Treatment of Sepsis

by Extracorporeal Blood Purification Systems (EBPS)

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Dr. M. Susca

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Severe Sepsis
Incidence and Mortality Compared with Other Major Diseases

Cases/100,000

Incidence of Severe Sepsis

Mortality of Severe Sepsis

AIDS*

Colon Breast
Cancer

CHF

Severe
Sepsis

AIDS*

Breast
Cancer

AMI

Severe
Sepsis

National Center for Health Statistics, 2001. American Cancer Society, 2001. *American Heart Association. 2000. Angus DC et al. Crit Care Med. 2001 .

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Sepsis Continuum
Infection/
Trauma

SIRS

Systemic Inflammatory Response Syndrome1:

defined by fulfills two of the following criteria:
Temperature > 38C or < 36C
Heart rate 90 bpm
Respiratory rate 20/min or
pCO2 < 32 mmHg
Leucocytes > 12.000/mm3 or
4000/mm3
or
> 10 % immature forms

severe Sepsis

Sepsis
SIRS
+
suspected or
evident infection

Sepsis with 1 organ dysfunction

Cardiovascular
(volume refractory hypotension)

Renal
Respiratory
Hepatic
Haematologic
CNS
Metabolic acidosis without
identifiable reason

20 %

28 day letality2

40 %

Shock

up to

80 %

1. Bone et al. Chest 1992; 101: 1644. *American College of Chest Physicians **Society of Critical Care Medicine
2. Brun-Buisson C. Intensive Care Med 2000; 26: S64.

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Endotoxin
Endotoxemia is associated with sepsis
Sources of Endotoxin are:

Gram negative organisms, Impaired permeability of the gut due to infection

with gram positive, fungal, viral organisms or to non-infective causes

Gram-negative bacterial endotoxin (lipopolysaccharide, {LPS})

O-specific polysaccharide chain

Core glycolipid

n
O-specific
(outer)
oligosaccharide
subunit
20.06.05

Lipid-A
(inner)

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Intervention strategy for Sepsis Therapy

Infection:
Release of toxins

Endotoxin

Translocation
from the gut

Hypoxemia, Burning,
Trauma

Elimination
Elimination of
of septic
septic focus
focus
Anti-infectious
Anti-infectious therapy
therapy

Removal of Endotoxin
and Cytokines by
Extracorporeal Blood
Purification
Systemcircuit

Supportive
Supportive Therapy
Therapy
of
of organ
organ failures
failures

Modified by Cohen J, Nature 2002

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Dr. M. Susca

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Sepsis & SIRS

Infection, hypoxemia, burning, trauma
Monocytes/Macrophages

1.
2.

Pro-inflammatoric cytokines:
TNF, IL-1, IL-6, IL-8, IFN, O-, C3a, C5a, pro-coagulation factors

Anti-inflammatoric counterreaction (immuno-paralysis):

TGF, IL-10

Inactivation of immunity and inflammatory system

Inactivation of Monocytes/Macrophages, O-
SHOCK SIRS MOF
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Conditions for Reduction of Endotoxin and Cytikines by EBPS

Molecular Weight
Protein Binding
Distribution Volume
Endogenous Clearance
Water soluble
Resynthesis
Rebound

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CVVH Continuous veno-venous hemofiltration

heater
PV

BLD
SAD

heparin
V

high-flux

PA

UF

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Dr. M. Susca

8/23

High Volume Haemofitration (HVHF)

B mmHg

high-flux

mmHg

F
B
H2O

S
water soluble molecules

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clearance ml/min
120
Cut-off

Kidney

80

40

HF

IL-8

0
10

102
urea creatinine

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103
Vit. B12

IL-1 IL-6 TNF

104
2-M

105
albumine

Dr. M. Susca

MW dalton

10/23

TNF (U/ml)

IL-1 (pg/ml)

IL-6 (U/ml)

IL-8 (pg/ml)

80
1500

IL-8
60

IL-1

1000

TNF

40

500

IL-6

20

0
0

t/h

Plasma concentrations in sepsis patients durin high-volume HF (Hoffmann, 1997)

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Dr. M. Susca

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Further Clinical Studies

Heering et al. (1997)
Oudemans et al. (1999)
Ronco et al. (2000)
Bellomo et al. (2001):
Convective and adsorbtive Technics like HVHF show better,
but still small extration ofmiddle molecules. Such
adsorption can temporarily reduce the concentration of
some cytokines and complement anaphylatoxins and could
have biological and clinical significans

20.06.05

Dr. M. Susca

12/23

PEX Therapeutic Plasma Exchange

Heater
PV

PPL

BLD

SAC

Heparin

V
V

PA

Plasma Filter

SAD

Pl.

Bilance

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Dr. M. Susca

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PEX in Sepsis Patients

35 patients with Immuno-paralysis (control-group 41 patients)
Deactivated monocytes (HLA-DR-Antigen-Expression)
No. of PEX

3 on 3 following days

Treated Plasmavolume

3 litres

Substitution

FFP

Result: Survival Rate 48% vs. 20%

Conclusion: the recovery of the immuno-competence is
an important condition of good prognosis in sepsis
(Reinke, 1997)

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Dr. M. Susca

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Further Clinical Studies

Berlot et al. (1997)
Exchange of 1 plasma volume.
Improvement of cardiac index and other cardiovascular
parameters.
Reeves et al. (1999)
Continuous exchange of 5 volumes of plasma by FFP,
colloids and cristalloids within 30-36 h.
Reduction of CRP, C3, haptoglobin, 1-antitrypsin, but less
of IL-6, thromboxane B2 and GSF.
Conclusions are not clear!
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Dr. M. Susca

15/23

PAP Plasma Adsorption

Heater
PV

PPL

BLD

Heparin

V
V

PA

Particle Filter

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Dr. M. Susca

Plasma Adsorber

SAC

Plasma Filter

SAD

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Plasma Adsorption/Perfusion (PAP)

Shoji et al. (1998)
Adsortion of Endotoxin by Polymyxin B cartridge.
Ronco et al. (2000)
Coupled Plasma Filtration Adsorption (CPFA) by using
synthetic resin cartridge and haemodialyzer.

Results
Increased cardiovascular resistance, reduction of
vasopressor drugs, improved oxygenesation index, cardiac
index and left ventricular stroke work index.

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Dr. M. Susca

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Selective Adsorption system For Endotoxin (S.A.F.E.)

- Extracorporeal Plasma Perfusion System -

Blood pump
60 120 ml/min
blood leak
Plasma pump
controller
15 30 ml/min

Plasma filter
HEMOSELECT 0,3m

Adsorption column

S.A.F.E.-Column
Material:
Membranous polyamide matrix with
functional groups made from di ethyl
amino ethyl
Binding capacity: > 3.000 ng LPS

air detection and

protection system

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Dr. M. Susca

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S.A.F.E. Adsorber
Principe of Adsorption
Potting

membrane
target
substance

pore

Tentacle:
DEAE-group

Housing
LPS

Plasma
Dead-End Design with Hollow Fibers
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Adsorptive Porous Systems

Dr. M. Susca

Clinical Study:
Elimination and Safety Profile of the Selective Adsorption system for
Endotoxin (S.A.F.E.) in healthy volunteers

Study design
Open prospective study; one study site
6 male healthy volunteers
Part A: In-vitro-adsorption profile from fresh donated heparine
anticoagulated human plasma

Part B: Influence of the S.A.F.E. on vital signs and laboratory parameters

in healthy volunteers
Aim of the study
Essential performance of the adsorption column (in vitro)
Safety of the Medical Device System S.A.F.E. under regular
clinical conditions of two procedures for two days running

20.06.05

Dr. M. Susca

20/23

Diapact CRRT
IV POLE
HIGH
RESOLUTION
SCREEN
WEIGHING
SYSTEM

20.06.05

HEATER
PUMP PANEL

FILTER
HOLDER

Dr. M. Susca

21/23

Diapact CRRT - a versatile system

No other equipment currently on the market offers the same
range of therapy modes as the Diapact CRRT:
Plasma therapies: PEX, PAP
Intermittent therapies: HF, HD, HFD

Continuous therapies: SCUF, CVVH, CVVHD, CVVHFD

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Dr. M. Susca

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Conclusions
A final conclusion on the efficacy of EBPS in treating
sepsis is not possible due to the heterogenous sepsis
petient.
The EBPS shows an effective reduction of endotoxin and
several cytokines.
The EBPS seams to be well tollerated, but side effects
have to be considered.
The treatment by EBPS has shown a clinical improvement
of cardio-circulatory parameters.
Further clinical studies are needed, because a sure
conclusion about any positive influence on mortality rate is
actually not possible yet.

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Dr. M. Susca

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