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Severe sepsis and septic shock Zsolt Molnár University of Szeged AITI

Severe sepsis and septic shock Zsolt Molnár University of Szeged AITI. Definition – 2000 years ago. Hippocrates: Breakdown of living tissues: „pepsis” and „sepsis” Celsus: Rubor Dolor Calor Tumor . Bőrtünetek: diffúz erythema. Definition – 2000 years ago. Hippocrates:

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Severe sepsis and septic shock Zsolt Molnár University of Szeged AITI

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  1. Severe sepsis and septic shockZsolt MolnárUniversity of SzegedAITI

  2. Definition – 2000 years ago • Hippocrates: • Breakdown of living tissues: „pepsis” and „sepsis” • Celsus: • Rubor • Dolor • Calor • Tumor

  3. Bőrtünetek: diffúz erythema

  4. 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

  5. Tumor: generalizált ödéma

  6. 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

  7. 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

  8. From blood poisoning to sepsis • „Sepsis-syndrome” and Las Vegas: • Fever or hypothermia (> 38 oC or < 36 oC) • Tachycardia (>90/min) • Leukocytosis or leukopenia (> 12 000cells/mm3, < 4000cells/mm3, or > 10% immature forms) • Hypotension (<90mmHg) 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

  9. Definitivediagnoses

  10. 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

  11. Why do septic patients get into trouble?

  12. The debt… • DO2= (SV•P) • (Hb•1.39•SaO2+0.003•PaO2) ~ 1000ml/m (SaO2=100%) • VO2 = CO • (CaO2 - CvO2) ~ 250 ml/min (ScvO2~70-75%) CO CaO2

  13. The debt… • DO2= (SV•P) • (Hb•1.39•SaO2+0.003•PaO2) ~ 1000ml/m (SaO2=100%) • VO2 = CO • (CaO2 - CvO2) ~ 250 ml/min (ScvO2~70-75%) • In critical illness: • Shock = VO2>DO2 CO CaO2 VO2 DO2

  14. Supportive therapy

  15. 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 A&E: • Control group (n=133): • O2 • CVP: 8-12 mmHg • MAP >65 mmHg • EGDT group (n=130): • Same goals • ScvO2 > 70% • More fluid and blood • More dobutamine Mortality: 46 vs. 30% (p=0.009)

  16. Hemodynamic support in sepsis • Ohm’s law:

  17. Hemodynamic support in sepsis • Ohm’s 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)

  18. How can we recognise it?

  19. Objective signs of organ dysfunction 0123 4 CNS (GCS) 15 13-14 10-12 7-9 ≤6 CVS (P, inotr., lactate) ≤120 120-140 >140 Inotr. seLactate>5 Resp (PaO2/FiO2) >300 226-300 151-225 76-150 ≤75 Ren (seCreat) ≤100 101-200 201-350 351-500 >500 Liver(seBi)≤ 20 21-60 61-120 121-240 >240 Hemat (TCT) >120 81-120 51-80 21-50 ≤20 • Most frequent early signs: • Arterial hypoxemia: 60% • Arterial hypotension: 57% • Metabolic acidosis: 47% • Atrial fibrillation: >10% • Altered level of consciousness: >10% Cook R et al. Crit Care Med 2001; 29: 2046 Bogár L. Infektológia 2007; 14: 1-6 Low DE, et al. J Gastrointest Surg 2007; 11: 1395

  20. Organ dysfunction and outcome • SOFA scoredinamics and outcome: • 0-1. day • CVS (p=0.0010) • Creat(p=0.0001) • PaO2/FiO2 (p=0.0469) • Se creatincrease and mortality • ~100µmol/24h p<0.05 Levy MM et al. Crit Care Med 2005; 33: 2194 Marshall JC et al. Crit Care Med 1995; 23: 1638

  21. Labortory signs of sepsis • Fever (>38oC), WBC (>12 000): • 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), p<0.05 • Specificity (%): 81(67-90) vs 67(56-67), p<0.05 Simon L et al.Clin Infect Dis 2004; 39: 206

  22. Procalcitonin increase in early identification of critically ill patients at high risk of mortality Jensen JU et al. Crit Care Med2006; 34: 2596-2602 • PCT change/24h • ≥1ng/ml or increasing (alert) • <1ng/ml or decreasing (non-alert)

  23. Procalcitonin increase in early identification of critically ill patients at high risk of mortality Jensen JU et al. Crit Care Med2006; 34: 2596-2602

  24. Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial Nobre V, et al. Am J Respir Crit Care Med. 2008;177:498-505 • PCT vscontrol • PCT-group(afterday 3): • 90% reduction • <0.25 ng/ml 3 vs 5 days 6 vs. 10 days

  25. High postop PCT ≠ sepsis S = 130 NS = 23 * *p<0.05 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

  26. Surviving Sepsis Campaign – 2008 Dellinger RP et al. Intensive Care Med2008; 34: 17-60

  27. Resuscitation, infection Dellinger RP et al. Intensive Care Med2008; 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)

  28. Recommendations Dellinger RP et al. Intensive Care Med2008; 34: 17-60 • Vasopressors, inotropes • Bloos products • Activated protein C (rhAPC) „Xigris” • Glucose control • Steroid • Stb…(85 recommendations)

  29. Therapeutic evidence and outcome

  30. Economic implications of an evidence-based sepsis protocol: Can we improve outcome and lower cost? Shorr AF et al. Crit Care Med2007; 35: 1257 • Módszerek • Retrospective post-hoc analysis • Pre-protocol: 2004-2005 (n=60) • Protocol: 2005-2006 (n=60) • Surviving Sepsis Campaign: • Early AB • EGDT • Vasopressor/inotrope • Transfusion • rhAPC • Corticosteroids

  31. Economic implications of an evidence-based sepsis protocol: Can we improve outcome and lower cost? Shorr AF et al. Crit Care Med2007; 35: 1257 Mortality: 48 vs. 30% (p=0.04)

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

  33. 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

  34. Motto Diagnosis can wait, but cells can’t! It doesn’t matter whether you’ve done the right thing, but whether you’ve done everything to do the right thing

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