PFO as a risk factor for Decompression Sickness

2. PFO as a risk factor for Decompression Sickness Dr Peter Germonpré, MD

3. 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

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

5. Decompression Algorhythms

6. 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 

7. Possible factorsinfluencing saturation (& desaturation) • Diffusion – related factors • Depth of dive ( alveolarN2 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…)

8. 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

9. 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%

10. Decompression Sickness : the cause

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

12. Decompression Algorhythms • Are humans animals ?

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

14. 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

15. Decompression Sickness : the cause

16. Boyle’s Law • Growth of bubbles in tissue (Yount 1989) • Coalescence of bubbles 1 ATA 0.75 ATA 0.5 ATA 0.25 ATA

17. The Decompression Sickness « Grey Zone »

18. Mechanism of disease

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

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

21. Mechanism of disease

22. 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

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

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

26. Reversal of inter-atrial pressures Balestra et al. 1998 (Undersea Hyperb Med)

28. Transthoracic echocardiography

29. Trans-oesophageal echo

30. C-TEE

31. 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

32. 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,…)

33. Standardised, optimised c-TEE technique • Based on intrathoracic pressure changes • Strict protocol and sequence c-TEE Balestra et al. Undersea Hyperb Med 1998; Germonpré et al. J Appl Physiol 1998

34. 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 : ?

35. 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

36. 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 ?

37. 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

38. 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)

39. 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)

40. 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”

41. Haldane’s work Pressure ratio of 2 / 1 = SafeStaged decompression = no DCS= no bubbles ?

42. Cardiac echography after a 25m/25min. Dive

43. Reversal of inter-atrial pressures

44. Retrospective studies : 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 • Incidence of DCS in study population :2.28 / 10.000 dives • DAN 1989-1995 : DCS risk of «european diver»: • 1 / 7.390all dives (> 30m…) • 1 / 35.105no decompression dives < 30m

45. 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

46. 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

47. 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 ?

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

49. 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

50. 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)