Septic shock Pathophysiology

1. Septic Shock
pathophysiology
basics
Dr.T.V.Rao MD
Dr.T.V.Rao MD 1

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. 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. Shock: Types
• Hypovolemic
• Septic (high CO, low SVRI)
• Cardiogenic (high CVP)
• Neurogenic
• Anaphylactic
• Adrenal insufficiency
Dr.T.V.Rao MD 4

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. 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. 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. 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. Clinical Spectrum of Infection
Infection
Sepsis
Severe Sepsis
Septic Shock
Bacteremia
Dr.T.V.Rao MD 9

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Bacterial infection
Sepsis and septic shock
Excessive host response
Host factors lead to cellular damage
Organ damage
Death

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. 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. 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. Management of Sepsis
• Recognition
• Supportive care
• Source control
• Antibiotics
• Specific (adjunctive) therapy

26. Issues in the rational choice of
antibiotics
EFFICACY
• Spectrum of activity
• Pharmacokinetics & pharmacodynamics
• Patterns of resistance
TOXICITY
COST

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. “Non-antibiotic” therapy for sepsis
• Low dose steroids
• Intensive insulin therapy
– tight glycaemic control
• Activated protein C
• Goal directed therapy

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. Best of the References
• Sepsis and Septic Shock, 2008 Prof J Cohen
Dr.T.V.Rao MD 31

31. Dedicated Hand Washing Continues to Save
Many Lives in Critical Care
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32. Brave and Committed Nurses, Doctors
Save Many Lives in spite of Shock
Dr.T.V.Rao MD 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