This document discusses septic shock and its management. It covers: - The pathophysiology of septic shock including absolute and relative hypovolemia, distributive shock, and impaired oxygen extraction. - The history of managing septic shock from focusing on normalizing blood pressure in the 1960s to measuring oxygen delivery and consumption in later decades. - Guidelines for initial resuscitation of septic shock patients, including targeting a MAP ≥65 mmHg, CVP of 8-12 mmHg, and ScvO2 ≥70%. - Use of fluid challenges to guide fluid resuscitation and options for vasopressors like norepinephrine if needed to support blood pressure.

1. Septic Shock
 Absolute hypovolemia
 Relative hypovolemia
 Distributive shock :areas
of VD/VC
 Cardiac dysfunction
 Impaired O2 extraction

2. History of Septic Shock
60’s hypotension vasopressors
 normalize BP
70’s Inadequate flow
 measure CO + inotrope
80’s Inadequate DO2
 DO2/VO2 + inotrope
90’s Regional circulations + dopexamine
 phi, lactate + dopexamine
00’s Microcirculation failure + vasodilators
 « open » capillary beds

3. CCM , 2008 , 36 , 296-327

4. Initial Resuscitation
MAP  65 mmHg
 CVP 8-12 mmHg
 UF  0.5 ml.kg -1.hr-1
ScvO2  70%
 SvO2  65%

5. BE SURE
THE PATIENT
IS ADEQUATLY
FLUID-
RESCUCITATED

6. Fluid challenge
Respiratory variation under MV
Parameter threshold
SAP 10 mmHg or 9%
5-6 %
down
PP
SVV
CVP
5 mmHg
12-13 %
9-10%
< 5 mmHg
French Consensus Conference 2005

7. Am J Respir Crit Care Med 2000; 162:134-8
162:134-
100
PP
80
SPV
Sensitivity (%)
60
RAP
40
20 PAOP
0
0 20 40 60 80 100
100- Specificity(%)

8. Passive Leg Rising Predicts Response to Fluid Loading
Rapid fluid loading :300 ml, > 20 min.
Boulain, Chest 2002, 121, 1245

9. Fluid challenge
500 ml (7 ml/kg)
(either colloid or crystalloid
20 – 30 min

10. Fluid Challenge and Severe Sepsis
Cristalloids Colloids
Schierhout BMJ 1998, 316, 961
Wilkes Ann Int Med 2001, 135, 149
Choi CCM 1999, 27, 200
Sibbald www.uptodate.com 2003, 1/03

11. Safe
Study
NEJM 2004 , 350 ,
2247-2256

12. Safe Study
NEJM 2004 , 350 , 2247-2256

13. HEA or Gelatine for Severe Sepsis ?
Schortgen et al Lancet 2001 , 357 , 911
Patients without Acute Renal Failure
Gelatine
HES

14. HEA or Gelatine for Severe Sepsis ?
Schortgen et coll Lancet 2001 , 357 , 911
Survivors

16. P=0.09
Subgroup Analysis
(</= 22mL/Kg/day)
P<0.001
(> 22mL/Kg/day)

17. Hydroxyethyl Starch
HES 200,000/0.6 HES 200,000/0.5
6% solution (60g/l) 6% solution (60g/l)
Na+ 154 mmol/l Na+ 154 mmol/l
12 - 24h 4 - 8h
33 ml / kg / 24h

18. 32 patients randomized : dopamine (Until 25 µg/kg/min) or norepi ( Until 5 µg/kg/min)
Objectif : PAM > 80 mmHg 6 h
Dopa (n=16) Norepi (n=16)
success (n=5) échec (n=11) success (n=15) failure (n=1)
10 to 25 µg/kg/min 25 µg/kg/min 1.5±1.2 µg/kg/min
1.5± 5 µg/kg/min
increase in urine output increase in urine output
decrease in lactate decrease in lactate
10 success with Dopa + Norepi (25 µg/kg/min +1.7±1.8 µg/kg/min)
+1.7±
increase in urine output
and decrease in lactate
Chest 1993, 103:1826-31

19. Dopamine or Norepinephrine ?
93%
69%
P < 0.001
31%
7% p < O. 001
Success Failures Success Failures
Dopamine Norepinephrrine
C. Martin et al Chest 1993, 103, 1826

20. Dopamine or Norepinephrine ?
Hyperdynamic septic shock
Dopamine Norepinephrine
(2.5-25 g /kg/min) (0.5-5.0 g/kg/min)
16 patients 16 patients
success : 5/16 (31%) success : 15/16 -93%)
p<0.001
failure : 11/16 failure : 1/16
success : 0/1 success : 10/11
C. Martin et al Chest 1993, 103, 1826

21. Resistance to Dopamine
110 patients
 MAP < 70 mmHg with 20 g/kg/min
60%
P < 0.001
40%
Dopa S Dopa R
Levy et al CCM 2005, 33.

22. Resistance to Dopamine
Levy et al CCM 2005, 33.

23. % Survival
Septic Shock :
100 Norepinephrine
90
80
70
60 Norepinephrine
50
40
p<0.0001
30
20 Martin C et al Crit Care Med
10 Other vasopressors 2000 , 28 , 2758 .
0
0 5 10 15 20 25 30 35 40 45 50
Days

24. CATS Study
(Epinephrine / norepi-dobu)
Epinephrine Norepi-dobu
n = 161 (n = 169)
Hospital survival Hospital survival
47.8% 51.5%
p = 0.51
D. Annane et al Lancet 2007,370,676-684

25. D. Annane et al Lancet 2007,370,676-684

26. MAP :
65-75-85
mmHg ???

27. 150 Renal Blood Flow
Renal Autoregulation
(% baseline) in Disease
Control
3 weeks
100
1 week
50
0 20 40 60 80 100
Renal Artery Pressure (mmH g)

28. 150 Renal Blood Flow
Renal Autoregulation
(% baseline) in Disease
Control
3 weeks
100
1 week
50
0 20 40 60 80 100
Renal Artery Pressure (mmH g)

29. 150 Renal Blood Flow
Renal Autoregulation
(% baseline) in Disease
Control
3 weeks
100
1 week
50
0 20 40 60 80 100
Renal Artery Pressure (mmH g)

30. 150 Renal Blood Flow
Renal Autoregulation
(% baseline) in Disease
Control
3 weeks
100
1 week
50
0 20 40 60 80 100
Renal Artery Pressure (mmH g)

31. 65 85

32. UF
Increasing MAP ?
65 Creatinine
85
Cr Cl
A Bourgoin et al
CCM 2005,33,780-786

33. MAP :
65 mmHg

36. Septic shock. Inotropic Therapy
. Dobutamine is the first
choice for patients with low CO
< 2.5 l/min/m2
after fluid resuscitation
after an adequate MAP (Level E)
. Dobutamine may cause hypotension
and /or tachycardia in some patients:
 especially those with low filling
pressure
Task Force of the SCCM. Crit. Care Med 2004,32,1928-1948

37. Initial Resuscitation
MAP  65 mmHg
 CVP 8-12 mmHg
 UF  0.5 ml.kg -1.hr-1
ScvO2  70%
 SvO2  65%

38. Early « Goal-directed therapy »
4981 ml 64.1% p < 0,001
P < 0,001
3499 ml
18.5%
contrôles GDT contrôles GDT
Expansion volémique Transfusion (% patients)
13.7%
0.8%
p < 0,001
contrôles GDT
Dobutamine (% patient)
Rivers et coll N Eng J Med 2001, 345, 1368-1377

40. Early « Goal-directed Therapy »
Hospital mortality
46.5%
30.5% (p = 0.009)
Controls GDT
Rivers et al NEJM, 2001, 345, 1368-1377

43. Rescue Therapy

44. 1-AR AC AC

 

Gs protein
 
P P P
Receptor
arrestin
resensitization
clathrin
Receptor endosome Receptor
internalization Receptor degradation
dephosphorylation

45. VASOPRESSIN
• Regulation of plasmatic
osmolarity and volemia
• Heterogeneous
vasoconstriction
Liard et al. Am J Physiol 1982
• Vasodilation in some
circulatory beds
Walker. Am J Physiol 1986

46. AVP

48. Norepinephrine > 15 mcg/min

49. Norepinephrine 5-14 mcg/min

50. Only as
rescue therapy

51. Terlipressin?  15 patients with catecholamine - resistant
septic shock: NE ( 2.2 mcg/kg/min )
dopamine ( 25 mcg/kg/min )
Terlipressin 1 or 2 bolus of 1 mg
MAP CI l/min/m2
mmHg 5.3+/-1.2
84+/- 6
4.7+/-1.3
55+/- 5 P< 0.01
NE + dopa TER NE + dopa TER
1147+/-134
SVRI dyn.sec 654+/-108
.cm-5.m-2
NE + dopa TER
Albanese , Martin Shock 2004,22,314-319

52. Terlipressin? 15 patients with catecholamine - resistant
septic shock: NE ( 2.2 mcg/kg/min )
dopamine ( 25 mcg/kg/min )
Terlipressin 1 or 2 bolus of 1 mg
UF 67+/- 33 P<0,01
ml/min
11+/-15
Cr CL ml/min NE + dopa TER
49+/-37 P<0.01
/ 1.74 m2
17+/-44
NE + dopa TER
Albanese , Martin Shock 2004,22,314-319

53. Dynamic Aspect
6th hour
2nd hour
1st hour
 blood gas
MAP>65 mmHg
 lactate
ScvO2 70%
 arterial%
 cultures line
SvO2 > 65
 ATB
 CVC SvO2
 plateau pressure
 peripheral IV
 <CVP > 5 mmHg
30 mmHg
 vasopressor
 fluid

54. Dynamic Aspect
1st hour 2nd hour 6th hour
 blood gas MAP 65 mmHg ScvO2 > 70%
 lactate  arterial line SvO2 > 65 %
 cultures  CVC SvO2  plateau pressure
 ATB  CVP > 5 mmHg < 30 mmHg
 peripheral IV
 vasopressor
 fluid