1. Mind, Brain & Consciousness During Cardiac Arrest Sam Parnia MD, PhD Pulmonary & Critical Care Medicine State University of New York Stony Brook, USA University of Southampton, UK

2. None Disclosures

3. What to do when someone dies? Historical Perspectives on Resuscitation Early in history – Galen: Life = Heat & Lifeless = Cold - Heat to prevent death from taking the person Bellows Method – started in 1530’s – lasted 300 yrs - Flagellation – to stimulate a response - Warm ash - Burning excrement or hot water on body Fumigation Method – 1700’s Inversion, Barrel, Trotting Horse - 1700- 1800’s Mouth-to-Mouth & Chest Compression - 1950-60’s

4. Irreversible Death Heart attack Causes of death Traffic accident Dying Process – potentially reversible Lasts: Few seconds – 10’s min’s – over an hour Cardiac Arrest/Clinical Death Impact of Resuscitation Science 50 Years on – Death not a “moment” it is a “reversible” process. Uncharted Territory Shock: 02 delivery organs inadequate

5. Cardiac Arrest “Global Stroke” Pathophysiology of Cardiac Arrest “Whole body ischemia”– lack oxygen Brain Oxygen & Energy Stores(ATP) depleted – Accumulation toxins (adenosine, lactate, H+) Cells Dysfunction – massive intracellular Ca+ accumulation – toxicity - death Permanent Brain Cell Death – ? Hours later

6. Does Brain Function During Cardiac Arrest? EEG during Cardiac Arrest – slowing - isoelectric (flatline) 10– 20 s Remain flat – until resumption of heartbeat if early intervention Prolonged cardiac arrest - EEG returns “hrs” after. Animal study - 15 min cardiac arrest then resuscitation: - EEG flat 21 ± 5.7 s (n=10) - 90 ± 24.7 min - bursts of slow waves Kano T, Hashiguchi A, Sadanaga M. Resuscitation 1993; 25: 265-281

7. So Why Does it Matter?

8. What are the wider implications of cardiac arrest research? - Can we bring people back safely? - What happens after we die?

9. What Happens When We Die? Near Death Experience (NDE) ‘Life after life’ Raymond Moody 1975 Reactions - ‘Life after life – Hallucination - Fabrication Retrospective Studies - Some describe negative NDE 4% prevalence of NDE in USA – Gallup 1982 Problem: Social & Medical Perception of Death – Irreversible

10. 19 th century Swiss accident survivors 15 th century Dutch painting – H Bosch Plato’s Republic & many others… Ascent to the Empyreon – H Bosch (1450 – 1516) Cognitive & Mental Activity – Near Death Experience (NDE)

11. NDE described in Japan, China, India and ++++ Consistent core features Studied in children Case of 3 year old sent to Southampton Cognitive & Mental Activity – Near Death Experience (NDE)

12. Physiological Psychological Transcendental WHY DO NEAR DEATH EXPERIENCES OCCUR? Other … Anticipation of death - ? ‘fear death’ experience Chemical changes in brain - hallucination True separation of mind/soul from body

13. WHY DO NEAR DEATH EXPERIENCES OCCUR? – Rumi’s Elephant in the Dark

14. Near Death Experience – Problems! Cardiac arrest – Biologically = death What do we mean by near death? – scientifically too vague – led to much controversy New Term: Actual Death Experience

15. Irreversible Death Heart attack Causes of death Traffic accident Dying Process – potentially reversible Lasts: Few seconds – 10’s min’s – over an hour Cardiac Arrest “Near Death” or “Actual Death” Experience

16. Parnia S, Waller D, Yeates R, Fenwick P, A qualitative and quantitative study of incidence, features and aetiology of NDE's in cardiac arrest survivors Resuscitation Feb 2001 48, 149-156 What happens to mind and consciousness during cardiac arrest?

17. 344 cardiac arrest survivors - 10 hospitals Largest NDE Study in Cardiac Arrest 41 (12%) reported core NDEs - No association with: 8 year follow up - positive change in life Did not test physiological parameters ?? Account for NDE through brain processes? Transformation following NDE Van Lommel P et al – Near-death experience in survivors of cardiac arrest: a prospective study in the Netherlands. Lancet 2001; 358:2039-2045 Medication Fear of death prior to cardiac arrest

18. Wider Implications of Consciousness During Cardiac Arrest ? Signify improved brain Resuscitation? - Need to study “real time” brain resuscitation. When is human mind/consciousness lost permanently and cannot be retrieved after death?

19. Death – Physical Process Changes in Cells including Brain – Cell damage within minutes Brain Cells undergo Irreversible Damage Eventually leads to bodily destruction Minutes Hrs - Days When do the mind & consciousness cease existing?

20. Scientific Paradox: ? mind/consciousness continue function when brain stopped working and reached the clinical criteria of death Five independent studies – published since 2001 UK, Holland, USA 10-20% people revived from cardiac arrest & clinical death – consciousness + thought processes + can “see” & “hear” Death – What Happens to Mind & Consciousness?

21. Paradox: Consciousness during Unconsciousness! Possible explanations: - Arise just before or after cardiac arrest - do not arise at all - Unlikely - ? millions of cases - Need to re-examine mind/brain theories

22. The relationship of mind and brain: Challenge for 21st century science?

23. How do we have ‘consciousness’ (psyche or soul) from brain processes? Mind and Brain - Problem of Consciousness, Psyche or Soul How do thoughts, feelings and all aspects of mind arise from brain processes?

24. Mind and Brain - Problem of Consciousness

25. Descartes - Cartesian model From: Brain Atlas Harvard Medical School Ancient Greeks - Human Soul Cerebral localisation -19 - 20C Modern scanning techniques - f MRI, PET History

27. Mapping the mind Complex thoughts = Activity in multiple areas of brain Identifying brain cell activity during thoughts – correlation NOT CAUSATION

28. Mind and Brain - Problem of Consciousness Current Views - - Others – Quantum processes - Hameroff/Penrose Irreducible entity: electromagnetic/mass/Gravity Chalmers Mind/Brain – Separate – Eccles/ Elahi - Conventional – Neural Networks Greenfield/Crick/Koch/ Dennett

29. Reality of any experience is socially determined - not ‘neurologically’ – Whether NDE/Love or otherwise… Are Experiences Real or Hallucinations? All experience mediated by brain pathways NDE – Out of body experiences - many claim objectively verifiable events – Can we test and determine its reality...?

30. First large scale study to examine claims to “see” and “hear” AWARE STUDY (AWAreness during Resuscitation) - launched 2008. International Multicentre Study of Consciousness during Cardiac Arrest Aim to use Sophisticated Technology (cerebral oximetry) to study brain oxygen delivery with consciousness

31. Cerebral Oximetry Optical Monitoring technique using Beer Lambert law Assesses regional O 2 (rSO 2 %) (balance O 2 delivery & uptake) Represents mostly cerebral venous saturation Acceptable Normal Values 60- 80%

32. Role of cerebral oximetry in predicting return of spontaneous circulation (ROSC) in cardiac arrest using manual CPR * * p = <0.0016 Mann-Whitney Test, ROSC = Return of Spontaneous Circulation(No ROSC n= 15, ROSC n= 7)

33. * Impact of Automated CPR (LifeStat) on rSO 2 * p= <0.0001 Mann-Whitney (Manual CPR n=22, Automated(LifeStat) CPR n=12)

34. Time (mins) % rSO2 Illustration of the Impact of Manual & Automated Chest Compression on Cerebral Perfusion in Two Patients Automated CPR (patient 1) Manual CPR (patient 2) ROSC = Return of Spontaneous Circulation

35. Manual CPRAutomated CPR * % Survival (ROSC) ROSC = Return of Spontaneous Circulation lasting > 20 mins. *p < 0.05 using Fischer's Exact test. (Manual CPR n=44, Automated CPR n=20) Automatic CPR leads to higher Return Spontaneous Circulation Following Cardiac Arrest

36. University of Southampton, Dr Peter Fenwick (Psychiatry), Dr Charles Deakin (cardiac anesthesia), Dr Paul Little (research design), Professor Robert Peveler 2 (Psychiatry), Ms Niki Fallowfield (Resuscitation) University of Cambridge: Ms Susan Jones (Resuscitation) Northampton Hospital: Ms Celia Warlow (Resuscitation), St Georges Hospital, London: Ms Leanne Smythe (Resuscitation), St Peters Hospital: Mr Paul Wills (Resuscitation), Mayday Hospital: London Mr Russell Metcalfe Smith (Resuscitation), Royal Bournemouth Hospital: Ms Hayley Killingback (Resuscitation), Morriston Hospital: Dr Penny Sartori (Critical Care Unit), Stevenage Hospital: Ms Salli Lovett (Critical Care) Salisbury Hospital: Mr Iain Macleod (Resuscitation), East Sussex Hospitals, Dr Harry Walmsley (Anaesthetics & Resuscitation) Hammersmith Hospital London: Mr Ken Spearpoint, (Resuscitation), AWARE STUDY – Investigators/advisors Indiana State University, Dr Mark Faber (Pulmonary & Critical Care), University of Virginia: Professor Bruce Greyson (Psychiatry), Dr Robert O’Connor (Emergency) Emory Medical Center: Dr Maziar Zafari (cardiology) University of Vienna: Professor Roland Beisteiner (Neurology), Dr Fritz Sterz (Emergency Medicine), Dr Michael Berger (Neuroscience)

37. METHODS – Hidden Targets Southampton

38. RESEARCH – Cardiac arrest – Humour!

40. Near Death Experience Research How do we study human mind and consciousness during cardiac arrest

41. METHODS Open question - ? memory of consciousness Study Experiences- Greyson scale - Cognitive recollections (study) - No cognitive recollections (control) -Physiological – O 2 / CO 2 – Electrolytes Drugs – Cardiac Rhythm - Psychological – ? Religion ? Practicing - Transcendental – Hidden targets … Study Brain & Resuscitation Processes:

42. RESULTS – Physiological Southampton Southampton Study: NDE in cardiac arrest 0 10 30 50 70 90 110 130 150 controlstudy Na mmol/l K PaCO2 KPa PaO2 KPa Parnia S, Waller D, Yeates R, Fenwick P, A qualitative and quantitative study of incidence, features and aetiology of NDE's in cardiac arrest survivors Resuscitation Feb 2001 48, 149-156

43. Current version – Fixed shelves with fixed images!

44. Future Version - Random image generators

45. Portable Brain (EEG) Monitor – during cardiac arrest

46. Cerebral oximetry – Our experience so far! N=10 - Useful in cardiac arrest - results so far similar to previous - 02% <20% - non survivors ROSC