IFAD 2013

1. IFAD Antwerpen 2013
Azriel Perel
Professor and Chairman
Department of Anesthesiology and Intensive Care
Sheba Medical Center, Tel Aviv University
Israel
Resuscitation from Severe Sepsis:
do we need care bundles?

2. Disclosure
The speaker is a member of the
Medical Advisory Board of
Pulsion Medical Systems,
Munich, Germany
Consulted until recently to BMEYE, FlowSense, iMDsoft

3. “Because of the complexity of
hemodynamics in sepsis, the goals of
therapy are much more difficult to
define with certainty than in other forms
of shock.”
Practice parameters for hemodynamic support of sepsis
in adult patients. 2004 update.
Hollenberg S et al. Crit Care Med 2004; 32:1928-48

4. Early goal-directed therapy
improves outcome in patients with
severe sepsis and septic shock.

6. The 6H bundle

7. The 6H bundle

8. Rivers, NEJM 2001

9. “In most patients with septic shock, CO will
be optimized at filling pressures (PAOP)
between 12-15 mmHg [26].
Increases above this range…increase the
risk for developing pulmonary edema.”
26. (III) Packman MJ, Rackow EC: Optimum left heart filling
pressure during fluid resuscitation of patients with
hypovolemic and septic shock. Crit Care Med 1983; 11:165-9
Level D recommendation
Practice parameters for hemodynamic support of sepsis
in adult patients. 2004 update.
Hollenberg S et al. Crit Care Med 2004; 32:1928-48

13. CCM 2007 35:64-8
Fluid overload!Fluid overload!
Possible
hypoperfusion!

14. Targeting dynamic measures of fluid responsiveness
during resuscitation, including flow (CO) and possibly
volumetric indices and microcirculatory changes, may
have advantages

16. Rivers, NEJM 2001

17. The ScvO2 serves as
a surrogate of CO

18. Rivers et al NEJM 2001
The normal
ScvO2 is
~70%

19. Crit Care Med 2006, 34:1025-1032
Initial ScvO2 72 ± 11%
Initial ScvO2 73 ± 13%
Initial ScvO2 74 ± 10%
Initial ScvO2 73 ± 11%
The mean ScvO2 of Rivers’ patients was 50%!!!
A normal/high SvO2 may be due to reduced O2
extraction and does not necessarily indicate
adequate tissue oxygenation

20. Severe Global Tissue Hypoxia and
Low O2 Extraction
Lactate > 4 mmol per liter and ScvO2 >70%
CCM 2007

22.  The extremely low ScvO2 values seen in Rivers’
patients on admission to the ED indicate that these
patients had very low cardiac outputs.
 The most probable cause for their low CO was a
combination of pre-existing co-morbidities and
hypovolemia, which may have developed due to a late
arrival to the hospital (black, low socioeconomic status,
no insurance).
 The very significant hypovolemic element of their
shock was successfully corrected by aggressive fluid
loading which was guided by a simple protocol that may
be unsuitable for many ICU septic patients.

23. Very recent literature from the US emphasizes the
effects of race and socio-economic conditions on
sepsis outcome.
 The Rivers study was done in the Department of
Emergency Medicine which serves “metro Detroit’s
largely poor, largely minority population, having poor
health status and high chronic disease incidence”
Ann Emerg Med Dec. 2008
 “Outcome of Americans without insurance who are
admitted to the ICU is worse, possibly because they
are sicker when they seek care.”
Danis M, et al. Crit Care Med 2006; 34:2043
Do the Rivers’ patients represent all septic patients?

25. “Shocked” wouldn't be accurate, since we were accustomed to
our uninsured patients' receiving inadequate medical care.
“Saddened” wasn't right, either, only pecking at the edge of
our response. And “disheartened” just smacked of victimhood.
After hearing this story, we were neither shocked nor saddened
nor disheartened. We were simply appalled…..
We find it terribly and tragically inhumane that Mr. Davis and
tens of thousands of other citizens of this wealthy country will
die this year for lack of insurance.

26. Dr. Rivers's explanation of the higher death
rate for those on conventional care
compared with data from other countries, is
that his patients were sicker.

28. Rawlins MR: De Testimonio.
Harveian oration 2008, Royal College of Physicians

30. There are only 10 references supporting
the 6H bundle; they have not been
updated over the years
Total number of references in the SSCG
grew form 135 (2004), to 341 (2008),
and to 636 (2012)

31. A large number of observational studies
have shown significant mortality reduction
compared to the institutions’ historical
controls.

32. Crit Care Med 2010; 38:668–678
As administered and studied to date, only
antibiotics meet the stated criteria of proof for
bundle inclusion.

33. The reported improved survival following the
adoption of these (SSC) Guidelines….cannot
be viewed as justification of the initial
hemodynamic resuscitation protocol.
Physiologically and clinically this protocol
may be wrong for many septic patients.

34. Attainment of a CVP of >8 mmHg and
ScvO2 of >70% did not influence
survival in patients with septic shock*.
*Voluntarily submitted data on 15,022 patients

35. Rivers EP et al,

36. Crit Care Med 2010; 38:668–678
Current sepsis bundles may force
physicians to provide unproven
or even harmful care.

37. Crit Care Med 2011; 39:259-65
778 septic shock pts from the VASST study

38. The toxic effects of EBM!

39. “Surely, we recognize the need to give up
some measure of autonomy…yield some
decision-making power…
The data certainly suggest that when we
surrender this autonomy and standardize
care, patients do better.”
M. Levy, SCCM 2009
38th SCCM Conference Perspectives

40. The 3 phases of the SSC
1. Introduction at several major international critical
care medicine conferences.
2. Creating evidence-based guidelines for the
management of severe sepsis and septic shock.
3. To operationalize the SSC guidelines into a set of
practical yet valid performance measure.

41. The sepsis bundle includes only
recommendations that can be converted into
data elements that can be precisely defined,
with clearly identified failure modes, and that
could be measured by retrospective chart
audit.

42.  The bundle is well-established, proven in
scientific tests and based on randomized
controlled trials, what we call Level 1 evidence.
C.H. PhD, IHI Vice President
and patient safety expert
 A bundle must be followed for every patient,
every single time. There should be no
controversy involved, no debate or discussion of
bundle elements.
 Addition of other strategies not found in the
bundles is not recommended.

44.  The guidelines attempt to include nearly every aspect
of critical care potentially related to sepsis, perhaps
losing focus in the process.
 The evidence behind some of the ‘bundles’ is not
strong, e.g., CVP.
 These bundles are being turned into quality measures
on which providers will be benchmarked, even though
clinicians may validly disagree with some of the
recommendations.

45. While only 47% of surveyed intensivists
believed that CVP should guide
resuscitation, 86% used it because of
the Surviving Sepsis Campaign
Guidelines.

46. Bundled performance
measures are ready made for
use in pay-for-performance
initiatives, which can base
reimbursement on
compliance with all the
components. Are you compliant?

47. Complete compliance with all applicable
elements of the sepsis resuscitation
bundle was 21.6% in the USA and 18.4%
in Europe.

48.  Even in these highly selected and committed
institutions compliance with both the
resuscitation and the management bundles
was only about 20%.
 This suggests that compliance is either quite
difficult, or that clinicians disagree with some
aspects of the guidelines and specifically do
not reach compliance.

49. http://survivingsepsis.org/Guidelines/Pages/default.aspx
In response to comments and
questions, the SSC leadership
has provided additional
background regarding the
guideline recommendation
regarding measurement of CVP,
ScvO2, and lactate.

50.  The performance indicators for bundle compliance now
call for measuring CVP and SCVO2, and re-measuring
lactate if the initial lactate was elevated.
 The rationale for the indicators’ being measurement
and not target achievement is that the decision to give
more fluid or add inotropes to the resuscitation should
be based on the entire clinical picture.
 Institutions that can bring more advanced technologies
to the bedside may do so and use those measurements
as part of the total clinical picture for decision making.

51.  The performance indicators for bundle compliance now
call for measuring CVP and SCVO2, and re-measuring
lactate if the initial lactate was elevated.
 The rationale for the indicators’ being measurement
and not target achievement is that the decision to give
more fluid or add inotropes to the resuscitation should
be based on the entire clinical picture.
 Institutions that can bring more advanced technologies
to the bedside may do so and use those measurements
as part of the total clinical picture for decision making.

52. Thank you for your attention!
Conclusions:
 Rivers et al have started one of the most
important process in modern critical care and
the SSC is saving lives as we speak.
 And yet, the physiological variables that the SSC
recommends to direct the initial hemodynamic
resuscitation are not suitable for all septic
patients and may be harmful.
 Attempts to protocolize care in critically ill
patients have to leave room for clinical judgment
that takes into account the whole clinical
picture.

54. Sponsoring Organizations
 American Association of Critical Care Nurses
 American College of Chest Physicians
 American College of Emergency Physicians
 American Thoracic Society
 Australian and New Zealand Intensive Care Society
 European Society of Clinical Microbiology and Infectious
Diseases
 European Society of Intensive Care Medicine
 European Respiratory Society
 International Sepsis Forum
 Society of Critical Care Medicine
 Surgical Infection Society

56. In part, physician noncompliance
with evidence-based guidelines can
be explained by weaknesses in the
evidence base itself.

57.  In recent years, the developers of practice guidelines
have started grouping evidence-based interventions into
“bundles,” on the theory that inducing physicians to
follow multiple recommendations written into a single
protocol has a measurable effect on patients’ outcomes.
 Seeing in these bundles a potentially powerful vehicle
for promoting their products, pharmaceutical and
medical-device companies have begun to invest in
influencing the adoption of guidelines that serve their
own financial goals.

58. “For every patient, every single time”
“No controversy involved, no debate or discussion”

59. “Clearly, SvO2 is the gold standard for
defining global adequacy of
cardiovascular performance.”
Crit Care Med 2005; 33:1119-22

60. It is useful to measure SvO2 because if
cardiac output becomes inadequate, SvO2
will decrease.
A low SvO2 should prompt rapid
intervention to increase oxygen delivery to
the tissues.

64. https://admin.emea.acrobat.com/_a45839050/p37057603/

66. “Medicine has become complex. Details
have become overwhelming for clinicians
to process at the bedside…
Surely, we recognize the need to give up
some measure of autonomy…yield some
decision-making power…
The data certainly suggest that when we
surrender this autonomy and standardize
care, patients do better.”
M. Levy, SCCM 2009
38th SCCM Conference Perspectives

68. Study Year Country
Compliance
6H bundle
Compliance
24H bundle
Overall
compliance
Gao F et al 2005 UK 52% 30%
Ferrer R et al 2008 Spain <10%
Mikkelsen ME et al 2010 USA 43%
Castellanos-Ortega et al 2010 Spain 34% 40%
Flavia R et al 2010 Brazil 9%
Levy MM et al 2010 USA 22% 26%
Vesteinsdotir E et al 2011 Iceland 35% 45%
Shiramizo SCPL et al 2011 Brazil 14% 44%
Tromp M et al 2011
Netherla
nds
27% 25%
Phua J et al 2011 Asia 8% 4%
Rinaldi L et al 2012 Italy 50 % 52% 39%
Wang Z et al 2013 China 1% 9%
Reported compliance rates with SSC bundles

69. These recommendations highlight the fact that the
GRADE system, though transparent, is still subjective
- the recommendations depend greatly on the values
and preferences of the committee members.
Developers are allowed to make strong
recommendations when the quality of evidence is
weak, or weak recommendations when the quality of
evidence is strong

70. Among the limitations of the guideline is the fact that
it attempts to include nearly every aspect of critical
care potentially related to sepsis, perhaps losing
focus in the process.
The guidelines also emphasize ‘bundles’ of care for
sepsis resuscitation, although the evidence behind
some of the bundled recommendations is not strong,
e.g., CVP.
Already, these bundles are being turned into quality

71.  CO = 12-15 L/min
 SVR = 400-500
 ITBVI = 1200 ml/m2 (800-1000)
 EVLW = 19-23 ml/kg (~7)
BP 70/40 mmHg
HR 155 bpm
CVP 5 cmH2O
PaO2/FiO2 80 (PEEP 16)
Low !!!
High !!!
High !!!
High !!!
Would you give fluids to this patient?
A patient with head injury, severe ARDS and septic shock
Noradrenaline + aggressive diuresis!
X
Can this patient “afford” the price of a possible mistake?

72. Some consensus
statements are being
turned into
performance measures
and other tools to
critique the quality of
physician care.
Are you compliant?

73. More than 80% of trauma centers that treat
mostly minority uninsured patients have
higher death rates than do trauma centers
that treat mostly white and insured patients.