septic shock pathophysiology
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Dr.T.V.Rao MD 1
Septic Shock pathophysiology
basicsDr.T.V.Rao MD
Dr.T.V.Rao MD 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 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 4
Shock: Types
• Hypovolemic• Septic (high CO, low SVRI)• Cardiogenic (high CVP)• Neurogenic• Anaphylactic• Adrenal insufficiency
Dr.T.V.Rao MD 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 usedACCP/SCCM Consensus Conference: Bone et al, Chest 1992 101:1644
Dr.T.V.Rao MD 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 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 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 9
Clinical Spectrum of InfectionInfection
Sepsis
Severe Sepsis
Septic Shock
Bacteremia
Dr.T.V.Rao MD 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 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 12
Some Characteristics ofSeptic 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 13
TerminologySystemic Inflammatory Response Syndrome (SIRS)
Temp > 38 or < 36HR > 90RR > 20 or PaCO2 < 32WBC > 12 or < 4 or Bands > 10%
SepsisThe systemic inflammatory response to infection.
Severe SepsisOrgan dysfunction secondary to Sepsis.e.g. hypoperfusion, hypotension, acute lung injury, encephalopathy, acute kidney injury, coagulopathy.
Septic ShockHypotension 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 criteriaacute change from baseline
Dr.T.V.Rao MD 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 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 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 17
Infection
Parasite
Virus
Fungus
BacteriaTrauma
Burns
Sepsis SIRSSevereSepsis
SevereSIRS
Adapted from SCCM ACCP Consensus Guidelines
shock
BSI
Where’s the infection ?Abdomen
15%
Culture Negative
20%
Lung47%
Urine 10%
Other8%
Bernard & Wheeler NEJM 336:912, 1997Dr.T.V.Rao MD 18
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
Dr.T.V.Rao MD 21
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.
Bacterial infection
Sepsis and septic shock
Excessive host response
Host factors lead to cellular damage
Organ damage
Death
Dr.T.V.Rao MD 23
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 24
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 25
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.
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• Patterns of resistance TOXICITYCOST
Dr.T.V.Rao MD 28
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
“Non-antibiotic” therapy for sepsis
• Low dose steroids
• Intensive insulin therapy
– tight glycaemic control
• Activated protein C
• Goal directed therapy
Dr.T.V.Rao MD 30
Shock: Realize the Facts • Shock = inadequate tissue perfusion • Types of shock: hypovolemic, septic,
cardiogenic, neurogenic, anaphylactic• Signs of shock: altered MS, tachycardia,
hypotension, tachypnea, low UOP• Always start with ABCs• Resuscitation begins with fluid
Dr.T.V.Rao MD 31
Best of the References • Sepsis and Septic Shock, 2008 Prof J Cohen
Dr.T.V.Rao MD 32
Dedicated Hand Washing Continues to Save Many Lives in Critical Care
Dr.T.V.Rao MD 33
Brave and Committed Nurses, Doctors Save Many Lives in spite of Shock
Dr.T.V.Rao MD 34
• 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
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