Severe sepsis and septic shock Zsolt Moln

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Severe sepsis and septic shock Zsolt
MolnárUniversity of SzegedAITI
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Definition 2000 years ago

• Hippocrates
• Breakdown of living tissues pepsis and
  sepsis
• Celsus
• Rubor
• Dolor
• Calor
• Tumor

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Bortünetek diffúz erythema
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Definition 2000 years ago

• Hippocrates
• Breakdown of living tissues pepsis and
  sepsis
• Celsus
• Rubor - Peripheral vasodilatation
• Dolor - Altered mental status
• Calor - Fever, hypothermia
• Tumor - Oedema

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Tumor generalizált ödéma
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Definition 2000 years ago

• Hippocrates
• Breakdown of living tissues pepsis and
  sepsis
• Celsus
• Rubor - Peripheral vasodilatation
• Dolor - Altered mental status
• Calor - Fever, hypothermia
• Tumor - Oedema
• Galen
• Functio laesa

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Definition 2000 years ago

• Hippocrates
• Breakdown of living tissues pepsis and
  sepsis
• Celsus
• Rubor - Peripheral vasodilatation
• Dolor - Altered mental status
• Calor - Fever, hypothermia
• Tumor - Oedema
• Galen
• Functio laesa - Organ dysfunction

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From blood poisoning to sepsis

• Sepsis-syndrome and Las Vegas
• Fever or hypothermia (gt 38 oC or lt 36 oC)
• Tachycardia (gt90/min)
• Leukocytosis or leukopenia (gt 12 000cells/mm3, lt
  4000cells/mm3, or gt 10 immature forms)
• Hypotension (lt90mmHg)
• Bone RC, et al. N Engl J Med 1987 317 654
• Consensus conference ACCP/SCCM
• Infection
• Bacteraemia
• Systemic inflammatory response syndrome (SIRS)
• Sepsis SIRS Infection
• Severe sepsis (Sepsis one organ dysfunction)
• Septic shock (hypoperfusion despite adequate
  fluid load)
• Multiple System Organ Failure (MSOF)
• ACCP/SCCM. Crit Care Med 1992 20 864

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Definitive diagnoses
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Pathomechanism
I n s u l t Endotoxin, Trauma, Sterile
inflammation, Operation, etc.
Humoral activity Interferon, Complement
M a c r o p h a g e s TNF IL-1,6,10 PAF
P M N FR, PAF, Chemotaxis
Fisiol. reactions Fever, Metabolic changes
E n d o t h e l NO, E-selectin, NFkB
Sepsis, SIRS
MSOF
Molnár and Shearer Br J Int Care Med 1998 8 12
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Why do septic patients get into trouble?
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The debt

• DO2 (SVP) (Hb1.39SaO20.003PaO2)
  1000ml/m (SaO2100)
• VO2 CO (CaO2 - CvO2) 250 ml/min
  (ScvO270-75)

CO
CaO2
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The debt

• DO2 (SVP) (Hb1.39SaO20.003PaO2)
  1000ml/m (SaO2100)
• VO2 CO (CaO2 - CvO2) 250 ml/min
  (ScvO270-75)
• In critical illness
• Shock VO2gtDO2

CO
CaO2
VO2
DO2
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Supportive therapy
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Early supportive treatment

• Early Goal-Directed Therapy (EGDT)
• Rivers E et al. N Engl J Med 2001 345 1368
• Septic patients treated for 6 hours in AE
• Control group (n133)
• O2
• CVP 8-12 mmHg
• MAP gt65 mmHg
• EGDT group (n130)
• Same goals
• ScvO2 gt 70

• More fluid and blood
• More dobutamine

Mortality 46 vs. 30 (p0.009)
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Hemodynamic support in sepsis

• Ohms law

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Hemodynamic support in sepsis

• Ohms law

• Severe sepsis, septic shock
• Vasodilatation SVR (MAP) low, CO high
• DO2/VO2 high
• Invasive haemodynamic monitoring
• Arterial central venous line
• Pulmonary artery catheter (Swan-Ganz)
• Arterial thermodylution (PiCCO)

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How can we recognise it?
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Objective signs of organ dysfunction
0 1 2 3 4 CNS (GCS) 15 13-14 10-12 7-9
6 CVS (P, inotr., lactate) 120 120-140 gt140 Inot
r. seLactategt5 Resp (PaO2/FiO2) gt300 226-300 151-2
25 76-150 75 Ren (seCreat) 100 101-200 201-350
351-500 gt500 Liver (seBi) 20 21-60 61-120 121
-240 gt240 Hemat (TCT) gt120 81-120 51-80 21-50
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Cook R et al. Crit Care Med 2001 29 2046

• Most frequent early signs
• Arterial hypoxemia 60
• Arterial hypotension 57
• Metabolic acidosis 47
• Atrial fibrillation gt10
• Altered level of consciousness gt10

Bogár L. Infektológia 2007 14 1-6
Low DE, et al. J Gastrointest Surg 2007 11 1395
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Organ dysfunction and outcome

• SOFA score dinamics and outcome
• 0-1. day
• CVS (p0.0010)
• Creat (p0.0001)
• PaO2/FiO2 (p0.0469)
• Se creat increase and mortality
• 100µmol/24h plt0.05

Levy MM et al. Crit Care Med 2005 33 2194
Marshall JC et al. Crit Care Med 1995 23 1638
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Labortory signs of sepsis

• Fever (gt38oC), WBC (gt12 000)
• Low sensitivity (50)
• Galicier L and Richet H. Infect Control Hosp
  Epidemol 1985 6 487
• Blood culture
• Early results after 24 h only
• Low sens/spec, especially in pneumonia caused
  sepsis (30)
• Meakins JL. In Crit Care State of the Art 1991
  12 141
• Luna CM et al. Chest 1999 116 1075
• TNF-?, IL-6,1,8
• Short half life
• Expensive tests
• Serum procalcitonin (PCT), C-reaktive protein
  (CRP)
• Senzitivity () 88(80-93) vs 75(62-84), plt0.05
• Specificity () 81(67-90) vs 67(56-67), plt0.05
• Simon L et al. Clin Infect Dis 2004 39 206

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Procalcitonin increase in early identification of
critically ill patients at high risk of mortality
Jensen JU et al. Crit Care Med 2006 34 2596-2602

• PCT change/24h
• 1ng/ml or increasing (alert)
• lt1ng/ml or decreasing (non-alert)

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Procalcitonin increase in early identification of
critically ill patients at high risk of mortality
Jensen JU et al. Crit Care Med 2006 34 2596-2602
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Use of procalcitonin to shorten antibiotic
treatment duration in septic patients a
randomized trial
Nobre V, et al. Am J Respir Crit Care Med.
2008177498-505

• PCT vs control
• PCT-group (after day 3)
• 90 reduction
• lt0.25 ng/ml

3 vs 5 days
6 vs. 10 days
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High postop PCT ? sepsis
S 130 NS 23

plt0.05
Data are presented as minimum, maximum, 25-75
percentile and median. For statistical analysis
Mann-Whitney U test was used.
Szakmány T, Molnár Z. Can J Anaesth 2003 50
1082-3 Molnár Z, Bogár L. Crit Care Med 2006 34
2687-8
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Surviving Sepsis Campaign 2008 Dellinger RP et
al. Intensive Care Med 2008 34 17-60
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Resuscitation, infection
Dellinger RP et al. Intensive Care Med 2008 34
17-60

• EGDT
• Chrystalloid or colloid (1B)
• Diagnosis
• 2/more immediate blood cultures (1C)
• Immediate radiology (1C)
• Antibiotics
• Within 1 h in severe sepsis (1D), septic shock
  (1B)
• Broad spectrum ABs (1B)
• De-escalation strategy (2D)
• Stop ABs in case of infection is not proven (1D)

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Recommendations
Dellinger RP et al. Intensive Care Med 2008 34
17-60

• Vasopressors, inotropes
• Bloos products
• Activated protein C (rhAPC) Xigris
• Glucose control
• Steroid
• Stb(85 recommendations)

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Therapeutic evidence and outcome
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Economic implications of an evidence-based sepsis
protocol Can we improve outcome and lower cost?
Shorr AF et al. Crit Care Med 2007 35 1257

• Módszerek
• Retrospective post-hoc analysis
• Pre-protocol 2004-2005 (n60)
• Protocol 2005-2006 (n60)
• Surviving Sepsis Campaign
• Early AB
• EGDT
• Vasopressor/inotrope
• Transfusion
• rhAPC
• Corticosteroids

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Economic implications of an evidence-based sepsis
protocol Can we improve outcome and lower cost?
Shorr AF et al. Crit Care Med 2007 35 1257
Mortality 48 vs. 30 (p0.04)
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Summary

• Severe sepsis mortality can be reduced!
• Recognition
• Rationalised clinical and biochemical
  investigations
• Prevention
• Oxygen fluid monitoring (EGDT ScvO2)
• Treatment
• EBM

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Summary

• Severe sepsis mortality can be reduced!
• Recognition
• Rationalised clinical and biochemical
  investigations
• Prevention
• Oxygen fluid monitoring (EGDT ScvO2)
• Treatment
• EBM

• Sepsis
• Less of a diagnosis
• more like a concept

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Motto
Diagnosis can wait, but cells cant!
It doesnt matter whether youve done the right
thing, but whether youve done everything to do
the right thing