Sepsis and Septic Shock Flashcards
Sepsis definition [2]
- Life threatening organ dysfunction
- Caused by a dysregulated host response to infection
What defines septic shock in the model? [2]
- severe sepsis and hypotension
Clinical definition of septic shock [2]
What is hospital mortality of patients with septic shock?
Criteria of septic shock:
> > persisting hypotension requiring vasopressors to maintain MAP >65mmHg
> > serum lactate of 2mmol/l despite adequate vol resus
Hospital mortality of 40%
What 3 criteria constitute qSOFA?
How many criteria is associated with greater risk of poor outcome?
> > Hypotension systolic BP <100 mmHg
altered mental status - confusion
Tachypnoea RR >22/min
- at least 2 suggests greater risk of poorer outcome)
Why is quick intervention key in sepsis?
Chance of mortality increases with each hour of delay of antibiotic administering
What intervention is key in reducing sepsis associated mortality and cost? [6]
SEPSIS 6 Give 3 Oxygen IV Ab IV fluid challenge
Take 3
Bloods
Lactate
Urine output
What is the bodys defences against sepsis?
3 main headings
> Physical barrier: skin, mucosa, epithelial lining
> innate immune system: IgA in GI tract, dendritic cells/macrophages
> adaptive immune system - lymphocytes, immunoglobulins
Pathophysiology of sepsis [4]
Sepsis originates from breach of host barrier.
Organism enters bloodstream creating septic state
»uncontrolled inflammatory response
»immunosuppression features (loss of delayed hypersensitivity/unable to clear infection/predisposed to nosocomial infection)
»Likely change of sepsis syndrome over time
(initial inc. in inflammatory mediators. Later shift towards anti-inflam immunosuppressive phase. Depends on patient health)
What are the 3 phases in pathogenesis of sepsis?
- release of bacterial toxins
- release of mediators
- effects of specific excessive mediators
Discuss phase 1: release of bacterial toxins?
Define [1]
Name commonly released toxins by gram +ve [1] bacteria
Name 2 commonly released toxins by gram -ve bacteria
-bacterial invasion into body tissues is source of dangerous toxins
-commonly released toxins:
>gram +ve (lipopolysaccharide)
>gram -ve (MAMP, superantigens)
Discuss phase 2: release of mediators in response to infection?
Endotoxin vs Exotoxin release
Effects of infections due to endotoxin release
>LPS needs LPS-binding protein to bind to macrophages. LTA doesnt need a protein
Effects of infections due to exotoxin release
>pro-inflammatory response
>small amount of superantigens will cause lots of mediators to be secreted (cascade effect)
Discuss phase 3: effects of specific excessive mediators?
Name 6 effects of pro-inflammatory mediators
Name 4 effects of anti-inflammatory mediators
Pro-inflammatory mediators
- promote endothelial cell (leukocyte adhesion)
- release of arachidonic acid metabolites
- complement activation
- vasodilation of blood vessels by NO
- inc coagulation by release of tissue factors and membrane coagulants
- cause hyperthermia
Anti-inflammatory mediators
- Inhibit TNF alpha
- augment acute phase reaction
- inhibit activation of coagulation
- provide negative feedback mechanisms to pro-inflammatory mediators
What can over production of pro-inflammatory mediators lead to?
septic shock with multi organ failure and death
What can over production of anti-inflammatory mediators lead to? [2]
- Immunoparalysis with uncontrolled infection
- multi organ failure
What are some general features of sepsis? [6]
- Fever >38 degrees (chills, rigors, flushes, cold sweats)
- Hypothermia <36 degrees (esp in elderly/young/immunosuppressed)
- Tachycardia >90bpm
- Tachynpoea >20 breaths/min
- altered mental status (esp in elderly)
- Hyperglycaemia >8mmol/l in absence of diabetes
What are inflammatory variables in sepsis? [5]
- Leucocytosis (WCC>12000/ml)
- Leucopenia (WCC<4000/ml)
- Normal WCC with >10% immature forms
- high CRP
- High calcitonin
What are some haemodynamic variables in sepsis? (3)
- Arterial hypotension (systolic <90mmHg or MAP <70mmHg)
- SvO2 >70%
What are some organ dysfunction variables in sepsis? (7)
- Arterial hypoxaemia (PaO2 <50mmHg)
- Oliguria (<0.5ml/kg/h)
- creatinine inc compared to baseline
- coag. abnormalities (PT>1.5/APTT>60s)
- Ileus
- Thrombocytopenia (<150000/ml
- Hyperbilirubinaemia
Tissue perfusion variables in sepsis:
What are 3 indicators of tissue hypo perfusion?
- High lactate
- Skin mottling
- Reduced capillary perfusion
What can affect sepsis presentation in a host? [6]
- Age
- Co-morbidities (COPD, DM etc)
- Immunosuppression (acquired - HIV/AIDS.
- Drug induced - steroids/chemo/biologics. Congenital
- Previous surgery - splenectomy
Type of bacteria if infection is above/below diaphragm? [2]
- Gram positive (infections above diaphragm)
- Gram negative (infections below diaphragm)
Patient presents with fever nausea, vomiting, abdominal pain. Other than sepsis what could the diagnosis be?
Acute pancreatitis
What is the SEPSIS6? (remember: take 3 give 3)
Take:
- blood cultures
- blood lactate
- measure urine output
Give:
- Oxygen aim sats 94-98%
- IV antibiotics
- IV fluid challenge
Details of SEPSIS 6
- blood cultures [2]
- blood lactate [1]
- low urine output [1]
Blood cultures
- If suspected IE, take 3 sets
- if temp spike take 2 sets
Blood lactate
-marker of generalised hypoperfusion, severe sepsis, poorer prognosis
Low urine output
-marker of renal dysfunction
How do you determine what antibiotics to give patient? [1] and what must you consider? [3]
- Based on working diagnosis from Hx +Exam
- Local antibiotic guidelines
Consider
- allergy
- previous MRSA, ESBL, CPE
- Abx toxicity/interactions
What do Type A [1] and B [4] lactate biomarkers indicate?
Type A: hypoperfusion Type B: mitochondrial toxins alcohol malignancy metabolism errors
What is the volume of IV fluids given for a fluid challenge?
30ml/kg fluid challenge (so 2.1L for 70kg patient)
When do you consider HDU referral? [6]
- low bp responsive to fluids
- lactate >2 despite fluid resus
- elevated creatinine
- oliguria
- liver dysfunction, bilirubin, PT, platelet count
- bilateral infiltrates, hypoxaemia
When do you consider ITU? [3]
- Septic shock
- multi organ failure
- needs sedation, intubation and ventilation
What is defined as organ dysfunction according to the SOFA score?
Organ dysfunction identified as an acute change in total SOFA score >2 points
What does the SOFA score tell us in terms of mortality rest?
> > SOFA score >2 reflects overall mortality risk of approx 10% in general hospital population with suspected infection
What are 2 MAMP toxins
LTA
Muramyl dipeptides
What are 2 super antigen toxins
Staphylococcal toxic shock syndrome toxin
Streptococcal exotoxins
With regards to phase 2 of sepsis pathogenesis:
What are the 2 types of mediators that can be released
Which ones are associated with pro-inflammatory and anti-inflammatory response
Mediator role on sepsis
>two types of mediators can be released: TH1 and TH2
>TH1: pro-inflammatory mediators causes inflammatory response that characterises sepsis
>TH2: compensatory anti-inflammatory reaction can cause immunoparalysis
What are 2 signs of the end point of a fluid challenge
MAP > 65mm Hg
HR <110 BPM
What 2 congenital problems can affect sepsis presentation in a host?
agammaglobulinaemia/phagocytic defects)
SOFA
Sequential organ failure assessment
Investigation
Bloods [6]
Other investigations [2]
Bloods:
- VBG (glucose and lactate), FBC, CRP, U&E and creatinine, clotting
Other ix:
- urinalysis and CXR
Red flag criteria [9]
- Responds to only voice or pain or unresponsive
- Acute confusional state
- SBP <90 or drop >40 from normal
- HR >130bpm
- Needs oxygen to keep >92%
- Non-blanching rash, mottled, ashen, cyanotic
- Failure to pass urine in last 18h or urine output <0.5ml/kg/h
- Lactate >2 mmol/L
- Recent chemo
Amber flag criteria [10]
- Relatives concern about mental status
- Acute deterioration in functional ability
- Immunosuppresson
- Trauma or surgical procedure in last 6w
- RR 21-24
- BP 90-100mmHg
- HR 91-130 or new arrhythmia
- Failure to pass urine in last 12-18h
- Temperature <36
- Clinical signs of wound, device or skin infection
Management of sepsis by HDU or critical care team [6]
- Glycaemic control
- Vasopressors or inotropes
- Corticosteroids
- DVT prophylaxis
- Nutrition
- Blood transfusion
Management of sepsis source unknown [3]
If penicillin allergy or known MRSA? [3]
- Amoxicillin 1g 8hrly IV
+ Gentamicin
+/- Metronidazole 500mg 8hrly IV (if anaerobic cover rqd) - Gentamicin
+ Vancomycin
+/- Metronidazole 500mg 8hrly IV
Bacterial sepsis causative organisms [5]
Gram positive:
- Staph aureus
- Strep pneumonia
Gram negative:
- E. Coli
- Kleb spp
- Pseudomonas aeruginosa