This document provides an overview of sepsis and septic shock, including definitions, epidemiology, pathogenesis, clinical features, investigation, treatment, complications, and prognosis. It defines sepsis as infection plus SIRS, and septic shock as sepsis that is not responsive to fluid resuscitation and requires vasopressors. The pathogenesis involves an initial inflammatory response to infection that can become dysregulated and lead to organ dysfunction. Treatment involves prompt resuscitation, antibiotics, source control, and organ support. Outcomes depend on factors like age, immune status, pathogen, and need for prolonged vasopressor support.

1. SEPSIS AND SEPTIC SHOCK
Dr. Olofin K. E
Dept. Of Surgery
Maitama District Hospital

2. OUTLINE
•Introduction
•Aetiology
•Risk factors
•Pathogenesis
•Clinical features
•Investigation
•Treatment
•Complications
•Prognosis
•Prevention
•Future trends
•Conclusion
•References

3. INTRODUCTION
DEFINATION OF TERMS:
Bacteremia : transient invasion of circulation by bacteria
Infection: 100,000/g of tissue or per milliliter of exudates
Septicemia: prolonged presence of bacteria in the blood accompanied by
systemic reaction ( this term is currently not in use)

4. SIRS (systemic inflammatory response syndrome )
American College of chest physicians and critical care in 1991
It is a syndrome characterized by the presence of two or more of the following
clinical criteria:
◦ Temperature(core) >38°C or<36°C
◦ Heart rate >90beats/min
◦ Respiratory rate >20b/min or PaC02 <32mmHg
◦ WBC >12000cells/ml or <4000cells/ml or >10% immature band forms.

5. Sepsis:
When SIRS is known or suspected to arise from infection the patient is said to
have sepsis
 SEPSIS = Infection + SIRS
“ Sepsis is a deregulated host response to a severe infection resulting in some
degree of organ dysfunction”

6. Diagnostic Criteria for Sepsis
Infection, documented or suspected, and some of the following:
General variables
• Fever (> 38.3°C)
• Hypothermia (core temperature < 36°C)
• Heart rate > 90/min–1 or more than two sd above the normal value for age
• Tachypnea
• Altered mental status
• Significant edema or positive fluid balance (> 20 mL/kg over 24 hr)
• Hyperglycemia (plasma glucose > 140 mg/dL or 7.7 mmol/L) in the absence of
diabetes

7. Inflammatory variables
• Leukocytosis (WBC count > 12,000 μL–1)
• Leukopenia (WBC count < 4000 μL–1)
• Normal WBC count with greater than 10% immature forms
• Plasma C-reactive protein more than two sd above the normal value ( < 10mg/L)
• Plasma procalcitonin more than two sd above the normal value ( < 0.15ng/ml)
Hemodynamic variables
• Arterial hypotension (SBP < 90 mm Hg, MAP < 70 mm Hg, or an SBP decrease > 40
mm Hg in adults.

8. Organ dysfunction variables
• Arterial hypoxemia (PaO2/FiO2 < 300)
• Acute oliguria (urine output < 0.5 mL/kg/hr for at least 2 hrs despite adequate fluid
resuscitation)
• Creatinine increase > 0.5 mg/dL or 44.2 μmol/L
• Coagulation abnormalities (INR > 1.5 or aPTT > 60 s)
• Ileus (absent bowel sounds)
• Thrombocytopenia (platelet count < 100,000 μL–1)
• Hyperbilirubinemia (plasma total bilirubin > 4 mg/dL or 70 μmol/L)

9. Tissue perfusion variables
• Hyperlactatemia (> 1 mmol/L)
• Decreased capillary refill or mottling

10. Diagnostic criteria for sepsis in the pediatric population
Signs and symptoms of inflammation plus infection
• hyper- or hypothermia (rectal temperature >38.5° or < 35°C),
• Tachycardia (may be absent in hypothermic patients)
At least one of the following indications of altered organ function:
• altered mental status,
• hypoxemia,
• increased serum lactate level,
• bounding pulses.

11. Severe sepsis: sepsis associated with organ dysfunction or hypoperfusion.
Sepsis-induced tissue hypoperfusion is defined as infection-induced hypotension,
elevated lactate, or oliguria.
Sepsis-induced hypotension is defined as a systolic blood pressure (SBP) < 90 mm Hg
or mean arterial pressure (MAP) < 70 mmHg or a SBP decrease > 40 mm Hg in the
absence of other causes of hypotension.
Multiple organ dysfunction syndrome (MODS) - Altered function of more than
one organ system in an acutely ill patient requiring medical intervention to
maintain homeostasis

12. SHOCK
It is the clinical manifestation of failure of cellular function due to inadequate
tissue perfusion and consequent cellular hypoxia resulting from a reduction in
the effective circulating blood volume.
CLASSIFICATION
The most common and clinically applicable way of classifying shock is that based
on the initiating mechanism
◦ HYPOVOLEMIC –reduction in effective circulating volume
◦ CARDIOGENIC- failure of cardiac pump
◦ DISTRIBUTIVE – vasodilation and peripheral pooling of blood
• SEPTIC
• ANAPHYLACTIC
• NEUROGENIC

13. SEPTIC SHOCK
This can be defined as severe sepsis which is not responsive to intravenous fluid
infusion for resuscitation and requires inotropic or vasopressor agent to maintain
systolic blood pressure

15. EPIDEMIOLOGY
4.6 cases/1000 persons in a study in US
200,000 cases annually with 50% mortality
M>F(most studies M=52-66%)
Extreme of ages are more affected
13th leading cause of death in US
Leading cause of death in ICU

16. Where’s the infection ?
Abdomen
15%
Culture
Negative
20%
Lung
47%
Urine
10%
Other
8%

17. Infection
Parasite
Virus
Fungus
Bacteria
Trauma
Burns
Sepsis SIRS
Severe
Sepsis
Severe
SIRS
Adapted from SCCM ACCP Consensus Guidelines
shock

18. AETIOLOGY
BACTERIA: Gram –ve nearly 2/3, gram +ve 1/3, of the gram –ve, E.coli is the
commonest.
Gram -ve
◦ Klebsiella,
◦ Entrobacter,
◦ Serratia,
◦ Proteus,
◦ Mirabillis/Vulgari,
◦ Pseudomonas and
◦ Bacteroides

19. GRAM +VE
◦ Streptococci
◦ Staphylococci
◦ Clostridia
◦ Pneumococci
Viruses, Fungi and Parasites in a few especially the immuno-compromised.

20. SOURCE
Endogenous –
◦ Skin- SSI
◦ urinary tract- UTI
◦ respiratory tract- LRTI
◦ GIT- bowel surgery, perforations
Exogenous.
◦ surgical instruments
◦ drapes
◦ imaging machines
◦ staff

21. RISK FACTORS
Age (<10 >70years)
Malnutrition
Anemia
Primary disease: malignancies, DM,
CLD, CRF
Immunosuppression,
immunosuppressive agents,
Necrotic tissue
Hematoma
Poor surgical technique
Catheterization
Prolong hospitalization
Major surgeries, trauma, extensive
burns

23. PATHOGENESIS
Micro-organisms or products of tissue damage stimulates production of pro-
inflammatory cytokines which in turn stimulate production of secondary
mediators of inflammation in order to localize infection and limit proliferation.
Anti-inflammatory and immunosuppressive cytokines such as IL-10 aided by IL-4
inhibits the activity of the pro-inflammatory cytokines to limit damage.
In severe sepsis they become immunosuppressive to patient.
However in poorly controlled sepsis or extensive tissue damage, there is
excessive inflammatory response which is poorly regulated.

24. PATHOGENESIS cont…

25. PATHOGENESIS cont…
VIRUSES PRODUCTS OF TISSUE DAMAGE BACTERIA
GRAM-VE GRAM+VE
LIPOPOLYSACCHARIDE LIPOTEICHOIC ACID
(ENDOTOXIN) (PEPTIDOGLYCAN)
FACTOR XII (MACROPHAGE,MONO,NEU,LYM,END) COMPLEMENT COMPONENT
PRO-INFLAMMATORY CYTOKINES

27. PATHOGENESIS cont …
PRO-INFAMMATORY CYTOKINE
TNF-α, IL-1β, IL-6, IL-8
CELL MEMBRANE PHOSPHOLIPID
PHOSPHOLIPASE A2
ARACHIDONIC ACID
CYCLO-OXYGENASE LIPO-OXYGENASE
SECONDARY MEDIATORS OF INFLAMMATION
PGI2, PGE2, TXA2, LT, PAF,NO, KININS, IL-1,IL-6, OXYGEN FREE RADICALS, PROTEASES.

28. PATHOGENESIS cont …
COMPLIMENT COMPONENT C3a, C5a(ANAPHYLACTOXINS)
Causes release of histamine from basophil and mast cells
DAMAGE OF VASODILATION ACTIVATION OF DIC
VASCULAR OF MICROCIRCULTION NEUTROPHILS
ENDOTHELIUM

29. PATHOGENESIS cont …
FACTOR XIIa
ENDOTHELIAL CELLS MACROPHAGES.
KININOGEN FACTOR XI (intrinsic pathway)
TISSUE FACTOR
(extrinsic pathway)
BRADYKININ COAGULATION
HYPOTENSION DIC

30. PATHOGENESIS cont…
Effects of secondary mediators
◦ Damage of vascular endothelium
◦ Vasodilation of microvasculature
◦ Activation of neutrophils (aggravates endothelial damage)
◦ Diminished force of cardiac contraction
Effect of compliment component
◦ vasodilatation and increase permeability
◦ Endothelial damage
◦ C5a causes aggregation of platelet and leucocytes thereby acting as procoagulant
leading to DIC
These ultimately lead to peripheral pooling of blood, extravasation of fluid, hypotension,
hypoxia and shock

31. PATHOGENESIS cont…
Pro-inflammatory cytokines reduces plasma levels of thrombomodulin,
coagulation inhibitors like protein S, protein C, and Antithrombin III.
Microvascular coagulation results which worsens DIC.
Hence there is acute inflammation, vasculitis, haemorrhage, capillary thrombosis
and necrosis seen in several vital organs.
Net effect:
◦ Maldistribution of blood flow at the microvasculature
◦ Arteriovenous shunting O2 utilization
◦ Interstitial loss effective vol. Hypovolemia
◦ Myocardial depression

32. PATHOGENESIS cont…
Vasodilatation of microcirculation Damage to vascular endothelium permeability
Peripheral pooling of blood Extravasation of fluid
Bradykinin
Cardiac depression
Arteriovenous shunt

33. CLINICAL FEATURES
It could be in inpatients receiving treatment for another condition
EARLY STAGE (compensated/warm shock )
Not associated with hypovolemia
◦ febrile (38.2-41°C )
◦ Shivering and malaise
◦ warm dry and flushed skin.
◦ hyperventilation
◦ rapid bounding pulse
◦ wide pulse pressure

34. CLINICAL FEATURES cont …
LATE STAGE (decompensated/ cold shock)
Hypovolemia with superimposed sepsis
◦ altered sensorium
◦ cold clammy skin
◦ Feeble pulse
◦ hypothermia, hypotension
◦ Oliguria
◦ Jaundice
◦ upper GI bleeding
◦ DIC

35. INVESTIGATION
NOTE THAT RESUSCITATION TAKES PRECEDENCE OVER INVESTIGATIONS, WHICH
SHOULD NOT DELAY INTERVENTION
INVESTIGATION GOES HAND-IN-HAND WITH RESUSITATION
1. FBC: there is leukocytosis after initial leucopenia. Thrombocytopenia
2. Septic work up
◦ Blood culture
◦ Sputum m/c/s
◦ Urine m/c/s
◦ Wound swab m/c/s
◦ Endocervical swab m/c/s or any exudate

36. INVESTIGATION cont …
Based on suspected source
Chest X-ray
Plain Abd X-ray
Abd-pelvic USS
CT Scan of various sites

37. TREATMENT
Septic shock is a medical emergency that requires prompt and efficient
resuscitation
If possible patient should be admitted to ICU
AIMS:
◦ Improve haemodynamic state
◦ Restore tissue perfusion thereby increasing O2 delivery to tissue.
◦ Combat the bacteria and cytokines
◦ Eliminate septic focus

38. TREATMENT cont …
RESUSITATION
1. VOLUME REPLACEMENT
◦ IV access with 2 wide bore cannulas are secured, samples taken for FBC,
E/U/Cr, GXM
◦ Crystalloids started(readily available ): 1L in 30-45min. Then re-assess, and
repeat as appropriate.
◦ Urethral catheter is passed to empty the bladder then to monitor the hourly
urine output 0.5mls -1 ml/kg/hr (30-50ml/hr)
◦ Central venous catheter is inserted(10-15cmH20)

39. TREATMENT cont.
After adequate fluid resuscitation or about 4L, with signs of fluid overload(basal
crepitation, high CVP) and persistent hypotension.
Vasopressor agents for use in septic shock:
Agent Typical Intravenous Dose Range
Dopamine
Epinephrine
Norepinephrine
Phenylephrine
vasopressin
6-25ug/kg/min
1-10ug/kg/min
1-30ug/kg/min
40-180ug/kg/min
0.01-0.04 units/min

40. 2. OXYGEN ADMISTRATION
In a cleared and patent airway, O2 is delivered via a face mask to increase O2
saturation. Increasing uptake and delivery to tissue.
3. ANTIBIOTIC
Antibiotics to be given based on:
◦ Efficacy
 Spectrum of activity
 Pharmacokinetics & pharmacodynamics
 Patterns of resistance

41. TREATMENT cont…
• TOXICITY
• COST
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

42. TREATMENT cont…
4. STEROIDS: Inhibits conversion of membrane phospholipid to arachidonic acid
hence inhibiting release of secondary mediators.
◦ Hydrocortisone 200mg daily in 4 divided doses is beneficial if given at the
onset.
5. NSAIDS: e.g. Ibuprofen inhibits
◦ the COX pathway there by PG and TBX synth.
◦ Prevent neutrophil aggregation and activation
◦ ↓production of superoxide radicals
◦ Stabilizes lysozomal membranes enzymes

43. 6. O2 Free radical scavengers
◦ superoxide dismutase
◦ Vitamin C, allopurinol, α-tocopherol
They have been shown to decrease tissue damage and MOD in septic shock if
given prophylactically.
7. Glycemic control- soluble insulin (GKI) to maintain blood sugar – 80- 120mg/dl
has been found to ↓morbidity/mortality.

44. 8. NALOXNE: it raises the blood pressure
9. PREVENTION OF FURTHER COAGULATION
◦ Antithrombin iii and C₁-esterase inhibitor
◦ Recombinant human activated protein C inhibits thrombosis and
inflammation, promotes fibrinolysis, and modulates coagulation and
inflammation.
10. SURGERY
◦ resuscitative & therapeutic
If septic focus is responsible for the shock it should be dealt with as soon as
possible especially if response to therapy is poor. E.g. debridement, drainage of
abscess

45. MONITORING
Clinical signs:
◦ Sensorium- consciousness regained, calm.
◦ Conjunctiva becomes pink
◦ venous /capillary feeling
◦ warm dry skin.
Urine output (best indicator): Hourly urine output(0.5-1ml/kg /h)
PR and BP: Quarterly pulse and BP
Central venous pressure (10-15cmH2O)
Lung and jugular veins
Arterial blood gases/ pulse oximeter (oxygen saturation :90-100%)

46. COMPLICATION
ARDS
ARF
DIC
Encephalopathy
Liver failure
MODS
Death

47. PROGNOSIS
Poor prognostic factor
◦ Advanced age
◦ Immunosuppression
◦ Infection with resistance organism, level of IL -6
◦ Need for inotrophs for > 24hrs
◦ MODS despite treatment

48. PREVENTION
Early recognition
Prompt treatment of infection
Meticulous surgical technique
Pre-op antibiotics
Aseptic technique
Sterilization of surgical equipment
Optimization of patient – e.g. DM

49. FUTURE TREND
Monoclonal antibodies to IL-1, IL-6, TNF Clinical trials have not been rewarding.
Recombinant activated protein C – inhibits Va & Viiia also TNF- ά, IL-1,IL-6
although it is associated with high risk of bleeding.
Research has focused on modifying the host response to sepsis via a number of
approaches, including the following:
Antibodies against gram-negative endotoxin
Gamma globulins

50. Monoclonal antibodies against tumor necrosis factor
Blockade of eicosanoid production
Blockade of interleukin (IL)–1 activity
Inhibition of nitric oxide (NO) synthase
These approaches have met with modest success in animal experiments, but at
present, they cannot be recommended for general use in humans.

51. Surviving Sepsis Campaign
It is a joint collaboration of the Society of Critical Care Medicine (SCCM) and
the European Society of Intensive Care Medicine (ESICM)
Committed to reducing mortality and morbidity from sepsis and septic shock
worldwide.
Initiated in 2002 at the ESICM’s annual meeting with the Barcelona Declaration

55. CONCLUSION
Septic shock is an emergency with high mortality even in the best centers
Early recognition and energetic treatment is the key to good outcome
Early detection of those at risk and prevention is the safest and cheapest way of
reducing the morbidity and mortality associated with it .

56. REFERENCES
Baja’s Principles and practice of surgery E. A.Badoe .et al 5th edition.
Bailey and Love’s Short Practice of Surgery, 26th Edition
Surviving Sepsis Campaign; International Guidelines for Management of Severe Sepsis
and Septic Shock: 2017
Sabiston textbook of surgery 18th edition
PubMed.gov US national library of med.
Wikipedia, encyclopedia. Septic shock
Medscape e-medicine. Septic shock

57. Thank you for your
attention.
.