Sepsis and septic shock Flashcards
What is sepsis (Definition)
meaning decay or decomposition.
Systemic illness caused by microbial invasion of normally sterile parts of the body
What is the traditional model of sepsis and features of
- SIRS >38 degrees, HR> 90, RR>20 OR PaCo2<32, WBC> 12,000
- Sepsis = SIRS and Infection
- Severe sepsis = Sepsis and End organ damage
- Septic shock = severe sepsis and hypotension
Examples of SIRS (3)
Pancreatitis
Burns
Trauma
What is sepsis (medical)
life-threatening organ dysfunction caused by dysregulated host response to infection
What is organ dysfunction
What SOFA score reflects an overall mortality risk?
be identified as an acute change in total SOFA score >2 points consequent to the infection
SOFA score >2 reflects an overall mortality risk of approximately 10% in a general hospital population with suspected infection
What is septic shock (medical)
What values need to be maintained?
sepsis with persisting hypotension requiring vasopressors to maintain MAP >65mmHg and having a serum lactate of >2mmol/l despite adequate volume resuscitation
Patients with septic shock have a hospital mortality of 40%
a qSOFA sepsis score
Hypotension - sys BP <100 mmHg
Altered mental status
Tachypnoea RR >22/min
Importance of sepsis (4)
Common condition
Becoming more common
Increased morbidity
Increased mortality
Survival in septic shock is based on
antimicrobial delay
Features of the septic six?
temp HR WCC RR MEN STATE GLUCOSE
Body’s defence against sepsis:
physical barrier:
Innate immune system:
Adaptive immune system:
skin, mucosa, epithelial lining
IgA in gastrointestinal tract, dendritic cells / macrophages
– lymphocytes, immunoglobulins
Origin of sepsis
breach of integrity of host barrier, whether physical or immunological
Organism enters the bloodstream creating a septic state
Pathophysiology of sepsis
Uncontrolled inflammatory response
Patients with sepsis have features consistent with immunosuppression: - what are they? (3)
Loss of delayed hypersensitivity
Inability to clear infection
Predisposition to nosocomial infection
What are the three phases in the pathogenesis of sepsis
Release of bacterial toxins
Release of mediators
Effects of specific excessive mediators
Phase 1: Release of bacterial toxins - features
name some commonly released toxins
- Bacterial invasion into body tissues is a source of dangerous toxins
- Gram negative Lipopolysaccharide (LPS) Gram positive Microbial-associated molecular pattern (MAMP) Lipoteichoic acid Muramyl dipeptides Superantigens Staphylococcal toxic shock syndrome toxin (TSST) Streptococcal exotoxins
Phase 2: Release of mediators in response to infection - endotoxin release
LPS needs an LPS-binding protein to bind to macrophages
LTA do not need such proteins
Phase 2: Release of mediators in response to infection - exotoxin release
Pro-inflammatory response
Small amounts of superantigens will cause a large amount of mediators to be secreted: cascade effect
Phase 2: Release of mediators in response to infection: iator role in sepsis (Th1 vs Th2)
Two types of mediators can be released
Pro-inflammatory mediators – causes inflammatory response that characterises sepsis
Compensatory anti-inflammatory reaction – can cause immunoparalysis
Phase 3: Effects of specific excessive mediators - give features of pro-inflammatory mediators
Promote endothelial cell – leukocyte adhesion
Release of arachidonic acid metabolites
Complement activation
Vasodilatation of blood vessels by NO
Increase coagulation by release of tissue factors and membrane coagulants
Cause hyperthermia
Phase 3: Effects of specific excessive mediators - give features of anti-inflmmatory mediators
Inhibit TNF alpha
Augment acute phase reaction
Inhibit activation of coagulation system
Provide negative feedback mechanisms to pro-inflammatory mediators
Septic shock with multi organ failure has a higher?
Pro-Inflammatory response
Immunoparalysis with uncontrolled infection and multiorgan failure has a higher?
Compensatory anti-inflammatory response
The clinical features of sepsis depends on a number of factors- what are they
Host
Organism
Environment
Organ dysfunction - clinical features
Altered consciousness
Confusion
Psychosis
Tachypnoea
PaO2: <70mmHg
Sats: <90%
Jaundice
↑ Liver enzyment
↓ Albumin
↑ PT
↓ Platelets
↑ PT/APTT
↓ Protein C
↑ D-dimer
Tachycardia
Hypotension
Oliguria
Anuria
↑ Creatinine
General features of sepsis and how they present
Fever >38oC – presenting as chills, rigors, flushes, cold sweats, night sweats, etc
Hypothermia <36oC – especially in the elderly and very young children (remember the immunosuppressed)
Tachycardia >90 beats/min
Tachypnoea >20 /min
Altered mental status – especially in the elderly
Hyperglycaemia >8mmol/l in the absence of diabetes
Inflammatory variables in sepsis (5)
Leucocytosis (WCC > 12,000/ml) Leucopenia (WCC < 4,000/ml) Normal WCC with greater than 10% immature forms High CRP High procalcitonin
Haemodynamic variables in sepsis (2)
Arterial hypotension (systolic <90mmHg or MAP <70mmHg)
SvO2 >70%
Organ dysfunction variables in sepsis (7)
Arterial hypoxaemia (PaO2/FiO2 < 50mmHg)
Oliguria (<0.5ml/kg/h)
Creatinine increase compared to baseline
Coagulation abnormalities (PT >1.5 or APTT >60s)
Ileus
Thrombocytopenia
(<150,000/ml)
Hyperbilirubinaemia
Tissue perfusion variables in sepsis (2)
High lactate
Skin mottling and reduced capillary perfusion
Effect of host on sepsis presentation (3) + examples
Age
Co-morbidities (COPD, DM, CCF, CRF, disseminated malignancy)
Immunosuppression
Acquired – HIV/AIDS
Drug-induced – steroids, chemotherapeutic agents, biologics
Congenital – agammaglobulinaemia, phagocytic defects, defects in terminal complement component
Previous surgery - splenectomy
Effect of organism on presentation of sepsis
Gram positive versus Gram negative
Virulence factors (example: MRSA, toxin secretion, ESBL, KPC, NDM-1)
Bioburden
The sepsis 6
oxygen blood culture antibiotics fluid challenge lactate urine output
The sepsis 6 - 2A’S , 2b’s and 2’cs
Air enriched with o2 Antibes after blood culture blod culture blood gas with lactate crystalloid bolus catheter if sep shock or severe sepsis
Why take blood cultures
make microbiological diagnosis (30-50% positive)
- if spike in temperature, take 2 sets
Lactate and low urine output are markers of
Lactate – marker of generalised hypoperfusion/severe sepsis/poorer prognosis
Low Urine output – marker of renal dysfunction
What Antibiotics - 5 criteria for prescribing
Based on working diagnosis from History and Examination Local antibiotic guidelines BUT consider allergy BUT consider previous MRSA, ESBL, CPE BUT consider Abx toxicity/interactions
Administer effective intravenous antimicrobials within the first hour of
of septic
shock (Grade 1B) and severe sepsis without septic shock (Grade 1C) as the goal of therapy.
Lactate - type A and B
Type A - Hypoperfusion
Type B – Mitochondrial toxins, Alcohol, Malignancy, metabolism errors
Of available biomarkers, lactate has the most support to identify adverse outcomes
IV fluids in sepsis
30ml/kg fluid challenge (expert opinion)
2.1L 70kg patient
When to consider HDU referral
Low BP responsive to fluids Lactate >2 despite fluid resuscitation Elevated creatinine Oliguria Liver dysfunction, Bil, PT, Plt Bilateral infiltrates, hypoxaemia
When to consider ITU
Septic shock
Multi-organ failure
Requires sedation, intubation and ventilation
Patients with severe sepsis and septic shock may experience ineffective arterial circulation
due to?
vasodilatation associated with infection or impaired cardiac output.
Fluid challenges require the definition of four components:- what are they
the type of fluid to be
administered; 2) the rate of fluid infusion (e.g., 500 mL to 1,000 mL over 30 minutes); 3) the
end points (e.g., mean arterial pressure of >65 mm Hg, heart rate of <110 beats per minute);
and 4) the safety limits (e.g., development of pulmonary edema).
