PFO as a risk factor for Decompression Sickness

Dr Peter Germonpré, MD

SCUBA diving is BIG FUN

In Belgium, 35.000 divers are performing each 30-100 dives per year 1- 3.000.000 dives /yrRecreational SCUBA diving is BIG BUSINESS :– Dive gear– Dive schools– Dive vacations

SCUBA Diving has it’s risksSCUBA Diving has it’s risks

… like any sport !Risks associated with the underwater environment:– Drowning– Hypothermia– Animal life– Pressure-related disorders

Decompression Algorhythms

Saturation = uptake (N2 = nitrogen) in tissues Desaturation = wash-out (N2) from tissues

Source = lungs = destinationVector = plasmaDestination = tissues = source

Dissolution Coefficients H2 He N2 Ar Water 0,017 0,009 0,013 0,027 Fat 0,036 0,015 0,067 0,140

Saturation & desaturation of inert gas

Possible factorsinfluencing saturation (& desaturation)

Diffusion – related factors– Depth of dive ( alveolar N2 pressure )– Descent to which depth ( pressure gradient for N2)– Residual N2 pressure in tissue (from previous dive)

Perfusion – related factors– Dive time (time at depth)– Ascent speed– Cardiac output, vasoconstriction,

personal (age, sex, health, VO2 Max…)

Risk factors for DCS

Depth – Time profile – Repetitive divesReverse dive profilesSpeed of ascentExercise during diveCold during deco stopsPersonal habits : poor physical condition, smoking, agePersonal factors : fat content, dehydration, alcohol use, sex

30-50 cases per year in Belgium (overall risk = 1/40.000 dives) Dive profile errors : 40%

normal saturation - insufficient off-gassing

“Logical” causes of decompression failure : 20%increased saturation - “normal” N2 off-gassing

increased or normal saturation - insufficient off-gassing

“Unexplained” : 40%

Decompression Sickness in Divers

Decompression Sickness : the cause

Haldane’s work (1908)

Pressure ratio of 2 / 1 = Safe

Staged decompression = no DCS

= no bubbles ?

Decompression Algorhythms

Are humans animals ?

Comex data base (JP Imbert)

12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60

5

20

30

60

90

120

0

5

10

15

Risk ofDCS

Depth

Time

DAN Europe: analysis of 202 cases of DCS DAN Europe: analysis of 202 cases of DCS 1989-19931989-1993

Depth > 30 mswDepth > 30 msw

Deco divingDeco diving

Error ascent / stopsError ascent / stops

Repetitive diveRepetitive dive

Stress – FatigueStress – Fatigue

Multiday divingMultiday diving

Material faultMaterial fault

Altitude after diveAltitude after dive

Decompression Sickness : the cause

Growth of bubbles in tissue (Yount 1989)Coalescence of bubbles

1 ATA 0.75 ATA 0.5 ATA 0.25 ATA

Boyle’s Law

The Decompression Sickness « Grey Zone »

Mechanism of disease

The Foramen Ovale

Fœtal circulation:– High MPAP– RAP > LAP– Fossa Ovalis– Valve-like structure

The Foramen Ovale

Neonatal circulation:– Low MPAP– LAP > RAP– Fossa Ovalis– Valve-like structure

Closure in 5-10 days (in seal pups)

Mechanism of disease

Germonpré et al. 1998 Germonpré et al. 1998 (J Appl Phys(J Appl Phys)) (c-TEE)(c-TEE) ::– Significant association PFO – cerebral DCSSignificant association PFO – cerebral DCS– No association PFO – Spinal DCSNo association PFO – Spinal DCS

Louge et al. 2001 (Crit Care Med)(Crit Care Med) (c-TCD)(c-TCD) : :– Cerebral DCS: 83% TCD posCerebral DCS: 83% TCD pos– Spinal DCS: 37.9% TCD posSpinal DCS: 37.9% TCD pos

Torti et al.Torti et al. 2004 2004 ((Undersea Hyperb Med) Undersea Hyperb Med) (c-TEE)(c-TEE) ::– > cerebral / vestibular symptoms> cerebral / vestibular symptoms

PFO-related DCS & the Brain

Patent Foramen Ovale

Anatomical variant rather than diseasePrevalence:

5-8mm long, 2-3mm wideValve-likestructure

Author 1 – 20 yrs 20-40 yrs > 40 yrs

Patten 1931 34.5% 27.2% 22.4%

Hagen 1984 35% 29% 20.4%

Author 1 – 20 yrs 20-40 yrs > 40 yrs

Patten 1931 34.5% 27.2% 22.4%

Hagen 1984 35% 29% 20.4%

Reversal of inter-atrial pressuresReversal of inter-atrial pressures

Vik et al., 1994 : Vik et al., 1994 : Increase of MPAP Increase of MPAP during «bubbling» during «bubbling» phase (>25%)phase (>25%)

Balestra et al. 1998 (Undersea Hyperb Med)Balestra et al. 1998 (Undersea Hyperb Med)

Reversal of inter-atrial pressuresReversal of inter-atrial pressures

Transthoracic echocardiography

Trans-oesophageal echo

C-TEE

Retrospective studies (1)Retrospective studies (1)1989: Moon et al. (Lancet) : 1989: Moon et al. (Lancet) : c-c-TTTTEE– PFOPFO 37% 37% in DCS diversin DCS divers– PFO PFO 61% 61% in neurologic DCSin neurologic DCS– PFO PFO 10.7% 10.7% in non-diversin non-divers

1989: Wilmshurst et al. (Lancet) : 1989: Wilmshurst et al. (Lancet) : c-c-TTTTEE– PFOPFO 66% 66% in early neurologic DCSin early neurologic DCS– PFOPFO 17% 17% in late neurologic DCSin late neurologic DCS (30 min) (30 min)– PFOPFO 24% 24% in control diversin control divers

Retrospective studies (2)Retrospective studies (2)

1998: Germonpré et al. 1998: Germonpré et al. (J Appl Physiol)(J Appl Physiol) – – c-c-TTEEEE– 37 37 DCS diversDCS divers (20 c (20 ceerreebral, 17 spinal)bral, 17 spinal)– 36 36 matched matched contrcontrooll divers divers (age, sex, BMI, (age, sex, BMI, smokingsmoking, physi, physical fitnesscal fitness, , diving diving

eexpxpeeriencerience))– semi-quantification semi-quantification of PFO (gr 0, 1, 2)of PFO (gr 0, 1, 2)

– ““undeserved DCSundeserved DCS””• No diving technical errorsNo diving technical errors• < 3 < 3 minor risk factorsminor risk factors (fatigue, effort, alco (fatigue, effort, alcohhol, ol, coldcold, dehydrat, dehydratiion,…)on,…)

Standardised, optimised c-TEE technique

Balestra et al. Undersea Hyperb Med 1998; Germonpré et al. J Appl Physiol 1998

Based on intrathoracic pressure changesStrict protocol and sequence c-TEE

PFO % Gr.2 PFO %

cerebral DCI 16/20 80% 14/20 70%

controls 5/20 25% 3/20 15%

p (Fisher) 0.012 0.002

spinal DCI 6/17 35.2% 5/17 29.4%

controls 8/16 50% 6/16 37.5%

p (Fisher) 0.49 0.29

all DCI vs ctl. p: 0.06 Fischer p: 0.03 Fischer

PFO % Gr.2 PFO %

cerebral DCI 16/20 80% 14/20 70%

controls 5/20 25% 3/20 15%

p (Fisher) 0.012 0.002

spinal DCI 6/17 35.2% 5/17 29.4%

controls 8/16 50% 6/16 37.5%

p (Fisher) 0.49 0.29

all DCI vs ctl. p: 0.06 Fischer p: 0.03 Fischer

Cerebral damage in divers

Adkisson et al. 1989 (Lancet) (SPECT):Adkisson et al. 1989 (Lancet) (SPECT):– Cerebral perfusion deficit after neurologic DCS & AGECerebral perfusion deficit after neurologic DCS & AGE

Knauth et al. 1997 (Lancet) (RNM)Knauth et al. 1997 (Lancet) (RNM) (87 divers):(87 divers):– Multifocal cerebral lesions Multifocal cerebral lesions

• 7 lesions in 7 divers without PFO7 lesions in 7 divers without PFO• 34 lesions in 4 divers with PFO grade 234 lesions in 4 divers with PFO grade 2• Total (TCD) 25 divers PFO, 13 grade 2Total (TCD) 25 divers PFO, 13 grade 2

– Auto-selection of divers : ?Auto-selection of divers : ?

Diver S. - 39 years old - 17 years diving experience - 800+ divesDiver S. - 39 years old - 17 years diving experience - 800+ dives

1 confirmed episode of vestibular / cerebellar decompression sickness - timely treated & 1 confirmed episode of vestibular / cerebellar decompression sickness - timely treated & completely recoveredcompletely recovered

Anamnesis: > 10 episodes of abnormal drowsiness, fatigue - during approx. 1 hour, after Anamnesis: > 10 episodes of abnormal drowsiness, fatigue - during approx. 1 hour, after divesdives

Nitrogen bubble embolisation may cause cerebral ischemic damage in divers ?

Nitrogen bubble embolisation may cause cerebral ischemic damage in divers ?

Brain Damage through diving ? Brain Damage through diving ?

Reul et al., Fueredi et al., Reul et al., Fueredi et al., Knauth et al.Knauth et al.

WEAK POINTSWEAK POINTS : :Selection bias : DCS ?Selection bias : DCS ?Morphological (MR) Morphological (MR) analysis : Wirchow analysis : Wirchow spaces ?spaces ?PFO detection method : PFO detection method : other shunts ?other shunts ?

Brain Damage through diving ? Brain Damage through diving ? Selection bias : DCS ?Selection bias : DCS ?

– 200 volunteer divers:200 volunteer divers:• Age < 40 yrsAge < 40 yrs• > 5 yrs diving, > 200 dives> 5 yrs diving, > 200 dives• No history of DCSNo history of DCS

– Random ¼ selectionRandom ¼ selection

Morphological (MR) analysis: Wirchow spaces ?Morphological (MR) analysis: Wirchow spaces ?– T1, T2, FLAIR sequences: diff diagnosisT1, T2, FLAIR sequences: diff diagnosis

PFO detection method : other shunts ?PFO detection method : other shunts ?– Standardised c-TEEStandardised c-TEE

Neuropsychometric testing: Neuropsychometric testing: WAIS, MMS subtests for neurotoxic solventsWAIS, MMS subtests for neurotoxic solvents

Results

– In experienced divers who never had DCS, In experienced divers who never had DCS, no increased prevalence of WML is found no increased prevalence of WML is found as compared to a control populationas compared to a control population

– In these divers, a high prevalence of PFO In these divers, a high prevalence of PFO is found (65%)is found (65%)

(Germonpré et al. EUBS Congress 2003)(Germonpré et al. EUBS Congress 2003)

Initial PFO prevalence:– 14/33 PFO (42.5%) – 5 Gr.1 - 9 Gr.2

Final PFO prevalence:– 17/33 PFO (51.5%) – 3 Gr.1 - 14 Gr.2

PFO grades:– Gr.0 Gr.1 : 3 /19 divers– Gr.0 Gr.2 : 1 /19 divers– Gr.1 Gr.2 : 4 / 5 divers– Gr.1 Gr.0 : 1 / 5 divers

(Germonpré et al. Am J Cardiol 2005)

Time-related opening of PFO in divers

Causes of DCS– normal saturation - insufficient N2 off-gassing – increased saturation - “normal” off-gassing– increased saturation - insufficient off-gassing– normal saturation - “normal” off-gassing -

clinical manifestation of “silent bubbles”

PFO : should every diver be screened ?

Haldane’s work

Pressure ratio of 2 / 1 = Safe

Staged decompression = no DCS

= no bubbles ?

Cardiac echography after a 25m/25min. Dive

Reversal of inter-atrial pressuresReversal of inter-atrial pressures

Germonpré et al. 1998 Germonpré et al. 1998 (J Appl Physiol)(J Appl Physiol) – – c-TEEc-TEE : :– Odds Ratio Odds Ratio PFO – no PFOPFO – no PFO : : 2.62.6– Odds Ratio Odds Ratio PFOPFO Gr 2 : Gr 2 : 3.23.2

Bove et al. 1998 Bove et al. 1998 (Undersea Hyperb Med)(Undersea Hyperb Med) - META : - META :– Odds Ratio Odds Ratio PFOPFO : 2.5 : 2.5– Incidence Incidence of DCS in study populationof DCS in study population : : 2.28 / 10.000 2.28 / 10.000 divesdives

DAN 19DAN 1989-199589-1995 : : DCS risk of «european diver»DCS risk of «european diver»::– 1 / 1 / 7.3907.390 all dives (> 30m…)all dives (> 30m…)– 1 / 1 / 35.10535.105 no decompression divesno decompression dives < 30m < 30m

ReRetrospectivetrospective studies : studies : risk quantificationrisk quantification

Vascular bubble disease

Vascular bubble formation dependent on– Nitrogen load – Rate of ascent– Gas nuclei (endothelial cell pockets)– Nitrogen off-loading capacity of circulatory and pulmonary

system (lung = bubble filter)– Cavitation at turbulence areas (heart valves)– Unknown factors

VGE : Venous Gas Embolism

Feeling cold during decostops

Leffler et al. Aviat Space Env Med 2001 : increased risk for DCS when divers are warm throughout the diveMarroni et al. EUBS Meeting 2001 : increased and prolonged bubble production when skin temperature was cold in end-stage of dive

Physical condition

Carturan – J Appl Physiol 1999High VO2max (= good fitness) less post-dive bubbles

Wisloff et al. J Physiol 2004Exercise at 20 hrs before dive prevents bubbles in rats – nitrix oxide (NO) or Heat Shock Protein (HSP) involved ?

Age

Aerospace medicine : age group of 40-45 yrs 3x more DCS than 20-25 yrs old

Smoking

HSE Report 2003 : smoking by itself not significant for DCS; lung function alteration 2x higher ORWilmshurst 2001 : smokers more likely for DCS-AGE

Detection Methods for PFODetection Methods for PFODiTullio et al. 1993 - Kerut et al. 1997DiTullio et al. 1993 - Kerut et al. 1997

c-c-TEETEE

TranscrTranscraaninialal Doppler (c- Doppler (c-TCDTCD))– SensitivitSensitivityy 68% 68% toto 90% - Specificit 90% - Specificityy 100% 100%

TransthoracTransthoracicic Echocardiograph Echocardiographyy (c-TT (c-TTEE))– SensitivitSensitivityy 47% - Specificit 47% - Specificityy 100% 100%

Right Heart Right Heart CatheterisationCatheterisation– SensitivitSensitivityy 80% - Specificit 80% - Specificityy 100% 100%

(Di Tullio et al: Stroke 1993 - Kerut et al.: Am J Cardiol 1997)(Di Tullio et al: Stroke 1993 - Kerut et al.: Am J Cardiol 1997)

False negative c-ECHO

Blood flow pattern SVC – IVCTurbulences Sinus Venosus - RA

C-TEE : gold standard ?

C-C-TransthoracicTransthoracic echocardiographyechocardiography– 10 – 18 %10 – 18 %

(Lynch et al. 1984, Van Hare et al. 1989)(Lynch et al. 1984, Van Hare et al. 1989)

C-Trans-oesophageal echocardiographyC-Trans-oesophageal echocardiography– Konstadt et al. 1991: 26 %Konstadt et al. 1991: 26 %– Fisher et al. 1995: 9.2 %Fisher et al. 1995: 9.2 %– Meissner et al. 1999: 25.6 %Meissner et al. 1999: 25.6 %

Anatomical prevalence : 25-30 % !Anatomical prevalence : 25-30 % !

Respiratory physiology: up to 12% anatomic venous-to-Respiratory physiology: up to 12% anatomic venous-to-arterial pulmonary shuntingarterial pulmonary shuntingSulek et al. (Anesthesiology 1999) : c-TEE + c-TCDSulek et al. (Anesthesiology 1999) : c-TEE + c-TCD– Cerebral embolisation of fat emboli after TKACerebral embolisation of fat emboli after TKA– after important emboli afflux (tourniquet release) after important emboli afflux (tourniquet release) – (even without PFO) : opening of intrapulmonary shunts(even without PFO) : opening of intrapulmonary shunts

Cardiology practice c-TEE :Cardiology practice c-TEE :– If bubbles observed after more than 3 (5) heartbeats after If bubbles observed after more than 3 (5) heartbeats after

appearance in RA appearance in RA « pulmonary passage of bubbles » « pulmonary passage of bubbles »

ReRetrospectivetrospective studies (4) studies (4)

Background

Sports diving is a widely performed recreational activity: in Europe, Sports diving is a widely performed recreational activity: in Europe, more than 1.000.000 divers practice it regularly (>50 dives/year)more than 1.000.000 divers practice it regularly (>50 dives/year)Decompression sickness (DCS) is caused by insufficient "off-Decompression sickness (DCS) is caused by insufficient "off-gassing" (release of inert nitrogen gas after the dive)gassing" (release of inert nitrogen gas after the dive)Dive tables and computers can only Dive tables and computers can only predict the "safe" decompression predict the "safe" decompression speed and schedule with relative speed and schedule with relative accuracy: other (unknown) factors accuracy: other (unknown) factors play an often important role.play an often important role.

Background

PFO = risk factor for PFO = risk factor for DCSDCS in sports in sports diving (high-spinal, diving (high-spinal, ccerebral, “un-deserved”)erebral, “un-deserved”) (Germonpre (Germonpre et al., 1998; Bove et al., 1998)et al., 1998; Bove et al., 1998)To quantify the relative risk To quantify the relative risk ((RR),RR), a a prospective study is neededprospective study is neededA large number of divers (n>4000) A large number of divers (n>4000) would have to be screened would have to be screened and and followed followed overover a 5 year study perioda 5 year study period in in order to obtainorder to obtain statistically statistically valid resultsvalid results

““Gold Standard” for PFO detection :Gold Standard” for PFO detection :Contrast -Transesophageal EchocardiographyContrast -Transesophageal Echocardiography

Time-consumingTime-consumingExpensive equipmentExpensive equipmentHospital-basedHospital-basedInvasiveInvasiveUnpleasantUnpleasantStandardised procedure Standardised procedure absolutelyabsolutely needed to minimise false-positive needed to minimise false-positive or false-negative results !or false-negative results !

• Hagen (autopsy): ± 30% PFOHagen (autopsy): ± 30% PFO• Various TTE, TCD & TEE studies: 16-47% !Various TTE, TCD & TEE studies: 16-47% !

Screening technique:Screening technique:“ideal” characteristics“ideal” characteristics

SimpleSimpleRapidRapidLow-costLow-costMinimally invasiveMinimally invasiveSafeSafeHigh specificity High specificity (few false positives)(few false positives)

Carotid Artery Carotid Artery Doppler ?Doppler ?

Carotid Doppler :Carotid Doppler : techniquetechnique

8 MHz probe8 MHz probeNaCl perfusionNaCl perfusion2-syringe system2-syringe systemStraining manoeuvreStraining manoeuvre3 injections 10cc3 injections 10cc

10-15 minutes10-15 minutes

Carotid Doppler Carotid Doppler

33 patients 33 patients ((non-non-divers)divers)Comparison Comparison C-TEE vs CDC-TEE vs CDProspective - Prospective - blindedblinded

FaFalselse positi positiveves 3 / 11s 3 / 11FaFalselse n neegatigativeves 0 / 22s 0 / 22

SensitivitSensitivityy 88 % - Sp 88 % - Speecificitcificityy 100 % 100 %

Confirmed by independent French study on 160 Confirmed by independent French study on 160 patients patients (Cochard 1999)(Cochard 1999)

Germonpré, Balestra et al. 1999Germonpré, Balestra et al. 1999

Carotid Artery DopplerCarotid Artery Doppler

Simple : Yes - easy to learnSimple : Yes - easy to learnRapid : Yes - 15 minutesRapid : Yes - 15 minutesLow-cost : YesLow-cost : YesMinimally invasive : YesMinimally invasive : YesSafe : better than C-TEESafe : better than C-TEESSensitivensitivity : 100 %ity : 100 %

Suitable for screening on a large scale : Suitable for screening on a large scale : prospective study on RR of PFOprospective study on RR of PFO

Carotid DopplerCarotid DopplerStudy Study

Data collection in volunteer Data collection in volunteer diversdivers– European scale (4000+ divers needed based European scale (4000+ divers needed based

on a 2.5 x increased DCS risk)on a 2.5 x increased DCS risk)– Blinded to the resultBlinded to the result– Instructed on “safe diving” (ethical committee)Instructed on “safe diving” (ethical committee)– Dynamic follow-up (research card, website)Dynamic follow-up (research card, website)– Follow-up period: 5-6 yearsFollow-up period: 5-6 years

a a DAN Europe Research ProtocolDAN Europe Research Protocol

Instructional VideoInstructional VideoInformation Webpage Information Webpage Central Data CollectionCentral Data CollectionStudy Package for DiversStudy Package for Divers

Carotid Artery DopplerCarotid Artery Doppler A prospective evaluation of the Risk of DCS in Divers with a Right-to-Left ShuntA prospective evaluation of the Risk of DCS in Divers with a Right-to-Left Shunt

Multicentric study, start : January 2003Multicentric study, start : January 2003Divers Alert Network support: participation of > 10 countries (incl. Divers Alert Network support: participation of > 10 countries (incl. Australia, South Africa)Australia, South Africa)Recruitment of divers through DAN publications, Recruitment of divers through DAN publications, investigator effortinvestigator effortSafety of saline contrast injectionSafety of saline contrast injectionPrecautions: oxygen on-site, no diving 24 hours before CDPrecautions: oxygen on-site, no diving 24 hours before CDInformed consent formInformed consent formDivulgation of results: DAN publications, international journalsDivulgation of results: DAN publications, international journals

Carotid Artery DopplerCarotid Artery Doppler A prospective evaluation of the Risk of DCS in Divers with a Right-to-Left ShuntA prospective evaluation of the Risk of DCS in Divers with a Right-to-Left Shunt

Divers Alert NetworkDivers Alert Network

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• Evaluation of caseEvaluation of case• Assisting evacuationAssisting evacuation

Research (PFO, Flying after Diving, Diabetics)Research (PFO, Flying after Diving, Diabetics)Training for Divers : Training for Divers : Oxygen Provider Course, other coursesOxygen Provider Course, other coursesInternet: Internet: www.daneurope.orgwww.daneurope.org