AA new diagnostic concept fornew diagnostic concept for

trauma patientstrauma patients onon thethe ICUICU regarding differentiation regarding differentiation

betweenbetween

inflammationinflammation andand infectioninfection

Prof. Dr. Dr. Martijn van Griensven, MD PhDProf. Dr. Dr. Martijn van Griensven, MD PhD

TRAUMA AUVA

Ludwig Boltzmann Institute for experimental and clinical traumatologyLorenz Böhler Trauma Hospital

early MODS

TraumaTrauma

mild SIRSmild SIRS

mild mild immunesuppressionimmunesuppression

severesevere SIRSSIRS

severesevere

immunesuppressionimmunesuppression

infectionsinfections lateMODS

EarlyEarly and and latelate phasephase immune immune reactionreaction

Döcke, Volk Tx Med 1997

SIRS

MODS

† survival

25-30% ICU patients50-80% mortality

Sepsis

Diagnosis of ≥ 2 following symptomsRectal temperature >38°C or <36°C

HF >90 beats per minuteAF >20 per minute or paCO2 <4,3kPaLeuco >12000/mm3 or <4000/mm3 or 10% preliminary

SIRSSIRS

sepsissepsis

severe Sepsissevere Sepsis

MODSMODS

SIRS with:documented infection

SIRS with:documented infectionand hemodynamic instability

physiological dysbalance, in which the organ function is not able to obtain homoeostasis

Time Time coursecourse of of organorgan failurefailure

11 22 33 weeksweeks

lung

liver

cardiovascular

kidney

�

ECG

Temperature

Ventilation parameter

RR, CVP

Blood drawing

DiagnosticsDiagnostics

primaryprimary

PROPRO--INFLAMMATORYINFLAMMATORY

REACTIONREACTION

TNFTNF--αα

ILIL--11

problem: Short half life

Undulating levels

sekundarysekundary

PROPRO

INFLAMMATORYINFLAMMATORY

REACTIONREACTION

ILIL--66

ILIL--88

ANTIANTI

INFLAMMATORYINFLAMMATORY

REACTIONREACTION

IL-10

IL-1RA

Good half life

Stabile levels

Do parameter exist that Do parameter exist that

have a prognostic value have a prognostic value

for SIRS and sepsis in a for SIRS and sepsis in a

differential waydifferential way

InclusionInclusion criteriacriteria

ISS ≥ 18

primary admission

16<age<70

survival > 3 days

ParameterParameter

ILIL--6/IL6/IL--1010

LBP/PCTLBP/PCT

SIRS/Sepsis

MODS

14 days observation

interleukininterleukin--66

0

1000

2000

3000

4000

5000

6000

7000

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

time after trauma (days)

[IL-6

] (pg/ml)

non-survivors (n = 20)

survivors (n = 160)

InterleukinInterleukin--66

ProPro--inflammatoryinflammatory

0

2000

4000

6000

8000

10000

12000

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

time after trauma (days)

[IL-6

] (pg/ml)

+MODS

-MODSMODS

InterleukinInterleukin--66

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

1 3 7 14

Days after trauma

[IL-6] (pg/m

l)

- complications (n = 130)

+ complications (n = 50)

*

*

IL-6 and MODS

ILIL--6 6 ↑↑↑↑↑↑↑↑ 22--3 3 daysdays beforebefore MODSMODS

CRP and MODSCRP and MODS

0

100

200

300

400

500

600

700

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

days after Trauma

[CRP] (mg/ml)

MODS

IL-6 and CRP

ILIL--6 6 ↑↑↑↑↑↑↑↑ 11--2 2 daysdays earlierearlier thanthan CRP CRP ↑↑↑↑↑↑↑↑

InterleukinInterleukin--66

SepsisSepsis

**

* * *

*

0

200

400

600

800

1000

1200

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Time after trauma (days)

[IL-6

] (pg/ml) +Sepsis (n=11)

-Sepsis (n=54)

IL-6 is a prognostic factorfor MODS and †

IL-6 1-2 days earlier than CRP

However, IL-6 ↑ during sepsis

ILIL--66 asas a a diagnosticdiagnostic tooltool

0

10

20

30

40

50

60

70

80

90

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Time after trauma (days)

[IL-1

0] (pg/ml)

+MODS (n=11)

-MODS (n=54)

ILIL--1010

MODSMODS

MODS

*

**

ILIL--1010

SepsisSepsis

**

**

**

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Time after trauma (days)

[IL-1

0] (pg/ml)

+Sepsis (n=11)

-Sepsis (n=54)

ILIL--1010

**

*

**

0

10

20

30

40

50

60

70

80

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Time after trauma (days)

IL-1

0 in pg/ml

Non-survivors

survivors

Endotoxin, or its components

can elicit septical complications

Schuster Med.Klin. 1989

ENDOTOXINENDOTOXIN

LBPLBP

CD14CD14

LipopolysaccharidLipopolysaccharid Binding ProteinBinding Protein

LBPLBP BPIBPI LPSLPS

11 22 33 44

TLR4TLR4

macrophagemacrophage

LBPLBP

LBP correlates with LPS concentration

Therefore, LBP correlates with the presence of bacteria

[LBP] is associated with the severity of sepsis

LBPLBP--levelslevels

0

20

40

60

80

100

120

140

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Time after trauma (days)

[LBP] (µg/ml)

+Sepsis (n=11)

-Sepsis (n=54)

LBPLBP

sepsissepsis afterafter traumatrauma

LBPLBP

SIRS vs. SepsisSIRS vs. Sepsis

Sepsis

*

** *

* *

*

* *

* * * *

0

20

40

60

80

100

120

140

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

time after trauma (days)

[LBP] (µg/ml)

+SIRS-Sepsis

+Sepsis (n=11)

0

50

100

150

200

250

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Time after trauma (days)

LBP in µ

g/m

l non-survivors

survivors

LBPLBP

LBPLBP

Increase and plateau during sepsis

During SIRS moderately increased

Helps differentiating SIRS vs. Sepsis

PCTPCT

MODSMODS

*

*

*

**

* * **

** *

0

5

10

15

20

25

30

35

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Time after trauma (days)

[PCT] (ng/ml)

+MODS (n=11)

-MODS (n=54)

PCTPCT

SepsisSepsis

*

*

**

0

5

10

15

20

25

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Time after trauma (days)

[PCT] (ng/ml)

+Sepsis (n=11)

-Sepsis (n=54)

PCTPCT

*

** *

*

*

* *

0

1

2

3

4

5

6

7

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Time after trauma (days)

[PCT] (ng/ml)

Non-survivors

survivors

conclusionconclusion

∅ Differentiation for the cause of MODS

IL-10 ↑ during MODS?

LBP follows the kinetics of sepsis

PCT early (per se in soft tissue trauma?)

IL-6 and LBP help to differentiate SIRS and Sepsis

WhatWhat doesdoes a a traumatrauma surgeonsurgeon do do

withwith thisthis informationinformation??

Treat early !

11 22 33 weeksweeks

InterleukinInterleukin--66

OperationsOperations

PTFF = polytrauma + femoral fracture (n = 40)IFF = isolated femoral fracture (n = 20)THA = total hip arthroplasty (n = 15)AF = ankle fracture (n = 15)

InterleukinInterleukin--66

FemoralFemoral fracturefracture in Polytraumain Polytrauma

Pre-OP 7h 24h 48h

(n = 30) (n = 25)

DamageDamage controlcontrol

2nd-4th day: vulnerable Phase(IL-6 increases!)

Postpone secondary surgery

Don‘t overactivate the immune system!

Watch the threshold!

early IL-6 Monitoring!