da tat Teapea Case reports

1
????da ??tat???? Te?ape?a?Case reports

• ???e 3? ???t? ??a ??? t? a?ad?µa??? ?t?? 2006-2007

2
??µ? pa???s?as?? pe??stat????

• ??sa?????? ep???aµµat??? s????? (d?µ???af???,
  a?t?a / ?????? / ?at?stas? e?sa????? st? ??T)
• ?a???sa ??s?? (ap? t?? a???)
• ?t?µ??? / ?????e?e?a?? a?aµ??st??? ??p
• ?????a e?sa????? st? ??T ??sta p??ß??µ?t??
  (?at? s?st?µata / e??ast???a?? e???µata)
• ??af????? d?????s? / p?????s?
• ?p????s? d?a???st???? / ?e?ape?t???? e?e??e??? µe
  ß?s? t? ß?ß?????af?a (Annotated references)
• ??ßas?

3
?p?peda ep?st?µ?????? e?????t?ta? ?at????? ???se??

• Level 1 Randomised, controlled trial with
  statistically significant results
• Level 2 Randomised, controlled trial with
  significant threats to validity (e.g, small
  sample size, inappropriate blinding, weak
  methodology)
• Level 3 Observational study with a concurrent
  control group
• Level 4 Observational study with a historical
  control group
• Level 5 Bench study, animal study, case series

4
Grade A

• Scientific evidence provided by randomised,
  well-designed, well-conducted, controlled trials
  with statistically significant results that
  consistently support the guideline
  recommendation
• Supported by Level 1 or 2 evidence

5
Grade ?

• Scientific evidence provided by well-designed,
  well-conducted observational studies with
  statistically significant results that
  consistently support the guideline
  recommendation
• Supported by Level 3 or 4 evidence

6
Grade C

• Scientific evidence from bench studies, animal
  studies, case studies
• Supported by Level 5 evidence

7
Grade D

• Expert opinion provides the basis for the
  guideline recommendation, but scientific evidence
  either provided inconsistent results or was
  lacking

8
??sa?????? s?????

• ?s?e???, ??t?a? 77 et??, 3? µ??a ??s??e?a? st?
  ??T, e?s???? ??a ?p?st????? ??t???? ?e?t???????
  µe e????a ?atap????a? ?a? a?ap?e?st????
  a?ep???e?a? t?? 1? µete??e???t??? µ??a µet? ap?
  e?te?e?t?µ? ??a ?????s? e?t???? sta p?a?s?a
  ap?f?a?t???? e??e?? ap? s?µf?se??

9
?a???sa ??s??

• ?p?f?a?t???? e??e?? ??a 3 µ??e? st? ??
• ?????a ??e?a? ?????a?
• ?e??????e?? µe e???µata ?s?a?µ?a? ?????s??
  ?ept?? e?t????
• ??te?e?t?µ? ?a? a?ast?µ?s?
• ?ete??e???t???, ?atap????a (??e?) ?a?
  a?ap?e?st??? a?ep???e?a
• ?etaf??? st? ??T / d?as?????s? 12h

10
???s?p??? / ?????e?e?a?? ?st?????

• ?e??t???t?da ad?e??????st?? a?t?a? p?? et??
• ???????sµ???
• ?s?a?µ??? ?a?d??p??e?a µe ?? p?? et???

11
?????a e?sa????? st? ??T(p??s????s? ?at?
s?st?µata)

• 1. ??? ????? d??µa
• ??? p?s???t??
• ????? - ???? ???a
• ?????????s?
• F?s???????? ????? ap? t?? ???

12
?????a e?sa????? st? ??T(p??s????s? ?at?
s?st?µata)

• 2. ??S / ??S / ??S
• S????t???? d?e?e?t????
• ??ta?a???se?? ??????

13
?????a e?sa????? st? ??T(p??s????s? ?at?
s?st?µata)

• 3. ?a?d?a??e?a??
• SAPlt80, HRgt T lt37 st?? e?sa????
• CVP 5, Lac 8, ScvO2 22

14
?????a e?sa????? st? ??T(p??s????s? ?at?
s?st?µata)

• 4. ??ap?e?st???
• pH 7.30, pO2 75, pCO2 29 (NRM)
• Extreme extraction

15
?????a e?sa????? st? ??T(p??s????s? ?at?
s?st?µata)

• 5. Gast?e?te????
• ???e??

16
?????a e?sa????? st? ??T(p??s????s? ?at?
s?st?µata)

• 6. ????p???t???
• ????????a
• ??eat????? 2.0mg/dl

17
??af????? d?????s?
18
??????s?
19
Lab results (haematology)
27/10
12/11
21/11
WBC
1900
6100
6170
Neut
77.5
82.1
60.9
Hgb
12.2
8.4
8.1
34.8
25.2
Hct
26.1
PLT
62000
124000
153000
1.10
Not done
INR
1.23
20
Lab results (biochemistry)
27/10
12/11
19/11
Glc
110
291
96
Urea
122
190
56
Creatinine
3.89
4.56
1.25
AST
42
45
36
LDH
488
2036
1197
11.2
Calcium
11.55
Not done
21
Fa?µa?e?t??? a????
22
???t?µata p??? s???t?s?

• ???????????e ? ???? d?a???st??? p??sp??as??
• ????e ???a??? a?t?µet?p?s? / a??ta???
• ???????????e ? e?dede??µ??? ?e?ape?t????
• - ???ta?? p?es??
• - ???ta?? ??de?s??
• - ???ta?? ????????a?
• - ???ta?? a?ap?e?st???? a?ep???e?a?

23
Christopher Reeve, our inspirational Chairman,
passed away on October 10, 2004 from heart
failure
CNN News Reeve went into cardiac arrest
Saturday at his home in Westchester County, New
York, after developing a serious systemic
infection during treatment for a pressure wound.
He slipped into a coma and died Sunday afternoon
at a hospital near his home
24
Sepsis Defining a Disease Continuum
Infection/Trauma
Sepsis
SIRS
Severe Sepsis

• A clinical response arisingfrom a nonspecific
  insult, including ?2 of the following
• Temp gt38oC or lt 36oC
• HR gt 90 beats/min
• Respirations gt 20/min
• WBC gt12,000/mm3 or lt4,000/mm3 or gt10 immature
  neutrophils

SIRS presumed or confirmed infectious process

• Sepsis Organ dysfunction
• Cardiovascular (refractory hypotension)
• Renal
• Respiratory
• Hepatic
• Hematologic
• CNS
• Metab. acidosis

SIRS systemic inflammatory response syndrome.
Bone et al. Chest. 19921011644. Wheeler and
Bernard. N Engl J Med. 1999340207.
25
A clinician, armed with the sepsis bundles,
attacks the three heads of severe sepsis
hypotension, hypoperfusion and organ dysfunction.
Crit Care Med 2004 320(Suppl)S595-S597
26
Hemodynamic ?arly intervention
27
6 hour Severe Sepsis/Septic Shock Bundle

• Serum lactate measured.
• Blood cultures obtained prior to antibiotic
  administration.
• Broad-spectrum antibiotics administered within 3
  hours of documented admission time.
• In the event of hypotension (SBP lt 90, MAP lt 70)
  or lactate gt 4 mmol/L, initial fluid
  resuscitation with 20-40 ml of crystalloid (or
  colloid equivalent) per estimated kg of body
  weight.

28
6 hour Severe Sepsis/Septic Shock Bundle

• Vasopressors employed for hypotension during and
  after initial fluid resuscitation.
• In the event of septic shock or lactate gt 4
  mmol/L, CVP and ScvO2 or SvO2 measured.
• Inotropes (and/or PRBCs if hematocrit lt 30)
  delivered for ScvO2 lt70 or SvO2 lt 65 if CVP gt
  8 mmHg.

29
24-Hour Severe Sepsisand Septic Shock Bundle

• Glucose control maintained on average(or median)
  lt 150 mg/dl (8.3 mmol/L) .
• Drotrecogin alfa (activated) administered in
  accordance with hospital guidelines.
• Steroids given for septic shock requiring
  continued use of vasopressors.
• Adoption of a lung protective strategy with
  plateau pressures lt 30 cmH2O for mechanically
  ventilated patients.

30
Patient enrollment and hemodynamic support
Rivers et al. N Engl J Med 2001
SIRS and PAS lt 90 mmHg or lactate gt 4
Standard strategy n 130
EGDT strategy n 130
Randomisation n 263
Vital and biological signs, ECG, SaO2, diuresis
monitoring, arterial and venous catheterism
CVP 8-12 mmHg
CVP 812mmHg
MAP gt 65 mmHg
Standard care
ScvO2 monitoring and  agressive  strategy
MAP gt 65 mmHg
Diuresis gt 0.5 ml/kg/h
Diuresis gt 0.5 ml/kg/h
ScvO2 gt 70
6 hours
SaO2 gt 93
Hte gt 30
Clinical and biol. monitoring 8-72 hours
Cardiac function
Treatment lt 6h n 14
VO2
Treatment lt 6h n 13
Evaluation
31
Tissue perfusion is modified in sepsis

• Vascular hyporeactivity and vasoplegia
• inductible NOS ?
• Catecholamine misuse
• Endogenous (epinephrine, norepinephrine,
  vasopressine)
• Exogenous
• Perfusion heterogeneity
• SVR is only a global estimation
• Modifications in tissue distribution and/or use
  of O2
• Interstitial oedema (O2 diffusion abnormalities)
• Hypoperfusion
• Mitochondrial dysfonction

32
PiCCO System
Central venous catheter
Thermodilution femoral arterial catheter
33
Transpulmonary thermodilution Cardiac output
measurement (vs Fick method)
Tibby et al. Intensive Care Med 1997
9
CO Fick (L/min)
n 24
r2 0.99
y 1.05x 0.085
0
0 9
CO FATD (L/min)
34
ScVO2 monitoring in ICU
Rivers et al. Current Opinion in Critical Care
2001 7 204-211
Factors that may influence SvO2 / ScvO2 value

• Global indice of O2 extraction
• if SaO2 1 ? SvO2 1 EO2
• of no interest when severe hypoxemia and/or
  large variations of SaO2

35
Comparison of central-venous to mixed-venous
oxygen saturation during changes in oxygen
supply/demand
Reinhart et al. Chest 1989 95 1216-1221

• Its not the same value but
• Evolution is similar
• Overestimation of SvO2 by ScvO2
• Same clinical signification

• In ICU patients
• low ScvO2 lt 60 shock ou cardiac insifficiency
• good correlation between ScvO2 and SvO2

Reinhart et al. Int Care Med 2004
36
Vasopressors

• Do not use low-dose dopamine for renal
  protection.
• Grade B

Bellomo R, et al. Lancet 2000 3562139-2143
37
Vasopressors Vasopressin

• Not a replacement for norepinephrine or dopamine
  as a first-line agent
• Consider in refractory shock despite high-dose
  conventional vasopressors
• If used, administer at 0.01-0.04 units/minute in
  adults
• Grade E

38
Inotropic Therapy

• Consider dobutamine in patients with measured low
  cardiac output despite fluid resuscitation.
• Continue to titrate vasopressor to mean arterial
  pressure of 65 mm Hg or greater.
• Grade E

39
Inotropic Therapy

• Do not increase cardiac index to achieve an
  arbitrarily predefined elevated level of oxygen
  delivery.
• Grade A
• Yu, et al. CCM 1993 21830-838
• Hayes, et al. NEJM 1994 330-1717-1722
• Gattinoni, et al. NEJM 1995 3331025-1032

40
Sepsis-related Acute Renal Failure
Mortality ()
p lt 0.001
OSF at inclusion
Neveu H. Nephrol Dial Transplant 1996
41
Dopamine renal dose

• 58 published studies, n 2149
• 18 RCT, n864
• Mortality 4,7 vs 5,6
• RR 0,83 (0.39-1.77)
• ARF 15,3 vs 19,5
• RR 0,79 (0.54-1.13)
• RRT 13,9 vs 16,5
• RR 0,89 (0.66-1.21)

Kellum J. Crit Care Med, 2001
42
Diuretics
Mehta R. JAMA 2002

• 552 patients, 326 with diuretics
• Prospective, obs. study
• Impact of diuretics (OR, IC 95 )
• Mortality 1.65 (1.05-2.58)
• Dialysis dep. 1.70 (1.14-2.53)

• Uchino, Crit Care Med 2004
• Use of diuretics unrelated to excess risk of
  death in ICU
• 54 centers, 23 countries, 1743 patients

43
Small differences in genotype make big
differences to phenotype
44
Genetic Polymorphisms
45
Relevant Polymorphisms
46
Mice Susceptibility to Infection with Group A
Streptococci
103 cfu Strepto Subcutaneous
Goldman O. J Infect Dis 2003187854-61.
47
Community-Acquired Pneumonia and TNF polymorphisms
280 CAP
No association with mortality rate
LTa250 AA genotype RR 2.48 (1.28 4.78),
Age-adjusted RR 3.64 (1.28 10.66)
Waterer GW. AJRCCM 2001 163 1599
48
4G/5G promoter polymorphism in the PAI-1 gene and
severe trauma patients
Menges, Lancet 20013571096
49
Mechanical Ventilation ofSepsis-Induced ALI/ARDS

• Reduce tidal volume over 12 hrs to 6 ml/kg
  predicted body weight
• Maintain inspiratory plateau pressure lt 30 cm H20
• Grade B

50
(No Transcript)
51
Sedation and Analgesia in Sepsis

• Sedation protocol for mechanically ventilated
  patients with standardized subjective sedation
  scale target.
• Intermittent bolus
• Continuous infusion with daily awakening/retitrati
  on
• Grade B
• Kollef, et al. Chest 1998 114541-548
• Brook, et al. CCM 1999 272609-2615
• Kress, et al. NEJM 2000 3421471-1477

52
The Role of IntensiveInsulin Therapy in the
Critically Ill

• At 12 months, intensive insulin therapy reduced
  mortality by 3.4 (Plt0.04)

Adapted from Figure 1B, page 1363, with
permission from van den Berghe G, Wouters P,
Weekers F, et al. Intensive insulin therapy in
critically ill patients. N Engl J Med
20013451359-67
53
Changing pH Has Limited Value

• Treatment Before After
• NaHCO3 (2 mEq/kg)
• pH 7.22 7.36
• PAOP 15 17
• Cardiac output 6.7 7.5
• 0.9 NaCl
• pH 7.24 7.23
• PAOP 14 17
• Cardiac output 6.6 7.3

Cooper DJ, et al. Ann Intern Med 1990
112492-498
54
Deep Vein Thrombosis Prophylaxis

• Heparin (UH or LMWH)
• Contraindication for heparin
• Mechanical device (unless contraindicated)
• High risk patients
• Combination pharmacologic and mechanical
• Grade A