Transcript Patent Foramen Ovale as a cause of Decompression Sickness

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 /yr
Recreational SCUBA diving
is BIG BUSINESS :
– Dive gear
– Dive schools
– Dive vacations
SCUBA Diving has it’s risks
… like any sport !
Risks associated with the underwater
environment:
–
–
–
–
Drowning
Hypothermia
Animal life
Pressure-related disorders
Decompression Algorhythms
Saturation & desaturation
of inert gas
Saturation = uptake (N2 = nitrogen) in tissues
Desaturation = wash-out (N2) from tissues
Source = lungs = destination
Vector = plasma
Destination = tissues = source
Dissolution Coefficients 
Water
Fat
H2
0,017
0,036
He
0,009
0,015
N2
0,013
0,067
Ar
0,027
0,140
Possible factors
influencing 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 dives
Reverse dive profiles
Speed of ascent
Exercise during dive
Cold during deco stops
Personal habits : poor physical condition, smoking, age
Personal factors : fat content, dehydration, alcohol use,
sex
Decompression Sickness in Divers
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 : 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)
Risk of
DCS
15
10
Time
5
120
90
60
0
57
60
5
54
51
45
48
42
36
39
20
30
33
24
27
18
21
12
15
30
Depth
DAN Europe: analysis of 202 cases of DCS
1989-1993
Depth > 30 msw
Deco diving
Error ascent / stops
Repetitive dive
Stress – Fatigue
Multiday diving
Material fault
Altitude after dive
Decompression Sickness : the cause
Boyle’s Law
Growth of bubbles in tissue (Yount 1989)
Coalescence of bubbles
1 ATA
0.75 ATA
0.5 ATA
0.25 ATA
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
PFO-related DCS & the Brain
Germonpré et al. 1998 (J Appl Phys) (c-TEE) :
– Significant association PFO – cerebral DCS
– No association PFO – Spinal DCS
Louge et al. 2001 (Crit Care Med) (c-TCD) :
– Cerebral DCS: 83% TCD pos
– Spinal DCS:
37.9% TCD pos
Torti et al. 2004 (Undersea Hyperb Med) (c-TEE) :
– > cerebral / vestibular symptoms
Patent Foramen Ovale
Anatomical variant rather than disease
Prevalence: Author
1 – 20 yrs
20-40 yrs
> 40 yrs
Patten 1931
34.5%
27.2%
22.4%
Hagen 1984
35%
29%
20.4%
5-8mm long, 2-3mm wide
Valve-like
structure
Reversal of inter-atrial pressures
Vik et al., 1994 :
Increase of MPAP
during «bubbling»
phase (>25%)
Reversal of inter-atrial pressures
Balestra et al. 1998 (Undersea Hyperb Med)
Transthoracic echocardiography
Trans-oesophageal echo
C-TEE
Retrospective studies (1)
1989: Moon et al. (Lancet) : c-TTE
– PFO 37% in DCS divers
– PFO 61% in neurologic DCS
– PFO 10.7% in non-divers
1989: Wilmshurst et al. (Lancet) : c-TTE
– PFO 66% in early neurologic DCS
– PFO 17% in late neurologic DCS (30 min)
– PFO 24% in control divers
Retrospective studies (2)
1998: Germonpré et al. (J Appl Physiol) – c-TEE
– 37 DCS divers (20 cerebral, 17 spinal)
– 36 matched control divers (age, sex, BMI, smoking,
physical fitness, diving experience)
– semi-quantification of PFO (gr 0, 1, 2)
– “undeserved DCS”
• No diving technical errors
• < 3 minor risk factors (fatigue, effort, alcohol, cold,
dehydration,…)
Standardised, optimised c-TEE
technique
Based on intrathoracic pressure changes
Strict 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
spinal DCI
6/17
35.2%
5/17
29.4%
controls
8/16
50%
6/16
37.5%
p
0.49
(Fisher)
all DCI vs ctl.
p: 0.06
0.002
0.29
Fischer
p: 0.03
Fischer
Balestra et al. Undersea Hyperb Med 1998; Germonpré et al. J Appl Physiol 1998
Cerebral damage in divers
Adkisson et al. 1989 (Lancet) (SPECT):
– Cerebral perfusion deficit after neurologic DCS & AGE
Knauth et al. 1997 (Lancet) (RNM)
(87 divers):
– Multifocal cerebral lesions
• 7 lesions in 7 divers without PFO
• 34 lesions in 4 divers with PFO grade 2
• Total (TCD) 25 divers PFO, 13 grade 2
– Auto-selection of divers : ?
Nitrogen bubble embolisation may cause
cerebral ischemic damage in divers ?
Diver S. - 39 years old - 17 years diving experience - 800+
dives
1 confirmed episode of vestibular / cerebellar decompression
sickness - timely treated & completely recovered
Anamnesis: > 10 episodes of abnormal drowsiness, fatigue during approx. 1 hour, after dives
Brain Damage through diving ?
Reul et al., Fueredi et al.,
Knauth et al.
WEAK POINTS :
Selection bias : DCS ?
Morphological (MR)
analysis : Wirchow
spaces ?
PFO detection method :
other shunts ?
Brain Damage through diving ?
Selection bias : DCS ?
– 200 volunteer divers:
• Age < 40 yrs
• > 5 yrs diving, > 200 dives
• No history of DCS
– Random ¼ selection
Morphological (MR) analysis: Wirchow spaces ?
– T1, T2, FLAIR sequences: diff diagnosis
PFO detection method : other shunts ?
– Standardised c-TEE
Neuropsychometric testing: WAIS, MMS subtests for
neurotoxic solvents
Results
– In experienced divers who never had DCS,
no increased prevalence of WML is found
as compared to a control population
– In these divers, a high prevalence of PFO
is found (65%)
(Germonpré et al. EUBS Congress 2003)
Time-related opening
of PFO in divers
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)
PFO :
should every diver be screened ?
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”
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 pressures
Retrospective studies : risk quantification
Germonpré et al. 1998 (J Appl Physiol) – c-TEE :
– Odds Ratio PFO – no PFO :
– Odds Ratio PFO Gr 2 :
2.6
3.2
Bove et al. 1998 (Undersea Hyperb Med) - META :
– Odds Ratio PFO : 2.5
– Incidence of DCS in study population : 2.28 / 10.000 dives
DAN 1989-1995 : DCS risk of «european diver»:
– 1 / 7.390 all dives (> 30m…)
– 1 / 35.105 no decompression dives < 30m
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 dive
Marroni 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 1999
High VO2max (= good fitness)  less post-dive bubbles
Wisloff et al. J Physiol 2004
Exercise 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 OR
Wilmshurst 2001 : smokers more likely for DCS-AGE
Detection Methods for PFO
DiTullio et al. 1993 - Kerut et al. 1997
c-TEE
Transcranial Doppler (c-TCD)
– Sensitivity 68% to 90% - Specificity 100%
Transthoracic Echocardiography (c-TTE)
– Sensitivity 47% - Specificity 100%
Right Heart Catheterisation
– Sensitivity 80% - Specificity 100%
(Di Tullio et al: Stroke 1993 - Kerut et al.: Am J Cardiol 1997)
False negative c-ECHO
Blood flow pattern SVC – IVC
Turbulences Sinus Venosus - RA
C-TEE : gold standard ?
C-Transthoracic echocardiography
– 10 – 18 %
(Lynch et al. 1984, Van Hare et al. 1989)
C-Trans-oesophageal echocardiography
– Konstadt et al. 1991: 26 %
– Fisher et al. 1995: 9.2 %
– Meissner et al. 1999: 25.6 %
Anatomical prevalence : 25-30 % !
Retrospective studies (4)
Respiratory physiology: up to 12% anatomic venous-toarterial pulmonary shunting
Sulek et al. (Anesthesiology 1999) : c-TEE + c-TCD
– Cerebral embolisation of fat emboli after TKA
– after important emboli afflux (tourniquet release)
– (even without PFO) : opening of intrapulmonary shunts
Cardiology practice c-TEE :
– If bubbles observed after more than 3 (5) heartbeats after
appearance in RA  « pulmonary passage of bubbles »
Background
Sports diving is a widely performed recreational activity:
in Europe, more than 1.000.000 divers practice it
regularly (>50 dives/year)
Decompression sickness (DCS) is caused by insufficient
"off-gassing" (release of inert nitrogen gas after the dive)
Dive tables and computers can only
predict the "safe" decompression
speed and schedule with relative
accuracy: other (unknown) factors
play an often important role.
Background
PFO = risk factor for DCS in
sports diving (high-spinal,
cerebral, “un-deserved”)
(Germonpre et al., 1998; Bove et
al., 1998)
To quantify the relative risk (RR),
a prospective study is needed
A large number of divers
(n>4000) would have to be
screened and followed over a 5
year study period in order to
obtain statistically
valid results
“Gold Standard” for PFO detection :
Contrast -Transesophageal Echocardiography
Time-consuming
Expensive equipment
Hospital-based
Invasive
Unpleasant
Standardised procedure absolutely
needed to minimise false-positive
or false-negative results !
• Hagen (autopsy): ± 30% PFO
• Various TTE, TCD & TEE studies: 16-47% !
Screening technique:
“ideal” characteristics
Simple
Rapid
Low-cost
Minimally invasive
Safe
High specificity
(few false positives)
Carotid Artery
Doppler ?
Carotid Doppler :
technique
8 MHz probe
NaCl perfusion
2-syringe system
Straining manoeuvre
3 injections 10cc
10-15 minutes
Carotid Doppler
Germonpré, Balestra et al. 1999
33 patients (non-divers)
Comparison C-TEE vs CD
Prospective - blinded
False positives 3 / 11
False negatives 0 / 22
Sensitivity 88 % - Specificity 100 %
Confirmed by independent French
study on 160 patients
(Cochard 1999)
Carotid Artery Doppler
Simple : Yes - easy to learn
Rapid : Yes - 15 minutes
Low-cost : Yes
Minimally invasive : Yes
Safe : better than C-TEE
Sensitivity : 100 %
Suitable for screening on a large scale :
prospective study on RR of PFO
Carotid Doppler
Study
Data collection in volunteer
divers
– European scale (4000+ divers needed based
on a 2.5 x increased DCS risk)
– Blinded to the result
– Instructed on “safe diving” (ethical committee)
– Dynamic follow-up (research card, website)
– Follow-up period: 5-6 years
Carotid Artery Doppler
A prospective evaluation of the Risk of DCS in Divers with a Right-to-Left Shunt
a DAN Europe Research Protocol
Instructional Video
Information Webpage
Central Data Collection
Study Package for Divers
Carotid Artery Doppler
A prospective evaluation of the Risk of DCS in Divers with a Right-to-Left Shunt
Multicentric study, start : January 2003
Divers Alert Network support: participation of > 10 countries
(incl. Australia, South Africa)
Recruitment of divers through DAN publications,
investigator effort
Safety of saline contrast injection
Precautions: oxygen on-site, no diving 24 hours before CD
Informed consent form
Divulgation of results: DAN publications, international journals
Divers Alert Network
Telephonic Emergency Consultation
24/24 Hotline: 0800-12382
• Evaluation of case
• Assisting evacuation
Research (PFO, Flying after Diving, Diabetics)
Training for Divers :
Oxygen Provider Course, other courses
Internet: www.daneurope.org
