A Critical Review of Early Goal Directed Therapy and Government Endorsement

Transcription

1 A Critical Review of Early Goal Directed Therapy and Government Endorsement Charles Natanson M.D. Critical Care Medicine Department Clinical Center National Institutes of Health Clinical Center

2 None Conflicts of Interest

3 Those who cannot remember the past are condemned to repeat it Jorge Santayana (1905) Reason in Common Sense, p. 284, volume 1 of The Life of Reason

4 Overview EGDT based on facts known before Process, Arise and Promise Clinical trial reproducibility in critical care How federal and state governments came to endorse the use of EGDT

5 Overview EGDT based on facts known before Process, Arise and Promise Clinical trial reproducibility in critical care How federal and state governments came to endorse the use of EGDT

6 Slides from a debate on Early Goal Directed Therapy (EGDT), between Dr. Rivers and myself Canadian Critical Care Medicine Meeting 2007 in Toronto

7 5. In the event of persistent hypotension despite fluid resuscitation (septic shock) and/or lactate > 4 mmol/l (36 mg/dl): Achieve central venous pressure (CVP of > 8 mm Hg) Achieve central venous oxygen saturation (ScvO2) of > 70%

8 Early Goal Directed Therapy and Sepsis Was the evidence sufficient? Debate 2007 Toronto.

9 Early Goal Directed Therapy Sepsis Trial SBP < 90 mmhg or Lactate > 4 mmol/l Standard Therapy N = 133 N Engl J Med 2001; 345:1368 Hemodynamic Goals Fluids and Pressors: CVP > 8-12 mmhg MAP > 65 mmhg Urine output > 0.5 ml/kg/h EGDT N = 130 ScvO 2 Goal 70% More standard Vasodilators therapy patients for failed 1. Transfuse to attain to these Hct 30% combined hemodynamic MAP > 90 mmhg goals (18 2. Dobutamine vs. 1 p<0.001) Why? Both arms had identical goals Debate 2007 Toronto.

10 N Engl J Med 2001;345:1368 Debate 2007 Toronto. Outcome of Early Goal Directed Therapy vs Standard Care Standard EGDT P value Patients Completed 6h 89% 90% In Hospital Mortality 45.6% 30.5% Fluids (liters) < RBC transfused (% of pts) 18.5% 64.1% < Dobutamine (% of pts) 0.8% 13.7% < 0.001

11 N Engl J Med 2001;345:1368 Debate 2007 Toronto. Outcome of Early Goal Directed Therapy vs Standard Care Standard EGDT P value Patients Completed 6h 89% 90% In Hospital Mortality 45.6% 30.5% Fluids (liters) < RBC transfused (% of pts) 18.5% 64.1% < Dobutamine (% of pts) 0.8% 13.7% < 0.001

12 N Engl J Med 2001;345:1368 Debate 2007 Toronto. Outcome of Early Goal Directed Therapy vs Standard Care Standard EGDT P value Patients Completed 6h 89% 90% In Hospital Mortality 45.6% 30.5% Fluids (liters) < RBC transfused (% of pts) 18.5% 64.1% < Dobutamine (% of pts) 0.8% 13.7% < 0.001

13 Outcome of Early Goal Directed Therapy vs Standard Care Standard EGDT P value Patients Completed 6h 89% 90% In Hospital Mortality 45.6% 30.5% Fluids (liters) < RBC transfused (% of pts) 18.5% 64.1% < Dobutamine (% of pts) 0.8% 13.7% < Fluids and Pressors to CVP > 8-12 mmhg MAP > 65 mmhg Urine output > 0.5 ml/kg/h N Engl J Med 2001;345:1368 Debate 2007 Toronto.

14 Outcome of Early Goal Directed Therapy vs Standard Care Standard EGDT P value Patients Completed 6h 89% 90% In Hospital Mortality 45.6% 30.5% Fluids (liters) < RBC transfused (% of pts) 18.5% 64.1% < Dobutamine (% of pts) 0.8% 13.7% < The hemodynamic Fluids goals are and the Pressors same but to the standard therapy arm got less fluid and did CVP not > meet 8-12 the mmhg combined hemodynamic goals MAP > 65 mmhg Urine output > 0.5 ml/kg/h N Engl J Med 2001;345:1368 Debate 2007 Toronto.

15 Outcome of Early Goal Directed Therapy vs Standard Care Standard EGDT P value Patients Completed 6h 89% 90% In Hospital Mortality 45.6% 30.5% Fluids (liters) < RBC transfused (% of pts) 18.5% 64.1% < Dobutamine (% of pts) 0.8% 13.7% < The hemodynamic Fluids goals are and the Pressors same but to the standard therapy arm got less fluid and did CVP not > meet 8-12 the mmhg combined hemodynamic goals MAP Protocol > 65 mmhg violation? Why was Urine the standard output > therapy 0.5 ml/kg/h arm undertreated? N Engl J Med 2001;345:1368 Debate 2007 Toronto.

16 N Engl J Med 2001;345:1368 Debate 2007 Toronto. Outcome of Early Goal Directed Therapy vs Standard Care Standard EGDT P value Patients Completed 6h 89% 90% In Hospital Mortality 45.6% 30.5% Fluids (liters) < RBC transfused (% of pts) 18.5% 64.1% < Dobutamine (% of pts) 0.8% 13.7% < 0.001

17 Outcome of Early Goal Directed Therapy vs Standard Care Standard EGDT P value Patients Completed 6h 89% 90% In Hospital Mortality 45.6% 30.5% Fluids (liters) < RBC transfused (% of pts) 18.5% 64.1% < Dobutamine (% of pts) 0.8% 13.7% < EGDT received more blood Wouldn t this result in less fluid, not more, than the standard therapy group to reach the same hemodynamic goals? N Engl J Med 2001;345:1368 Debate 2007 Toronto.

18 N Engl J Med 2001;345:1368 Debate 2007 Toronto. Outcome of Early Goal Directed Therapy vs Standard Care Standard EGDT P value Patients Completed 6h 89% 90% In Hospital Mortality 45.6% 30.5% Fluids (liters) < RBC transfused (% of pts) 18.5% 64.1% < Dobutamine (% of pts) 0.8% 13.7% < 0.001

19 Debate 2007 Toronto. Time in Emergency Room with Early Goal Directed Therapy vs Standard Care Standard EGDT P value Patients who completed 6 hour protocol in Emergency Room Actual time (hours) in Emergency Room 117 of 130 (90%) N Engl J Med 2001;345:1368

20 Debate 2007 Toronto. Early Goal Directed Therapy Arm Time given in ED hours 16% of patients < 5.9 hours Rate given Only 13 /130 < 6 hours 10% of patients < 6 hours Consistent with a normal distribution for the six hour time spent receiving the hemodynamic protocol in the Emergency Room 2% 14% 5.9h 8.0h - 3 sd -2 sd - sd mean + sd +2 sd +3 sd

21 N Engl J Med 2001;345:1368 Debate 2007 Toronto. Time in Emergency Room with Early Goal Directed Therapy vs Standard Care Standard EGDT P value Patients reported to have completed 6 hour protocol in Emergency Room Actual time (hours) in Emergency Room 119 of of 130 (89%) (90%) < 0.001

22 Debate 2007 Toronto. Standard Therapy Arm Time given in ED BUT, data provided: Data from the standard therapy group hours 14 is /133 not consistent < 6 hours with a normal distribution unlike the data from EGDT patients 50% of patients i.e. 11% of patients < 6.3 hours < 6 hours If the time spent in the ER for standard therapy group was h and 89% were there at least 6 h, then: Most were discharged exactly between h And a small number spent days in ER 50% The standard therapy arm appears to have been treated differently than EGDT patients and 6.3h not according to protocol - 3 sd -2 sd - sd mean + sd +2 sd +3 sd

23 Outcome of Early Goal Directed Therapy vs Standard Care Standard m sd EGDT m sd P value CVP goal (mmhg) CVP actual at 6h (mmhg) MAP goal (mmhg) > 65 > 65 and < 90 MAP actual at 6h (mmhg) MAP > 90 mmhg Vasodilators given until < 90 mmhg N Engl J Med 2001;345:1368 Debate 2007 Toronto.

24 Debate 2007 Toronto. Slides presented by Dr. Rivers in the 2007 debate

25 Digoxin is not an effective treatment for dobutamine-induced tachycardia and The New England Journal article does not mention digoxin as part of the EGDT protocol Debate 2007 Toronto.

26 THURSDAY, AUGUST 14, 2008 May/June 2002

27 During unblinded treatment in the ED, the same hemodynamic goals of CVP between 8 THURSDAY, AUGUST 14, 2008 and 12 mm Hg and of MAP between 65 and 90 mm Hg were used to trigger fluid boluses and vasopressor therapy in both groups, but the control group received less fluid.

28 THURSDAY, AUGUST 14, 2008 Consistent with this treatment difference, CVP and MAP were both lower in the control group at 6 hours.

29 Furthermore, 18 of 133 patients in the control THURSDAY, AUGUST 14, 2008 group but only 1 of 130 patients in the EGDT group did not reach the combined physiologic end points for CVP, mean arterial blood pressure, and urine output of at least 0.5 ml/kg per hour (P < 0.001).

30 Because of these protocol inconsistencies, we did not recommend EGDT, rather THURSDAY, AUGUST 14, 2008 Clearly, septic patients are best served by promptly initiating antimicrobial therapy and rapid lifesaving resuscitation based on frequent physiologic measurements. Charles Natanson, MD Robert L. Danner, MD

31 Debate 2007 Toronto. Summary / Limitations Using an ScvO 2 catheter to give blood and dobutamine over 6h, In-hospital mortality was decreased by 34% Limitations Small, single center, unblinded study Actual data comparing the control and treatment groups were inconsistent with set hemodynamic goals and completion of the 6h ED protocol Previous experience with other inventions in sepsis suggests that confirmatory studies are essential to change practice

32 Overview EGDT based on facts known before Process, Arise and Promise Clinical trial reproducibility in critical care How federal and state governments came to endorse the use of EGDT

33 Debate 2007 Toronto. The Importance of Quality and Reproducibility in Medicine Is a single RCT sufficient to highly recommend and widely adopt a therapeutic intervention for sepsis?

34 Debate 2007 Toronto. Metaanalyses of Sepsis Trials with at least One Significant Beneficial Trial

35 Beneficial Non-Antibiotic Sepsis Trials Anti-Endotoxin J5 Antiserum Benefit Harm Monoclonals Benefit Harm High Dose Corticosteroids Benefit Harm * p = 0.59 p = 0.60 * p = * 1 1 OR Dying OR Dying IL-1RA Benefit Harm Activated Protein C Benefit Harm 1 OR Dying Intensive Insulin Benefit Harm * * p = 0.14 p = 0.55 p = 0.32 * 1 OR Dying 1 OR Dying * Shift from beneficial to last trial, p = OR Dying Debate 2007 Toronto.

36 Beneficial Non-Antibiotic Sepsis Trials Anti-Endotoxin J5 Antiserum Monoclonals Benefit Harm Benefit Harm High Dose Corticosteroids Benefit Harm IL-1RA Benefit Harm * * * * 1 OR Dying 1 OR Dying 1 OR Dying 1 OR Dying Activated Protein C Intensive Insulin Early Goal Benefit Harm Directed Therapy Benefit Harm Benefit Harm * * 1 OR Dying p = OR Dying * Shift from beneficial to last trial, p = OR Dying

37 Beneficial Non-Antibiotic Sepsis Trials J5 Antiserum Benefit Harm 1 OR Dying Anti-Endotoxin * Activated Protein C Benefit Harm Rivers Monoclonals * 1 OR Dying Early Goal Intensive Insulin Benefit Harm High Dose Corticosteroids Directed Benefit Harm Therapy Benefit Harm Benefit Harm ProCESS, ARISE * and ProMISE 1 OR Dying Early Goal Directed Therapy Benefit Harm IL-1RA Benefit Harm * 1 OR Dying * 1 OR Dying * 1 OR Dying p = OR Dying * Shift from beneficial to last trial, p = Rivers 1 OR Dying ProCESS, ARISE and ProMISE

38 Beneficial Non-Antibiotic Sepsis Trials J5 Antiserum Benefit Harm 1 OR Dying Anti-Endotoxin * Activated Protein C Benefit Harm Rivers Monoclonals * 1 OR Dying Intensive Insulin Benefit Harm p=0.01 High Dose Corticosteroids Directed Benefit Harm Therapy Benefit Harm Benefit Early Goal Harm Combined * ProCESS, ARISE and ProMISE 1 OR Dying Early Goal Directed Therapy Benefit Harm IL-1RA Benefit Harm * 1 OR Dying Rivers Combined (ProCESS, ARISE and ProMISE) * 1 OR Dying * 1 OR Dying p = OR Dying * Shift from beneficial to last trial, p = p= OR Dying

39 Anti-Endotoxin J5 Antiserum Monoclonals Summary High Dose Corticosteroids Benefit Harm Benefit Harm Benefit Harm IL-1RA Benefit Harm Next an airing of the * * * * EGDT controversy in OR Dying OR Dying OR Dying OR Dying Activated Protein C Intensive Insulin Early Goal Directed Therapy Benefit Harm Benefit Harm the lay press Rivers Benefit Harm Combined (ProCESS, ARISE and ProMISE) * * p= OR Dying p = OR Dying * Shift from beneficial to last trial, p = OR Dying

40 THURSDAY, AUGUST 14, 2008 Front page article New Therapy for Sepsis Infections Raises Hope but Many Questions By THOMAS M. BURTON Direct quotes from Wall Street Journal concerning unreported intention to potential treat and conflicts the 25 missing of interest patients Statisticians [senior.in In Edwards statisticians The...(NEJM) 2005, an author] April a.. said, resident were interview article (from it and has especially paid the analyzed doing hospital describing Study) [the concerned follow-up senior 263. who over how But worked author] the when research it years also {the on they $158,000 said have it noticed received author} complained to (NEJM that make 288 that EGDT proceeded, speeches patients least to a relatively senior article) $404,000 were about said hospital "evaluated," had his high "all from concerns research, 288 proportion officials Edwards, are randomized about $20,000 whom of the the the 25 Irvine, to data other 25 Calif., data. reimburse and "were (randomized recalculated excluded company The him hospital for but says the patent did excluded) results convened not legal consent with a fees, panel.were all to $36, participate." of either inquiry, conventional-therapy which reimbursed patients, concluded the expenses death-rate the issues and patients $40,000 gap had wasn't who been in survived consulting satisfactorily statistically fees. patients resolved, [The significant senior on aggressive author also therapy held the who ScVo2 died catheter The patent hospital and transferred declined to it make to the the hospital] panel's report available.

41 Overview EGDT based on facts known before Process, Arise and Promise Clinical trial reproducibility in critical care How federal and state governments came to endorse the use of EGDT

42 For the basis of effective government is public confidence, and that confidence is endangered when ethical standards falter or appear to falter. John F. Kennedy Special Message to the Congress on Conflict-of-Interest Legislation and on Problems of Ethics in Government

43 The National Quality Forum and Performance Measures The National Quality Forum is a not-forprofit organization composed of medical societies, healthcare corporations, insurers, trade associations, and manufacturers National Quality Forum by law selects performance measures for use by the Centers of Medicare and Medicaid (CMS)

44 The National Quality Forum and Performance Measures Performance measures are processes of care designed to improve clinical outcomes Used for professional accreditation and some serve directly as a basis for third-party reimbursement (pay-for-performance) The National Quality Forum states that its performance measures are the gold standard for healthcare quality and undergo rigorous scientific and evidence-based reviews

45 Performance Measure: The Severe Sepsis and Septic Shock Management Bundle In 2008 the National Quality Forum endorsed a performance measure submitted by Henry Ford Hospital, entitled the Severe Sepsis and Septic Shock: Management Bundle The NQF did not endorse the central venous pressure and oxygen saturation monitoring components

46 F. In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or lactate >= 4 mmol/l (36 mg/dl) measure central venous pressure and central venous oxygen saturation

47

48 The Severe Sepsis and Septic Shock: Management Bundle Performance Measure In 2013, in contrast to its 2008 decision, the National Quality Forum endorsed the full sepsis performance measure including its requirement for central venous pressure and oxygen measures After: Voting at each level of approval involves members of medical societies, healthcare corporations, insurers, trade associations, and manufacturers Steering committee vote Member organization vote Board of Directors approval

49 Performance Measure: The Severe Sepsis and Septic Shock Management Bundle This endorsement occurred despite: Objections from multiple professional societies No new data to validate use of central venous pressure and oxygen measures for sepsis Three ongoing multicenter RCTs testing the effectiveness of CVP and ScVO2 measures for the management of persistent septic shock (i.e. PROCESS, ARISE, and PROMISE)

50 The Sepsis Performance Measure Application Did Not Meet the National Quality Forum s Criteria for Unambiguous Evidence The 2012 application included four sources of evidence: The Surviving Sepsis Campaign guidelines A retrospective analysis from approximately 15,000 patients 55 individual studies 3 meta-analyses

51 The Sepsis Performance Measure Application Did Not Meet the National Quality Forum s Criteria for Unambiguous Evidence Examining each in turn: The Surviving Sepsis guideline gave the evidence supporting central venous pressure and oxygen saturation measures a weak grade C, yet inexplicably gave the measures a high grade recommendation for use The retrospective analysis of 15,000 patients was based on uncontrolled data from un-refereed sites and could not account for confounding variables

52 The Sepsis Performance Measure Application Did Not Meet the National Quality Forum s Criteria for Unambiguous Evidence Of the fifty-five individual studies cited: 31% did not compare the survival effects of a sepsis bundle to a control or were duplicates Of the 38 studies providing comparative data, only four were RCTs One RCT was a single center trial that as noted earlier had been cited for lapses in data integrity The other three cited RCTs were performed in China, where the patient mix and medical practice differ markedly from Western countries

53 The Sepsis Performance Measure Application Did Not Meet the National Quality Forum s Criteria for Unambiguous Evidence Of the three meta-analyses cited: One concluded that the studies provided no convincing evidence to support the sepsis bundle Another meta-analysis examined 21 studies: 20 were observational The only RCT that compared EGDT components had no controls The third meta-analysis included studies with treatment times >6h and non septic patients

54 The Performance Measure Endorsement Did Not Follow The National Quality Forum s Policy For Avoiding Potential Conflicts of Interest Edwards Life Sciences, a manufacturer of ScVO 2 catheters, stood to profit directly from the sepsis performance measures full endorsement Since 2008, Edwards chief executive officer (CEO) served as the chairman and then member of the board of directors of AdvaMed, a medical technology trade association One of the primary purposes of trade groups, particularly in the United States and to a similar but lesser extent elsewhere, is to attempt to influence public policy in a direction favorable to the group's members

55 The Performance Measure Endorsement Did Not Follow The National Quality Forum s Policy For Avoiding Potential Conflicts of Interest AdvaMed nominated its vice-president to the National Quality Forum steering committee reviewing the sepsis performance measure This vice president served as co-chair of that steering committee in 2013 The NQF should not have accepted the recommendations of Edward s trade association for steering committee membership NQF involvement of industry in the performance measure approval process is not ideal

56 The Performance Measure Endorsement Did Not Follow The National Quality Forum s Policy For Avoiding Potential Conflicts of Interest NQF endorsement process for performance measures (PMs) lacks an adequate firewall AdvaMed nominated its vice-president to the National Quality Forum steering committee reviewing the sepsis performance measure This vice president was co-chair of that steering committee in 2013, a very influential position Once Edwards CEO was elected to AdvaMed s board of directors, the National Quality Forum should not have accepted the trade association s recommendations for steering committee membership evaluating the sepsis performance measure application

57 The Performance Measure Endorsement Did Not Follow The National Quality Forum s Policy For Avoiding Potential Conflicts of Interest NQF endorsement process for performance measures (PMs) lacks an adequate firewall AdvaMed nominated its vice-president to the National Quality Forum steering committee reviewing the sepsis performance measure Industry representatives are voting members at every level of the approval process This vice president was co-chair of that steering committee in 2013, a very influential position Once Edwards CEO was elected to AdvaMed s board of directors, the National Quality Forum should not have accepted the trade association s recommendations for steering committee membership evaluating the sepsis performance measure application

58 The Performance Measure Endorsement Did Not Follow The National Quality Forum s Policy For Avoiding Potential Conflicts of Interest NQF endorsement process for performance measures (PMs) lacks an adequate firewall AdvaMed nominated its vice-president to the National Quality Forum steering committee reviewing the sepsis performance measure Industry representatives are voting members at every level of the approval process This vice president was co-chair of that steering committee in 2013, a very influential position Competing or similar commercial interests with elements of a PM are always possible Once Edwards CEO was elected to AdvaMed s board of directors, the National Quality Forum should not have accepted the trade association s recommendations for steering committee membership evaluating the sepsis performance measure application

59 The Performance Measure Endorsement Did Not Follow The National Quality Forum s Policy For Avoiding Potential Conflicts of Interest NQF endorsement process for performance measures (PMs) lacks an adequate firewall AdvaMed nominated its vice-president to the National Quality Forum steering committee reviewing the sepsis performance measure Industry representatives are voting members at every level of the approval process This vice president was co-chair of that steering committee in 2013, a very influential position Competing or similar commercial interests with elements of a PM are always possible Once Edwards CEO was elected to AdvaMed s board of directors, the National Quality Forum should not have accepted the trade association s recommendations for steering committee membership evaluating the sepsis performance measure application The FDA by contrast would not base approval of drugs on such a process

60 NQF Response After Negative RCTs Less than a year after NQF endorsement of the sepsis PM, the PROCESS trial was published showing that routine use of CVP and ScVO 2 measures did not improve the outcome for persistent septic shock Following publication of PROCESS, the National Quality Forum changed the requirement for CVP and ScVO 2 to optional and endorsed a revised version of the sepsis PM

61 reached a compromise solution between the measure developer, Henry Ford Hospital, and Direct quote from website: The endorsement follows an ad hoc review of the measure key stakeholders, including the Society of by NQF s Patient Safety Standing Committee, in light of new scientific Critical evidence Care that Medicine found that patients and the with American severe sepsis who received College this invasive of Emergency monitoring (known Physicians. as early goaldirected therapy) had no different outcomes than those who received care without it. After initially recommending the removal of the element of the measure pertaining to invasive monitoring, the committee reached a compromise solution between the measure developer, Henry Ford Hospital, and key stakeholders, including the Society of Critical Care Medicine and the American College of Emergency Physicians. The revised measure allows reassessment of a septic patient s condition through other means.

62 NQF-Endorsed Voluntary Consensus Standard for Hospital Care (SCP-1) Numerator Statement: Patients who received ALL of the following: Received within three hours of presentation of severe sepsis: Initial lactate level measurement Broad spectrum or other antibiotics administered Blood cultures drawn prior to antibiotics AND received within six hours of presentation of severe sepsis: Repeat lactate level measurement only if initial lactate level is elevated AND ONLY if Septic Shock present: Received within three hours of presentation of septic shock Resuscitation with 30 ml/kg crystalloid fluids AND ONLY IF hypotension persists after fluid administration, received within six hours of presentation of septic shock: Vasopressors AND ONLY if hypotension persists after fluid administration or initial lactate 4 mmol/l, received within six hours of presentation of septic shock: Repeat volume status and tissue perfusion assessment consisting of either A focused exam including: Vital signs, AND Cardiopulmonary exam, AND Capillary refill evaluation, AND Peripheral pulse evaluation, AND Skin examination OR Any two of the following four: Central venous pressure measurement Central venous oxygen measurement Bedside Cardiovascular Ultrasound Passive Leg Raise or Fluid Challenge

63 NQF-Endorsed Voluntary Consensus AND ONLY if hypotension Standard persists for Hospital after fluid Care administration (SCP-1) or initial Numerator lactate Statement: 4 mmol/l, Patients who received ALL within of the following: six hours of presentation of Received within three hours of presentation of severe sepsis: septic Initial lactate shock: level measurement Repeat Broad spectrum volume or other status antibiotics and administered tissue perfusion assessment consisting Blood cultures drawn prior to antibiotics AND of received either within six hours of presentation of severe sepsis: Repeat lactate level measurement only if initial lactate level is elevated A focused exam including: AND ONLY if Septic Shock present: Received within Vital three signs, hours of AND presentation of septic shock Resuscitation with 30 ml/kg crystalloid fluids AND ONLY Cardiopulmonary IF hypotension persists after exam, fluid administration, AND received within six hours of presentation of septic shock: Capillary refill evaluation, AND Vasopressors Peripheral pulse evaluation, AND hours of Skin presentation examination of septic shock: Repeat volume status and tissue perfusion assessment consisting of either A focused OR exam including: Vital signs, AND Any two of the following four: Cardiopulmonary exam, AND Central Capillary refill venous evaluation, pressure AND measurement Peripheral pulse evaluation, AND Central Skin examination venous oxygen measurement Bedside OR Cardiovascular Ultrasound Any two of the following four: Passive Leg Raise or Fluid Challenge AND ONLY if hypotension persists after fluid administration or initial lactate >= 4 mmol/l, received within six Central venous pressure measurement Central venous oxygen measurement Bedside Cardiovascular Ultrasound Passive Leg Raise or Fluid Challenge

64 Advanced Hemodynamic Monitoring Early Goal-Directed Therapy Treatment Protocol Edwards Lifesciences Corporation. All Rights reserved Edwards Lifesciences Corporation. All Rights reserved.

65 Reduce sepsis-related mortality by 46% Edwards Lifesciences Corporation. All Rights reserved.

66 The NY Times quote was from a coauthor THURSDAY, DECEMBER 20, 2012 of the Performance Measure submitted in 2013 to the National Quality Forum, One Boy s Death Moves State to Action to Prevent Others which By JIM required DWYER a catheter to measure central Direct venous quotes from New York pressure Times and oxygen content. (A coauthor The of coauthor the sepsis PM) said was New also York s a past actions were bold, pioneering and grounded in president of the Society of Critical Care good scientific evidence, adding, The Medicine commissioner and has their taken representative the first step even to the before the federal government. National Quality Forum

67 July 2013 (vi) All protocols must clearly describe an explicit and quantitative approach used to guide resuscitation, including the following:

68 July What physiologic thresholds and/or clinical conditions will require insertion of central venous catheter with or without central venous pressure and central venous oxygen saturation monitoring to be considered

69 Consistent with the regulation, all hospitals will be required to submit protocols on or before September 3, 2013 and once approved, to implement such protocols on or before December 31, 2013.

70 Conclusions EGDT represents the failure of the academic-medicalindustrial complex to adequately evaluate a new therapy Clinical trial results which cannot be reproduced have no value in directing patient care Components of EGDT measuring ScVO 2 and CVP in septic shock, shown to have no benefit, do not belong in routine medical practice or government-sponsored performance measures

71 Conclusions (cont d) Journals, societies, guideline committees and hospitals should examine their role in promoting the wide-spread adoption of the EGDT bundle for sepsis Providers should reconsider the flawed processes that contributed to this misadventure and demand changes to safeguard patients The National Quality Forum and NY legislature should examine why they approved ineffective components of EGDT as performance measures for use by the Centers for Medicare and Medicaid and NY Hospitals (respectively)

72 Conclusions (Cont d) Trade associations or other commercial entities and their representatives can propose performance measures, but should be excluded from granting approval CMS should only contract with NQF for reviewing its performance measures if the approval process is made more comparable to the FDA and free of industry influence

73