration of carbon monoxide elimination in man by high pressure oxygen. Science 1950; 111: 652d654. 23. Smith G, Ledingham I M, Sharp G R et al. Treatment of coal-gas poisoning with oxygen at 2 atmospheres pressure. Lancet 1962; 1: 816d818. 24. Scheinkestel C D, Bailey M, Myles P S et al. Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial. Med J Aust 1999; 170: 203d210. 25. Moon R, DeLong E. Hyperbaric oxygen for carbon monoxide poisoning. Med J Aust 1999; 170: 197d199. 26. Pitkin A D, Broome J R, Salmon J. Hyperbaric oxygen therapy in intensive care. Part II: carbon monoxide poisoning. Br J Intens Care 1999; Nov/Dec: 189d195. 27. Hawkins M, Harrison J, Charters P. Severe carbon monoxide poisoning: outcome after hyperbaric oxygen therapy. Br J Anaesth 2000; 84: 584d586.