1. The Potential of Non-Invasive Goal Directed Therapy Maxime CANNESSON MD PhD Associate Professor Department of Anesthesiology & Perioperative Care University of California, Irvine

2. « The function of the circulation is to service the needs of the body tissues, to transport nutrients to the body tissues, to transport waste products away, to conduct hormones from one part of the body to another, and, in general, to maintain an appropriate environment in all the tissue fluids of the body for optimal survival and function of the cells. » Arthur Guyton Textbook of Medical Physiology « To be achieved, this goal requires two physiological objectives: 1) adequate perfusion pressure in order to force blood into the capillaries of all organs 2) adequate cardiac output to deliver oxygen and substrates, and to remove carbon dioxide and other metabolic products »

3. « Don’t throw the baby out with the bath water»

5. Preload Stroke Volume 0 0 Cardiac Output Optimization Concept Cardiac Ouput Maximization

6. “Dynamic Parameters of Fluid Responsiveness”

7. % increase in stroke volume after volume expansion. Responders ≥ 15 %Responders ≥ 15 % Non Responders < 15%Non Responders < 15% Fluid Responsiveness The Goal is to Improve Oxygen Delivery

8. Preload Stroke Volume 0 0 Normal Heart Failure Frank-Starling relationship

9. Mechanical Ventilation Paw  Venous Return  RVEDV  RVSV    LVEDV  LVSV Pulmonary Vascular transit Time Respiratory Variations in LV Stroke Volume Static Parameters vs. Dynamic Parameters

10. Cardiopulmonary Interactions “The more sensitive a ventricle is to preload, the more the stroke volume will be impacted by changes in preload due to positive pressure ventilation.” Preload Independent Preload Dependent AP ΔSV = SVmax – SV min (SVmax + SV min)/2

11. American Society of Anesthesiology 1983

13. 120 120mmHg 40 Arterial Pressure Arterial Pressure PP max PP min PP max - PP min PP max - PP min (PP max + PP min ) /2 ∆PP = Am J Respir Crit Care Med 2000; 162:134-138

14. The Pulse Oximeter Waveform Analysis

15. Pulse Oximeter Waveform Volume – Not Pressure !!

16. Courtesy Dr. Kirk Shelley, Yale University, New Haven, CT

18. Respiratory Variations in the Pulse Oximeter Waveform

19. Partridge BL. Use of the pulse oximetry as a non invasive indicator for intravascular volume status. J Clin Monit 1987; 3:263-8

21. Pulse Oximeter Waveform Cannesson et al. Crit Care 2005

23. Cannesson et al. Anesthesiology 2007

24. Pleth Variability Index to Monitor the Respiratory Variations in the Pulse Oximeter Plethysmographic Waveform Amplitude and Predict Fluid Responsiveness in the Operating Room Cannesson et al. BJA 2008

27. Major Limitations of Dynamic Parameters for Fluid Responsiveness Assessment Mechanical Ventilation General Anesthesia Tidal volume > 8 mL/Kg No arrhythmia HR/RR < 3.6 RV dysfunction… ? Vasomotor tone SVV PPV SPV ΔPOP

28. ΔPOP in the ICU 14 ICU patients Vasoactive drugs Arterial pressure and plethysmographic waveforms recording Software for automatic calculation of ΔPOP Relationship between ΔPOP & ΔPOP Anesthesiology 2008

31. Anesth Analg 2008

32. Statistical Approach

33. ROC curve analysis: old statistical tool (WWII) with numerous limitations Quantitative tests do not perfectly discriminate between subjects with and without a given status (fluid responder or not in the present case) The grey zone approach: avoid the binary constraint of a “black or white” decision that does not fit the reality of clinical or screening practice Most previous studies used small sample of patients Most commonly published threshold : 13 % Using the Gray Zone Approach to Assess the Ability of Pulse Pressure Variations to Predict Fluid Responsiveness During General Anesthesia M Cannesson, M.D., Ph. D., Y Le Manach, M.D., CK Hofer, M.D., A Derichard, M. D., DG Altman, Ph. D, JJ Lehot, M.D., Ph. D., B Tavernier, M. D., Ph. D.

34. Multicenter study (Lille, Lyon, Paris, Zürich, Irvine) 414 patients studied during anesthesia Volume expansion and CO monitoring Stats: Gray Zone approach Bootstraping Cost analysis Using the Gray Zone Approach to Assess the Ability of Pulse Pressure Variations to Predict Fluid Responsiveness During General Anesthesia M Cannesson, M.D., Ph. D., Y Le Manach, M.D., CK Hofer, M.D., A Derichard, M. D., DG Altman, Ph. D, JJ Lehot, M.D., Ph. D., B Tavernier, M. D., Ph. D.

35. Using the Gray Zone Approach to Assess the Ability of Pulse Pressure Variations to Predict Fluid Responsiveness During General Anesthesia M Cannesson, M.D., Ph. D., Y Le Manach, M.D., CK Hofer, M.D., DG Altman, Ph. D, JJ Lehot, M.D., Ph. D., B. Vallet, M. D., Ph. D., B Tavernier, M. D., Ph. D. Submitted for Publication

36. Using the Gray Zone Approach to Assess the Ability of Pulse Pressure Variations to Predict Fluid Responsiveness During General Anesthesia M Cannesson, M.D., Ph. D., Y Le Manach, M.D., CK Hofer, M.D., DG Altman, Ph. D, JJ Lehot, M.D., Ph. D., B. Vallet, M. D., Ph. D., B Tavernier, M. D., Ph. D.

37. April 2008 May 2008

38. Preload Stroke Volume 0 0 Cardiac Output Optimization Concept Cardiac Ouput Maximization

39. Preload Stroke Volume 0 0 Preload Dependence Optimization Concept ∆PP /∆POP Minimization

40. Goald Directed Therapy Based on Dynamic Parameters of Fluid Responsiveness

42. ControlIntervention

45. Major abdominal Surgery Control group vs SPV group (10 %) 40 pts in each group No difference in SvO2 No difference in post op lactates No difference in outcome BJA 2008

47. n= 30 vs n=30

51. Anesth Analg 2010 (In Press)

52. 82 patients Reduced postoperative lactate levels…. Anesth Analg 2010 (In Press)

53. Clinical Applicability

54. Respiratory Variation in Pulse Pressure: Intraoperative Applicability in an American Academic Center Sinead Maguire M.D., Joseph Rhinehart M.D., Shermeen Vakharia M.D., Maxime Cannesson M.D. Ph.D. Submitted for Publication University of California Irvine Information system Input from clinicians and automatic recording Observational study Main OR Jan 1st –Dec 31st 2009 12,308 patients

55. Respiratory Variation in Pulse Pressure: Intraoperative Applicability in an American Academic Center Sinead Maguire M.D., Joseph Rhinehart M.D., Shermeen Vakharia M.D., Maxime Cannesson M.D. Ph.D. Submitted for Publication

56. Conclusion

57. Conclusion Is it the Monitor?… Is it the Protocol? Cardiac output: We have the data but who monitors it? And who optimizes it? International Prospective: Colloids vs Cristalloids? US vs Europe? Pre, vs Per, vs Post operative optimization?

58. So What…? How to justify the cost? Where to run the Studies? Is it possible to show that a diagnostic tool (a monitor) can improve patients’ outcome?? The human brain processes several informations at the same time… One parameter alone is probably not sufficient…