Sepsis is a systemic inflammatory response to infection that can progress to severe sepsis and septic shock. Severe sepsis is defined as sepsis with organ dysfunction or hypotension, while septic shock involves hypotension despite fluid resuscitation and signs of hypoperfusion. Treatment involves identifying and treating the infection source, administering IV fluids and vasopressors to restore perfusion, and giving broad-spectrum antibiotics. The goal is to reverse hypoperfusion and prevent further organ damage.

1. SEPSIS AND SEPTIC SHOCK
Ratna savitrie

2. Sepsis Definitions
 Infection
• Inflammatory response to microorganisms or invasion of normally sterile tissues
 Sepsis
• The systemic response to infection – i.e., confirmed or suspected infection plus 2 SIRS criteria
 Severe Sepsis
• Sepsis associated with organ dysfunction, hypoperfusion, or hypotension
• Hypoperfusion abnormalities may include but are not limited to lactic acidosis, oliguria, acute
alteration in mental status

3. Sepsis Definitions:
The Update
 Altered mental status
 Edema or increased fluid balance
 Hyperglycemia (absent diabetes)
 Increased CRP or procalcitonin
 Hypotension
 Increased SvO2
 CI > 3.5 L/min/m2
 Arterial hypoxemia (PaO2/FiO2 <300)
 Acute oliguria (> 2 hours)
 Increased serum Cr (> 0.5 mg/dL)
 Coagulopathy (INR > 1.5)
 Ileus (absent bowel sounds)
 Thrombocytopenia (< 100,000/uL)
 Hyperbilirubinemia (> 40 mg/dL or 70 mmol/L)
 Hyperlactatemia (> 1 mmol/L)
 Decreased capillary refill or mottling

4. Pathophysiology of Sepsis
 The release of mediators (Pro & Anti Inflammatory) by PMNs at the site of
injury or infection is responsible for the cardinal signs of local inflammation:
-Local vasodilation and hyperemia
-Increased microvascular permeability, resulting in protein-rich edema
 Sepsis results when mediator release proceeds unchecked and exceeds the
boundaries of local infection leading to a systemic response that may result in
remote tissue and organ injury. Severe sepsis & (MODS)

6. Determinants of Severity in Sepsis
 Bacterial factors
 Degree of Hypoperfusion & Hypoxia
 Abnormal host response to infection
 Site and type of infection
 Timing and type of antimicrobial therapy
 The development of shock

7. Bacterial Factors
 Endotoxin is found in the cell wall of gram negative bacteria (
Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter, E coli
)
 Endotoxin can accelerate sepsis in gram negative bacterial infections.
Elevated plasma levels of endotoxin are associated with shock and
multiple organ dysfunction syndrome (MODS)
 The coagulation, complement, and contact fibrinolytic systems are all
activated by endotoxin .
 This leads to the production of vasoactive substances which enhance
endothelial permeability.
 Activation of the coagulation system leads to DIC

8. Hypotension= MAP< 60 / SBP< 90
Goals are adequate perfusion =
Lactic acid < 18 or Urine Output responds to fluid
 This is in part due to a 3 rd spacing caused by reduced arterial
vascular tone and increased endothelial permeability.
 Other changes that occur include venous dilation thereby diminishing
venous return to the heart and ultimately causing decreased CO.
 Sepsis is associated with a decrease in the number of functional
capillaries which results in hypoperfusion, hypoxia, and lactic acid
production
 When prolonged hypotension (MAP <60) complicates sepsis remote
organ injury results in Severe Sepsis and if prolonged or not corrected
rapidly Septic Shock

9. Organs Commonly Affected
 Lung - ALI/ARDS
 Kidney -Acute renal failure due to acute tubular necrosis
 CNS -Altered sensorium and peripheral neuropathy manifested as muscle
weakness and loss of sensation to light touch
 Liver -Liver dysfunction can prevent the elimination of endotoxin and
bacteria-derived products via the RES thereby permitting direct spillover of
these toxic products into the systemic circulation
 Gut- Sepsis may depress the gut's normal barrier function, allowing
translocation of bacteria and endotoxin into the systemic circulation
 Heart- Myocardial depression

10. DEGREES OF SEVERITY
 Inflammatory mediators & bacterial toxins spread
systemically from a localized infection to affect remote
tissues and organs of the body. PROGRESSIVE degrees of
severity occur as the infection spirals out of control as
below
 SIRS 7% Mortality
 SEPSIS 16% Mortality
 SEVERE SEPSIS 20% Mortality
 SEPTIC SHOCK 46% Mortality
 Refractory shock > 50

11. Systemic Inflammatory Response Syndrome
SIRS
 TWO OR MORE of the following conditions:
 KP Temp >100.5 (38.1c) or < 96.8 (36.0c)
 Lit Temp >101.3 (38.5c) or < 95.0 (35.0c)
 Heart rate of >90 beats/min
 Respiratory rate of >20 breaths/min or PaCO2 of <32 mm Hg
 and WBC count of >12,000, <4000 or >10 percent immature (band) forms

12. Patients Who Present With
SIRS WHAT DO I DO
 Recognize the diagnosis of SIRS
 Determine the SEVERITY & SOURCE of Infection via labs & cultures ;
including Lactic Acid
 Start empiric / appropriate antibiotics
 Correct Fluid Deficit

13. Early Treatment for SIRS/SEPSIS
 Open sepsis order set
- SEPSIS ICU IP SCAL NATL AND ORDER LABS / BLOOD CULTURES ANTIBIOTICS / FLUID BOLUS AS
DIRECTED IN
 Address the Source of Infection
 Start Antibiotics within 1 Hr / Maintain SaO2 > 96%
 IV NS 1-1.5 liter bolus within 1 hour ( 20-30 ml/Kg)
 CBC with Diff / Lactate STAT / Blood Cultures
 INR/PTT/Fibrinogen / LDH / LFT’s & Total bilirubin / BUN / Cr / Lytes / Glucose / Calcium
 CXR & Suspected Source Cultures
 If lactate >/= to 18 but < 36 repeat Q 6 hours until < 18. Consider continuation of fluid bolus
500 ml NS Q 30 min until lactate < 18 or BP responds with goals MAP > 60 or SBP > 90 with a
maximum of 40-60 ml NS / Kg or complication by pulmonary edema onset. Should goals not be
met or pulmonary edema ensues an Arterial line and Central line in addition to ICU transfer
recommended

14. Early Treatment for SIRS/SEPSIS
 Transfer to ICU for goal directed therapy if no response
to fluid boluses or severe sepsis is present
 Goal directed therapy requires an Arterial line & Central
line within 2 hours of admission to guide further Tx
Goals

15. Fluid Goals/Endpoints
 INITIAL rapid infusion (30min) of 1-1.5 liter NS
 Start with ~20-30 ml/Kg
 Continue with fluid Bolus NS 500 ml q 30 minutes until goals reached
 Stop @ 40-60ml/Kg or if perfusion goals not met or with Pulmonary Edema onset as a complication
AND Transfer to ICU TO FACILITATE GOAL DIRECTED THERAPY VIA ARTERIAL LINE & CENTRAL LINE
 Low threshold for RBC transfusion (goal of 30%)
 IF MAP < 60-65 & CVP < 8 and/or lactate > 18 Continue fluid Boluses 500 mL-1000mL (Q 30 Min)
Evaluate before/after each fluid bolus/Achieve goal < 6 Hrs
 Volume Status (CVP) goal 8-12
 Blood Pressure (MAP) goal >65 or SBP >90
 Tissue Perfusion (LA) goal < 18 mg/dl

16. Fluid Goals/Endpoints
 Start @ 20ml/Kg Continue with 500 ml NS Q 30 Until goals met OR Pulmonary
Edema Stop @40-60ml/Kg
 Rapid bolus of 1L-1.5L NS in 30 min
~135 lbs
20ml X 60kg = 1200ml
40ml X 60Kg = 2400ml
60ml X 60Kg = 3600ml
~175 lbs
20ml X 80Kg = 1600ml
40ml X 80Kg = 3200ml
60ml X 80Kg = 4800ml

17. Empiric Antibiotics for
Suspected SIRS / Sepsis
 Suspect Pyelonephritis START GENTAMICIN PLUS ONE OF EITHER : FortazR 1g
IV q8 OR ZosynR 3.375 g IV q 6
 Suspect community acquired Pneumonia Ceftriaxone 2g IV q24hrs and
Zithromax 500mg IV Q 12 hours
 Suspect GI SOURCE Vancomycin 1 g IV q 12hrs Zosyn 3.375 g IV q 6hrs

18. Sepsis
LACTATE < 36 mg/dl
AND EVIDENCE OF ONLY 1 OR NONE signs of ORGAN
DYSFUNCTION
 SEPSIS = SIRS with DOCUMENTED infection
-Culture or Gram stain of blood, sputum, urine, amniotic fluid etc, positive for bacteria
-OR focus of Infection identified by visual inspection, eg, purulent amniotic fluid or
cervical discharge, infected incision
 If lactate >/= to 18 but < 36 repeat Lactate Q 6 hours until < 18. Consider continuation
of fluid bolus 500 ml NS Q 30 min after initial fluid bolus of 20-30 ml NS /Kg until lactate
< 18 or BP responds with goals MAP > 60 or SBP > 90 with a maximum of 40-60 ml NS /
Kg or complication by pulmonary edema onset. An evaluation for pulmonary edema
should be performed (lung ausculation/SaO2) prior to each fluid bolus. Should goals not
be met or pulmonary edema ensues an Arterial line and Central line in addition to ICU
transfer is recommended.

19. Severe Sepsis
SEPSIS PLUS TWO OR MORE ABNORMAL VALUES
REPRESENTING SEVERE ORGAN DYSFUNCTION
ADMIT TO ICU FOR GOAL DIRECTED THERAPY
 Serum Lactate >/= 36 mg/dl
 Urine output <0.5 mL/kg after fluid bolus OR Cr >2.0 OR Cr incremental increase =/>
than 0.5 above baseline
 INR>1.5 or PTT > 60 sec or Total bilirubin >4.0
 Platelet count of <100,000 cells/mL
 ARDS or Acute Lung Injury ( PaO2/FiO2 < 300 )
 Mottled skin or capillary refill >or= to 3 seconds
 Abrupt change in mental status
 Cardiac dysfunction by echocardiography

22. Septic Shock
 Sepsis-induced hypotension despite adequate fluid resuscitation along
with the presence of perfusion abnormalities that may include, but are
not limited to, lactic acidosis, oliguria, or an acute alteration of mental
status; patients receiving inotropic or vasopressor agents may not be
hypotensive at the time that perfusion abnormalities are measured.

23. Pathogenesis of Septic Shock

24. Pathogenesis of Septic Shock

25. Septic Shock Hemodynamics
Warm (hyperdynamic) shock
 hypotensive
 tachycardia
 tachypnea
 bounding pulse
 warm, well perfused
 extremities
 skin flushed, moist
Cold (hypodynamic) shock
 hypotensive
 tachycardia
 tachypnea
 narrow, thready pulse
 cold, poorly perfused
 extremities
 skin pale, dry

26. Septic Shock Hemodynamics
 CVP does not accurately estimate ventricular filling pressures in the critically ill.
 When PWP is appropriately elevated to 12 - 15 mm Hg with fluid resuscitation, 90% of patients with
septic shock exhibit a hyperdynamic circulatory state.
 Hyperdynamic state persists to death

27. 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 increase O2 delivery to tissue.
Administer O2
Combat the bacteria and cytokines
Eliminate septic focus
 RESUSITATION
1. VOLUME REPLACEMENT
 Iv access with 2 wide bore cannulas are secured, samples taken for FBC, EUCr, 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(30-50ml/hr)
 Central venous catheter is inserted(10-15cmH20)

28. Treatment
 Vasopressor
After adequate fluid resuscitation or about 4L, with signs of fluid overload(basal crepitation, high CVP) and
persistent hypotension.
 Norepinephrine – α & β
1st line for septic shock refractory to volume replacement
Vasoconstriction & reflex bradycardia 5-20mcg/min
 Dopamine – systemic vasoconstriction, inotropic, renal vasodilatation 2-20mcg/m
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
 Give in large doses IV to combat infection. Empirical
 IV Broad spectrum bactericidal & anerobe coverage (3rd generation cephalosporin) Ceftriaxone 50-
100mg/kg up to 2gm daily + Metronidazole 500mg 8hrly

29. Treatment
 4. STEROIDS: Inhibits conversion of membrane
phospholipid to arachidonic acid hence inhibiting release of secondary mediators.
Hydrocortisone 2-6g daily for 2days 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
 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.

30. Treatment
 8. NALOXNE: it raises the blood pressure
 9. PREVENTION OF FURTHER COAGULATION
Atiii and C₁-estrase 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
respose to therapy is poor. E.g debridement, drainage of abscess

31. 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 :80-100mmHg

32. COMPLICATION
 ARDS
 ARF
 DIC
 Encephalopathy
 Liver failure
 MODS
 Death

33. PROGNOSIS
Poor prognostic factor
 Advanced age
 Immunosuppresion
 Infection with resistance organism, level of IL -6
 Need for inotrophs for > 24hrs
 Mods despite treatment

34. PREVENTION
 Early recognition
 Prompt treatment of infection
 Meticulous surgical technique
 Pre op antibiosis
 Aseptic technique
 Sterilization of surgical equipments
 Optimization of patient – eg DM

35. 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 .

36. SEPSIS & SEPTIC SHOCK
 Even with optimal treatment mortality due to severe sepsis or septic
shock can be > 40%
 Find Source and remove Infection if possible / Start Antibiotics < 1 hr / IV
fluids 1-1.5 Liters infused within 1hour / Goals Guide Tx ie Central & Art
line if necessary should be in placed within 2 hours
 Consultation with IM and transfer to ICU

37. EARLY TREATMENT
FIND THE SOURCE
 Antibiotics Alone : Pyelonephritis
Abortion / Chorio & Metritis
 Drainage AND/OR Excision/Removal
PPROM / Appy / Surgical complication
Necrotizing Fasciitis esp if IDDM

38. EARLY TREATMENT
A B C
Antibiotics/Airway
 The time to initiation of appropriate Antibiotics is a strong predictor of mortality. Each
hour delay increases mortality by > 7.5%
 THERFORE Start ATB within 1 Hr
Crit Care Med. 2006 Jun;34(6):1589-96

39. Empiric Antibiotics
Should be initiated within 1 hour
 If the potential bacteria or infection source is NOT immediately obvious Give VANCOMYCIN
plus one of the following:
 Beta-lactam / beta- lactamase inhibitor eg. piperacillin-tazobactam ie Zosyn®P
 Cephalosporin 3rd or 4th generation (eg, ceftriaxone ie Rocephin® or Ceftazidime ie
Fortaz®P if Pseudomonas suspected)
 Carbapenem (eg, meropenem ie MerremRP)

40. AIRWAY & BREATHING
 Airway – O2 by face mask and document response with continuous pulse
oximetry
 CXR and ABG should be obtained to help diagnose acute lung injury (ALI)
or acute respiratory distress syndrome (ARDS) which frequently complicate
sepsis.
 Ventilator may be required to support the increased work of breathing
that typically accompanies sepsis

41. Circulation / Hypoperfusion
 HypOperfusion can occur in the absence of hypotension (MAP<65) OR (SBP <
90) especially during early sepsis. Peripheral BP Cuff may be unreliable
therefore place an arterial line
 Other Signs of HypOperfusion include: Serum Lactate >/= 36 mg/dl Urine
output of <0.5 mL/kg after fluid bolus OR Cr >2.0 INR>1.5 or PTT > 60 sec or
Total bilirubin >4.0 Platelet count of <100,000 cells/mL ARDS or Acute Lung
Injury ( PaO2/FiO2 < 300 ) Mental status change ie Obtunded

42. Terima Kasih