Keith Lurie MD Professor of Emergency Medicine and Internal Medicine University of Minnesota

1. August 15, 2010 Harnessing the Intrathoracic Pump Mechanisms to Enhance Circulation Keith Lurie MD Professor of Emergency Medicine and Internal Medicine University of Minnesota Chief Medical Officer Advanced Circulatory Systems

2. Index Case 1987 Saved by a Household Plunger San Francisco General Hospital

3. Intrathoracic Pressure Regulation Therapy ResQPOD: for CPR CirQlator: for hypotension in apneic pts ResQGARD: for hypotension in spontaneously breathing pts All 3 devices cleared by FDA for clinical use

4. Effect of Inspiratory Impedance During CPR on Airway Pressures 1. Lowers intrathoracic pressure 2. Mimics gasping reflex 3. Lowers ICP 4. Refills the heart 5. Doubles circulation Conventional or ACD CPR with ITD Conventional CPR Enhanced Vacuum

5. Effect of Inspiratory Impedance During Spontaneous Respiration 1. Lowers intrathoracic pressure 2. Lowers ICP 3. Refills the heart 4. Increases cerebral and systemic circulation 5. Harnesses the sympathetic nervous system 6. Mimics stress response to central hypovolemia • Intrathoracic Pressure .

6. Effect of Intrathoracic Pressure Regulators 1. Lowers intrathoracic pressure 2. Lowers ICP 3. Refills the heart 4. Increases cerebral and systemic circulation or

7. Active Compression Decompression CPR Metronome Force Gauge Suction Cup Handle

8. Randomized Clinical Trial (Paris, France) Survival After Cardiac Arrest 40 STD (n = 377) 35 ACD (n = 373) 30 25 20 15 Percent * *Statistically significant 10 * 5 0 ICU Hosp Disch 1 Hr 24 Hr 1 Yr ROSC Admit Plaisance P et al. Standard CPR and ACD resuscitation for out-of-hospital cardiac arrest. N Engl J Med. 1999;341:569-75.

9. An impedance threshold device (ITD) selectively prevents unnecessary air from entering the chest during the recoil (decompression) phase of CPR

10. Using an ITD

11. Human Data: Blood Pressure Milwaukee, WI * *p<0.05 BP after 14 Minutes of ITD Use n = 22 Pirrallo et al. Resuscitation 2005;66:13-20.

12. A Tale of Six EMS Systems: An Impedance Threshold Device and ‘New CPR’ Improves Survival Rates after Out-of-hospital Cardiac ArrestAufderheide et al Heart Journal 2010

13. 120 100 STD CPR 80 mmHg 60 ACD + ITD 40 20 0 Systolic Diastolic ACD CPR + ITD in HumansThe Future Baseline (Normal) Plaisance et al. Circulation 2000;101:989-994

14. ACD CPR + ITD in Humans Witnessed VF not resuscitated with 3 initial shocks (n = 70) Wolcke et al. Circulation 2003;108:2201-05. * * * * Percentage * *p<0.05

15. ↑ Preload ↑ Coronary Artery Perfusion ↑ Blood Flow to Vital Organs ↑ Cardiac Output Greater Intrathoracic Vacuum  Intracranial Pressure  Resistance to Forward Blood Flow  Cerebral Blood Flow Inspiratory Impedance Effect Inspiration through the ITD-7

16. Emergency Room EMS NASA Astronauts Orthostatic Hypotension Dialysis Clinical Experience with Hypotensive Patients

17. Benefit in Patients (n=10) with no IV 10 pts from Toledo and Minneapolis studies combined: P<0.01 Smith et al J. Emerg Med 2010

18. Harnessing the Thoracic Pump in the Apneic Patient

19. Effect of ITPR on Tracheal Pressure and ICP in Apneic Pigs ITPR Application Tracheal Pressure 1min ITPR ICP

20. Used in pigs in Cardiac Arrest, Hemorrhagic Shock, Sepsis, TBI

21. CirQlator™ Human Studies Ventilation Source ITPR Bacterial Filter ET Tube Vacuum Source

22. Clinical Experience at U of MN: Intra-operative Hypotension (Birch et al ASA 2010)

23. Clinical Experience U of VA(Dr. Ed Nemergut ASA 2010) Neuro ICU (n=10): To date there has been a consistent decrease in ICP from ~ 20 mmHg to 15 mmHg and an increase in cerebral perfusion pressure

24. Combined Results: ICP 21 % 33 % 27 % 17 % Device 1 Device 2 Baseline 2 4 6 8 10 Baseline 2 4 6 8 10

25. ResQVent

26. The Future Feedback control loops to regulate intrathoracic pressure (positive and negative pressures, tidal volume, ventilation rate) to optimize cerebral and systemic circulation

27. Thank you Questions?