Sepsis is a life-threatening condition caused by the body's response to infection. It has been defined in various ways over time, with the most recent Sepsis-3 definition describing it as a dysregulated immune response leading to organ dysfunction. Diagnosis involves assessing symptoms, signs of infection and organ dysfunction, along with diagnostic tests. Management involves rapid fluid resuscitation, antibiotics within 1 hour of recognition, vasopressors to maintain blood pressure and organ perfusion, and treatment of the underlying infection in an intensive care unit. Delays in recognition and treatment can increase mortality risk.

1. SEPSIS
PRESENTER: WONG SHIN YIING
SUPERVISOR: DR LYDIA / DR JEE

2. HISTORY OF SEPSIS
• Recognition of sepsis changed markedly over time
• 4th century BC - Hippocrates was the first to use the term sipsi
(Greek for make rotten)
• Discoveries of microorganism
• Development of germ theory of disease
• 1989 - Dr Roger C. Bone published a paper described sepsis as a state of
invasion of microorganism into blood stream and its clinical complication

3. EVOLUTION OF SEPSIS DEFINITIONS
1991
2001
2016
SEPSIS -1 :
INFECTION + SIRS
= SEPSIS
SEPSIS-2:
SURVIVING SEPSIS
CAMPAIGN
SEPSIS -3 :
q-SOFA

4. INFECTION SIRS SEPSIS
SEPSIS-1 DEFINITION (1991)
• American College of Chest Physician (ACCP) and Society of Critical Care Medicine (SCCM)

6. SEPSIS -2 DEFINITION (2001)
• International Sepsis Definitions Conference
• American College of Chest Physician (ACCP), Society of Critical Care Medicine (SCCM), American
Thoracic Society (ATS), European Society of Intensive Care Medicine (ESICM) and Surgical
Infection Society (SIS)
INFECTION SIRS SEPSIS
Expanded
criteria:
General
Inflammatory
Hemodynamic
Tissues
perfusion

8. INFECTION
≥2 SOFA/
q-SOFA
SEPSIS
SEPSIS -3 DEFINITION (2016)
• Life threatening organ dysfunction due to a dysregulated host response to
infection
• Clinical criteria – organ dysfunction is defined as an increase of 2 points or
more in the Sequential Organ Failure Assessment score (SOFA)

9. SEPSIS -3 DEFINITION (2016)
Septic Shock
• Subset of sepsis in which underlying circulatory and cellular / metabolic
abnormalities are profound enough to substantially increase mortality
• Clinical criteria – sepsis and (despite adequate volume resuscitation) both of :
persistent hypotension requiring vasopressors to maintain MAP greater than or
equal to 65 mmHg, and lactate greater than 2 mmol/L

11. RISK FACTOR
• Age – infant and old age
• Gender - Males are 25% to 30% more likely to develop sepsis than females
• Ethnicity/ race
• Genetics - Interleukin 1β-511 homozygosity is increased risk of mortality from sepsis
• Factors that breach natural barriers to pathogen invasion or compromise immune function:
• Recent surgery or hospitalization
• Indwelling urinary catheters, intravascular access devices, endotracheal tubes
• Malnutrition
• Burns and/or trauma
• Chronic illness (eg, cancer, diabetes)
• Immunosuppression
• IVDU
• Pregnancy or recent childbirth, miscarriage, or termination of pregnancy

12. PATHOPHYSIOLOGY OF
SEPSIS

13. NORMAL RESPONSE TO INFECTION
• The host response to infection starts when innate immune cells like macrophages recognize
and binds to microbial components.
This can occur by:
• Pattern Recognition Receptors (PRR) on host cells which bind to Pathogen Associated
Molecular Patterns (PAMP) in microbes
• PRR include Toll Like Receptors (TLR) and nucleotide-binding oligomerization domain-like
receptors (NOD)-like receptors (NLRs)
• PRR can also recognize endogenous signals such as danger-associated molecular patterns
(DAMPs) that are released during the inflammatory insult.
• DAMPs are nuclear, cytoplasmic, or mitochondrial structures acquiring new functions when
released in the extracellular environment.

15. NORMAL RESPONSE TO INFECTION
• Binding of host immune cell receptors to microbial components causes polymorphonuclear
leukocytes (PMNs) become activated and express adhesion molecules that cause aggregation
and margination to the vascular endothelium.
• The release of mediators by PMNs at the site of infection is responsible for the cardinal signs
of local inflammation: warmth and erythema due to local vasodilation and hyperaemia, and
protein-rich oedema due to increased microvascular permeability
• The balance of pro-inflammatory and anti-inflammatory mediators regulates the inflammatory
processes, including adherence, chemotaxis, phagocytosis of invading bacteria, bacterial killing,
and phagocytosis of debris from injured tissue.
• If the mediators balance each other and the initial infectious insult is overcome, homeostasis
will be restored. The end result will be tissue repair and healing.

17. TRANSITION TO SEPSIS
• Sepsis occurs when the release of pro-inflammatory mediators in response to an infection
exceeds the boundaries of the local environment, leading to a more generalized response.
• This causes decreased oxygen utilization associated with mitochondrial dysfunction rather
than or in addition to poor oxygen delivery to tissues.
• The cellular injury, accompanied by the release of pro-inflammatory and anti-inflammatory
mediators, often progresses to organ dysfunction and leads to high mortality.

20. WHY WOULD AN IMMUNE RESPONSE
SPREAD BEYOND AN INFECTIOUS POINT?
EFFECTS OF MICROORGANISM
• Endotoxins (LPS) found in gram
negative organisms.
• Caused release of pro
inflammatory cytokines (TNF-a
and IL-1)
• Stimulate activation of
coagulation and fibrinolysis
leads to thrombosis.
COMPLEMENT ACTIVATION
• Protein cascade, which
promoting, and coordinating
inflammation response.
• Regulate btw innate and
adaptive immunity.
• When pathogen escaped from
being eliminate, complementary
system continue its effort by
exacerbate inflammation which
eventually leads to SIRS.
GENECTIC SUSCEPTIBILITY
• Polymorphisms in genes coding
for proteins involved in the
recognition and the response to
bacterial pathogens can
influence the amount or
function of the protein
produced in response to
bacterial stimuli.

22. SYSTEMIC EFFECTS OF SEPSIS
When the immune response becomes generalized during an infection, widespread cellular injury
may occur
Mechanisms proposed to explain the cellular injury include:
• Tissue ischemia (insufficient oxygen relative to oxygen need)
• Cytopathic injury (direct cell injury by pro-inflammatory mediators and/or other products of
inflammation)
• Altered rate of cell death pathways
• Activation of the coagulation system and vascular endothelium

23. • Hypotension due to diffuse vasodilation
• ▼ventricular performance due to release of myocardial depressant substances
• Interfere with redistribution of blood flow from splanchnic organs to core organs
(heart and brain) when oxygen delivery is depressed
CIRCULATION
• Endothelial injury ▼pulmonary
blood flow, ▲ microvascular
permeability, leads to pulmonary
edema ▶V/P mismatch, hypoxia
LUNGS
• The circulatory abnormalities in
sepsis may depress the gut's
normal barrier function
• allows translocation of bacteria
and endotoxin
GI SYSTEM
• Systemic hypotension, direct renal
vasoconstriction, release of
cytokines contribute to renal
injury
RENAL
• Liver dysfunction can prevent the
elimination of enteric-derived
endotoxin and bacteria-derived
products, which prevents the
appropriate local cytokine
response.
LIVER
• The most common CNS
complications are an altered
sensorium (encephalopathy).
• The pathogenesis of the
encephalopathy is poorly defined.
• CNS dysfunction has been
attributed to changes in
metabolism and alterations in cell
signalling due to inflammatory
mediators.
CNS
EFFECTS OF
SEPSIS

24. DIAGNOSTIC
PROCEDURES

25. HISTORY
TAKING
CLINICAL
EXAMINATION
LABORATORY
INVESTIGATION
IMAGING
SEVERITY
ASSESMENT–
SOFA/ q-SOFA

26. HISTORY TAKING
•Thorough and timely history focuses on symptoms, comorbidities, recent surgery, recent
antibiotic use, presence of medical devices, and travel
• Common generalized symptoms of sepsis include: fever, chills, rigors, nausea, vomiting,
lethargy, malaise, myalgia, dyspnoea
• Localizing symptoms:
• CNS: headache, photophobia, neck stiffness, seizure etc
• Respiratory: cough (chesty/ dry), runny nose, shortness of breath, pleurisy
• Abdomen: pain, diarrhoea, dysuria, haematuria, cloudy urine
• Peripheral: wounds, joint pain, swelling
•Elderly persons may have limited or nonspecific symptoms (eg, poor oral intake, inanition)

27. CLINICAL EXAMINATION
Physical examination focuses on detecting generalized signs of sepsis and on determining the
source.
Generalized evidence of sepsis is highly variable but commonly includes:
₋ Fever (more than 38.5°C) or hypothermia (less than 36°C)
₋ Hypotension - Presenting sign in 40% of patients with sepsis
₋ Tachycardia
₋ Tachypnoea
₋ Altered mental status; older patients may present with irritability or agitation
₋ Increased capillary refill time (more than 3 seconds)
₋ Mottled/ clammy skin
Systemic examination should be carried out thoroughly as it may uncover an unexpected site.

28. LABORATORY INVESTIGATION
 Full blood counts : TWC ↑, Platelets ↓, HB ↓ / ↔
 Coagulation profile
 Renal profile: Urea/ Creat ↑ (AKI)
 Liver function test: transaminitis
 Blood gas : acidosis
 Lactic acid ↑
 Biomarkers: CRP, PCT
 Microbiology: Blood cultures, Urine cultures, Sputum cultures
 Urine dipstick : look for UTI

32. Biomarkers for sepsis
• May be used for early diagnosis of sepsis, to predict outcome and to guide the choice of
antibiotic therapy.
• Many potential biomarkers have been evaluated – CRP and PCT remain the most commonly
used and widely available.
• To date, no single ideal biomarker for sepsis hence a combination of biomarkers + clinical
assessment are used for early Dx and better risk assessment.
C- REACTIVE PROTEIN:
Produced in the liver in response to infection
and/or inflammation.
Increase within 4-8H of inflammatory stimulus
and peak after 36-72 H
Slowly normalise
Low specificity – drawback as biomarker of
sepsis in adults.
PROCALCITONIN:
Released in parenchymal cells in response to
bacterial toxins
Increase within 2-4H of inflammatory stimulus
and peak after 8-24 H
Normalise quick with patient in recovery
Levels are slightly elevated in severe parasite
and fungal infections
Levels are low in viral diseases

33. Imaging
₋ Radiography:
₋ Chest: pneumonia/ tuberculosis/ effusions / mass or lesions
₋ Abdomen: perforation / stones etc
₋ Ultrasonography
₋ Abdominal ultrasonography is used to identify abdominal infections (eg, appendicitis, cholecystitis,
pancreatitis)
₋ Renal ultrasonography is used to identify renal obstruction or pyelonephritis
₋CT:
₋ CT of abdomen and pelvis to identify abdominal or pelvic abscesses (eg, pancreatic abscess, renal
abscess) or ischemic bowel
₋ CT may also be used to determine depth and extent of some serious soft tissue infections (eg,
necrotizing fasciitis)
₋ MRI of brain and/or spine is used in evaluation of meningitis, encephalitis, and epidural abscess

36. MANAGEMENT OF
SEPSIS

38. INITIAL RESUSCITATION
•At least 30 mL/kg of intravenous (IV) crystalloid fluid should be given within the first 3 h of
resuscitation
•To avoid over- and under-resuscitation, fluid administration beyond the initial resuscitation
should be guided by careful assessment of intravascular volume status and organ perfusion.
•Dynamic parameters include response to a passive leg raise or a fluid bolus, using stroke
volume (SV), stroke volume variation (SVV), pulse pressure variation (PPV), or
echocardiography, should be use to assess fluid responsiveness.
•Serum lactate is an important biomarker of tissue hypoxia and dysfunction. It was suggested to
decrease serum lactate in patients with elevated lactate level.
•Capillary refill time to guide resuscitation as an adjunct to other measures of perfusion.

39. HEMODYNAMIC MANAGEMENT
•Keep MAP > 65mmHg
• Crystalloid as first line fluid for resuscitation.
• To start vasopressor early.
•Delay in initiation of vasopressor therapy was
associated with an increased mortality risk.
• Avoid overload. Faster achieving target MAP,
preventing onset or progress of organ
dysfunction.
• Noradrenaline as first line agent. Epinephrine as
second line.

40. 5 fundamental questions to assessment
of hemodynamic:
1. Should I give more fluids?
- Stroke volume variation
- Pulse pressure analysis
2. Is giving more fluid harmful?
- ultrasonography of lungs
3. Is inotrope needed?
4. Is vasoactive agent needed?
- Continuous oesophageal Doppler
- Velocity time integral (VTI) of left ventricular
outflow tract (LVOT)
- Passive leg raising test
5. Is the organ/ tissue perfusion adequate?
- Capillary refill time
- Serum lactate
- Mottling score

43. ICU
Delayed admissions of critically ill patients
from ED are associated with decreased
sepsis bundle compliance and increased
mortality, ventilator duration, and ICU and
hospital length of stay

44. VENTILATION

45. CONCLUSION
• Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection.
• Sepsis and septic shock are medical emergencies, treatment should be started immediately
upon recognition.
•Initial resuscitation and antibiotics should be given within 1 hour (infection present)
•Adequate fluid resuscitation and early starting of vasopressor to prevent overloading and
achieve target MAP faster.
• Keep MAP > 65 mmHg
•ICU admission within 6 hours is recommended.