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

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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.

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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

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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

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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

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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

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• 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