1. 3100B Ventilator

2. VIASYS Healthcare, Inc. 3100B Ventilator Approved for sale outside the US in 1998 for patients weighing > 35 kg failing CMV Approved September 24, 2001 by the FDA for sale in the US

3. VIASYS Healthcare, Inc. Pulmonary Injury Sequence There are two injury zones during mechanical ventilation Low Lung Volume Ventilation tears adhesive surfaces High Lung Volume Ventilation over- distends, resulting in “Volutrauma” The difficulty is finding the “Safe Window” Froese AB, Crit Care Med 1997; 25:906

4. VIASYS Healthcare, Inc. High Frequency Ventilation Advantages- Enables ventilation above the “closing volume” with lower alveolar pressure swings. Safe way of using “Super PEEP”.

5. VIASYS Healthcare, Inc. Theory of Operation Controls for Oxygenation and Ventilation are mutually exclusive. Oxygenation is primarily controlled by the Mean Airway Pressure (Paw) and the FiO 2. Ventilation is primarily determined by the stroke volume (Delta-P) and the frequency of the ventilator.

6. VIASYS Healthcare, Inc. Large Patient Strategies When to consider HFOV use? As with all candidates, the earlier the better FiO 2 >60, PEEP>10 with PaO 2 /FiO 2 ratio<200 Relative contra-indications Obstructive lung disease Elevated ICP

7. VIASYS Healthcare, Inc. Acute Respiratory Distress Syndrome

8. VIASYS Healthcare, Inc. 19 yo female - Pneumococcal pneumonia (Day 1) FiO 2 100%, PEEP 20, PIP 60, SpO 2 80%

9. VIASYS Healthcare, Inc. 19 yo female - Pneumococcal pneumonia (Day 2) FiO 2 100% SpO 2 - 78%

10. VIASYS Healthcare, Inc. 19 yo female - Pneumococcal pneumonia (Day 3) FiO 2 100% and SpO 2 70%

11. VIASYS Healthcare, Inc. What if physiologic goals can’t be met using lung protective strategies?

12. VIASYS Healthcare, Inc. Large Patient Strategies ARDS FiO 2 matched Paw 5 cmH 2 O above CMV Power of 4.0 and then adjust for good CWF Bias flow >20 lpm, higher if required to maintain Paw Frequency determined by patient size and compliance I-Time set to 33%

13. VIASYS Healthcare, Inc. Oxygenation Strategies  Paw until you are able to  FiO 2 to 60% with a SaO 2 of 90% Avoid hyperinflation Optimize preload, myocardial function Ventilation Strategies –CWF- adjust Power Setting to target PaCO 2 to between 45-55 mmHg –  frequency by 1Hz increments if Amplitude is maximized –Induce cuff leak –allow permissive hypercarbia if indicated, keeping pH>7.25

14. VIASYS Healthcare, Inc. HFOV Strategy If CO 2 retention persists, decreasing cuff pressure to allow gas to escape around the ET tube will move the fresh gas supply from the wye connector to the tip of the ET tube

15. VIASYS Healthcare, Inc. Clinical Tips Failure Criteria Inability to decrease FiO 2 by 10% within the first 24 hrs. Inability to improve ventilation or maintain ventilation (after optimizing both frequency and amplitude) with PaCO 2 7.25. A transcutaneous monitor is useful for trending CO 2.

16. VIASYS Healthcare, Inc. Clinical Assessment Suctioning Indicated by decreased or absence CWF, decrease in O 2 saturation, or an increase in TcCO 2. Remember that each time the patient is disconnected from HFOV, they will potentially de-recruit lung volume. Closed suction catheters may mitigate de-recruitment It may be necessary to temporarily  Paw or perform recruitment maneuver

17. VIASYS Healthcare, Inc. Derecruitment during Disconnect Minimize suction attempts Use closed suction systems Avoid unnecessary disconnects May require RM or  FiO 2 to return SaO 2 to baseline

18. VIASYS Healthcare, Inc. Clinical Assessment Chest Wiggle factor (CWF) must be evaluated upon initiation and followed closely after that. CWF absent or becomes diminished is a clinical sign that the airway or ET tube is obstructed. CWF present on one side only is an indication that the ET tube has slipped down a primary bronchus or a pneumothorax has occurred. Check the position of the ET tube or obtain a CXR. Reassess CWF following any position change.

19. VIASYS Healthcare, Inc. Clinical Assessment Chest X-rays Obtain the first x-ray at the (4) hour mark to determine the lung volume at that time. Paw may need to be re-adjusted accordingly. Always obtain a CXR, if unsure as to whether the patient is hyper-inflated or has de-recruited the lung.

20. VIASYS Healthcare, Inc. Clinical Assessment Auscultation Breath sounds-listen to the “intensity or sound” that the piston makes, it should be equal throughout. Heart Sounds - stop the piston, (the patient is now on CPAP); listen to the heart sounds quickly, and restart the piston.

21. VIASYS Healthcare, Inc. Clinical Tips Weaning - Wean FiO 2 for arterial saturation > 90% Once FiO 2 is 60% or less, re-check chest x-ray and if appropriate inflation, begin decreasing the Paw in 1cmH 2 O increments Wean Delta-P in 5 cmH 2 O increments for PaCO 2 Once the optimal frequency is found, leave it alone

22. VIASYS Healthcare, Inc. Aerosol Therapy Patients who are actively wheezing or have RAD administration via bagging- try to coordinate with suctioning IV terbutaline for patients who do not tolerate disconnects promising new nebulizer technology

23. VIASYS Healthcare, Inc. Practical Considerations Humidification of bias flow accomplished with a traditional heated humidifier Longer, flexible circuit allows patient positioning to prevent skin breakdown Infection control issues

24. VIASYS Healthcare, Inc. Managing Large Patients Most patients will require heavy sedation and occasional neuromuscular blockers to be maintained on the 3100B.

25. VIASYS Healthcare, Inc. HFOV Management Guidelines for Transition to CMV Paw < 24 cmH 2 O or stalled FiO 2 < 50% or stalled > 4 days HFOV Return to CMV at similar Paw

26. VIASYS Healthcare, Inc. 3100B Rescue Trial Fort P, et al. High-frequency oscillatory ventilation for adult respiratory distress syndrome-a pilot study. Crit Care Med 1997; 25:937-947 Seventeen patients failing inverse ratio ventilation recruited for rescue with HFOV (3100B) Predicted mortality > 80 percent

27. VIASYS Healthcare, Inc. 3100B Rescue Trial Fort P, Crit Care Med 1997; 25:937

28. VIASYS Healthcare, Inc. 3100B Rescue Trial Fort P, Crit Care Med 1997; 25:937

29. VIASYS Healthcare, Inc. Multicenter Oscillator ARDS Trial Prospective Randomized Controlled Trial of the SensorMedics 3100B HFOV for adults with ARDS Follow-up to MOAT Pilot Rescue Trial Early Entry, Non-Crossover Trial Ten Institutions, North American Study Derdak, AJRCCM 2002

30. VIASYS Healthcare, Inc. Patient Demographics - Baseline HFOVCV N7573 Age48 (17)51 (18) Kg78 (25) 81 (26) Apache II22 (6)22 (9) Sepsis47%47% Pneumonia19%16% Trauma21%18% Immune Compromised 12% 14% Airleak16%19% *NS

31. VIASYS Healthcare, Inc. Ventilator Strategies - Goals Normalize lung volume Minimize peak ventilator pressures Physiological targets included: Oxygen Saturation > 88% Delay weaning mPaw until FiO 2 < 50% pH > 7.15 PaCO 2 in the range of 40 – 70 mmHg

32. VIASYS Healthcare, Inc. Primary Outcome: Status at 30d HFOVCMV N7573 Died37%*52% Alive + RS 41%**22% Alive - no RS 21%26% *P=0.098 ** HFOV 61% on vent vs CMV 73% on vent

33. VIASYS Healthcare, Inc. MOAT2 - Secondary Outcomes HFOV(n=75) CV(n=73)  Blood Pressure0% 3% Airleak9% 12% O2 Failure (OI >42 after 48h) 5% 8% pH < 7.155% 8% Mucus Plug5% 4% *NS

34. VIASYS Healthcare, Inc. MOAT2 Conclusions Based on a study of 148 patients, use of HFOV for the treatment of severe ARDS resulted in an absolute reduction in mortality by 15%. This reduction trend in mortality is still recognizable at six months in this same population. There may also be benefits related to chronic lung change as reflected by the small but extended use of respiratory support in the conventional ventilation managed patients.

35. VIASYS Healthcare, Inc. MOAT - Comparison with ARDSnet MOATARDSnet (6ml/kg) 30d mortality37%31% P/F114138 Paw 2217 PEEP 139 OI 2412 Sepsis 47%27% ARDS NET, NEJM 2000

36. VIASYS Healthcare, Inc. Changing Medical Practice Changing Medical Practice is the Most Difficult Task 6 ml/kg tidal volume ventilation for ARDS Reasons of Non-Compliance Reluctance to give up control to a protocol Patient comfort Acidosis Oxygenation Therefore: Most patients with ARDS are not managed with LPV HFOV has the potential to remove most barriers to use of LPV 7%3%1%After publication 9%6%3%Before publication Day 7Day 3Day 0Compliance with LPV Rubenfeld GD et al ATS 2001

37. VIASYS Healthcare, Inc. A Prospective Trial of HFOV in Adults with ARDS Patient Population 23 Adults 10F, 13M Age 48 + 15 yrs Weight 72 + 17 kg Apache II 21 + 7 LIS 3.4 + 0.6 Diagnosis Pneumonia/Sepsis 12 Burn 5 Bone Marrow Transplant 4 Other 2 Mehta et al. CCM 2001;1360-1369

38. VIASYS Healthcare, Inc. A Prospective Trial of HFOV in Adults with ARDS Patient Population Prior Vent Days6.1 + 5.6 days PaO 2 /FiO 2 (mm Hg)100 + 41 OI (FiO 2 xPaw x 100/PaO 2 )33 + 20 Pressures during CMV PIP (cmH 2 O)37 + 4 Paw 24 + 3 PEEP13.8 + 2.4 Mehta et al. CCM 2001;1360-1369

39. VIASYS Healthcare, Inc. A Prospective Trial of HFOV in Adults with ARDS Outcomes Reason for HFOV withdrawal –Successfully weaned 10 –Withdrawal of life support/death11 –Technical problem2 ICU Survival7/23 (30%) –Nonburn patients7/17 (41%) –Burn patients0/5 Mehta et al. CCM 2001;1360-1369

40. VIASYS Healthcare, Inc. A Prospective Trial of HFOV in Adults with ARDS Days of Prior Ventilation Non Survivors 7.8 + 5.8 days Survivors1.6 + 1.2 days Mehta et al. CCM 2001;1360-1369

41. VIASYS Healthcare, Inc. HFOV in Adults with ARDS 42 patients failing CMV Baseline P/F ratio = 99(+46) increased to 191(+121) after 24 hours without HFOV related adverse events. 30 day mortality was 43% Subset analysis showed higher 30 day mortality in patients on CMV>3 days(67%) M David et al ICM July,2003

42. VIASYS Healthcare, Inc. Rescue Therapy with HFOV: Don’t wait too late

43. VIASYS Healthcare, Inc. Adjunctive Therapies - iNO Post hoc analysis of 108 pediatric patients in a RCT with AHRF and iNO Comparisons HFOV plus iNO (n=14) HFOV alone (n=12) CMV plus iNO (n=35) CMV alone (n=38) Dobyns CCM 2002;30(11):2425

44. VIASYS Healthcare, Inc. Conclusions P/F ratio greatest in the HFOV plus iNO group at 4 and 12 hours After 24 hours, both the HFOV plus iNO and HFOV alone resulted in greater P/F ratio improvement Speculation that enhanced lung recruitment by HFOV enhances the effects of iNO on gas exchange

45. VIASYS Healthcare, Inc. Adjunctive Therapies - Proning Case report 56 yo man d/w drug overdose and aspiration failing CMV and iNO transitioned to HFOV plus iNO with improved ventilation proning (q 6-8h) initiated due to worsening oxygenation transitioned to CMV post 4 days, iNO weaned after 9 days patient subsequently weaned and discharged Anesthesiology 2001;95(3)797

46. VIASYS Healthcare, Inc. Unresolved Issues What is the best way to set Paw What are the best recruitment strategies How are hemodynamic parameters best assessed How are aerosols best delivered How to best predict responders Does HFOV result in less VILI than a conventional lung protective strategy

47. VIASYS Healthcare, Inc. Take Home Messages Ventilation Strategies do affect patient outcomes Volume and pressure swings promote lung injury and mediator release. Identify patients at risk for developing VILI early- before the fibroproliferative stage Alternative therapies such as HFOV may offer lung protection that may improve outcomes for patients with ARDS