Bubble trouble: a review of diving physiology and disease

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1 1 Centre for Altitude, Spae and Extreme Environment Mediine, UCL, London, UK; 2 Hyperbari Servie, The Alfred Hospital, Melbourne, Australia Correspondene to: Dr D Levett, Centre for Altitude, Spae and Extreme Environment Mediine, UCL, 1st Floor Charterhouse Building, Arhway Campus, Highgate Hill, London N19 5LW, UK; denny.levett@ ul.a.uk Reeived 14 May 2008 Aepted 18 August 2008 Bubble trouble: a review of diving physiology and disease D Z H Levett, 1 I L Millar 2 ABSTRACT Exposure to the underwater environment for rereational or oupational purposes is inreasing. Approximately 7 million divers are ative worldwide and more are training every year. Diving related illnesses are onsequently an inreasingly ommon linial problem with over 1000 ases of deompression illness reported annually in the USA alone. Divers are exposed to a number of physiologial risks as a result of the hyperbari underwater environment inluding: the toxi effets of hyperbari gases, the respiratory effets of inreased gas density, drowning, hypothermia and bubble related pathophysiology. Understanding the nature of this pathophysiology provides insight into physiologial systems under stress and as suh may inform translational researh relevant to linial mediine. We will review urrent diving pratie, the physis and physiology of the hyperbari environment, and the pathophysiology and treatment of diving related diseases. We will disuss urrent developments in diving researh and some potential translational researh areas. Diving exposes humans to immersion and to elevated ambient pressures, whih result in a range of physiologial effets and potentially pathophysiologial sequelae over and above the risk of drowning. Despite these hallenges, rereational suba diving is popular. The world s largest diver training ageny, PADI, ertifies approximately new divers annually and it is estimated that around 7 million divers are urrently ative worldwide. Although modern equipment and training have made diving relatively safe, an average of 100 diving related deaths and 1100 ases of deompression illness are reported annually in the USA alone. 1 In addition to rereational diving, many dives are undertaken for sientifi, seafood harvesting, onstrution, maintenane, filming, military, forensi and resue purposes. Currently, the hallenging forms of oupational diving assoiated with offshore oilfield exploration and onstrution are undergoing a major resurgene. This review will address: the types of diving pratised today the physial and physiologial effets of the underwater environment the breathing gases used by divers and their toxi effets the aetiology and pathophysiology of diving diseases the management priniples of diving diseases urrent developments in diving researh and areas of translational researh. Review TYPES OF DIVING Diving an be undertaken in three fundamentally different manners: breath-hold diving, boune diving with breathing apparatus, or saturation diving. Breath-hold and boune diving are regularly used for both rereational and oupational purposes, while the ost and logisti omplexity of saturation diving usually limits its use to the high value onstrution and maintenane work assoiated with the oil industry. Breath-hold diving This most anient and basi means of submergene remains a ore means of olleting seafood, but it has also reently developed as a ompetitive sport, often referred to as apnoea diving. There are a number of ompetitive apnoea diving disiplines depending on the mode of submergene and the type of assistane allowed (for example, fin swimming for asent or desent, assisted desent with weights, assisted asent with buoyany devies). As of January 2008, ompetitive surfae, fae immersed breath-hold durations had reahed 9 min, horizontal underwater swims with fins, 244 m distane, and free diving desent with fin propulsion only, 112 m deep (1232 kpa). A world reord 214 ms (700 feet; 2262 kpa) no limits desent was ahieved by Herbert Nitsh in 2007 using a releasable weight to desend rapidly and a non-ompressible buoyant and hydrodynami hat to asend, baked up by high speed winhes, in a dive that lasted 4 min 6 s. 2 Diving with breathing apparatus Diving using a helmet supplied with free flowing air has a history of many hundreds of years, but modern rereational and oupational diving has grown from the development of the self ontained underwater breathing apparatus (SCUBA), whih was pioneered by Cousteau and Gagnan in The modern single hose demand suba regulator was subsequently invented by Eldred, and first sold as the Porpoise regulator in Its elements remain unhanged today: a high pressure air ylinder arried on the bak with a two stage demand valve system, whih allows the diver to breath air from a mouthpiee with inspiratory and expiratory pressures that vary by only a few entimetres of water pressure above and below ambient. More hallenging oupational diving usually uses surfae supplied breathing gas and full fae masks or helmets equipped with voie ommuniations (surfae supplied breathing apparatus, SSBA). The final gas delivery of SSBA systems usually works on the same priniple as the demand regulator of the rereational suba Postgrad Med J: first published as /pgmj on 22 Deember Downloaded from on 17 June 2018 by guest. Proteted by opyright. Postgrad Med J 2008;84: doi: /pgmj

2 diver but some other systems, suh as free flow helmets, are in use. Seafood harvesters often use a simplified form of SSBA involving a single floating hose and rereational suba style half mask and mouth held regulator. Free swimming diving an also be undertaken using losed iruit rebreather (CCR) apparatus with a arbon dioxide absorbent and oxygen injetion to ompensate for respiratory onsumption. Oxygen only CCRs were developed for bubble-free overt military operations, but the tehnology has advaned signifiantly in reent times to involve trimix (oxygen, helium and nitrogen) systems ontrolled by gas analyser ells and omputers that enable dives in exess of 100 m deep for many hours in duration. Saturation diving Saturation diving is used for deeper dives lasting many days and this requires divers to live inside a pressure hamber usually loated on a diving support vessel (DSV) or an oil platform. The pressure used approximates that of the depth of water in whih the diving work is required and teams of divers are transported from the living hamber to the dive site by a submersible pressurised transport hamber usually referred to as a diving bell. Two or more teams enable 24 h underwater produtivity over several weeks, at the end of whih the diving team is brought to surfae pressure with minimal risk of deompression sikness by deompressing the hamber over several days. Sine the deompression requirement for saturation divers may be more than a week, pressurised DSVs represent one of the most remote environments on earth. In addition to the normal diving environments of fresh or salt water, oupational divers are oasionally alled to work in fluids as hallenging as raw sewage, fermenting heese whey and radioative nulear power station ooling water. Non-immersed pressure exposure also ours in some tunnelling and aisson work and for patients and linial staff in hyperbari oxygen therapy hambers. While muh of what follows also applies to these situations, these environments will not be speifially disussed. PHYSICAL AND PHYSIOLOGICAL EFFECTS OF THE UNDERWATER ENVIRONMENT Most physiologial hallenges of the underwater environment flow from the physis of immersion and the pressure assoiated with inreasing depth. Immersion auses a entral redistribution of blood volume, whih is inreased if old water triggers vasoonstrition. This indues antidiureti hormone (ADH) release and results in a diuresis, rendering the diver relatively hypovolaemi on surfaing. Breathing dry ylinder gas exaerbates any fluid defiit rendering divers at high risk of dehydration whih inreases their suseptibility to diving related illness. The rate and quantum of pressure hange involved in diving greatly exeed anything that humans normally enounter as a result of altitude hange. The ambient pressure at highest point on the earth, the summit of Mount Everest (8500 m) is approximately one third of the sea level value (33 kpa). In ontrast water s density is approximately 1000 times that of sea level air and ambient pressure inreases linearly with depth of submergene at a rate of 1 additional atmosphere (1 bar or 101 kpa) for eah 10 m of sea water (msw). As a result, rereational suba divers diving from sea level to 30 msw experiene a fourfold pressure inrease from 101 kpa to 404 kpa absolute. The deepest in-water working dives have taken human beings to depths of 534 msw (5494 kpa) while the highest human pressurisation reorded was 701 msw (7181 kpa) by the Comex Hydra 11 team in Thus divers are exposed to variations in ambient pressure far in exess of those experiened by high altitude limbers or astronauts. These pressure hanges have profound effets on the behaviour of gases with important impliations for divers. The partial pressures exerted by eah omponent of the diver s breathing gas inreases proportionally with the total ambient pressure as depth inreases (Dalton s law) (fig 1). Exposure to supranormal pressures of gases results in proportionately supranormal quantities of gas being dissolved in body tissues (Henry s law), with profound physiologial effets inluding seizures in the ase of oxygen toxiity or impaired erebral funtion with nitrogen narosis (disussed in greater detail below). On returning to the surfae, the redution in ambient pressure results in supersaturation of tissues with gases, whih is assoiated with bubble formation and in some ases pathologial onsequenes. The inrease in pressure with depth also has impliations for gas filled tissue spaes as pressure and volume are inversely related (Boyle s law). Unvented gas spaes will be ompressed on desent and will expand on asent if ontained within distortable tissues (for example, the bowel, and lungs during breath-hold). In non-distortable tissues suh as the middle ear and sinuses, a pressure gradient will develop between any isolated gas and surrounding tissues resulting in barotrauma. Inreased ambient pressure brings with it inreased density of breathing gas. This, ombined with immersion, brings about redued pulmonary ompliane, inreased airways resistane, inreased VQ mismath, and an inrease in the work of breathing. This inrease in the work of breathing is one of the fators whih limits maximum diving depth. The helium oxygen mixtures that usually replae air as a breathing mixture for dives over 50 m are muh less dense and have redued visosity ompared with air. Despite this, the work of breathing at great depths beomes suh that inspiratory and expiratory mehanial assistane systems have been developed to enable underwater work. 4 Hydrogen has also been explored as the least dense diluent for oxygen but adverse neurologial effets offset any potential gain over heliox or trimix (helium, oxygen, nitrogen). 5 Regardless of breathing gas, poor breathing apparatus design, high work rates or failure of absorbent in rebreathing iruits an lead to CO 2 retention, espeially during deeper Figure 1 depth. Nominal volume, pressure and partial pressure hanges with Postgrad Med J: first published as /pgmj on 22 Deember Downloaded from on 17 June 2018 by guest. Proteted by opyright. 572 Postgrad Med J 2008;84: doi: /pgmj

3 dives, and this has aused a signifiant number of underwater deaths and near misses. A further hallenge is that of temperature regulation. The high thermal ondutivity and apaity of water and dense breathing gas and the old water render the diver at risk of hypothermia. This is a partiular threat in deep tehnial dives in non-tropial waters (suh as the UK), whih neessitate long deompression periods with little ativity. Appropriate exposure suits are essential and for all divers to minimise heat loss (dry suits or wet suits). In saturation diving warmed suit systems and warmed breathing gas supplies are often employed to maintain ore body temperature. DIVING GASES: CHARACTERISTICS AND TOXIC EFFECTS Although a gas supply is essential for survival in the underwater environment, breathing gas under onditions of inreased partial pressures is not without ompliation. Oxygen annot be used alone as it is toxi under hyperbari onditions (see below). Even remarkably inert gases (suh as nitrogen) have toxi properties in hyperbari onditions. There is no ideal gas mixture and the hoie of diving gas is determined by balaning the physiologial effets of eah gas and the diving hallenge (depth and duration). The ommonly used gas mixtures inlude ompressed air, oxygen, nitrox (nitrogen oxygen mix), heliox (helium oxygen) and trimix (helium, oxygen, nitrogen). The harateristis of these gases and their ommon uses are outlined in table 1. Below 50 m, helium oxygen or helium nitrogen oxygen mixtures usually replae air as a breathing gas, both to avoid inert gas narosis and to redue breathing gas visosity. Despite optimising the gas mixture, all diving gases have potentially dangerous toxi effets. An appreiation of these is essential for the diver to identify warning symptoms (if present). The linial syndromes assoiated with dissolved gases are disussed below. Oxygen toxiity Oxygen is toxi under hyperbari onditions. As a result, it is unsuitable as a pure breathing gas for all but very shallow dives Table 1 Properties of ommonly used diving gases Gas Advantages Disadvantages Use Compressed air Cheap and readily available Nitrogen narosis below 30 msw Density inreases work of breathing below 50 msw and a arrier gas must be used with it. The risk of oxygen toxiity is dose dependent (depth, inspired oxygen fration and duration) although there is onsiderable inter-individual and intra-individual variability in suseptibility. Long term hyperoxi exposure must generally be limited to around bar in order to avoid pulmonary oxygen toxiity, as applies in linial pratie. Short term oxygen exposure an be muh higher but exposure to partial pressures greater than 1.6 atmospheres (atm) (.70 msw breathing air; 6 msw breathing 100% oxygen) may ause aute entral nervous system (CNS) toxiity. The manifestations of this are legion and non-speifi, but loss of onsiousness is ommon and, in many ases, grand mal seizures our without prodromal symptoms (box 1). 6 Seizures spontaneously terminate upon essation of oxygen inhalation but for unonsious divers who are not immediately resued, drowning is almost inevitable. Fortunately the threshold for CNS toxiity is higher for resting, dry exposures in the absene of hyperarbia and oxygen is regularly breathed at partial pressures up to 2.8 bar during the treatment of deompression illness and the provision of hyperbari oxygen therapy. Nitrogen narosis Nitrogen is naroti when breathed under hyperbari onditions. 7 Nitrogen narosis is haraterised by euphoria, intoxiation and progressive depression of entral nervous system funtion (table 2). The onset is insidious and an result in irrational behaviour, impaired judgement and a false sense of seurity. Although there is onsiderable variation in individual suseptibility, performane is impaired in all individuals and short term adaptation to the naroti effets does not our. Many divers believe that they an develop resistane to nitrogen narosis with pratie but it has been shown that while habituation redues subjetive symptoms, performane remains impaired. 8 Narosis indued over onfidene and impaired performane represents an important, and probably underestimated, threat to diver safety. In the Australasian diving fatality database, Most ommon breathing mixture for rereational diving 100% oxygen Minimal naroti poteny CNS oxygen toxiity above 2 bar Military and experimental divers Deompression gas in tehnial divers Limited to depths of 6 8 msw Nitrox (nitrogen oxygen, nitrogen,80%) Heliox (helium oxygen) Trimix (helium nitrogen oxygen) Inreased dive time Redued deompression time Redued narosis Redued density Redued narosis Redued density Redued high pressure neurologial syndrome risk on deep diving Avoid hyperoxia CNS, entral nervous system; msw, metres of sea water. Potential for oxygen toxiity if inappropriate mixture used at depth High thermal ondutivity Speeh distortion High pressure neurologial syndrome beneath 200 msw Cost Taste loss Cost Compliated mixing and risk of error Tehnial rereational diving Deompression gas for tehnial divers Commerial diving.50 msw Military diving Tehnial rereational diving Deep ommerial diving Deep tehnial rereational diving Postgrad Med J: first published as /pgmj on 22 Deember Downloaded from on 17 June 2018 by guest. Proteted by opyright. Postgrad Med J 2008;84: doi: /pgmj

4 Box 1: Clinial features of oxygen toxiity Aute oxygen toxiity symptoms V: vertigo, visual disturbane E: ears, exitability, euphoria N: nausea, numbness T: tinnitus, twithing, tremor I: irritability, irrational behaviour D: dizziness, disorientation, depression C: onvulsions Projet Stikybeak, it was estimated that nitrogen narosis ontributed to death in 9% of ases. High pressure neurologial syndrome and helium Helium is used for deep diving beause of an absene of naroti effets. However, at depths below 120 m divers may develop high pressure neurologial syndrome (HPNS), involving hyper-exitatory symptoms suh as tremor, myoloni jerks and irritability thought to be due to membrane and neurotransmitter mediated effets of pressure The effets are reversible on return to normal ambient pressure but limit the performane of divers at extreme depths. Admixture of nitrogen into the heliox mixture, to reate trimix, provides some ounter-ating naroti effet that minimises this problem. 11 Contaminant gas toxiity The partial pressure of any breathing gas ontaminant rises with inreasing depth, mandating high standards of purity for breathing gas. Carbon monoxide poisoning has been responsible for many divers deaths, and low moleular weight volatile hydroarbon ontamination is urrently reeiving attention as a possible ause of some ases of underwater inapaitation and post-dive malaise. 12 Table 2 Typial linial features of nitrogen narosis Nitrogen partial pressure (bar) Symptoms and signs 2 4 Mild impairment of performane of unpratised tasks Mild euphoria 4 Impaired reasoning and immediate memory Delayed response to visual and auditory stimuli Inreased reation time 4 6 Overonfidene and fixed thinking Calulation errors 6 Impaired judgement Halluinations 6 8 Laughter approahing hysteria Talkative, oasional dizziness 8 Severely impaired intelletual performane Mental onfusion, impaired onentration 10 Stupefation.10 Halluinations, unonsiousness, death DIVING DISEASES: AETIOLOGY AND PATHOPHYSIOLOGY Barotrauma Barotrauma an affet any non-vented gas ontaining spae with damage ourring during ompression ( squeeze ) or due to gas expansion on asent. Desent of as little as 1 2 m is enough to ause pain, oedema and even haemorrhage (fig 2) in paranasal sinuses with bloked ostia or middle ears where there is Eustahian tube dysfuntion. Middle ear barotrauma is the most ommon diving related pathology but is usually minor and self limiting. Tympani membrane rupture an our, however, and inner ear barotraumas with rupture of the round or oval window and perilymph fistula are partiularly serious. Differential ear equalisation an result in the self explanatory and usually transient syndrome of alternobari vertigo. The reords set by apnoea divers are remarkable with respet to pulmonary barotrauma, as a 20-fold ompression of the lung volume would probably result in fatal intrapulmonary haemorrhage for most untrained persons. Apnoea divers train to minimise their residual volume and also maximise their pre-dive total lung apaity by using an oropharyngeal breath staking tehnique that overinflates the lung. Pursed lips expiration after surfaing reates positive expiratory pressure aimed at reduing the risk of pulmonary oedema that sometimes ours. Some divers may develop ysti emphysematous lung hanges as a result of hyperinflation over a prolonged period. Pulmonary barotrauma of asent and arterial gas embolism Unlike breath-hold divers, divers using breathing apparatus maintain relatively normal pulmonary volumes while diving but during asent, the ompressed gas in their lungs expands with the falling ambient pressure. If intrapulmonary gas is prevented from esaping as a result of a losed glottis, bronhospasm or gas trapping, exessive transpulmonary pressures will result. Differential alveolar ompliane results in differential expansion of adjaent lung units ausing foal shearing between vessels and airways and rupture of small airways and/or alveoli. Esaping gas an enter the pleural avity (pneumothorax), mediastinum (mediastinal emphysema that may extend down into the retroperitoneum or appear around the nek as subutaneous emphysema), periardial avity (pneumoperiardium) or pulmonary venules (whih transits the left heart to Figure 2 A diver with sinus barotraumas blood is seen in the mask from sinus haemorrhage. Postgrad Med J: first published as /pgmj on 22 Deember Downloaded from on 17 June 2018 by guest. Proteted by opyright. 574 Postgrad Med J 2008;84: doi: /pgmj

5 result in arterial gas embolism). The subsequent pathophysiologial proesses and linial presentation are similar to those aused by iatrogeni gas embolism suh as may our during laparosopi surgery or ardiopulmonary bypass. Gas bubbles entering the systemi irulation are distributed by buoyany and blood flow. The erebral irulation and the middle erebral artery in partiular are ommon sites of bubble distribution. Most bubbles pass through the erebral vasulature after varying delay, although sustained olusion resulting in infartion may our. 15 Intravasular bubbles trigger an aute inflammatory response with haematologial and vasular omponents, whih may result in redued erebral blood flow, dereased integrity of the blood brain barrier and erebral oedema. Cerebral arterial gas embolism (CAGE) lassially presents within seonds to minutes of a diver surfaing, with profound neurologial symptoms whih may resemble a erebrovasular aident. Clinial features inlude paralysis, onvulsions and oma, often aompanied by ardiovasular instability or ardia arrest. Most ases improve partially or ompletely over a short period as blood flow is re-established, but relapse is ommon over the hours following due to re-embolisation or post-embolism vasular leak and inflammation. Box 2 lists the various types of barotraumas. Deompression sikness: The bends During a dive, inert gas beomes dissolved in tissues as a funtion of time and depth. After many hours, a state of equilibrium an be reahed between the breathing gas and the tissues, known as saturation. As divers asend to the surfae, the nitrogen or helium diffuses from tissues into the blood and from blood into the lungs. As the partial pressure of inert gas in the blood and tissues exeeds ambient pressure, bubbles form in the tissues and blood vessels, whih may result in the linial syndrome of deompression sikness. The linial manifestations of deompression sikness are protean, refleting the effets of bubble formation in diverse anatomial loations (table 3). Multiple systems may be involved. Symptoms may our immediately on surfaing, or onset may be delayed for up to 48 h. The disease may be progressive or may stabilise or an be relapsing and remitting in nature. It may be minor and self limiting in nature, but an be Box 2: Types of barotrauma Ear, nose and throat Mask squeeze Sinus barotrauma Tooth barotrauma Middle ear barotrauma Inner ear barotrauma Gastrointestinal trat Hollow visus perforation Pulmonary barotrauma Surgial emphysema Pneumomediastinum Pneumothorax tension Arterial gas embolism Coronary artery gas embolism Cerebral artery gas embolism atastrophi resulting in permanent paralysis and death. Altitude has a signifiant triggering and exaerbating effet and emergeny transport of divers should avoid signifiant altitude exposure. Bubbles exert their pathophysiologial effets by mehanially distorting tissues, obstruting blood flow and initiating an inflammatory response. Doppler ultrasound has demonstrated that deompression sikness is assoiated with venous intravasular bubbles and that the bubble load is proportional to the deompression stress. However, it should be emphasised that the presene of bubbles is not always assoiated with overt linial symptoms and many, if not most, dives result in silent bubbles. The majority of intravasular bubbles in deompression sikness our in the venous irulation. The lungs at as a filter, trapping and exreting venous bubbles and preventing their passage into the systemi irulation. Exeptions to this rule our in severe deompression sikness where the pulmonary irulation is overwhelmed by the bubble load ( the hokes ), in right-to-left intraardia shunts (for example, patent foramen ovale (PFO)), via intrapulmonary shunting and as a result of pulmonary barotrauma, where bubbles diretly enter the pulmonary irulation. In these ases bubbles enter the arterial irulation resulting in gas embolism with the onsequenes disussed previously. Of partiular reent interest has been the observation that individuals with large PFOs have an inreased risk of neurologial deompression sikness and partiularly spinal ord disease. 18 Intravasular bubbles damage both the blood vessel luminal surfatant layer and endothelial ells. This redues the integrity of the vessels and auses endothelial ativation. Bubbles also interat with formed elements of blood and plasma proteins. They may ause platelet and leuoyte aggregation, ytokine release, and ativate the omplement, kinin, fibrinolyti and oagulation asades. The subsequent aute inflammatory response results in inreased apillary permeability and haemoonentration. 21 Pulmonary oedema Aute pulmonary oedema is a rare but dramati result of some or all of a group of fators that an inrease pulmonary vasular distension and generate negative airways pressures. Immersion, old, vigorous exerise, hyperventilation, poorly funtioning breathing regulators and fluid overload as a result of over zealous attempts to avoid dehydration have all been impliated. 22 There may be a ommon onstitutional risk fator with hypertension as non-hypertensives who experiene an episode may be predisposed to developing hypertension in the years that Table 3 Clinial features and inidene in deompression sikness: data from 1170 ases reorded in the Institute of Naval Mediine, UK between 1990 and 1999 (personal ommuniation) Manifestation Prevalene (%) Neurologial symptoms (inluding 77 auditory) Limb pain 48 Constitutional 29 Skin 9.7 Respiratory 3.7 Girdle/bak pain 3.2 Lymphati 0.9 Postgrad Med J: first published as /pgmj on 22 Deember Downloaded from on 17 June 2018 by guest. Proteted by opyright. Postgrad Med J 2008;84: doi: /pgmj

6 follow. 23 Differential hanges in right versus left sided ardia ontratility have also been hypothesised as ontributing. The syndrome usually resolves rapidly but may be the ause of some deaths attributed to drowning. Long term effets of diving Diving appears generally well tolerated, but regular divers probably self selet as healthy survivors. In ontrast, suseptible individuals or those who expose themselves to less ontrolled diving an experiene neuroognitive dysfuntion, dysbari osteonerosis, hearing loss and pulmonary funtion hanges. 24 The Evaluation of Long Term Health Impats of Diving (ELTHI diving study) projet undertaken by Aberdeen University on behalf of the UK Health and Safety Exeutive has ompared the long term health of offshore oil industry divers with other offshore workers and found some inrease in self reported omplaints of forgetfulness, loss of onentration, hearing loss and musuloskeletal symptoms among divers; however, overall health quality of life was not signifiantly different from other workers and the overall findings did not exeed the threshold of linial signifiane. 25 Subsequent analysis has suggested some assoiation between the reported defiits and underwater welding work but it remains a possibility that at least some individuals an arue symptomati health derements as a result of diving, even when overt deompression illness has not ourred. 26 PREVENTION AND TREATMENT OF DIVING DISEASE Avoiding deompression sikness Divers use various forms of deompression proedures to minimise the risk of deompression sikness. Dive omputers, published tables and personal omputer software algorithms reommend limits on dive duration for any given depth and presribe maximum asent rates and deompression stops for various ombinations of depth, dive time and breathing gas mixture. Repetitive dives and dives at altitude require more onservative exposures. Deompression models are variously based on theoretial exponential wash-in and washout urves for inert gas uptake and exretion by the tissues and/or data from both researh and field dives. Many models involve very omplex and relatively poorly validated mathematis, but despite this, implementation of the most ommon approahes has effeted both rereational and oupational deompression with illness rates as low as 1:5000 dives or less where diving is undertaken in well ontrolled and non-experimental settings. 1 There seems to be pronouned inter-individual variability in suseptibility to deompression sikness as well as many fators that an vary the risk for any one individual. As a onsequene, some individuals will experiene symptoms even if they stritly follow established deompression proedures. Fators assoiated with an inreased risk of deompression sikness inlude obesity, fatigue, old, dehydration, and inter-urrent illness. 27 Regular diving may produe tolerane in some individuals while preonditioning via vigorous exerise shows some promise, although this may only be protetive within speifi pre-dive time windows. 28 Treatment for deompression sikness and gas embolism In addition to normal first aid proedures, oxygen administration is a priority. Oxygen not only treats arterial hypoxaemia but also enhanes the rate of elimination of inert gas and the resolution of bubbles. During transport and treatment, divers should be kept in a supine position to minimise the risk of further erebral artery embolism. Intravenous fluid resusitation is reommended to ounterat the intravasular depletion and ompromised miroirulation aused by pressure indued diuresis, endothelial damage and inreased apillary permeability. In the absene of intravenous fluids, oral rehydration is reommended. The definitive treatment is reompression in a hyperbari hamber. Early treatment results in a better prognosis. 1 Compression physially redues bubble volume in aordane with Boyle s law. The use of 100% oxygen as the breathing gas during reompression is therapeuti via various mehanisms inluding rapid elimination of inert gas, maximal oxygenation of ishaemi tissues, redution of oedema, and inhibition of seondary inflammatory and reperfusion injury, inluding via inhibition of neutrophil adhesion moleule expression. 29 Reompression shedules for the treatment of deompression sikness onsist of a rapid reompression to a speified pressure with oxygen breathing interrupted periodially by air breaks and ontinuing during a subsequent slow and staged deompression. The most ommonly used initial shedule ( USN6 or RN62 ) takes approximately 5 h. If symptoms do not resolve ompletely, treatments are repeated one or twie daily, until the symptoms are relieved or a plateau in improvement is reahed. The vast majority of patients only require one to three treatments. 30 A number of adjuntive treatments have been used in deompression sikness. A reent double blind randomised ontrolled trial indiates that non-steroidal anti-inflammatory drugs an redue the number of reompression sessions required, although symptomati outome was not improved. 31 Steroids and aspirin are sometimes used but appear not to improve outome. 32 Similarly antioagulation with heparin is probably not benefiial and may inrease the risk of spinal ord haemorrhage. 33 An interesting development has been the use of lignoaine in aute deompression sikness. Lignoaine has been shown to redue brain dysfuntion after air embolism in animal models. 34 Several ase reports suggest that lignoaine has a benefiial effet on outome in deompression sikness, even if treatment has been delayed and the symptoms had been previously refratory to reompression. Putative mehanisms for the effiay of lignoaine inlude an anti-leuoyte effet and the deeleration of ishaemi transmembrane ion shifts. 37 A ontrolled trial is awaited. Box 3 lists the deompression sikness hotlines in the UK. NEW DEVELOPMENTS AND POTENTIAL TRANSLATIONAL RESEARCH RELEVANT TO MEDICINE In reent years, sophistiated eletronially ontrolled mixed gas rebreather systems have beome available for advaned rereational divers, enabling untethered diving to depths well in exess of the normal rereational range. This has brought about a range of new omputer algorithms for alulating deompression based upon widely varying datasets, underlying mathematis and physiologial assumptions. Some inorporate muh deeper deompression stops than used traditionally, but it is far from lear whether this is advantageous. An analysis of this pratie will be reported in the proeedings of an expert workshop on the subjet that was run by the Divers Alert Network in June With regard to medial fitness to dive, traditional deterministi views on who is fit to dive are being hallenged by permissive risk assumption philosophies and this, ombined with an aumulation of data on uneventful dives by divers with health problems, has led to many ontraindiations previously held to be absolute beoming relative. In partiular, Postgrad Med J: first published as /pgmj on 22 Deember Downloaded from on 17 June 2018 by guest. Proteted by opyright. 576 Postgrad Med J 2008;84: doi: /pgmj

7 Box 3: Deompression sikness hotlines in the UK and a seletion of international diving medial soieties Sottish Diving Hotline, Aberdeen Royal Infirmary: (24 h) English Diving Hotline, Institute of Naval Mediine: (24 h) British Hyperbari Assoiation: (UK hamber information) South Paifi Underwater Mediine Soiety: Undersea and Hyperbari Mediine Soiety: European Underwater and Baromedial Soiety: DAN: Divers Alert Network: UK Sport Diving Medial Committee: some diabeti and asthmati subjets are now undertaking suba diving, prinipally in the rereational setting. 38 It is hoped that more sophistiated registries will be developed to provide a better evidene base for estimating the signifiane of suh risks. The possibility of there being gender differenes in deompression illness risk has long been a subjet of speulation. A prospetive trial of altitude exposure showed no net differenes between men and women in risk for altitude deompression illness, but there was some assoiation with menstrual yle phase in subjets taking oral ontraeptives. 39 Prospetive data on over rereational dives by women submitting dive data to an ongoing projet by the Diving Diseases Researh Centre also suggests an assoiation of risk with phase of the menstrual yle, with problems more likely to be reported during the last and first weeks of the yle With the trauma literature suggesting that female sex hormones play a modulating role in seondary inflammatory proesses after trauma, there is lear potential for further work in this field. Preonditioning, oxidant stress and seondary injury modulation are ative researh areas that may produe results relevant to divers. Likewise, divers may prove a testing ground for therapeuti substanes. Deompression illness treatments, whih target the seondary effets of bubbles, are urrently a fous of researh. Modifiation of leuoyte behaviour in partiular may beome a major therapeuti modality in the future. Monolonal antibodies to leuoyte adhesion moleules are urrently being investigated in animal models of deompression illness. 44 Perfluoroarbons have the potential to enhane off-gassing while providing favourable oxygen delivery and possibly useful surfatant and immunomodulatory effets. 45 A preonditioning agent of partiular interest is oxygen breathed under pressure. Rapidly evolving researh with hyperbari oxygen demonstrates that the oxidative stress this therapy provides an upregulate endogenous antioxidants, moderate inflammatory injury and inhibit reperfusion injury and apoptosis in a variety of settings Exposure to hyperbari oxygen exposure before diving shows potential to redue the risk of deompression illness If they were able to be aessed, the growing pool of nitrox and rebreather divers ould provide data on a natural human experiment that is testing both tolerane to prolonged hyperoxia and the interation of hyperoxia with deompression illness risk. The apparently dramati inter-individual variations in suseptibility to diving illnesses and oxygen toxiity are almost ertainly the result of onstitutional and genetially determined fators. As exposure to the physiologial stress of diving is ommon, divers ould provide a fruitful soure of material for genomi and proteomi analysis against markers suh as Doppler bubble soring and ytokines or other markers of endothelial injury. In the diving oriented basi siene laboratory, muh useful oxygen toxiity researh ontinues; one partiularly interesting reent finding is that pulmonary oxygen toxiity at pressure appears modulated via neurologial pathways that are quite different to the oxygen toxiity generated by prolonged ventilation on high frational inspired oxygen (FiO 2 ) values at sea level. 55 With respet to the moleular mehanisms of inert gas narosis and HPNS, muh remains unknown but there is almost ertainly ommon ground with mehanisms of anaesthesia and the toxiity of various gases. Investigations into the roles of mironulei, aveoli, surfatants and the nature and assoiations of endothelial miropartiles seem likely to enhane our understanding of not only deompression illness but also how to minimise the risks of ognitive impairment and other side effets of ardia bypass and proedures assoiated with the potential for gas embolism. The hyperbari environment presents an opportunity to study normal physiologial systems under extreme environmental stress, giving an insight into the limits of physiologial tolerane. The pathophysiology of diving related syndromes suh as deompression illness, nitrogen narosis and oxygen toxiity may provide insight into the pathologial proesses underlying linial situations suh as aute lung injury, systemi inflammatory response syndrome, mehanisms of anaesthesia and post-anaestheti and post-ardia bypass morbidity. SUMMARY The underwater environment presents a number of hallenges, both physial and physiologial, to the diver. Diving is assoiated with multiple risks, some potentially fatal inluding drowning, hypothermia, inert gas narosis, oxygen toxiity, arterial gas embolism, deompression sikness, high pressure neurologial syndrome, hroni joint dysfuntion and neuroognitive impairment. In spite of these risks, it is an inreasingly popular pastime and the boundaries of both rereational and oupational diving are ontinuously being expanded. Consequently, general physiians may enounter diving related pathology in their aute medial pratie and an understanding of diving pathophysiology is inreasingly important. As more patients with medial omorbidity undertake diving, an appreiation of the impliations of hroni medial onditions for diving will also beome valuable. Finally, researh in extreme environments allows exploration of human physiology at its limits. This has the potential to provide valuable insights into pathophysiology and mediine and has potential translational relevane to the linial arena. Key learning points There is wide inter-individual variability in suseptibility to deompression illness. Supplemental oxygen and rapid transfer to a reompression faility are the treatment priorities in diving related illness. Prevention of deompression illness by safe diving pratie is key. Inflammation is an important mehanism of injury in bubble related disease. Gas embolism may benefit from hyperbari oxygen treatment. Breathing oxygen under onditions of inreased pressure is potentially toxi. Postgrad Med J: first published as /pgmj on 22 Deember Downloaded from on 17 June 2018 by guest. Proteted by opyright. Postgrad Med J 2008;84: doi: /pgmj

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