The Magnificent Seven - PowerPoint PPT Presentation

1 / 66
About This Presentation
Title:

The Magnificent Seven

Description:

Sedation stopped at discretion of clinicians. Intervention ... Daily interruption of Sedation. SSC. What about combined strategies? Resuscitation Bundle ... – PowerPoint PPT presentation

Number of Views:45
Avg rating:3.0/5.0
Slides: 67
Provided by: chrisc58
Category:

less

Transcript and Presenter's Notes

Title: The Magnificent Seven


1
The Magnificent Seven
  • Chris Cairns
  • SRI
  • 2007

2
(No Transcript)
3
Sepsis
  • 25 deaths per 100,000 in Scotland
  • Hospital mortality
  • 47 in adults (MOF)
  • 10 in children
  • 5 yr mortality 74
  • Patients with severe sepsis account for 45 of
    all ICU bed-days
  • Considerable short and long term morbidity
  • High cost US 120,000 at 5yrs

4
In other words sepsis is bad!
5
Historical Management of Sepsis
  • ABC
  • Antibiotics / surgery
  • Goal directed therapy

6
History of Goal directed therapy
  • Shoemaker Arch. Surg. 1973
  • Increased DO2, increased survival
  • Vallet CCM 1993
  • Dobutamine challenge test
  • Ronco JAMA 1993
  • Critical DO2 needed is less
  • VO2 mirrors DO2
  • Hayes NEJM 1994
  • Goal directed approach leads to worse outcome in
    sepsis
  • Hayes CCM, 1997
  • Sub-group analysis
  • Survivors can increase DO2 VO2 (reserve)
  • Non-survivors reduced reserve, fail to increase
    VO2 with resus, O2 extraction falls with
    aggressive inotropes

7
Why not that simple ?
  • Not just about oxygen delivery
  • Oxygen consumption also important
  • Critically ill different from surgical patient
  • Flogging the struggling patient does harm

8
What goals work?
  • High risk surgery
  • Early intervention in Sepsis

9
  • High risk surgery or patients
  • Three groups
  • Control
  • Invasive monitoring, fluids, adrenaline to
    increase DO2
  • Invasive monitoring, fluid, dopexamine to
    increase DO2
  • Improved outcome in treatment groups (15 reduced
    hospital mortality NNT 7)
  • Less side effects with Dopexamine
  • Most benefit from fluid

10
But
  • Poor control results
  • Impractical?

11
What do I do?
  • Measure CO in theatre
  • Give more fluid pre KNS
  • Use dopexamine more

12
(No Transcript)
13
(No Transcript)
14
(No Transcript)
15
Early intervention
  • Six hours only in AE HDU (but its the first 6
    hours)
  • More fluid (blood) earlier
  • Less inotropes and ventilation later
  • NNT 7

16
But..
  • Are you doing it?
  • How easy is it?
  • What does it cost?

17
What do I do..
  • Easy in ICU
  • Use CV sats- more blood and dopexamine
  • Measure CO less noradrenaline
  • Difficult in HDU
  • Difficult in AE
  • Impossible on the wards?

18
(No Transcript)
19
  • Randomized, double-blind, placebo controlled
  • Multicenter, international
  • Strict patient selection patients with systemic
    inflam. organ failure due to acute infection.
  • 96 hours of 24mcg/kg/hr activated protein C
  • 28 day mortality used as primary endpoint

20
Results
  • All patients
  • 28 day mortality Placebo 30.8 Treatme
    nt 24.7 (p0.005)
  • Reduction in the relative risk of death of 19.4
  • Absolute reduction in risk of death of 6.1
  • NNT 16
  • In MOF
  • 28 day mortality
  • Placebo 33.9
  • Treatment 26.5
  • NNT 13.5

21
But..
  • Is Lilly trying to take over the world?
  • Is it worth the money?
  • Do we need another trial first?
  • How would randomize for another trial?

22
Cost Effectiveness
  • USA
  • 48,800 per QALY overall
  • 27,400 per QALY if APACHE II gt25
  • UK
  • 10,000 per QALY if same treatment effect as
    PROWESS
  • ARR would have to drop to 2 to 3 before cost
    exceeded 30,000 per QALY (Davies in press)

23
Cost Comparison
  • aPC 10,000 per QALY
  • Infliximab 100,000 per QALY
  • rTPA 19,400 per QALY

24
Current Situation
  • Poor efficacy in
  • Single organ failure (especially surgical
    patients)
  • Usage
  • ICS/SICS aPC appropriate for severe sepsis with
    2 or more organ failures
  • ? APACHE gt25
  • Variable usage
  • Trial in the pipeline

25
What do I do?
  • Give to
  • Septic shock
  • 2 or more organ failures despite resuscitation
  • Earlier rather than later

26
aPC
27
  • Control BM 10 - 11 mmol/l
  • Experimental 4.4 - 6.1 mmol/l

28
But..
  • Majority of patients post cardiac surgery
  • Most benefit however
  • Septic
  • ICU for more than 3 days
  • Non cardiac patients
  • Trials awaited in general ICUs
  • Benefit due to glycaemic control rather than
    insulin per se. (Van den Berghe, CCM, 2003)

29
Intensive Insulin - Medical
Patients in ICU for 3 days
All patients
30
What do I do?
  • Currently
  • Tight control as per Annane
  • The future
  • Not so sure!
  • Await ANZICS study.

31
Intensive Insulin Therapy
32
Relative adrenal insufficiency
  • Definition
  • Difficult
  • Admission cortisol lt25mcg/dl (690nml/l)
  • Incidence
  • 30 of all ICU patients
  • 50-60 in sepsis
  • Marik PE, Zaloga GP. Adrenal insufficiency in the
    critically ill. Chest 2002 1221784-1796.
  • Marik PE, Zaloga GP. Adrenal insufficiency during
    septic shock. Crit Care Med 2003 31141-145.

33
Annane, JAMA, 2002
  • 300 patients with septic shock
  • Hydrocortisone 50mg q6h
  • ACTH test (high dose)
  • Improved outcome in non-responders
  • NNT (hospital mortality) 6
  • Annane D, Sebille V, Charpentier C, et al. Effect
    of treatment with low doses of hydrocortisone and
    fludrocortisone on mortality in patients with
    septic shock. JAMA 2002 228862-871.

34
Relative adrenal insufficiency
  • Diagnosis
  • Admission cortisol
  • Cortisol if deterioration
  • Management
  • 50mg hydrocortisone q6h iv in septic shock
  • Stop if result suggests cortisol level sufficient
    (lt25mcg/dl (690nml/l))

35
Cheap easy. But
  • Who gets them?
  • For how long?
  • ACTH?
  • Random level?
  • Harm?
  • Is one trial enough?

36
CORTICUS
  • 500 patients
  • 2002-2005
  • Less sick than Annane study
  • Sepsis for longer
  • Non mortality difference
  • Steroid vs placebo
  • Responders vs non-responders

37
What do I do?
  • Give to
  • Septic shock
  • Resuscitate first
  • Higher dose noradrenaline
  • Random level pre first dose
  • Stop
  • Watch for response or level back
  • Stop abruptly

38
Steroids
39
  • 838 critically ill patients with Hb lt 9 within 72
    hrs of ICU admission
  • Hb controlled to 7-9g or 10-12g
  • Results
  • ARR of 5.8 - Hospital mortality
  • NNT 17
  • No change in 30 day mortality (except if APACHE
    lt20, lt55 yrs restrictive better)
  • MI or unstable angina ?

40
But.
  • Is anaemia better or transfusion harmful?
  • J-L Vincent, JAMA, 2002, Transfusion associated
    with higher mortality.
  • Leuco-depleted blood?
  • Long term effects?
  • Do we do what we think we do?
  • Ischaemic heart disease?
  • Wu, NEJM, 2001, Transfusion improved outcome in
    MI if admission Hct lt30.

41
What do I do?
  • Most patients
  • Transfuse one unit when Hb lt7
  • Exceptions
  • Ischaemic
  • MI
  • Early intervention DO2 optimization.
  • Future
  • Long term QOL studies

42
Restrictive Transfusion
43
Restrictive Ventilation
  • 861 patients, ALI/ARDS
  • Control
  • 12ml/kg TV, Pplat lt50cmH2O
  • Mim TV 4ml/kg (Pp gt50 if pHlt7.15)
  • Intervention
  • 6ml/kg TV, Pplat lt30cmH2O
  • Min TV 4ml/kg (Ppgt30 if pHlt7.15)
  • Bicarbonate for severe acidosis

44
Results
  • Marked reduction in hospital mortality NNT 11
  • With restrictive policy
  • Lower TVs and Pp
  • Higher FiO2 Peep (until day 7)
  • Higher pCO2 (pO2 similar)
  • Lower pH
  • Increased ventilator-free days
  • Decreased other organ failure

45
But.
  • Difficult to do?
  • Pressure control ventilation?
  • What do you do?
  • Surely bigger is better?

46
What do I do?
  • Beat by head against the wall!!
  • Use APRV

47
Restrictive Ventilation
48
  • 128 ventilated patients, sedated by infusion
  • Control
  • Sedation stopped at discretion of clinicians
  • Intervention
  • Sedation stopped daily, until patient awake
  • Both groups sub-divide into propofol / morphine
    or midazolam / morphine

49
Results
  • Duration of ventilation reduced by 2.4 days
  • ICU stay reduced by 3.5 days
  • No difference in adverse events
  • No difference between propofol and midazolam

50
What do I do?
  • Encourage daily sedation vacation
  • Then.Switch off sedation myself
  • Use less propofo and more MM
  • Use less noradrenaline
  • Use less steroids
  • Need to reassure that not torturing patients
  • Need to communicate and be on hand

51
Daily interruption of Sedation
52
SSC
  • What about combined strategies?

53
Resuscitation Bundle
  • As soon as possible (but within 6 hours)
  • Measure lactate
  • BCs prior to antibiotics
  • Broad spectrum Abs within 1-3 hours
  • If hypotension and/or lactate gt4mmol/l
  • 20ml/kg fluid challenge
  • Norad. If no response to fluid (MAPgt65)
  • If persistant hypotension and/or lactate
  • CVP gt8mmHg
  • CVsat gt70

54
Management Bundle
  • As soon as possible (but within 24hrs)
  • Low-dose steroids as per unit policy
  • aPC as per unit policy
  • Glucose control
  • Protective ventilation if appropriate

55
  • NNT 4 for 6 hr bundle
  • But
  • Bundles different
  • Numbers small

56
Out-of-hospital cardiac arrest
Hypothermia post out-of-hospital cardiac arrest
improves outcome
The hypothermia After Cardiac Arrest Study Group
(2002). Mild Therapeutic Hypothermia To Improve
Neurologic Outcome After Cardiac Arrest. NEJM
3468549-56
Bernard SA, TW Gray, MD Buist, BM Jones, W
Silvester, G Gutteridge, K Smith.  Treatment of
Comatose Survivors of out-of-hospital Cardiac
Arrest with Induced Hypothermia NEJM 2002
3468557-63
57
..cooling
  • Target 32-34C
  • Aim to reach target within 4 hours
  • Cool for 24 hrs (external)
  • Passive rewarming over 8 hrs
  • All patients sedated, paralysed, ventilated

58
.. Results..
59
also
  • Fear of creating poor outcome survivors has not
    materialized

60
But.
  • Select group of patients
  • Small of Cardiac arrests
  • Not necessarily a bad thing
  • Aftercare varies hugely

61
What do I do?
  • If they come to ICU then they get cooled

62
SSC
63
SSC survivors?
Too hard?
Harm?
Too hard?
Harm?
64
SSC survivors?
65
The Fabulous 5?
66
sicsebm.org.uk
Write a Comment
User Comments (0)
About PowerShow.com