1. Christian RICHARD Bicêtre Hospital AP- HP PARIS XI University FRANCE Which shocked patients should be monitored with a pulmonary artery catheter and does it impact their outcomes?

2. « Pulmonary artery catheter is not just important for the speciality of critical care, it is responsible for the speciality of critical care » Marino PL. the ICU Book, 2 nd edition, Williams and Wilkins 1997 The Arc of the Pulmonary Artery Catheter Robert A. Fowler, MD; Deborah J. Cook, MD, JAMA. 2003;290:2732-2734.

4. Assessment of a monitoring technology Safety (effectiveness): safe and accurate monitoring, without explicit recommendations and guidance to the clinician.Safety (effectiveness): safe and accurate monitoring, without explicit recommendations and guidance to the clinician. Efficacy (impact on the outcome): explicit treatment protocols; goal oriented therapy (GOT) protocols.Efficacy (impact on the outcome): explicit treatment protocols; goal oriented therapy (GOT) protocols.

5. SAFETY EFFECTIVENESS (Technology used as a monitor and without explicit guidance to the physician) PAC without GOT versus no PAC

6. JAMA 1996; 270:899-897 Prospective cohort of 5735 ICU patients with 9 disease categories PAC inserted in 38 % Patients with a PAC were matched with patients without a PAC who had comparable diagnosis and severity based on a 18-item propensity score

7. No RHC Proportion surviving Follow-up time (days) Follow-up time (days) JAMA 1996; 270:899-897 RHC p = 0.02

8. Significantly higher mean cost of hospital stay: 49300 versus 35700 US Dollars.Significantly higher mean cost of hospital stay: 49300 versus 35700 US Dollars. Significantly longer length of stay in ICU :14.8 versus 13.0 daysSignificantly longer length of stay in ICU :14.8 versus 13.0 days Higher baseline probability of surviving at two months, highest relative risk of death with PAC useHigher baseline probability of surviving at two months, highest relative risk of death with PAC use

9. Non randomized clinical trials - Mackirdy et al: Clin Intensive Care 1997;8:9-13 (Scottish ICU) Similar results than Connors AF et al - Polanczyk CA et al: Jama 2001; 286: 309- 314 (non cardiac surgery) Significant increase in post operative major cardiac and non cardiac events in patients undergoing PAC

10. MORTALITY: 1087/4181 (26%), 12.6% in patients without PAC 42.9% in those with a PAC (P<0.0001). « PAC was, associated with mortality when no adjustment had been made for severity of illness. » Pulmonary artery catheterization and mortality in critically ill patients S. D. Murdoch, A. T. Cohen and M. C. Bellamy Br J Anaesth 2000; 85: 611–5 « The data we have examined show no increase in mortality in those patients receiving a pulmonary artery catheter, nor do we demonstrate a beneficial effect of its use. These results were observed after correction for treatment bias using a propensity score »

12. Sakr et al, Chest 2005, 128: 2722- 2731 Mortality (PAC): -ICU, 28 VS 17% -In Hospital, 33 VS 23% Propensity score to match patients

13. SAFETY/ EFFECTIVENESS Randomized clinical studies Rhodes A, Intensive Care Med 2002; 28: 256- 264Rhodes A, Intensive Care Med 2002; 28: 256- 264 Richard C, JAMA 2003; 290: 2713- 2720Richard C, JAMA 2003; 290: 2713- 2720 Harvey S, Lancet 2005; 366: 472- 477Harvey S, Lancet 2005; 366: 472- 477

14. 201 patients, 95 PAC + and 106 PAC - 201 patients, 95 PAC + and 106 PAC -mortality: PAC + PAC - 46/95, 47.9% 50/106, 47.6 % 46/95, 47.9% 50/106, 47.6 % More fluids (day 1), renal failure and thrombocytopenia in the PAC + (day 3) in the PAC + (day 3) Underpoweredstudy

15. JAMA 2003; 290:2717-2720 Shock 64 % ARDS ARDS 30 % Shock + ARDS 6 % 676 patients JAMA 2003, 290:2717-20

16. Admission characteristics of the patients Type of admissions medical scheduledsurgery unscheduledsurgery PAC + PAC - %

17. Diagnostic categories at inclusion PAC + PAC - shock shock / ARDS ARDS %

18. Mortality at day 28 Days after randomization 0246810121416182022242628.1.2.3.4.5.6.7.8.9 1 0 PAC - (n=341) PAC + (n=335) p (log-Rank test) = 0.82 Overall Survival %

19. Richard C et al JAMA 2003; 290: 2713- 2720

21. Complications related to PAC Richard C et al Jama, 2003, 290, 2713 Arterial puncture (n= 17) Arterial puncture (n= 17) Hemothorax (n=1) Hemothorax (n=1) Arrhythmias,conduction disturbance (n=60) Arrhythmias,conduction disturbance (n=60) Knots (n=6) Knots (n=6) No death attributable to the PAC No death attributable to the PAC No pulmonary embolism No pulmonary embolism Primary positive blood cultures in 2 of 10 patients with positive PAC culture after insertion Primary positive blood cultures in 2 of 10 patients with positive PAC culture after insertion PAC left indwelling for a mean for a mean 2.3 days (range, 1- 10)

22. JAMA 2003; 290:2717-2720 Clinical management involving the early use of PAC in patients with shock, ARDS or both did not significantly affect morbidity and mortality.

25. Control PAC Survival probability (%) Time from randomisation (days) 1041 pts

27. Is there a proven benefit of pulmonary artery catheter use in the overall management of patients? EFFICACY (The technology linked to explicit treatment protocols dictated by the study)

28. PAC with GOT versus no PAC High risk surgical patients High risk surgical patients Congestive heart failure patients Congestive heart failure patients

29. High risk surgical patients Twelve post operative hours:Twelve post operative hours: higher mean values of CI (4.5 L/min/m2), DO2 (600 mL/min/m2) and VO2 (170 mL/min/m2) in survivors than in non survivors Physiologic compensation for the increased metabolic demandPhysiologic compensation for the increased metabolic demand Supraphysiologic hemodynamic values could represent target goals to achieve to improve prognosis.Supraphysiologic hemodynamic values could represent target goals to achieve to improve prognosis. Shoemaker et al. Chest 1988; 94: 1176- 1186

30. N Engl J Med 2003, 348:5-14 > 60 yrs, ASA class III or IV risk, scheduled for urgent or elective major surgery, followed by a stay in ICU. 997 pts received PAC with a goal-oriented protocol 997 patients did not receive PAC with standard care randomization

31. Goal oriented therapy objectives DO2 >550 mL/min/m2 CI> 3.5 L/min/ m2 MAP> 70 mmHg PAPO= 18 mmHg HR< 120 bpm Ht> 27 %

33. Proportion surviving months Standard care PAC ns Sandham et al N Engl J Med 2003; 348:5-14

34. One or more adverse effects: 1.5 % with PAC 0.7 % with standard care

35. 433 patients: « sufficiently ill with advanced heart failure « sufficiently ill with advanced heart failure to make use of the PAC reasonable, but also sufficiently stable to make cross- over to PAC for urgent management unlikely »

39. Discussion (RCTs PAC versus no PAC) No need for the routine use of a cardiovascular monitoring tool. The clinical evaluation of the patients is widely sufficientNo need for the routine use of a cardiovascular monitoring tool. The clinical evaluation of the patients is widely sufficient. Need for a safe cardiovascular monitoring to understand what we do and to try to improve prognosis.Need for a safe cardiovascular monitoring to understand what we do and to try to improve prognosis. PAC with GOT versus PAC without GOT

40. -High risk surgical patients - Critically ill patients

41. Postoperative days Patients surviving % Protocol (n=53) Control (n =54) p = 0.015 JAMA 1993; 270:2699- 2707 PAC with or without oriented therapy

42. Effects of maximizing oxygen delivery on morbidity and mortality in high risk surgical patients.n=37 Lobo et al. Lobo et al. Crit Care Med 2000; 28: 3396-3404 0 10 20 30 40 50 60 Time, days 100 90 80 60 50 40 30 Protocol group Controlgroup Control group 10 0 70 20 p = 0.01 Survival, % PAC with or without oriented therapy

43. A significant improved outcome was observed when PAC with GOT was used early or prophylactically in patients who were optimized preoperatively and maintained in the intraoperative and immediate post operative period » « A significant improved outcome was observed when PAC with GOT was used early or prophylactically in patients who were optimized preoperatively and maintained in the intraoperative and immediate post operative period »

44. Critically ill patients PAC with GOT versus PAC without GOTPAC with GOT versus PAC without GOT Gattinoni et al Alia et al Hayes et al

45. Alia et al. Chest 1999; 115:453-61 Length of stay in the intensive care unit after enrollment (days) Survival probabilty Gattinoni et al. N Engl J Med 1995; 33: 1025-32 Days after randomization Probability of survival 0.0 0.2 0.4 0.6 0.8 1.0 0 45 90 135 185 0 45 90 135 185 Control group Cardiac-index group Oxygen-saturation group no difference Hayes et al. N. Engl. J. Med. 1994 ; 330 : 1717-1722 Days % of patients surviving p= 0.04 N=762 N=63 N= 100

46. Could it possible to ameliorate the results of these PAC (or any other cardiovascular monitoring device) with GOT versus PAC without GOT studies?

47. Limitations of these studies Heterogeneity of the population Heterogeneity of the population Very late inclusion of the patients when MOF is definitively installed Very late inclusion of the patients when MOF is definitively installed Well known difficulties to achieve pharmacological goals Well known difficulties to achieve pharmacological goals

48. CON Difficulties to achieve hemodynamic targets

50. PRO PatientsPatients Hemodynamic targetsHemodynamic targets Primary end pointsPrimary end points

51. RCT in Homogeneous Population Early goal directed therapy in the treatment of severe sepsis and septic shock Early goal directed therapy in the treatment of severe sepsis and septic shock (Rivers et al New Engl J Med 2001; 345: 1368- 1377) Septic patients included very early after the diagnosis

52. Crit Care Med 2004; 32:911-915 To examine the association between PAC and mortality rate To examine the association between PAC and mortality rate in critically ill patients with a higher vs a lower severity of illness in critically ill patients with a higher vs a lower severity of illness Aim : Design : Observational cohort study including 7310 pts (28 % with PAC)

53. 80 70 60 50 40 30 20 10 0 APACHE II < 18 APACHE II 18-24 25-31 >31 % Mortality Chittock et al. Crit Care Med 2004 * * NS # PAC no PAC

55. FCTT Fluids and catheter treatment trial 1000 patients with acute respiratory distress syndrome1000 patients with acute respiratory distress syndrome 2X2 factorial design to a liberal vs conservative fluid treatment strategy and to therapy guided by a PAC or central venous catheter2X2 factorial design to a liberal vs conservative fluid treatment strategy and to therapy guided by a PAC or central venous catheter Primary end point: 60 days mortalityPrimary end point: 60 days mortality Transiently suspended by the office for human protections from researchTransiently suspended by the office for human protections from research After extended review restarted in 2002 without major revisionsAfter extended review restarted in 2002 without major revisions

56. Crit Care Med 2005; 33:1119-22 Mixed venous oxygen saturation Normal hemodynamic targets Hemodynamic targets

58. Primary end points

60. Conclusion PAC is a classical tool for hemodynamic assessment since it enables continuous monitoring of numerous hemodynamic parameters such as tissue oxygenation variables and estimates of cardiac filling pressures that are not provided by other monitoring devices.PAC is a classical tool for hemodynamic assessment since it enables continuous monitoring of numerous hemodynamic parameters such as tissue oxygenation variables and estimates of cardiac filling pressures that are not provided by other monitoring devices. A large recently published metaanalysis of RCT demonstrated that its use does not cause harm to critically ill patients.A large recently published metaanalysis of RCT demonstrated that its use does not cause harm to critically ill patients. (Shah et al JAMA. 2005;294: 1664-1670) The heterogeneous results of the GOT should be interpreted in light of the specific interventions tested, the delay for inclusion and the case mixed of the patients, and not of the choice of PAC per se as a monitoring tool.The heterogeneous results of the GOT should be interpreted in light of the specific interventions tested, the delay for inclusion and the case mixed of the patients, and not of the choice of PAC per se as a monitoring tool.

61. CONCLUSION Whether goal- oriented therapeutic protocols based on an individualized analysis of PAC data are able to improve the outcome of the critically ill remains to be investigated. Whether goal- oriented therapeutic protocols based on an individualized analysis of PAC data are able to improve the outcome of the critically ill remains to be investigated. It appears of paramount importance to develop educational programs to improve the quality of recording and the acuity of the interpretation of the data afforded by PAC as well as by all other cardio- vascular monitoring devices It appears of paramount importance to develop educational programs to improve the quality of recording and the acuity of the interpretation of the data afforded by PAC as well as by all other cardio- vascular monitoring devices

62. CONCLUSION « PAC ( and all cardiovascular monitoring tool) should not be used for the routine treatment of patients in the ICU until or unless effective therapy can be found that improve outcomes when coupled with the diagnostic tool. » « PAC ( and all cardiovascular monitoring tool) should not be used for the routine treatment of patients in the ICU until or unless effective therapy can be found that improve outcomes when coupled with the diagnostic tool. » (Shah et al JAMA. 2005;294: 1664-1670) (Shah et al JAMA. 2005;294: 1664-1670) The exact role of a cardiovascular monitoring tool in ICU patients remains to be determined The exact role of a cardiovascular monitoring tool in ICU patients remains to be determined