STF23 A95010 Gradering: Åpen. Behandling av dekompresj onssykdom ULJlW UNIMED

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1 STF23 A95010 Gradering: Åpen Behandling av dekompresj onssykdom ULJlW UNIMED

2 - / - ULJ1ILL UNIMED 11TTEL Behandling av dekompresjonssykdom SINTEF UNIMED Ekstreme arbeidsmiljo Postadresse: 7034 Trondheim Besøksadresse: OlaV Kyrresgt. 3 Telefon: Telefax: Telex: sintf n Foretaksnr.: FORFATTER(E) Brubakk, A.0.; Molvær, 0.1.; Risberg, 1.; Flook, V.; Langø, T.; MØrland, T. OPPDRAGSGIVER(E) OMEGA (Statoil, Norsk Hydro, Saga Petroleum og Oljedirektoratet) ARKIVKODE GRADEFIING OPPDRAGSGIVERS REF. Apen Cato Hordnes ELEKTRONISK ARKIVKODE PROSJEI(TNR. ANTALL SIDER OG BILAG M:\13A0BE353.W ISBN PRISORUPPE FAGLIG ANSVARLIG Alf 0. Brubakk RAPPORTNR. DATO ANSVARLIG SIGNATUR S3 SAMMENDRAG A Arvid Påsche Behandling av dekompresjonssydom er fortsatt et problem. Optimale behandlingsrutiner er ikke utviklet og dokumentert. - Dokumentet gir en oversikt over litteraturen og viser ved hjelp av simuleringer muligheter for forbedringer. Det anbefales at videre studier forventes for å forbedre behandling av alvorlige symptomer og bruk av oksygen på overflaten. rfl(kord NELS( GRUPPE I Helse Health GRUPPE 2 Dykking Diving EGENVALGTE Dekompresjon Decompression Dekompresjonssyke Decompression sickness

3 3UEÏEE UNIMED INNHOLDSFORTEGNELSE INNLEDNING SAMMENDRAG v vi DEL 1: DECOMPRESSION ILLNESS. WHAT DO WE KNOW, WHAT WE DO NOT KNOW, Alf 0. Brubakk INTRODUCTION 2 IS DECOMPRESSION ILLNESS A DISEASE7 3 PROPHYLAXIS 4 TRE DECOMPRESSION PROCESS 5 CLINICAL DIAGNOSIS AND REPORTING 6 RELATIONSHIP BETWEEN VASCULAR BUBBLES 7 ARE BENDS A RED HERRING 8 EFFECT OF BUBBLES 9 CENTRAL NERVOUS SYSTEM 10 TREATMENT OF DCI 11 CONCLUSIONS 12 ACKNOWLEDGMENT 13 REFERENCES AND DCI DEL 2: BEHANDLING AV TRYKKFALLSSYKJE, Otto Molvær 1 INNLEIING 2 VARIABLAR MÆD RELASJON TIL TRYKK-KAMMERBEHANDLING 2.1 Tid frå symptomstart til behandling sstart 2.2 Behandlingstrykk 2.3 Gassblanding Luft Oksygen Blandingsgass Karbondioksiddeitrykk 2.4 Tid under trykk Tabell Tabell Repetisjonsbehandling Mettingsbehandling 2.5 Tabellprofil 2.6 Temperatur 2.7 Relativ fukt 2.8 Fysisk aktivitet 3 EVALUERINGSMETODAR 4 DOKUMENTASJON AV EFFEKT 5 VURDERING 6 KONKLUSJON 7 REFERANSAR M:\BAOBE353.W5 I

4 METNINGSDYKKING påvirkning 2.2 Sykdomsmekanismen ved TFS - mulighet for farmakologisk Behandlingsgass 2.1 Innledning 2 MEDIKAMENTELL TILLEGGSBEHANDLING VED TRYKKFALLSSYKE 1.3 Anbefalinger 1.1 Rekompresjons 2 i BEHANDLING AV DEKOMPRESJONSSYKDOM UNDER DEL 3: BEHANDLING AV DEKOMPRESJONSSYKDOM, Jan Risberg 11 M:\BAOBE353.W5 I 3.7 The normal end to the Sur-D proffie 9 INTRODUCTION Rapid decompression USN Cx RN Cx USN6A USN6 7 3 PERFORMANCE OF TREATMENT TABLES Primary decompression USN Sur-D profile 4 2 PRIMARY DECOMPRESSION PROFILES Treatment tables 2 MODEL OF GAS DYNAMICS AND BUBBLE GROWTH, Valerie Flook DEL 4: A STUDY OF TREATMENT TABLES USING A MATEMATICAL 6 REFERANSER 5.10 Norge 5.7 Italia 5.8 Tyskland 5.5 Diver s alert nework (USA) 5.2 Finland. 5.3 Sverige. 5.4 Danmark 5.6 Storbritania 5.9 USA Innledning INTERNASJONAL PRAKSIS EFFEKT FOR BEHANDLINGSRESULTAT AV LATENSTID MELLOM 2.5 Kolloider (Dextran) 2.8 Lidokain SYIVIPTOMDEBUT OG BEHANDLINGSTART 4 GJENTATTE REKOMPRESJONSBEHANDLINGER 2.4 Acetylsalicylsyre 2.10 Sammendrag Peroral og parenteral rehydrering Steroider 2.7 Diazepam 2.9 Andre medikamenter krystalloider UNIMED

5 DEL 5: DEKOMPRSJONSSYKDOM. STUDIUM AV GRUNNLEGGENDE TEORI MED MATEMATISK UTLEDNING AV EN ENKEL BEHANDLINGS MODELL, Thomas Langø & Terje MØrland 7 REFERENCES 5 COMPARISON BETWEEN TABLES 6 CONCLUSION USN 6 and Comex CxandUSN5 4.1 Flying following treatment 4 PROBLEMS ASS OCIATED WITH THE REMAINING 5.3 USN 6A and RN GAS PHASE 10 M: BAOBE353.W5 i 2.2 Patologiske effekter Sekundære effekter Kliniske symptomer ved DKS Opptak og eliminasjon av inerte gasser. I KOMPRESJONS- OG DEKOMPRESJONSTEORI FORORD INNLEDNING 3.4 Gasskifter Visjon og praktisk fremgangsmåte ved modelleringen Input og output Utgangspunkt for beregningene Endring av bobleradius pga. diffusjon av én inertgass Rekompresjon 31 4 EN ENKEL BEHANDLINGSMODELL Diskusjon og kommentarer Uttrykk for volumreduksjonen Oksygen som inértgass Gassutveksling generelt Oksygeneffekten Medikamenter og andre muligheter for tilleggbehandling Innledning 40 3 BEHANDLING AV DEKOMPRESJONSSYKDOM 30 2 DEKOMPRESJONSSYKDOM Bakgrunn for bobledannelse Historisk oversikt Perfusjonsbegrenset kinetikk Diffusjonsbegrenset kinetikk Primære effekter Behov for modell Kompartmentbeskrivelse Trykkgradienten rundt boblen Estimenng av P02 vev og Pc 02 vev Modelitype og grunnleggende antakelser Effekt av metabolske gasser Gassutveksling mellom boble og vev Effekter av metabolske gasser Bobler i kroppen Prinsipper LØselighet Kort om dekompresjonsmodeller UNIMED 111 UE11IIi

6 APPENDIKSER LJflERATURLISTE Inkludering av gassskifter Den endelige énkompartmentmodellen Volumreduksjonen Skjematisk oppsummering av modellen 60 VEIEN VIDERE Initielle kalkulasjoner 58 M:\BAOBE353.W51 3UEiM UNIMED

7 1ÏEE UNItAED INNLEDNING v ble det i regi av Omega-prosjektet startet et forprosjekt vedrørende behandling av dekompresjonssyke. Bakgrunnen for dette var et Ønske om å få en samlet oversikt over dagens behandling, og å søke å se på de forskjellige faktorer som kan bidra til et godt behandlingsresultat. En optimalisering av behandlingsresultater for dekompresjonssykdom er viktig av flere grunner. Hvert år blir en rekke dykkere behandlet for denne tilstanden, og nyere undersøkelser tyder på at et stort flertall av dykkerne har symptomer fra sentralnervesystemet før behandling. Spesielt i de tilfellene der det går timer imellom symptomdebut og behandling, vil en bare kunne oppnå fullstendig symptomfrihet i ca. 50% av tilfellene. En rekke av de pasienter som ikke får fullstendig symptomfrihet vil ha permanente forandringer. Det er også fra flere undersøkelser vist at en rekke dykkere ikke rapporterer symptomer og tegn i forbindelse med dekompresjonen. Det kan være mange grunner til dette, men en av dem kan være at de behandlings- og oppfølgingsprosedyrer vi følger er så omfattende at dykkerne føler at rapportering vil være en for stor belastning. Det ville i tilfelle være ønskelig å bruke betydelig enklere behandlingsformer, det er foreløpig ingen som vet om dette vil være tilstrekkelig for å forhindre skader. Nyere kunnskaper om mekanismene for skader ved dekompresjonssykdom, og hvordan gassbobler påvirker organismen, gjør det sannsynlig at en kan ha nytte av behandling med meclikamenter av forskjellig art i forbindelse med dekompresjonssykdom. Det er foreløpig lite kunnskaper om hvilken effekt slike medikamenter vil ha, og hvordan disse eventuelt kan kombineres med bruk av konvensjonell behandling. Bruk av medikamenter kan være særlig aktuelt i forbindelse med nøddekompresjon, i de tilfelle der en er nødt til å dekomprimere dykkere raskt for å få dem ut av en farlig situasjon. Den foreliggende studien har vært et resultat av et samarbeid mellom NUTEC, SINTEF og Universitetet i Trondheim. Den er presentert som en serie med delstudier, og representerer den første omfattende oversikt over dette i Norge. M:\BAOBE353.W5 I

8 UEÏEE UNIMED vi SAMMENFATNING OG ANBEFALINGER Hovecikonklusjonene fra studien er følgende: - Gassbobledannelse i vev og blodkar er den utløsende mekanisme for DCI. - Mekanismen for hvordan gassboblene skader organismen er for en stor grad ukjent, selv om det finnes plausible modeller for deler av den patofysiologiske prosessen. - Oksygen og lave trykk er fortsatt den beste initiale behandling, selv om det optimale trykk og oksygentensjon ikke er kjent. - Behandling med 100% oksygen før trykksetting synes å ha gunstig effekt på behandlings resultatet. - Bare ca. 50% av pasientene oppnår fullstendig symptomfrihet etter første behandling, spesielt hvis det er lang tid mellom den utløsende dekompresjon og behandlingen. Behandlingsresultatene synes uavhengig av hvilken tabell som brukes. - Moderate sentralnervøse symptomer forekom like hyppig hos dykkere som hadde vært behandlet, som dykkere som har hatt somptomer uten behandling i den norske spørreundersøkelsen. Selv om sannsynligvis de initiale symptomer var alvorligere hos de dykkere som ble behandlet, tyder dette på at behandlingen ikke er i stand til helt å forhindre slike symptomer. - Bruk av 600 Kpa tabeller (USN 6A) med luft synes ikke å gi bedre resultater enn bruk av 280 kpa oksygen (USN 6). Bruk av mtrox ved 600 kpa kan være gunstig. - Heliox har vært foreslått som et alternativ for behandling, effekten av dette er dårlig dokumentert. Teoretiske studier (simuleringer) tyder på at den anbefalte helioxprosedyre (Comex CX3O) fører til Økt gassdannelse under behandlingen. - Det synes ikke å være enighet om den optimale tid under trykk etter symptomfrihet. Dette gjelder også for bruken av metningsbehandling. Simuleringer tyder på at behandlingsprosedyren bør tilpasses dykket som har forårsaket problemet. - Væskebehandling er akseptert som viktig, det er ingen generell enighet om effekten av andre medikamenter. - Tilfredsstillende prosedyrer for nød-dekornpresjon finnes ikke. M:\BAOBE353.W5 I

9 UEE UNIMED vii Anbefalinger Selv om bruk av US Navy Tabell 6 synes å være adekvat behandling i en lang rekke tilfeller, er behandlingen av alvorlige symptomer fortsatt utilfredsstillende. Gruppen vil anbefale at dette studeres nærmere, spesielt bruk av heliox og bruk av forskjellige oksygentensjoner. Bruk av oksygen på overflaten før trykksetting anbefales idag av de fleste amatørdykker organisasjoner. Effekten av en slik behandling, eventuelt bruk av denne behandling som eneste tiltak, er dårlig dokumentert, og bør studeres nærmere. Bruk av medikamenter for å forhindre varige skader er dårlig dokumentert, og er et område som bør studeres nærmere. Studier som nevnt ovenfor vil være vanskelig å gjennomføre hos mennesker, både da det er (J vanskelig å få tilstrekkelig stort antall pasienter, og av etiske grunner. Det anbefales derfor at det utvikles en hensiktsmessig dyremodell for studie av disse problemene. M:\BAOBE353.W51

10 Forfatter DEL1 i LJNIMEØ M:\8A0BE355.W5 i what do we know, what we do not know DECOMPRESSION ILLNESS Institutt for biomedisinsk teknikk Universitetet i Trondheim Alf 0. Brubakk

11 Decompression has generally been regarded as safe as long as it does not lead to clinical symptoms requiring treatment. Traditionally, the symptoms following decompression (dysbarism) has been Table i Ciassification of decompression disorders (dysbarism). Decompression sickness distinguished according to where the main symptoms occur: i INTRODUCTION 2 M:\BAOBE355.W5 I For discussing the more general problem related to the effect of decompression, several other definitions may be used: about ciassification. For instance, cerebral DCS can in many cases not be distinguished from arterial This ciassification implies that the different categories are well defined clisease entities and that mere and a study by Kemper et al (2) demonstrate mat mere is considerable uncertainty between experts from joints are quite rare, they are usually accompanied by central nervous symptoms (3,4). Extreme fatigue can be ciassified as a harmiess sign or be a sign of subclinical pulmonary embolism (5). Francis et al (6) therefore suggested the term decompression iliness to include bom decompression sickness and arterial gas embolism. They furthermore suggested that the ciisease should not development. Using this ciassification scheme, a high degree of concordance between different doctors was reached (7). ciassified as Type I and type II, but instead described according to clinical symptoms and their gas embolism or vestibular barotrauma. Furthermore, several studiles have shown that symptoms only is reasonable agreement between doctors about the ciassification Boffi the study of Smith et al (1) Barotraurna Arterial gas e,nbolism - Lymph Muscles - Skin - - MalaisefFatigue? Cardiopulmonary (Chokes) and/or joints (bends, niggies) Cerebral Vestibular Spinal Type I (rnild) Type II (serious) UNIMED

12 U1ÏtE UNIMED 3 Table 2 Possible definitions of decompression disorders. 1. Acute clinical symptoms requiring treatment in inclividuals who have been exposed to a reduction in environmental pressure. 2. Acute clinical symptoms in individuals who have been exposed to a reduction in environmental pressure. 3. Organic and/or functional decrements in individuals who have been exposed to a reduction in environmental pressure. 4. Vascular gas bubbies without reported clinical symptoms in individuals exposed to a recluction in environmental pressure. The first definition is tlie one tradlitionally used and is incidentally the one used to evaluate the effectiveness of decompression procedures. This is probably quite accurate If serious symptoms occur. If however, the symptoms are less marked, a considerable under reporting of symptoms may happen (see below) and the second definition may prove to give a more accurate description. The third definition includes both acute and chronic changes related to decompression. These may be related to acute climcal symptoms or develop subclinically. A recent consensus conference determined that such changes, even in individuals with few or no reported symptoms, have been found in the bones, central nervous system and the lungs (8). The last definition is similar to the so-called silent bubbies described by Behnke (9). Most will probably not regard this as DCI. However, the fact that such bubbies are present during most decompressions is similar to the situation in many infectious diseases with detectable pathological flora and lille or no symptoms. The question 5111 remains if these bubbles can have an effect on the organism. There is probably littie argument that severe violation of decompression procedures will lead to serious symptoms and that this is caused by widespread gas bubbie formation in many different organs. However, decompression iliness requiring treatment is a rare disease. In commercial diving, the incidence of treated DCI is probably below 0.1% (10). In sport-divers, the incidence is probably considerably below this. However, these general numbers hide the fact mat some types of dives, even in commercial operations, have a much higher incidence of DCI. Figure i show an example of this. M:\BAOBE355.W5 i

13 - Maxlmum Ldence 17% >27 msw. >80 min 12 dives, 2 DCS. SMSC 1992 DCS incidence O4% Air Dives, UEME ii 11 I I 4 A9 r Sur D02. 4 I I si * UNIMED <27 msw <80 min, 451 dives, 0 DCS eab.ei Det.intei.I.. P.Iiilo.ial il, dlveii 6.fiimlne W,iw,r1S1Izo 154 * DCSI se *_: _.JI* * I II III 121 depit. m.w M:\BAOBE355.W51 II**II. I* * 1I*.. Figure i DCS incidence in a series of air clives using surface deompression. Lee (il), where the majority of the incidents happened in the more stressful dives, as defined by a ihese data is taken from a commercial air diving operation in Norway, where all incidents happened bigh pöt, where p is the maximal depth of the dive in bar and t is the duration of the dive. However, other studies show a different picture, as is demonstrated in Figure 2. on the deeper and longer dives. This is the same results that was seen in the study by Shields and Figure 2 Incidences of DCS related to depth and bottom time in professional air divers in Norway.

14 UEi1i1I UNIMED Here we see the relationship between depth and duration of the dive for professional divers treated for decompression iliness in Norway in the time period (Risberg, personal communication 1994). As can be seen, a large number of the incidents happened on short, shallow dives. Even if decompression iliness is quite rare, a large percentage of dilvers have been treated. In a survey among divers in an off-shore diving company in 1985, 38% of the divers with 1-9 years experience and 62% of those with years of experience had been treated for decompression sickness (12). A recent survey of a large population of Norwegian divers, showed that 3% of the sportsdivers and 28% of the experienced professional divers had been treated (13). M:\BAOBE355.W5 I

15 3UEÏEE UNIMED 6 2 IS DECOMPRESSION ILLNESS A DISEASE? According to Webster (14) a disease is: a condition of an organ, part, structure or system of the body in which there is incorrect function resulting from the effect of heredity, infection, diet or environment. A disease is a serions, active, prolonged and deep-rooted condition. In contrast to this A disorder is usually a physical or mental derangement, frequently a slight or transitory one. I think there is probably no disagreement when we say that DCI is potentially a disease if it is not treated properly, I will also claim tliat it can be a disorder If proper actlon is taken. The aim of all our effort must be to keep DCI as a disorder. In order to do this we need a much more extensive knowledge of the decompression process and its effect on the body. M:\BAOBE355.W5 i

16 cause of DCI is separation of gas in the body. Furthermore, it is also well established that this gas separation is determined by the degree of gas supersaturation in ciliferent tissues. However, ifiere is produce quite a different amount of gas in two clifferent individuals as can be demonstrated in Figure 3. Furthermore, differences in work bad, temperature and blood tbow, may have a significant effect upon decompression outcome (15). This can be seen in Figure 4, where the Doppler scores stil! many factors about this that are very poorly understood. fle same decompression stress will Everybocly involved in problems related to decompression would probably agree that the primq4y 3 PROPHYLAXIS UNIFidIED 7 a dry dive in a chamber is significantly less ifian mat from a group of divers working in the water in At 44m DEEP-EX 81 DIVER 2 DIVER 3 50 min after decompression from 500 m 2 m/min M:\BAOBE35S.W51 Figure 3 (las bubbies in the femoral vein in two divers performing an ascending excursion from 500 msw. Bbood flow vebocity at the top, reflected signal intensity at the bottom. The best prophylaxis is properly performed decompressions. One of the major problems is ifiat we pointed out by Behnke in 1951 (9). have a very limited knowledge about how to do this. We still are still in the position mat was hot-water suits during the bottom time. from two group of divers are depicted. The Doppler score from the group of inclividuals performing UDflhiW

17 Doppler Score 1,5 1,0 0,5 14 I 2,0 2,5 Max Doppler Score ElMean Doppler Score NHC 1993 Nean Air dives, SurDO2 M:\BAOBE355.W51 evaluate our procedures. As is described below, there are many reasons why this may not be decompression is, like for instance the formation of gas (16,17). The main reason for our uncertainty is that we have to rely on reported clinical symptoms to adequate. Another approach is to try to use some objective means of deternhining how effective not been solved although there now has accumulate a mass of empirical data which have led to The problem of bringing a diver or caisson worker out of a compressed-air atmosphere has reasonably safe procedures. The water clive: Divers performing work in water using hot water suits. Figure 4 Doppler scanes from two groups of divers. Dry dive: Divers sitting quitely in the chamber. In Water dive (n=12) Dry Dive (n=12) 0,0 UNIMED 8 3EJ1i

18 UNIMED 9 4 THE DECOMPRESSION PROCESS Already in 1715, van Musschenbroek (18) described that he believed that the main problem in decompression was that the bubbies blocked the vessels and interfered with the blood supply, which was particularly damaging to the brain. A very significant factor in decompression is the fact that since the introduction of ultrasound, it has been demonstrated that gas bubbies will probably be formed in the vasculature during all decompressions (19). Several studies have documented that there is a relationship between the occurrence of many bubbles and the risk for dinical symptoms requiring Ireatment. Tissue bubbles are probably also formed during the majority of decompressions (20). Due to tlie fact ifiat even very severe violations of the decompression procedures will not always lead to clinical symptoms, this means that the sites where bubbies are formed must have considerable resistance to the effects of these bubbles. The most predominant theory about the growth of bubbles is that bubbles grow from preformed nuclei, as the resistance of pure solutions to supersaturation and gas phase development is considerable (21) The fact that bubbles seem to be detected at all supersaturations, makes it likely that the nuclei are composed of small (approx. 1 micron) stable gas bubbles (22). The speed of growth of these bubbies is significantly influenced by the size of the nuclei. If gas bubbles are present before the dive, the growth can be explosive as is demonstrated in Figure 5. Altitude dives 23 Ss M.iI3 20 IS is /.5 I.5 8 Figur 5 Gas bubbles in Ihe pulmonary artery. Gas is infused into an artery at arrow. M:\BAOBE355.W5 i

19 U1E UNIMED 10 In this experiment, gas was inadvertently infused into an ammal at altitude prior to a dilve to 22.5 msw for 40 minutes. Afier the dive, Ihis led to an explosive bubbie formation and death. The response of another animal without prior bubbies can be seen for comparison. M:\BAOBE355.W51

20 UEi1ÏE UNIMED 11 5 CLINICAL DIAGNOSIS AND REPORTING The major symptoms and signs of decompression sickness are pain (bends), asphyxia (chokes) and paralysis. Minor effects are rash and fatigue. The parts of the body chiefly involved are the extremities (bends), cardiorespiratory system (chokes) and the spinal cord. (9) Even today, there is probably littie to add to this description of Behnlce in 1951, with the possible exception that we believe today that the brain may be more frequently involved than previously thought and that extreme fatigue may be a more serious sign than previously thought (5). Table 3 shows an overview of symptoms of decompression sickness in several studies over a time period of 90 years. Table 3 Incidence of symptoms in DCI. Caisson US Navy Prof. Divers Amateurs Amateur workers Prof. Keays 1909 Behnke 1947 Rivera 1964 Kidd 1969 DAN 1993 Kelleher (23) (9) (24) (25) (26) 1944 (4) n 3, , Pain Rash Paralysis Fatigue Visual dist Chokes/ Dyspnoea % Even given the possibility that there may be differences in reporting, there are remarkable differences in the symptomatology. Of particular interest is to note that pain is only present in about half of the cases in the amateur divers. Furthermore, that serious injuries of the spine and symptoms -from the lungs are quite common in the amateur divers. This might fit in with the observation that 17% of the amateurs had experienced extreme fatigue. Tbis sign has been clescribed as a sign of subclinical pulmonary embolism (5). According to Lehner et al (27), short and long or deep and short dives have a high incidence of chokes. The latter dives also have a high incidence of central nervous DCI. The main difference between Ihese dives are the tissues that will be supersaturated. Thus, tlie change in symptomatology might indicate a diliferent diving practice and that the decompression procedures are not adequate for the more stressful dives. M:\BAOBE355.W51

21 UNIMED 12 There has for many years been anecdotal evidence that cimcal symptoms of DCS is underreported to a consicierable degree. We have recently asked a large group of Norwegian divers about this (13). 19% of the sports divers, 50% of the professional air divers and 63% of the saturauon divers reported that they had symptoms that had not been treated, a majority of these symptoms were related to the CNS. Interestingly enough, there was a statistical relationship between tliis and later minor central nervous symptoms. M:\BAOBE355.W51

22 UNIMED 13 6 RELATIONSifiP BETWEEN VASCULAR BUBBLES AND DCI There is littie reason to doubt that the localized pain in a joint is caused by local gas formation. This has been elegantly demonstrated by Webb (28), who showed that gas could be seen in periarticular and perivascular tissue spaces, and that there was a correlation between the occurrence of gas and pain. Ferris and Engels further demonstrated that stram and muscular activity were correlated with pain at the site where the stram bad been applied (29) One further observations would tend to support this, namely the fact ifiat local compression can in many cases remove the pain. An interesting observation is in this connection that Ferris and Engels claim that the pain can be eliminated by eliminating arterial inflow. Given tlie fact that vascular gas bubbles is quite common, the above seems to indicate that if the diver complains of pamn in a joint, he is most likely suffering from two different disease entities, namely tissue gas in and around the joint and vascular gas in the pulmonary circulation. It has often been claimed ttiat gas bubbies as can be detected in the pulmonary artery is a poor predictor of DCI. The main reason for this is that gas bubbles has been detected without clinical signs of DCI (30). There seems, however, to be agreement that the risk of DCI increases with increasing number of bubbies. In my own experience, afier carefully having monitored many hunclrecls of air clives and numerous saturation dlives, I have never seen an individual without pulmonary artery gas bubbies who had clinical symptoms. The same observation was made by Davies (31), who claims that clinical symptoms were never observed when gas bubbies could not be detected in the muscles of the thigh. Nishi (32) points out that for air dives, decompression iliness was always accompanied by bubbies If all monitoring sites are considered. Published data seem to support this. In Table 4, an overview of several studies have been made. Table 4 AIR dives, precordial bubbies at rest. Bubbie grade 0 1-1V Nishi 1993 (33) n 1, DCI incidence (%) Spencer & Johansen 1974 (33) n DCI incidence (%) Nashimoto & Gotho 1977 (34) ti DCI incidence (%) 0 19 One interesting observation is the considerable differences in DCI incidence in tlie different studies. In all groups with bubbies, the incidence is considerably above what is considered acceptable. It can M:BAOBE355.W51

23 uïi1i UNIMED 14 be very difficult in many cases to distinguish between an occasional bubbie and no bubbles using the Doppler method (35). Thus it is possible that the few individuals with DCI and no observed gas bubbies actually had a few bubbies that were not detected. We performed a study where we compared Ihe incidence of gas bubbies in two surface decompression procedures (36). One was the USN standard surface decompression table using oxygen, the other a new table developed by the Institute of Environmental Medicine (IFEM), University of Pennsylvarna). The DCI cases were all skin rashes, except one case of knee pain. The divers were monitored postdive using Doppler equipment, the results were graded according to the Kisman-Masurel scale. Table 5 Comparison of bubbie grades after surface decompression (KM scale). Dept (feet)/ n USN DCI mc n IFEM DCI mc Duration (min) Max bubbie % Max bubble % grade grade 80/ / / / Mean (all dives) One individual wfth transitory and spontaneously resolved shoulder pain. This study only considers few subjects, but seem to indicate that a bubble grade in excess of 2 increases the nsk of DCI: When evaluating tbis, it must be kept in mmd that the grading system used is non-linear and probably ciose to logarithmic (Eftedal and Brubakk, unpublished). The data shown above indicate that even few bubbies in the pulmonary artery increases the fisk of having ciinical symptoms. An interesting set of data from recent animal experiments support the assumption that bubbies in the pulmonary artery is a good indicator of decompression stress. In pigs, the circulation to one limb was reduced during decompression. The consequence of this is a considerable increase in super saturation in this leg as compared to the other, with very few bubbles transported to the pulmonary artery.. In the pulmonary artery, a considerable increase in gas bubbies could be seen when circulation was restored, as is demonstrated in Figure 6. M:\BAOBE355.W5 i

24 UNIMED 15 Gas bubbies puhnonary artery Fw miwn 4f i Figure 6 Gas bubbies in the pulmonary artery. Flow restriction to one leg, related at affow. Furthermore, changes in the skin, a symptom often related to serious pulmonary decompression iliness (chokes), could only be seen in the leg where the circulation had been restrained, as is demonstrated in Figure 7. Riaht side, normal circulation Leif side,reduced circulation Figure 7 Skin changes after decompression realted to circulation. M:\BAOBE355.W51

25 UNIMED 16 7 ARE BENDS A RED HERRING? Skin rash, muscle pain and other minor symptoms are regarded as non-serious symptoms of DCI and a decompression procedure is usually considered aclequate if only such symptoms occur in a small percentage of cases. Generally, standard treatment proceciures will adequately eliminate these symptoms. The question remains, however, to which extent gas bubbles are also formeci simultaneously at other sites and if the treatment procedures are just as effective in eliminating these. This is a question that at the present time can not be adequately answered, but there seems to be no doubt (hat the lungs are involved in all cases of DCI, and probably also in all decompressions regardless of symptomatology. It is well documented from older literature (hat severe central nervous decompression symptoms frequently have been accompanied by symptoms from the lungs (24,27). M:\BAOBE355.W5 I

26 In vitro studies have demonstrated that gas bubbies have an effect upon both formed elements and biochemical processes in the body. Using gas bubbies in vitro, Thorsen et al (38), showed ifiat gas bubbies lead to aggregation of thrombocytes. Furthermore, the degree of aggregation does not seem saturation dive (40). As is shown in Figure 8, tbrombocyte aggregation can also be seen following it has been demonstrated hat the activation of thrombocytes occur during the bottom phase of a to be dependent upon the gas content of the bubbie, but only on its surface properties (39). In vivo, 8 EFFECT OF BUBBLES M:\BAOBE355.W5 I Ward et al (41) demonstrated that gas bubbies could activate complement in-vitro. Using a different technique, Bergh et al (42) was able to verify tbis. During this study, it was also shown that the response was similar regardiess of the content of the bubbie, indicating that it was the surface of the bubbie that was of importance for activation (Figure 9). Figure 8 Effect of hypoxia and diving on thrombocytes. Data rom altitude experiements in pigs. s *10911 Thrombocyte 400 kpa hrs. at min. kpa 69kPa 326kPa At 100 After 3 After 20 At I I I I $ I I I I I Pig 3 rri IPig#2 RPig#1 I SI Effect ofhypoxia and diving on thrombocytes exposure to hypoxia. Thus, in-vivo, thrombocyte aggregation caused by decompression and gas bubbies will be added on to the effects or other environmental factors. UNIMED 17 uiijiïti

27 UNIMED 18 Figure 9 Compleent activation following insuvation with air bubbies. Effect of different gas composition of the bubbies. However, Ward et al also showecl that inchviduals could be divided into sensitive and non-sensitive inclividuals according to the degree of activation of complernent aud that clinical symptoms of decompression illness was related to the degree of activation (43). In a recent study on air divers, Hjelde et al has not been able to verify this (44). However, interestingly enough, those inclividuals who had a low level of C5a before the dive, produced many gas bubbies, as is shown in Figure 10. Furthermore, a single air dive seemed to reduce the level of C5a. This seems to indicate that diving and gas bubbies may activate C5a receptors as well as C5a. If this is the case, this raises the possibility of ways to treat the effect of gas bubbies on the organism. C5a ng/mi C5a levels predive Air dives I HeOx decompression Bubbie grade Figure 10 Relationship between C5a levels predive aud gas bubbles after decompression in man. M:\BAOBE3S5.W5 I

28 UNIMED 19 Activation of C5a has also been demonstrated by Stevens et al (45) in divers up to 14 hours after they had been treated for DCI. Complement activation is an interesting and plausible model for how intravascular gas bubbies effect the organism. As can be seen from Figure 11(46), complement activation will lead to activation of neutrophils and the formation of multiple membrane attack complexes (MAC) that wffl lead to destruction of nucleated ceils. CIas.Ic.I pathway I L Cl AI(ernaflve pathway C3b activatlng surface C4 C2 C4b2a C3 c3bbb Neulrophil actveiion C6,7 C8,9n C5b C5b67 C5b-9 Target cell membrane [. Membrene attack complex Figure 11 Activation of complement and neutrophuls. This process leads to adhesion of leukocytes to the endothelial layer and eventually to its transport through the endothelium. That decompression lead to activation of neutrophils can be demonstrated by comparing the activation of neutrophils at surface, after pressure exposure and during decom pression (Bjerkvik. personal communication 1994, 47), Figure r Ctr activation at I bar 400 B Activationatpressure Leucocyte activation 0 I 4Oe,V4Ob D fld.oomp. Bjerkvik et at 1994 Benestad et at 1990 Figure 12 Activation of leucocytes at pressure and diving decompression. M:BAOBE355.W5 i

29 u1t1ïti UNIMED 20 In the skin, C5a will lead to erythema and edema and promote infiltration of infiammatory celis (48). Hus is a picttire that is very similar to what can be actually observed in the skin of pigs undergoing decompression, as can be seen in Figure 13. Figure 13 Skin changes following decompression. Another important effect of C5a is that it leads to vasoconstriction and a reduction in flow (49). If cireulation of blood is reduced in a leg during clecompression, this leads to a reduction in gas elimination and considerable bubbie formation. Afier circulation is restored, flow to the affected leg does not show the expected reaction, where ischemia normally is followed by a considerable overshoot of flow (Figure 14). Both vascular bubbies and C5a activation may contribute to this. - (dib4) 0 f. (1.4» c E E I. IL ti Time [minuteel Figure 14 Flow changes in the leg as a result of construction and release. The changes seen in the lungs in pigs after decompression are similar to what could be expected after complement activation. This is demonstrated in the pig, where considerable leukocyte invasion M:\BAOBE355.W5 i

30 UNIMFD 21 is seen in the lungs from a pig that had been exposed to a considerable amount of bubbies (Grade 111-1V KM scale) for about 100 minutes after decompression (Figure 15). Figure 15 Lung changes following decompression. Complement activation seems to be the main mechanism for acute lung injury (50). The changes in lung function seen in divers, with a reduction in carbon monoxide diffusion capacity and reduction in compliance (51), would support the hypothesis that infiarninatory processes in the lungs is a result of the decompression process. The reduction in diffusion capacity is quite rapid and follows the development of bubbies as can be seen from Figure 16 (52). 60 D11. gt o..l DLco CHANGES AFTER SINGLE AIR DIVE 3.f 4PPL PHY5loL j3; i: I j I 0.5 D C.-15 H N G 20 E P.R.EDIVE POSTDIVE (min) DiCOcorr air ZJ Dubble grade air ± DLCOcorr oxygen Bubbie grade oxygen Figure 16 The effect of gas bubbies on diffusing capacity of the lung. M:\BAOBE355.W5 I

31 UNIMED 22 Neutrophil activation leads to tjie production of oxygen radicals (53), thus it is reasonable that exposure to increased oxygen tensions would lead to similar changes and that actually increased oxygen tension and bubbies may have additive effect. This could have implications for treatment of DCI. Based on the above, the lungs must be considered a primary target organ for gas bubbies, and is probably exposed to gas bubbies to a larger or smaller degree in all decompressions. Generally, the main focus on the lungs has been on its role as a Biter, where the bubbies are eliminated before they can be transmitted to the arterial side, where their potential for damage is greater. However, if the gas bad on the lungs is large, the filtering capabilities of the lungs will be exceeded and gas will enter the arterial circulation (54). Furthermore, if an open Foramen Ovale is present, as it is in about 25-30% of the younger population (55), gas bubbies will be transmitted to the arterial side at much lower pressures. Figure 17 shows an example of this in the pig mmhg mrnlig PigwimaPFO. Pig widæuc PFO Time (min) Figure 17 Pulmonary artery pressure where gas bubbles enter the left side of the heart after decompression (arrows) in animals with or without PFO. These data clearly show that, at least in the pig, an increase in pulmonary artery pressure of only about 30% is sufficient to facilitate arterialization of venous gas bubbbes. In addition to this, bubbies will increase the shunt fraction of the lungs considerabby (56), causing a reduction of arterial oxygen tension. An increase in inspired oxygen tension, will have the same effect, where an increase from 21 to 100 to 200 kpa in the inspired gas will increase shunt fraction from 7 to 21 to 45% respectively (56). (Figure 18). M:\BA0BE355.W5 I

32 50- a 5 minutes 40- S55minutes I... HADESI993/94 Shunt fraction, 23 M:\BAOBE355.W5 I Figure 18 Shunt fraction in the lung related to oxygen tension. Inspired oxygen tension 21 kpa 100 kpa 200 kpa UNIMED

33 vascular bubbies and in-vivo bubbie formation probably plays a role (57). A large percentage of Figure 19 Central nervous changes in DCI are probably caused by several mechanisms. In severe DCI, both divers performing excursions (58). The possible effects of these gas bubbies are of importance. saturation diving, ft has been shown that gas bubbles are present in the carotid artery in nearly all clivers probably are exposed to bubbies in the cerebral circulation regularly. For instance, in deep 9 CENTRAL NERVOUS SYSTEM 24 UNIMED UE1E r embolism. It is thus of interest to note that the changes were more marked in air divers than in may be related to circulatory changes that may cause changes in venous pressure; e.g. pulmonary group of divers (60). This is probably not an effect of intravascular gas bubbies in the brain, but by gas bubbies in the spinal fluid, such bubbles will probably primarily adhere to the limng of the saturation divers, maybe due to the fact that air divers are subjected to more severe clecompressions with bigher amounts of pulmonary gas. Another possible explanation is that this damage is caused of the blood- brain-barrier (61). Broman et al has demonstrated that even very short contact between ventricles. Chrysanteou et al have shown that animals exposed to decompression will show breakage rabbits indlicate that such contact leads to endothelial damage and progressive reduction on cerebral gas bubbies and endothelium (1-2 minutes) will lead to such breakage (62). Furthermore, studiles in Exposure to vascular bubbies do not seem to have a serious effect upon the spinal cord (59). In this blood flow and function (63). group of 10 amateur and 10 professional divers, five of whom had suffered from DCI, no changes In Figure 19, an overview of the possible effects of gas bubbies in the vessels is seen. could be seen. In the brain, changes in the endothelial layer of the ventricies could be detected in a M:\BAOBE355.W5 i Theoretical model of the effect of gas bubbles on the vessels. VIQ mismatch H

34 Many different treatment protocols are in use, while the USN6 is probably tlie one used most extensively. Experience till now seems to indlicate that this is adequate in Ihe majority of cases initiating treatment, and may of the secondary effect described above may play a role. For instance, where treatment is initiated immediately following the insult. Usually, there is considerable delay in Kelleher has recently shown that initial treatment is only effective in about 66% of the cases (4). Usually, the treatment protocol is determined by the severity of the clinical symptoms. Studies have 10 TREATMENT OF DCI M:\BAOBE355.W5 i important role in DCI, then drugs that can interfere with this is of considerable interest. If complement activation and in particular its effect on the leukocyte-endothelium adhesion plays an There are, however, some interesting possibilities that have only been insufficiently been tested. One plasma. In a study in rats, Lutz and Herrmann (67) were able to substantially reduce the mortality of rats undergoing rapid decompression from 8 ATA If a fluorocarbon was infused after decompression. is the use of fluorocarbons, substances that have a much higher solubility for nitrogen than has Over the years, many attempts have been done to improve treatment of decompression by way in wbich gas interacts with the body is not known. introducing drugs. Generally, this have had littie success, mainly because our understanding of the be of advantage. disappear more quickly from the spinal cord at 1 ATA if heliox is used instead of pure oxygen (65). cinical data seem to indicate that helium is of benefit. Experimentally, air bubbies in tissue The use of different gas mixes, particularly helium as the breathing gas is controversial. Some However, at a pressure of 2.8 bar, the reverse is true (66). Our own data, showing an increased shunt in the lung as well as a reduction of gas elimination at increased oxygen tensions, would indicate that there is actually littie benefit in using high oxygen tensions and that lower tensions may a decompression part, further gas may be picked up during this phase. Finally, as mentioned above, of helium ancl mtrogen in different tissues. Furthermore, as the treatment procedure always contains be different. Heliox dives may differ from air dives, due to the differences in partition coefficients demonstrated, however, that none of the proposed protocols are superior to table USN 6A (64). However, the severity of symptoms is not the only variable worth considering. As the diliferent have a different location in long dives than in short dives and thus, treatment protocols may have to tissues has a clifferent rate of uptake and elimination of gas, the majority of the gas bubbies may gas elimination (Flook et al, Unpublished 1994). increased oxygen tensions may increase the shunt fraction in the lung and also decrease the rate of 25 UNIMED

35 vanous conditions and an increased understanding of the individual factors that may influence the vessels, as this is the only feature that has been demonstrated to be present in most if not all This review has focused upon several factors that may be of importance for evaluating decom two possible ways to go. One is to develop decompression procedures that reduces the amount of gas to the lowest possible amount. Tbis will require studies on gas elimination and uptake under pression iliness. It has deliberately been aimed at describing the changes caused by gas bubbies in decompressions used today. If we want to reduce the incidence of decompression iliness, there are 11 CONCLUSIONS M:\BAOBE355.W51 We also need to know more precisely the relationship between minor clinical symptoms and signs well as improving the medical follow up of all divers. and the changes in ilie body. In order to do this we will have to improve the reporting system as understand how gas bubbies effect the body. Tbis will enable us to specifically treat tlie biochemical effect of gas on the body, not only its mechanical effect. bubbie formation. Among these are for example differences in surface tension. The other is to UNIMED 26 U[1E

36 The heip and participation of researchers and students of tlie Trondheim group is gratefully Gas, University of Trondheim and SINTEF UNIMED is gratefully acknowledged. FUDT/OMEGA program), the Norwegian Oil Directorate, Health and Safety Executive, UK, British acknowledged. Wilhout their enthusiastic support this study would not have been possible. 1]ae econornic support of Philhps Petroleum Norway (the HADES program), Statoil, Hydro, Saga (The 12 ACKNOWLEDGMENT M:BAOBE355.W5 i UNIMED 27 UEflJ1i

37 with Ihe current ciassification of diving disorders. Undersea Biomed Res Type I/Type II decompression sickness. Aviat Space Environ Med 1992;63:386. Undersea & Hyperbaric Medicine 1993;20(suppl): Kemper GB, Stegman BJ and Pilmanis AA. Inconsistent ciassification and treatment of 3. Denoble P, Vann RD, Dear GdeL. Describing decompression iliness in recreational divers. 1992; 19(suppl): Smith DJ, Francis TJR, Pethybridge RJ, Wright JM, Sykes JJW. Concordance: A problem 13 REFERENCES M:BAOBE355.W51 organisms. Tapir Publishers Trondheim l989:pp A0, Hemingsen BB, Sundnes G.(eds), Supersaturation and bubble formation in fluids and 15. Vann RD. Exercise and circulation in the formation and growth of bubbles. In Brubakk New York Webster s Encyclopedic unabridged Dictionary of the English Language. Gramercy Books, A93053, Trondheim f. Brubakk A0, Bolstad G, Jacobsen. Helseeffekter av luftdykking. SINTEF Report STF23 (ed). Proc XII EUBS, Rotterdam 1986: Brubakk AO, Fyllingen J. Occupational health service for diving ships. In: Schrier LM 029. Robert Gordons Institute of Technology, Aberdeen offshore air-diving operations on Ihe UK continental shelf during OT Shields TG, DuffPM, Lee WB, Wilcock SE. Decompression sickness from commercial l993:pp Imbert JP. Decompression safety. In:Subtech 93, Kluwer Academic Publishers Decompression sickness. WB Saunders Company, London 1951: pp Behnke AR. Decompression sickness following exposure to high pressures. In: Fulton JF (In press). 8. Hope A, Elliott DII, Halsey M (ecis). Long term health effects of diving. NUTEC, Bergen 1993;20(suppl): 17 classification of decompression disorders. Undersea & Hyperbaric Medlicine 7. Smith DJ, Francis TJR, Tehybridge RJ, Wright JM, Sykes JJW. An evaluation of the INM Report No. R93002, Institute of Naval Medicine, Alverstoke, Francis TJR, Smith DJ, Sykes JJW. The prevention and management of clicing accidents. Lambertsen CJ (ed). Underwater Physiology V, Fed Am Soc Exp Biol, Bethesda l975:pp 5. Hallenbech JM, Elliott DH, Bove AA. Decompression sickness studies in the dog. In decompression illness. INM Report No. R93048, Institute of Naval Meclicine, Alverstoke 4. Kelleher PC, Francis TJR. INM diving accident database analysis of 225 cases of UNIMED 28 Ufli1E

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