Leber bei TPE und Kurzdarmsyndrom

Der Darm als zentrales Sepsisorgan
H. Lochs
Medizinische Klinik mit
Schwerpunkt Gastroenterologie,
Hepatologie und Endokrinologie
[email protected]
Oberfläche 300m²
Nervenzellen 108
Bakterien 1014
Immunzellen 50%
Blutfluss 25 - 40%
Energieumsatz 40%
Proteinsynthese 50%
Funktionen des Darmes
• Resorption
– 10-12 l Wasser, Elektrolyte, 2- 300 kcal,
50 – 100 g Protein
• Sekretion
– 7- 8 l Wasser, Elektrolyte, 1 Liter 1N HCl,
Bicarbonat Enzyme, IgA, Mucine, Hormone
• Motilität, Sensorik, Vasomotorik
• Barriere, Immunfunktionen
Proteinsynthese g/Tag
• Gesamtorganismus 350
•
•
•
•
•
•
Magen- Darmtrakt
Leber, Niere, Muskel
Leukozyten
Plasma
Haut
Hämoglobin
150
100
50
20
10
8
Darm bei Sepsis
• Persfuion bei Sepsis
– Ischämie, NO Produktion
• Darm als Sepsisauslöser
– Aspiration, Translokation
• Immunreaktion und Darm
– Zytokinesekretion
Intestinal Blood Flow in Sepsis
Hiltebrand et. al. Crit. Care Med 2000
Intestinal Blood Flow in Sepsis
Hiltebrand et. al. Crit. Care Med 2000
Intestinaler Blutfluss – Sepsis
Krejci et al.Crit. Care Med. 2006
Intestinaler Blutfluss –Beatmung
Putensen et al. Curr. Op. Crit. Care 2006
Intestinale Glukosekonzentration
bei reduziertem Blutfluss
Krejci et al. Crit. Care Med. 2006
iNOS Expression in different Organs
Bultink et al. FASEB 2006
Wild Type/iNOS deficient mice, BMT and Salmonella stimulation
C TNF LPS BCG
C
Brush Border Enzyme
bei kritisch Kranken
300
Critically Ill ( n = 14 )
Units/g Protein
250
Controls ( n = 16 )
200
150
100
50
0
Sucrase
Maltase
Alkaline Pase
Intestinal Permeability in ICU
Johnston et. al., Crit. Care Med. 1996
Enteral Nutrition and Permeability
Alscher et. al., AJP 2001
Secretory IgA - Effect of
Starvation and Steroid Stress
Spitz et. al., Crit. Care Med 1996
IgA and bacterial
Adherence
Spitz et al, Crit Care Med 1996
The gut as origin of sepsis
MacFie et al, GUT, 1999
n = 279 surgical patients
Comparison of bacterial species in gastric aspiration,
mesenteric lymph nodes and postoperative sepsis
• Translocation was found in 59 pts (21%)
• Most common organism in lymph nodes was E. coli (48%)
Genetic Identity was found:
• Nasogastric aspirate and septic focus (30%)
• Nasogastric aspirate and lymph node (31%)
• Lymph nodes and septic focus (45%)
Gastric pH and Sepsis
Macfie et al., BJS 2006
Fecal Organic Acids in SIRS
Shimizu et al. J. Trauma 2006
Fecal Flora in SIRS vs. Normal
Shimizu et al. J. Trauma 2006
Effect of VSL3
on TNF Production
in Mice
Madsen et. al Gastro 2002
Darm bei Sepsis
•
•
•
•
Perfusion bei Sepsis
Darm als Sepsisauslöser
Immunreaktion und Darm
Therapeutische Konsequenzen?
– Enterale Ernährung
– Spezielle Substrate
– Probiotika
Enterale Ernährung –
Effekt auf Mucosaoxygenierung
Braga et. al., Crit. Care Med. 2001
Enteral Nutrition – IgA
Ohta et. al. A.J.Surg
parenteral
enteral
2003
Bakterien in Rektumbiopsien bei ITS Patienten
Klarin et al. Crit Care 2005
Kontrolle vs. Lactobac. 299v
Lactobacillus – Infections after LTX
Group1
SBD
(n=32)
Patients with
15
infections ( n )
Group 2
Lactobacillus
( n = 31 )
4
Group 3
Placebo
( n=32 )
11
p
0,017
ICU days
15,7±12
11,7 ±7
13,5 ±12
n.s.
Hospital days
39 ±5
35 ±2,4
36 ±2,7
n.s.
7 ±7
12 ±18
n.s.
12 ±17
Antibiotic
therapy (days)
Rayes et. al. Transplantation 2002
Synbiotika bei kritisch Kranken
Jain et. al. Clin. Nutr. 2004
Enteral Nutrition
intestinal Barrier in hemorrhagic Shock
Luyer et. al. Shock 2004
Starved
16,7% Fat
52,2% Fat
Glutamine in critically ill - LOS
Novak et. al. Crit. Care Med. 2003
Immunonutrition in critically ill
Beale et al, Crit Care Med 1999
Gut Dysfunction after Cardiac Arrest
L‘Her et al., Resuscitation 2005
Darm bei Sepsis
• Sepsisfolge und
Sepsisursache
• Durchblutung kritisch
• Resorption und
Barriere eingeschränkt
• Enterale Ernährung
sinnvoll
• Spezielle Substrate
– Glutamin
– Immunonutrition
• Probiotika?
NO Production in Septic Shock
Bultink et al. FASEB 2006
Wild Type/iNOS deficient mice, BMT and Salmonella stimulation
Fecal Flora in SIRS
Shimizu et al. J. Trauma 2006
Bacterial Translocation- Risk Factors
Macfie et al., BJS 2006
Stress and bacterial Adherence
Söderholm et. al. Gastro 2002
Secretory IgA - Effect of
Starvation and Steroid Stress
Spitz et. al., Crit. Care Med 1996
IgA and bacterial Adherence
Spitz et al, Crit Care Med 1996
Mucosal biofilm in CHF
Bauditz & Swidsinski et al., DDW 2006, Poster # M1168
Low colonised
large intestinal mucosa
Controls
Highly colonised
large intestinal mucosa
Chronic heart failure
Enteral Nutrition – IgA
Ohta et. al. A.J.Surg
parenteral
enteral
2003
Lactobacillus – Infections after
LTX
Group1
SBD
(n=32)
Patients with
15
infections ( n )
Group 2
Lactobacillus
( n = 31 )
4
Group 3
Placebo
( n=32 )
11
p
0,017
ICU days
15,7±12
11,7 ±7
13,5 ±12
n.s.
Hospital days
39 ±5
35 ±2,4
36 ±2,7
n.s.
7 ±7
12 ±18
n.s.
12 ±17
Antibiotic
therapy (days)
Rayes et. al. Transplantation 2002
Effect of Bacteria on tight junctions
Otte et. al. AJP 2004
Control
S. Dublin
Pretreatment
E. Coli Nissle
Effect of VSL3
on TNF Production
in mice
Madsen et. al Gastro 2002
Inhibition of IFNγ Secretion by
Bacterial DNA in Colon
Jijon et. al. Gastro 2004
Enterale Ernährung –
Effekt auf Mucosaoxygenierung
Braga et. al., Crit. Care Med. 2001
Effect of SDD on Infections
Stoutenbeek et al. Int. Care Med. 2007
Trauma Patients,
no difference in long term mortality
n=201
n=200
Effect of SDD on inflammatory reaction
Horton et al., J. Appl. Phys. 2007
Rats, Burn + intratracheal S. pneumoniae, Cardiac myocyte cytokine production
Effect of SDD on inflammatory reaction
Horton et al., J. Appl. Phys. 2007
Rats, Burn + intratracheal S. pneumoniae, Left ventricular function
Enteral Nutrition
Effect on intestinal
Enzyme Activation
In sepsis
Alscher et. al., AJP 2001
Fecal Organic Acids in SIRS vs. Normal
Shimizu et al. J. Trauma 2006
Fecal Organic Acids in SIRS vs. Normal
Shimizu et al. J. Trauma 2006
Antioxydants and
outcome in ICU
Nathens et. al., Ann. Surg 2002
Pneumonia
595
595patients,
patients,91%
91%trauma
trauma
Standard
Standardtherapy
therapyvs.
vs.
Supplementation
Supplementationof
of
1000IU
1000IUTocopherol+
Tocopherol+
1000mg
1000mgVit.
Vit.C.
C.q8h
q8h
MOF
Oberfläche 300m²
Nervenzellen 108
Bakterien 1014
Immunzellen 50%
Blutfluss 25 - 40%
Energieumsatz 40%
Proteinsynthese 50%
Stoffwechseltherapie
Pathophysiologie von Stoffwechselstörungen
¾ Stoffwechseltherapie der Katabolie
¾ Kritisch Kranke
¾ Geriatrie und chronisch Kranke
¾ Therapie des metabolischen Syndroms
¾ Komplikationen des Diabetes, Adipositas
¾ Workshop Bioelektrische Impedanzanalyse
¾ Kurs ambulante enterale
Ernährungstherapie
www.dgem.de
Programme an der Registrierung
Lp 299v in ICU
Mc. Naught et al. Clin. Nutr. 2005
Critically Ill patients,
n= 103,
Proviva vs. Placebo,
no difference
in outcome and
inflammatory
parameters
Bacterial Translocation and Sepsis
Macfie et al., BJS 2006
Bakterien in Rektumbiopsien bei ITS Patienten
Klarin et al. Crit Care 2005
Kontrolle vs. Lactobac. 299v
Effect of Probiotics on Intestinal Barrier
in S. Dublin infection, Otte et. al. AJP 2004
Intestinal Blood Flow in Shock
Tsakadse et al. Surg. 2006
Isotonic
Red cells
Hypertonic
Hypertonic
Red cells
Hypertonic
Isotonic
Glutamine in critically ill - Mortality
Novak et. al. Crit. Care Med. 2003
Probiotika ICU – Risiko
• Saccharomyces Sepsis
(P. Munoz et al. Clin. Infect. Dis. 2005)
– 60 Fälle beschrieben, 17 verstorben
– 60% auf ITS
– 71% an PE oder EE
– 43% Probiotika
– Bei 3 Fällen identer Keim in Probiotikum und
Blutkultur
– Auch bei Nachbarpatienten!
(Cassone et al. J. Clin. Microbiol. 2003)
Probiotika ICU – Risiko
• Lactobacillen
– 89 Fälle,1 Monat Mortalität 26%,
prädisponierende Faktoren unklar
( Salminen et al. Clin. Infect. Dis. 2004 )
– 2 Sepsisfälle bei Kindern mit
identifiziertem Keim
(Land et al. Pediatrics 2005 )
Probiotics in critically Ill
McNaught et al. Clin. Nutr. 2005
Endotoxemia in chronic heart disease
Sharma R et al, Am J Cardiol 2003; 92: 188-193
Intestinal Permeability in ICU
Johnston et. al., Crit. Care Med. 1996
1.5
12
10
8
r= 0.49
p=
0.045
6
0
0 1
2
3
4
5 6
wall thickness [mm]
hs CrP (log [µg/mL])
blood leucocytes [1000 /µL]
Bowel wall thickness and
inflammation in CHF
r= 0.57
p= 0.005
1
0.5
0
0
1
2
3
4
5
wall thickness [mm]
Bauditz J et al., DDW 2006, Poster # M1168
6
Interaktion Bakterien Darm
Alverdy et al., Curr. Op. Clin Nutr. Metab. 2005
Synbiotika bei selektiver Abdominalchirurgie
Anderson et. al. Gut, 2004
Synbiotika auf ITS ( n= 90 )
Einfluss auf Intestinale Permeabilität
Jain et al. Clin. Nutr. 2004
Lp 299v in ICU
Mc. Naught et al. Clin. Nutr. 2005
Critically Ill patients, n= 103, Proviva vs. Placebo,
no difference in outcome and inflammatory paramters
Gut Sepsis Hypothesis
Gatt et al., APT, 2007
Intestinaler Blutfluss – Sepsis
Dubin et al. Int. Care Med. 2007
Der Darm in der Intensivmedizin
Darm – ITS
Resorption
Immunorgan
Barriere
Gut Sepsis
Parenterale
Ernährung
1970
1980
Bakterien
NO Produktion
Kreislauf
Immuno
nutrition
Enterale
Ernährung
1990
Functional
Food
Probiotika
2000
2007