1. Role of Ventilation during CPR: Embracing the Science OR Bracing for Science? Tom Rea MD, MPH King County Emergency Medical Services Harborview Medical Center University of Washington

2. Disclosures Investigator in an ongoing randomized trial of dispatcher-assisted CPR comparing chest compression alone versus chest compression plus ventilation. Trial is supported in part by the Laerdal Foundation and the Medic One Foundation.

3. Disclaimers I don’t know?……….

4. What do we know?

5. Normal Physiology Effective coupling of heart and lung

6. Cardiac Arrest?

7. Cardiac arrest due to a heart cause Agonal respirations which may help facilitate some oxygenation, ventilation, and forward flow of blood. This mechanism is present in only a percentage. Agonal respirations dissipate over the course of several minutes. TIME

8. Cardiac arrest due to non-cardiac cause Increasing hypoxemia and hypercarbia over time TIME 0

9. Population distribution of etiology Cardiac Pulmonary What is the etiology underlying pathology?

10. What do we know about CPR?

11. Modeled after normal physiology – coupling of heart and lung

12. Mechanism of CPR benefit Traditional Paradigm Compressions and decompressions (and ventilations) push some measure of oxygenated blood forward to the critical end-organ tissues.

13. Mechanism of CPR benefit Evolving Paradigms Mechanical effect Compressions (and ventilations) decompress the stretched, overfilled right ventricle enabling the left ventricle to fill. Post-ischemic conditioning (metabolic effect) Compressions (and ventilations) upregulate protective pathways to protect against reperfusion injury. Chamberlain et al Resuscitation 2008 Rea et al Resuscitation 2008

14. How does CPR work? Combination of traditional and evolving paradigms(?) Different mechanisms for different persons(?) ………….So what(?)

15. The Great Debate Chest compression alone (CC) vs Chest compression plus ventilation (CC+V)

16. Animal Studies Animal studies provide conflicting results. Several show comparability or superiority for CC

17. However some indicate superiority of CC + V Carotid Blood Flow (ml x min -1 ) BaselineCPRCPR plus ITD 0 25 50 75 100 125 150 RR 2 RR 10 p<0.04 Carotid Blood flow Lurie et al Respiratory Care in press RR = 2 RR = 10

18. Challenges of Translation

19. Translation – You Pick’em Animal evidence….. Always Often Seldom Never translates to the human cardiac arrest experience.

20. Translation – You Pick’em Animal evidence….. Always Often Seldom Never translates to the human cardiac arrest experience

21. Translation – You Pick’em Animal evidence….. SOMETIMES translates to the human cardiac arrest experience.

22. Challenges of Translation Differences? (No comments please)

23. Differences? Etiology of Arrest Cardiac……………………..……...Pulmonary Anatomy and Physiology of Arrest Airway anatomy and agonal breathing Challenges to Delivering Care VS

24. HUMAN EVIDENCE

25. Human Experience Changing physiology over time Changing ventilation effectiveness over time Bystander EMS EMS Mouth-to-Mouth BVM ETT TIME 0

26. Human Experience Single level 1 study (RCT) – Dispatch CPR CC aloneCC + V Survival 14.6% 10.4% (p = 0.1) Hallstrom et al NEngl J Med 2000 ~4% absolute difference VS

27. What else do we know? Restricted to cardiac etiology – Trend in the opposite direction for non-cardiac etiology If you include non-cardiac etiology the absolute Difference decreases from 4% to 2% EMS response in the study community is extremely quick (3-4 minutes) VS

28. Human Experience Changing physiology over time Changing ventilation effectiveness over time Bystander EMS EMS Mouth-to-Mouth BVM ETT TIME 0 Hallstrom Study

29. Summary Human cardiac arrest is heterogeneous and the role of hypoxia may be an important contributor to the arrest. A combination of ventilation and compression is the standard based on normal physiology and careful work by resuscitation scientists. CPR benefit may occur by a variety of different mechanisms. (We do not completely understand how CPR works in humans) Animal studies provide mixed results. Challenges in translating animal to human experiences.

30. Summary Paucity of high-level, rigorous human evaluation. The single human RCT showed no difference and one must consider the chllenge of generalizability.

31. Round 2 The Rebuttal

32. The observational studies comparing bystander CC vs CC + V are important.

33. The Rebuttal They are nice additions but …….. 1. No survival difference between the 2 types of CPR 2. Important limitations - Substantial confounding (not RCTs) - Generalizability Iwami Circulation 2007 - Restricted to witnessed arrest due to heart disease. Excluded 80% of treated cases which accounted for ~ 50% of their survivors.

34. The Rebuttal The observational before-and-after studies of EMS CPR indicate CC alone is superior.

35. The Rebuttal They are provocative additions but …….. 1.There were multiple interventions and a new (likely unprecedented) attention to care. 2. King County experience VF survival 33% to 46% with specific changes BUT maintained a 15:2 ratio (now 30:2) 3.Other communities have reported substantial improvement in survival by instituting active tracking and QA without specific protocol changes. Toronto VF survival - 10% to 20% with QA (no other specific changes)

36. The Rebuttal How about a bipartisan approach?

37. Consider Community A An improved approach “Pool” of Cardiac Arrest Victims N = 1000

38. No CPR Survivors “Pool” of Cardiac Arrest victims N = 1000 Survivors N = 50

39. Chest compression alone Survivors “Pool” of Cardiac Arrest victims N = 1000 Survivors N = 100

40. Chest compression plus ventilation Survivors “Pool” of Cardiac Arrest victims N = 1000 Survivors N = 100

41. CC alone vs CC plus ventilation Are we saving different patients? “Pool” of Cardiac Arrest victims N = 1000 CC alone CC + V

42. CC alone vs CC plus ventilation Are we saving different patients? “Pool” of Cardiac Arrest victims N = 1000 CC alone CC + V 70% N=70 N = 30

43. CC alone vs CC plus ventilation Correctly allocate care to the crescents CC aloneCC + V 70% N=70 N = 30 Survival = 70 + 30 + 30 = 130 30% improvement in outcome

44. Conclusions The approach of CC + V attempts to mirror normal physiology and is derived from careful work by resuscitation scientists. Evidence from animal results are mixed and may not translate directly to human experience. Observational studies have major limitations and to date demonstrate no difference between CC vs CC+V. Sufficient, methodologically-rigorous human data are largely lacking…….the field needs this high level of evidence to make genuine progress.

45. What’s the best approach? I don’t actually know but…….. For now, CPR with ventilations especially among trained persons is a reasonable approach. Let’s brace for and then embrace rigorous human evidence.