PFO as a risk factor for Decompression Sickness

1. PFO as a risk factor for Decompression Sickness a DAN Europe Research Programme research@daneurope.org

2. SCUBA Diving has it’s risks • … like any sport ! • Risks associated with the underwater environment: • Drowning • Hypothermia • Animal life • Pressure-related disorders

3. Decompression Sickness in Divers • Overall risk (DAN Europe data): • 1 / 7.390all dives (> 30m…) • 1 / 35.105no decompression dives < 30m • 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%

4. 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 • ..... ?

5. Decompression Sickness : the cause

6. Decompression Algorhythms

7. Saturation & desaturation of inert gas • Saturation = uptake (N2 = nitrogen) in tissues Desaturation = wash-out (N2) from tissues • Source = lungs = destinationVector = plasmaDestination = tissues = source • Dissolution Coefficients 

8. Haldane’s work (1908) Pressure ratio of 2 / 1 = SafeStaged decompression = “no DCS”No bubbles ?

9. Risk ofDCS Time Depth Comex data base (JP Imbert)

10. 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

11. Decompression Sickness : the cause

12. Boyle’s Law • Growth of bubbles in tissue (Yount 1989) • Coalescence of bubbles 10msw 5msw 2msw surface

13. The Decompression Sickness « Grey Zone »

14. Mechanism of disease

15. Causes of right-to-left shunting • Functional shunts • Opening of intrapulmonary shunts: pulmonary artery pressure increase due to embolisation of nitrogen bubbles (Vik et al., 1994 : Increase of MPAP during «bubbling» phase (>25%)) • Bubble recompression (yo-yo diving at end of dive)

16. Causes of right-to-left shunting • Anatomical shunts • Intrapulmonary shunts (congenital) • Extrapulmonary shunts (acquired; e.g. orthodeoxia-platypnea syndrome) • Intracardiac shunts: patent foramen ovale

17. The Foramen Ovale • Fœtal circulation: • High MPAP • RAP > LAP • Fossa Ovalis • Valve-like structure

18. The Foramen Ovale • Neonatal circulation: • Low MPAP • LAP > RAP • Fossa Ovalis • Valve-like structure • Closure in 5-10 days (in seal pups)

19. Mechanism of disease

20. Patent Foramen Ovale • Anatomical variant rather than disease • Prevalence: • 5-8mm long, 2-3mm wide • Valve-likestructure

22. Transthoracic echocardiography

23. Trans-oesophageal echo

24. C-TEE

26. PFO-related DCS • 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

27. PFO-related DCS • 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

28. Risk Quantification : • Germonpré et al. 1998 (J Appl Physiol) – c-TEE : • Odds Ratio PFO – no PFO : 2.6 • Odds Ratio PFO Gr 2 : 3.2 • Bove et al. 1998 (Undersea Hyperb Med) - META : • Odds Ratio PFO : 2.5 • DCS risk of «european diver»: • DAN 1989-1995 : • 1 / 7.390all dives (> 30m…) • 1 / 35.105no-decompression dives < 30m • BSAC 2004: • 1 / 10.500 dives (mostly deeper than 30msw, cold dives)

29. Cardiac echography after a 25m/25min. dive

30. Reversal of inter-atrial pressures

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

32. 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

33. 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 – nitrox oxide (NO) or Heat Shock Protein (HSP) involved ?

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

35. 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

36. Venous inflow increase in the heart Balestra et al. 1998 (Undersea Hyperb Med)

37. Not all R-L shunts are a PFO ! • Respiratory physiology: up to 12% anatomic venous-to-arterial 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 »

38. 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 : ?

39. 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

40. 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 ?

41. 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

42. 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)

43. 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)

44. Detection Methods for PFODiTullio 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)

45. C-TEE : gold standard ? • C-Transthoracicechocardiography • 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 % !

46. False negative c-ECHO • Blood flow pattern SVC – IVC • Turbulences Sinus Venosus - RA

48. Prospective study • To quantify the relative risk (RR) of PFO in diving,a prospective study is needed • A large number of divers (n>4000) would have to be screened and followed overa 5 year study periodin order to obtainstatistically valid results • Test all divers • Do not inform them of the result • Let them dive « at leisure » • Collect data and evaluate after a total of 200.000 dives

49. Screening technique:“ideal” characteristics • Simple • Rapid • Low-cost • Minimally invasive • Safe • High specificity (few false positives) Carotid Artery Doppler ?

50. Carotid Doppler :technique • 8 MHz probe • NaCl perfusion • 2-syringe system • Straining manoeuvre • 3 injections 10cc • 10-15 minutes