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Septic Shock
pathophysiology
basics
Dr.T.V.Rao MD
Dr.T.V.Rao MD 1
Background
• In 1914, Schottmueller
wrote, “Septicaemia is a
state of microbial invasion
from a portal of entry into
the b...
Definition of Septic Shock
• Septic shock is a medical condition as a result of
severe infection and sepsis, though the mi...
Shock: Types
• Hypovolemic
• Septic (high CO, low SVRI)
• Cardiogenic (high CVP)
• Neurogenic
• Anaphylactic
• Adrenal ins...
Definitions
• Infection: microbial phenomenon
characterised by an inflammatory response to
the presence of micro organisms...
Definition
• Shock:- When the cardiovascular system fails to deliver
enough oxygen and nutrients to meet cellular
metaboli...
Infection, SiRS, Sepsis
Bone, R., Balk, R., Cerra, F., Dellinger, R., Fein, A., Knaus, W., Schein, R., et al. (1992). Defi...
Causes of Septic Shock
• As mentioned any type of bacteria in the bloodstream
causes septic shock and this can occur from ...
Clinical Spectrum of Infection
Infection
Sepsis
Severe Sepsis
Septic Shock
Bacteremia
Dr.T.V.Rao MD 9
Aetiology of Septic shock
• When bacteria or viruses are present in the bloodstream, the
condition is known as bacteraemia...
Systemic inflammatory response syndrome
(SIRS)
• Systemic inflammatory response syndrome (SIRS) is a term that
was develop...
Some Characteristics of
Septic Shock
• Systemic vasodilation and hypotension
• Tachycardia; depressed contractility
• Vasc...
Terminology
Systemic Inflammatory Response Syndrome (SIRS)
Temp > 38 or < 36
HR > 90
RR > 20 or PaCO2 < 32
WBC > 12 or < 4...
Changing criteria of sepsis
• With sepsis, at least 1 of the following manifestations
of inadequate organ function/perfusi...
Pathophysiology
• The nidus of infection:
–Localized infections (
otitis, pneumonia, meningitis etc.,)
–Colonization of mu...
Causes of Septic Shock
• As mentioned any type of bacteria in the bloodstream
causes septic shock and this can occur from ...
Infection
Parasite
Virus
Fungus
Bacteria
Trauma
Burns
Sepsis SIRSSevere
Sepsis
Severe
SIRS
Adapted from SCCM ACCP Consensu...
Where’s the infection ?
Abdomen
15%
Culture
Negative
20%
Lung
47%
Urine
10%
Other
8%
Bernard & Wheeler NEJM 336:912, 1997 ...
What’s the infection?
0
10
20
30
40
50
60
70
80
Gram pos Gram neg Fungal
Early
Late
Pure isolates, total n = 444 pts, 61% ...
Septic Shock
• Septic shock- once a
uniformly fatal
condition with 100%
mortality.
• Present recovery rates
are up to 50%....
Bacterial infection
Sepsis and septic shock
Excessive host response
Host factors lead to cellular damage
Organ damage
Death
How likely is it that the diagnosis of sepsis
is being missed? Is it...
17%
27%
51%
2%
0%
3%
0%
1%
16%
51%
29%
3%Extremely...
Microbial Triggers
• Gram-negative bacteria:
• lipopolysaccharide
• Gram-positive bacteria Lipoteichoic
• acid/cell wall m...
Pathogenesis of Septic Shock
LPS LBP
LPS
ENDOTHELIAL CELL
Bacteria
LPS
LBP LPS
CD 14
MONOCYTE
soluble CD 14
TNF-A
Journal ...
Management of Sepsis
• Recognition
• Supportive care
• Source control
• Antibiotics
• Specific (adjunctive) therapy
Issues in the rational choice of
antibiotics
EFFICACY
• Spectrum of activity
• Pharmacokinetics & pharmacodynamics
• Patte...
Choosing antibiotics in sepsis
• There is no, single, “best” regimen
• Consider the site of the infection
• Consider which...
“Non-antibiotic” therapy for sepsis
• Low dose steroids
• Intensive insulin therapy
– tight glycaemic control
• Activated ...
Shock: Realize the Facts
• Shock = inadequate tissue perfusion
• Types of shock:
hypovolemic, septic, cardiogenic, neurog
...
Best of the References
• Sepsis and Septic Shock, 2008 Prof J Cohen
Dr.T.V.Rao MD 31
Dedicated Hand Washing Continues to Save
Many Lives in Critical Care
Dr.T.V.Rao MD 32
Brave and Committed Nurses, Doctors
Save Many Lives in spite of Shock
Dr.T.V.Rao MD 33
• Programme Created by Dr.T.V.Rao MD
for Basic understanding in Septic Shock
for Medical Students in the Developing
World
...
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Septic shock Pathophysiology

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  1. 1. Septic Shock pathophysiology basics Dr.T.V.Rao MD Dr.T.V.Rao MD 1
  2. 2. Background • In 1914, Schottmueller wrote, “Septicaemia is a state of microbial invasion from a portal of entry into the blood stream which causes sign of illness.” The definition did not change much over the years, because the terms sepsis and septicaemia referred to several ill-defined clinical conditions present in a patient with bacteraemia. Dr.T.V.Rao MD 2
  3. 3. Definition of Septic Shock • Septic shock is a medical condition as a result of severe infection and sepsis, though the microbe may be systemic or localized to a particular site. It can cause multiple organ dysfunction syndrome (formerly known as multiple organ failure) and death. Its most common victims are children, immunocompromised individuals, and the elderly, as their immune systems cannot deal with the infection as effectively as those of healthy adults. Frequently, patients suffering from septic shock are cared for in intensive care units. The mortality rate from septic shock is approximately 25–50%.Dr.T.V.Rao MD 3
  4. 4. Shock: Types • Hypovolemic • Septic (high CO, low SVRI) • Cardiogenic (high CVP) • Neurogenic • Anaphylactic • Adrenal insufficiency Dr.T.V.Rao MD 4
  5. 5. Definitions • Infection: microbial phenomenon characterised by an inflammatory response to the presence of micro organisms or the invasion of normally sterile host tissue by these organisms • Bacteraemia: the presence of bacteria in the bloodstream •Septicaemia: no longer used ACCP/SCCM Consensus Conference: Bone et al, Chest 1992 101:1644 Dr.T.V.Rao MD 5
  6. 6. Definition • Shock:- When the cardiovascular system fails to deliver enough oxygen and nutrients to meet cellular metabolic needs. • Sepsis:- Presence of bacteria in the blood stream. • Septic Shock:- Begins with the development of septicaemia usually from bacterial infections, but can be viral in origin. This is the most common type of Distributive Shock. Dr.T.V.Rao MD 6
  7. 7. Infection, SiRS, Sepsis Bone, R., Balk, R., Cerra, F., Dellinger, R., Fein, A., Knaus, W., Schein, R., et al. (1992). Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest, 101(6), 1644–1655. Dr.T.V.Rao MD 7
  8. 8. Causes of Septic Shock • As mentioned any type of bacteria in the bloodstream causes septic shock and this can occur from many infections, for example:  The pope died from septic shock caused by a urinary infection  Simon has a chest infection  Other common reasons according to Collins (2000) are, major abdominal surgery and an invasive catheter. Dr.T.V.Rao MD 8
  9. 9. Clinical Spectrum of Infection Infection Sepsis Severe Sepsis Septic Shock Bacteremia Dr.T.V.Rao MD 9
  10. 10. Aetiology of Septic shock • When bacteria or viruses are present in the bloodstream, the condition is known as bacteraemia or Viremia. Sepsis is a constellation of symptoms secondary to infection that manifest as disruptions in heart rate, respiratory rate, temperature and WBC.. Once severe sepsis worsens to the point where blood pressure can no longer be maintained with intravenous fluids alone, then the criteria have been met for septic shock. The precipitating infections which may lead to septic shock if severe enough include appendicitis, pneumonia, bacteraemia, diverticulitis, pyelonephritis, meningitis, pancreatitis, and necrotizing fasciitis. Dr.T.V.Rao MD 10
  11. 11. Systemic inflammatory response syndrome (SIRS) • Systemic inflammatory response syndrome (SIRS) is a term that was developed in an attempt to describe the clinical manifestations that result from the systemic response to infection. Criteria for SIRS are considered to be met if at least 2 of the following 4 clinical findings are present: • Temperature greater than 38°C (100.4°F) or less than 36°C (96.8°F) • Heart rate (HR) greater than 90 beats per minute (bpm) • Respiratory rate (RR) greater than 20 breaths per minute or arterial carbon dioxide tension (PaCO2) lower than 32 mm Hg • White blood cell (WBC) count higher than 12,000/µL or lower than 4000/µL, or 10% immature (band) forms Dr.T.V.Rao MD 11
  12. 12. Some Characteristics of Septic Shock • Systemic vasodilation and hypotension • Tachycardia; depressed contractility • Vascular leakage and oedema; hypovolemic • Compromised nutrient blood flow to organs • Disseminated intravascular coagulation • Abnormal blood gases and acidosis • Respiratory distress and multiple organ failure Dr.T.V.Rao MD 12
  13. 13. Terminology Systemic Inflammatory Response Syndrome (SIRS) Temp > 38 or < 36 HR > 90 RR > 20 or PaCO2 < 32 WBC > 12 or < 4 or Bands > 10% Sepsis The systemic inflammatory response to infection. Severe Sepsis Organ dysfunction secondary to Sepsis. e.g. hypoperfusion, hypotension, acute lung injury, encephalopathy, acute kidney injury, coagulopathy. Septic Shock Hypotension secondary to Sepsis that is resistant to adequate fluid administration and associated with hypoperfusion. Bone, R., Balk, R., Cerra, F., Dellinger, R., Fein, A., Knaus, W., Schein, R., et al. (1992). Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest, 101(6), 1644–1655. TWO out of four criteria acute change from baseline Dr.T.V.Rao MD 13
  14. 14. Changing criteria of sepsis • With sepsis, at least 1 of the following manifestations of inadequate organ function/perfusion is typically included: • Alteration in mental state • Hypoxemia (arterial oxygen tension [PaO2] < 72 mm Hg at fraction of inspired oxygen [FiO2] 0.21; overt pulmonary disease not the direct cause of hypoxemia) • Elevated plasma lactate level • Oliguria (urine output < 30 mL or 0.5 mL/kg for at least 1 h) Dr.T.V.Rao MD 14
  15. 15. Pathophysiology • The nidus of infection: –Localized infections ( otitis, pneumonia, meningitis etc.,) –Colonization of mucosal and invasion ( Hib, menigococci) –Occult bacteremia ( 3mo to 3 years ) –Nosocomial : ‘at risk patients’ Dr.T.V.Rao MD 15
  16. 16. Causes of Septic Shock • As mentioned any type of bacteria in the bloodstream causes septic shock and this can occur from many infections, for example:  The pope died from septic shock caused by a urinary infection  Simon has a chest infection  Other common reasons according to Collins (2000) are, major abdominal surgery and an invasive catheter. Dr.T.V.Rao MD 16
  17. 17. Infection Parasite Virus Fungus Bacteria Trauma Burns Sepsis SIRSSevere Sepsis Severe SIRS Adapted from SCCM ACCP Consensus Guidelines shock BSI Dr.T.V.Rao MD 17
  18. 18. Where’s the infection ? Abdomen 15% Culture Negative 20% Lung 47% Urine 10% Other 8% Bernard & Wheeler NEJM 336:912, 1997 Dr.T.V.Rao MD 18
  19. 19. What’s the infection? 0 10 20 30 40 50 60 70 80 Gram pos Gram neg Fungal Early Late Pure isolates, total n = 444 pts, 61% micro documented Cohen et al, J Infect Dis 1999 180:116
  20. 20. Septic Shock • Septic shock- once a uniformly fatal condition with 100% mortality. • Present recovery rates are up to 50%. • Significance: Frequent occurrence and high mortality. Dr.T.V.Rao MD 21
  21. 21. Bacterial infection Sepsis and septic shock Excessive host response Host factors lead to cellular damage Organ damage Death
  22. 22. How likely is it that the diagnosis of sepsis is being missed? Is it... 17% 27% 51% 2% 0% 3% 0% 1% 16% 51% 29% 3%Extremely likely Very likely Somewhat likely Not very likely Not likely at all Not sure Total (n=497) Intensive Care Physicians (n=237) Ramsay, Crit Care 2004 8:R409. Dr.T.V.Rao MD 23
  23. 23. Microbial Triggers • Gram-negative bacteria: • lipopolysaccharide • Gram-positive bacteria Lipoteichoic • acid/cell wall muramyl • peptides • – Superatigens Staphylococcal Toxic Shock Syndrome Toxin, • TSST • Streptococcal pyrogenic exotoxin • , SPE Dr.T.V.Rao MD 24
  24. 24. Pathogenesis of Septic Shock LPS LBP LPS ENDOTHELIAL CELL Bacteria LPS LBP LPS CD 14 MONOCYTE soluble CD 14 TNF-A Journal of Infection 1995; 30: 201-206. Dr.T.V.Rao MD 25
  25. 25. Management of Sepsis • Recognition • Supportive care • Source control • Antibiotics • Specific (adjunctive) therapy
  26. 26. Issues in the rational choice of antibiotics EFFICACY • Spectrum of activity • Pharmacokinetics & pharmacodynamics • Patterns of resistance TOXICITY COST
  27. 27. Choosing antibiotics in sepsis • There is no, single, “best” regimen • Consider the site of the infection • Consider which organisms most often cause infection at that site • Choose antibiotic(s) with the appropriate spectrum • After obtaining cultures, give antibiotics quickly and empirically at appropriate dose Dr.T.V.Rao MD 28
  28. 28. “Non-antibiotic” therapy for sepsis • Low dose steroids • Intensive insulin therapy – tight glycaemic control • Activated protein C • Goal directed therapy
  29. 29. Shock: Realize the Facts • Shock = inadequate tissue perfusion • Types of shock: hypovolemic, septic, cardiogenic, neurog enic, anaphylactic • Signs of shock: altered MS, tachycardia, hypotension, tachypnea , low UOP • Always start with ABCs • Resuscitation begins with fluidDr.T.V.Rao MD 30
  30. 30. Best of the References • Sepsis and Septic Shock, 2008 Prof J Cohen Dr.T.V.Rao MD 31
  31. 31. Dedicated Hand Washing Continues to Save Many Lives in Critical Care Dr.T.V.Rao MD 32
  32. 32. Brave and Committed Nurses, Doctors Save Many Lives in spite of Shock Dr.T.V.Rao MD 33
  33. 33. • Programme Created by Dr.T.V.Rao MD for Basic understanding in Septic Shock for Medical Students in the Developing World • Email • doctortvrao@gmail.com Dr.T.V.Rao MD 34
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