Temp high or low HR >90 RR >20/PaCO2 12000 or <4000

Sepsis and Septic Shock Flashcards by Peter Savage

What is SIRS?

Temp high or low
HR >90
RR >20/PaCO2 <32
WBC >12000 or <4000

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What is sepsis?

SIRS + Infection

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What is severe sepsis?

Sepsis + end organ damage

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What is septic shock?

Severe sepsis + Hypotension

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How is sepsis defined?

Life-threatening organ dysfunction caused by dysregulated host-response to infection
SOFA score >2

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A SOFA score >2 reflects what?

Overall mortality risk of 10%

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How is septic shock defined?

Sepsis with persisting hypotension requiring vasopressors to maintain MAP >65mmHg
AND serum lactate >2mmol/l

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What is the qSOFA definition of sepsis?

Systolic BP <100mmHg
Altered mental state
Tachypnoea >22/min

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Survival in septic shock is inversely proportional to what?

Time taken to give antibiotics

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How does septic shock mortality correlate with with delay in administration?

Each hour = 7.6% increase in mortality risk

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What are the body’s defences against sepsis?

Physical barrier
Innate immune system
Adaptive immune system

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What structures make up the physical barrier against sepsis?

Skin
Mucosa
Epithelial lining

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What structures make up the

innate immune system against sepsis?

IgA in GIT

Dendritic cells/macrophages

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What structures make up the

adaptive immune system against sepsis?

Lymphocytes

Immunoglobulins

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What is the pathophysiology of sepsis?

Uncontrolled inflammatory response
Features consistent with immunosuppression
Probably change to sepsis syndrome

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Why is sepsis said to have features consistent with immunosuppression?

Loss of delayed hypersensitivity
Inability to clear infection
Predisposition to nosocomial infection

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What is the change of sepsis to sepsis syndrome?

Initial increase in inflammatory mediators

Later shift towards an anti-inflammatory immunosuppressive phase

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The change to sepsis syndrome depends on what?

Health of the individual patient

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What are the phases of sepsis pathogenesis?

Release of bacterial toxins
Release of mediators
Effects of specific excessive mediators

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What is the first phase of sepsis?

Release of bacterial toxins
Bacterial invasion into body tissues
May or may not be cleared by immune system

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What are the commonly released toxins of gram -ve bacteria?

Lipopolysaccharide (LPS)

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What are the commonly released toxins of gram +ve bacteria?

Microbial-associated molecular pattern (LTA)
(Lipoteichoic acid, Muramyl dipeptides)
Superantigens (TSST, streptococcal exotoxins)

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What is the 2nd phase of sepsis?

Release of mediators in response to infection

Endo/exotoxin release effects

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What is the effect of endotoxin release in sepsis?

LPS needs an LPS binding protein, LTA do not

These bind to macrophages and trigger mediator release

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What is the effect of exotoxin release in sepsis?

Pro-inflammatory response | Small amount of superantigens release large amounts of mediators

What is the cascade effect of exotoxin release?

Small amount of superantigens release large amounts of mediators

Superantigens act on what?

T-lymphocytes

When Superantigens act on T-lymphocytes, they release what?

IL-2 | IFN-y

IL-2 effects what?

Macrophage to release mediators

IFN-y effects what?

Macrophage to release mediators | Endothelial cells to release NO

What are the types of mediators released in sepsis?

Pro-inflammatory mediators | Compensatory anti-inflammatory reaction

What can the Compensatory anti-inflammatory reaction cause?

Immunoparalysis

What is stage 3 of sepsis?

Effects of specific excessive mediators (pro- and anti-inflammatory)

What are the effects of pro-inflammatory mediators?

``` Promote endothelial cell-leukocyte adhesion Release arachidonic acid metabolites Activate complement Vasodilation (NO) Increase coagulation Cause hyperthermia ```

What are the effects of anti-inflammatory mediators?

Inhibit TNF alpha Augment acute phase reaction Inhibit activation of coagulation system Provide negative feedback mechanisms

What is septic shock?

Imbalance between pro-inflammatory mediators and anti-inflammatory mediators (too much pro-)

What is immunoparalysis with uncontrolled infection?

Imbalance between pro-inflammatory mediators and anti-inflammatory mediators (too much anti-)

The clinical manifestation of sepsis depends on what?

Host Organism Environment

What are the neurological effects of sepsis-induced organ dysfunction?

Altered consciousness Confusion Psychosis

What are the respiratory effects of sepsis-induced organ dysfunction?

Tachypnoea Low PaO2 Reduced O2 saturation

What are the hepatic effects of sepsis-induced organ dysfunction?

Jaundice Increased liver enzymes Low albumin Increased INR

What are the haematological effects of sepsis-induced organ dysfunction?

Decreased platelets Decreased protein C Increased D-dimer

What are the cardiac effects of sepsis-induced organ dysfunction?

Tachycardia | Hypotension

What are the renal effects of sepsis-induced organ dysfunction?

Oliguria Anuria Increased creatinine

What are the general features of sepsis?

``` Fever - chills/rigors/flushes Hypothermia Tachycardia Tachypnoea Altered mental state - esp. elderly Hyperglycaemia ```

Hypothermia is a more common sepsis symptom in who?

Elderly Very young Immunosuppressed

What inflammatory markers are changed in sepsis?

↑ or ↓ WCC (may be normal) ↑ CRP ↑ Procalcitonin

What are the tissue perfusion variables in sepsis?

High lactate Skin mottling Reduced capillary perfusion

What factors in the host can effect the presentation of sepsis?

Age Co-morbidities Immunosuppression Previous surgery i.e splenectomy

What are the main forms of immunosuppression?

Acquired Drug induced Congenital

What are the common causes of Drug induced immunosuppression?

Steroids Chemotherapeutic agents Biologics

What are the common causes of Congenital immunosuppression?

Agammaglobulinaemia Phagocytic defects Defects in complement

What factors in the pathogen can effect the presentation of sepsis?

Gram +ve vs -ve Virulence factors Bioburden

What are the Sepsis 6?

Take 3:Give 3 2As, 2Bs, 2Cs ``` Air enriched with O2 Antibiotics after blood culture Blood culture Blood gas + lactate Crystalloid bolus (fluids) Catheter if severe ```

What is the diagnostic criteria for sepsis?

``` Infection - documented and suspected plus some of: General variables Fever or Hypothermia Tachycardia Tachypnea Altered mental status Significant edema or positive fluid balance Hyperglycemia (in the absence of diabetes) Inflammatory variables Leukocytosis Leukopenia Normal WBC count with greater than 10% immature forms Elevated plasma CRP Elevated procalcitonin Hemodynamic variables Arterial hypotension Organ dysfunction variables Arterial hypoxemia Acute oliguria Creatinine increase Coagulation abnormalities Ileus Thrombocytopenia Elevated biliruben Tissue perfusion variables Hyperlactatemia Decreased capillary refill Mottling ```

What does lactate tell us?

Marker of generalised hypoperfusion/severe sepsis

What does oliguria tell us?

Renal dysfunction

What do blood cultures tell us?

Microbiological diagnosis

How should blood cultures be taken if theres a spike in temperature?

Take 2 sets

What must be considered when giving antibiotics for sepsis?

``` Working Dx Guidelines Allergy Previous infection Consider toxicity/interactions ```

What is type A lactate?

Hypoperfusion

What is type B lactate?

Mitochondrial toxins Alcohol Malignancy Metabolism errors

What does lactate tell us about sepsis?

Prognostic indicator

How should fluids be given in sepsis?

30ml/kg

When should you consider a HDU referral?

``` Low BP response to fluids Lactate >2 despite fluids Elevated creatinine Oliguria Liver dysfunction (Bilirubin, PT, Platelets) Hypoxaemia ```

When should you consider ITU?

Septic shock Multi-organ failure Requires sedation, intubation and ventilation