1. Dr. VENKAT NARAYANA GOUTHAM.V

2.  In 1914, Schottmueller wrote, “Septicemia is
a state of microbial invasion from a portal of
entry into the blood stream which causes sign
of illness.”

3.  Infection A microbial phenomenon
characterized by an inflammatory response to
the presence of microorganisms or the invasion of
normally sterile host tissue by those organisms.
 Bacteremia The presence of viable bacteria in
the blood.
 SIRS systemic level of acute inflammation, that
may or may not be due to infection, and is
generally manifested as a combination of vital
sign abnormalities.
 Severe SIRS SIRS in which at least 1 major organ
system has failed

4.  Sepsis SIRS which is secondary to infection.
 Severe sepsis Severe SIRS which is secondary to infection.
 Shock It is a serious, life threatening medical condition
characterized by a decrease in tissue perfusion to a point that is
inadequate to meet cellular metabolic needs.
 Septic shock sepsis with hypotension(arterial bp<90mm
hg systolic) for 1 hr despite adequate fluid resuscitation.(
Or ).need for vassopressors to maintain systolic
bp>=90mm or mean arterial pressure >=70mmhg.
 Multiple Organ Dysfunction Syndrome (MODS) The presence of
altered organ function in an acutely ill patient such that
homeostasis cannot be maintained without intervention.

5.  Requires 2 of the following 4
features to be present:
o Temp >38° or <36.0° C
o Tachypnea RR>20
o Tachycardia (HR>90, in the
absence of intrinsic heart
disease)
o WBC > 12,000/mm3 or
<4,000/mm3 or >10% band forms
on differential

6.  Must meet criteria for SIRS, plus 1 of the
following:
o Altered mental status
o SBP<90mmHg or fall of >40mmHg from baseline
o Impaired gas exchange (PaO2/FiO2 ratio<200-250)
o Metabolic acidosis (pH<7.30 & lactate > 1.5 x
upper limit of normal)
o Oliguria (<0.5mL/kg/hr) or renal failure
o Hyperbilirubinemia
o Coagulopathy
o platelets < 80,000-100,000/mm3,
o INR >2.0, PTT >1.5 x control,
o elevated fibrin degredation products

7. Altered
Tachycardia
Consciousness
Hypotensio
Confusion
n
Psychosis
 CVP
 PAOP
Tachypnea
PaO2 <70 mm Oliguria
Hg Anuria
SaO2 <90%  Creatinine
PaO2/FiO2 300
 Platelets
Jaundice  PT/APTT
 Enzymes  Protein C
 Albumin  D-dimer
 PT

8. BACTEREMIA TRAUMA
INFECTION SEPSIS
SEPSIS SIRS BURNS
PANCREATITIS

9.  It is not precisely understood, but it involves a complex
interaction between the pathogen and the host's immune
system.
 Physiological response to localized infection:
o Influx of activated PMN leukocytes & monocytes  release of
inflammatory mediators
o Local vasodilatation & increased endothelial permeability
o Activation of the coagulation cascade.
 The same occurs in septic shock but at a systemic level.
 Diffuse endothelial disruption
 Increased vascular permeability
 Vasodilatation
 Thrombosis of end organ capillaries

10. Infection
Inflammatory Endothelial
Vasodilation
Mediators Dysfunction
Hypotension Microvascular Plugging Vasoconstriction Edema
Maldistribution of Microvascular Blood Flow
Ischemia
Cell Death
Organ Dysfunction

13. 1. Extremes of age
2. Indwelling lines/catheters
3. Immunocompromised states
4. Malnutrition
5. Alcoholism
6. Malignancy
7. Diabetes
8. Cirrhosis
9. Male sex
10. Genetic predisposition?

14. Recognition of Septic Shock:
 Inflammatory triad-
 Fever
 Tachycardia
Warm
 flushed skin
 Hypoperfusion shock
 Altered sensorium
 Urine output
 Wide pulse pressure.......bounding
pulses

15.  Hypotension
 Cold and clammy skin
 Mottling
 Tachycardia Cold shock
 Cyanosis
 Narrow pulse pressure
 Hypoxemia
 Acidosis.

16.  Localizing symptoms that are most useful clues to
the etiology sepsis:
 Head and neck infections - Severe headache, neck
stiffness, altered mental status, earache, sore throat, sinus pain or
tenderness, cervical or submandibular lymphadenopathy
 Chest and pulmonary infections - Cough (especially if
productive), pleuritic chest pain, dyspnea.(Streptococcus
pneumoniae,Klebsiella pneumoniae,Staphylococcus aureus)
 Abdominal and GI infections - Abdominal
pain, nausea, vomiting, diarrhea(E coli,Acinetobacter species,Enterobacter
species,Salmonella species)
 Pelvic and genitourinary infections - Pelvic or flank pain, vaginal or
urethral discharge, dysuria, frequency, urgency(E coli,Proteus
species,Klebsiella species)
 Bone and soft-tissue infections - Focal pain or tenderness, focal
erythema, edema, fluctuance(S aureus,Staphylococcus
epidermidis,Streptococci)

17.  Laboratory studies
o CBC
o Comprehensive chemistry panel
o Coagulation studies
o Blood & urine cultures
 Imaging studies
o Chest radiography
o Abdominal radiography
o Others according to the suspected cause.

18.  CBC:
o The WBC count and differential.
o Hemoglobin concentration dictates oxygen-carrying
capacity in blood.
o The goal is to maintain hematocrit >30% and hemoglobin >10 g/dL.
o Platelets are an acute-phase reactant and are typically
elevated in the setting of inflammation. However, platelet
counts may decrease in the setting of DIC.

19.  Sodium and chloride levels are abnormal in severe
dehydration.
 Decreased bicarbonate can point to acute acidosis.
 Increased BUN and creatinine levels can point to severe
dehydration or renal failure.
 Glucose control is important in the management of
sepsis, with hyperglycemia associated with higher mortality.
• LFTs and bilirubin, alkaline phosphatase, and lipase levels
are important in evaluating multiorgan dysfunction or a
potential source (eg, biliary
disease, pancreatitis, hepatitis).

20.  It is the best serum marker for tissue perfusion.
 There is also evidence that lactate can be elevated in sepsis
in the absence of tissue hypoxia due to mitochondrial
dysfunction and down-regulation of pyruvate
dehydrogenase, which is the first step in oxidative
phosphorylation.
 Lactate levels >2.5 mmol/L are associated with an increase in
mortality.
 It has been hypothesized that lactate clearance is a measure
of tissue reperfusion and an indication of adequate therapy.

21.  Coagulation studies (PT/aPTT)
o PT and activated aPTT are elevated in DIC.
o Fibrinogen levels are decreased and FDP are increased in the setting of DIC.
 Blood cultures
o Blood cultures should be obtained in patients who have suspected sepsis in order to
isolate a specific organism and tailor antibiotic therapy.
o Positive in < 50% of cases of sepsis.
o A set of cultures from an indwelling intravenous catheter is especially important, as these
catheters are a frequent source of bacteremia.
 Urinalysis and urine culture
o Urinary tract infection is a common source of sepsis, especially in elderly patients.
o Febrile adults without localizing symptoms or signs have a rate of occult urinary tract
infection of 10-15%.
 Gram stain and culture, when applicable
o Sputum specimen should be obtained if pneumonia is suspected.
o Any abscess should be drained promptly, and purulent material sent to the microbiology
laboratory for analysis.
o CSF specimen should be obtained if meningitis is suspected.

22. • CXR  routine in the workup of fever with an unclear etiology.
o Infiltrates are detected with a chest radiograph in about 5%
of febrile adults without localizing signs of infection.
 Abdominal plain films should be obtained if clinical
evidence of bowel obstruction or perforation exists.
 Abdominal ultrasonography is indicated when
evidence of acute cholecystitis or ascending
cholangitis exists

23. The initial treatment of sepsis
and septic shock involves the
administration of
supplemental oxygen and
volume infusion with isotonic
crystalloids

24.  Broad spectrum antibiotics
 Abscess should be drained, necrotic tissue excised
 Blood glucose levels normalized
 Replacement-dose corticosteroids

25.  Patients with septic shock should be treated in an
ICU. Apache score
 The following should be monitored frequently:
o systemic pressure
o CVP
o pulse oximetry
o ABGs
o blood glucose
o lactate, and electrolyte levels
o renal function
o Urine output, a good indicator of renal perfusion, should be
measured, usually with an indwelling catheter

26. An initial assessment of airway and breathing is very
important in a patient with septic shock.
Supplemental oxygen should be administered to all
patients with suspected sepsis.

27.  Patients with suspected septic shock require an initial crystalloid fluid
challenge of 20-30 mL/kg (1-2 L) over a period of 30-60 minutes with
additional fluid challenges at rates of up to 1 L over 30 minutes.
 Crystalloid administration is titrated to a CVP goal between 8 and 12 mm
Hg or signs of volume overload (dyspnea, pulmonary rales, or pulmonary
edema on the chest radiograph).
 A fluid challenge refers to the rapid administration of volume over a
particular time period followed by an assessment of the response.
 Patients with septic shock often require a total 4-6 L or more of
crystalloid resuscitation.
 It is also important to monitor urine output (UOP) as a measure of
dehydration.
 UOP <30-50 mL/h should prompt further fluid resuscitation

28.  Vasopressor administration is required for persistent
hypotension once adequate intravascular volume expansion
has been achieved.
 Persistent hypotension is typically defined as systolic blood
pressure (SPB) <90 mm Hg or mean arterial pressure (MAP) <65
mm Hg with altered tissue perfusion.
 The goal of vasopressor therapy is to reverse pathologic
vasodilation and altered blood flow distribution.
 The recommended first-line agent for septic shock is either
norepinephrine or dopamine

29.  Norepinephrine:
 Has predominant alpha-receptor agonist effects results in potent
peripheral arterial vasoconstriction without significantly increasing
heart rate or cardiac output.
 So it is preferred in warm septic shock where peripheral
vasodilatation exists in association with normal or increased
cardiac output.
 Dose: 5-20 mcg/min
 Dopamine:
 has a much greater effect on beta-receptors  increasing mean
arterial pressure primarily through increasing myocardial
contractility, stroke volume, and heart rate.
 At high doses it has some alpha-receptor effect and so causing
peripheral vasoconstriction.
 It is more useful in the setting of cold shock, where peripheral
vasoconstriction exists and cardiac output is too low to maintain
tissue perfusion.
 Doses range from 2-20 mcg/kg/min.

30.  Antibiotics should be administered within the first hour of
recognition of septic shock, and delays in antibiotic
administration have been associated with increased
mortality.
 Selection of particular antibiotic agents is empirically based
on
 an assessment of the patient's underlying host defenses,
 the potential source of infection, and
 the most likely responsible organisms.
 Antibiotic choice must be broad spectrum, covering gram-
positive, gram-negative, and anaerobic bacteria when the
source is unknown.

31. Clinical condition Antibiotics regimens(intravenous
therapy)
Immunocompetent adult Ceftriaxone(2g q24h) or piperacillin-
tazobactum(3.375g q4-6h)or
meropenem(1g q8h) or(cefepime 2g
q12h)
AIDS piperacillin-tazobactum(3.375g q4-6h)or
meropenem(1g q8h) or(cefepime 2g
q12h)

32.  One regimen for septic shock of unknown cause is
 Ceftriaxone(2g q24h) or piperacillin-
tazobactum(3.375g q4-6h)or meropenem(1g q8h)
or(cefepime 2g q12h)
 Vancomycin must be added if resistant staphylococci or
enterococci are suspected.
 If there is an abdominal source, a drug effective against
anaerobes should be included “metronidazole”
 Antibiotics are continued for at least 5 days after shock resolves
and evidence of infection subsides
 Abscesses must be drained and necrotic tissues (eg, infarcted
bowel, gangrenous gallbladder, abscessed uterus) surgically
excised.

33.  It has theoretical benefits in the setting of severe sepsis by
inhibiting the massive inflammatory cascade.
 Recent guidline is that steroids should be administered only in
patients with septic shock whose hypotension is poorly
responsive to fluid resuscitation and vasopressor therapy.
 Hydrocortisone 200–300 mg/day, for 7 days in three or four divided doses or
continuos infusion.

34.  Recombinant drug with fibrinolytic and anti-inflammatory
activity, seems beneficial for severe sepsis and septic shock if
begun early; benefit has been shown only in patients with
significant risk of death.
 Dose: 24 mcg/kg/h by continuous IV infusion for 96 h.
 Bleeding is the most common complication;
 Contraindications include:
 hemorrhagic stroke within 3 mo,
 spinal or intracranial surgery within 2 mo,
 acute trauma with a risk of bleeding
 intracranial neoplasm.

35.  Normalization of blood glucose improves outcome in critically
ill patients, even those not known to be diabetic.
 A continuous IV insulin infusion (crystalline zinc 1 to 4 U/h) is
titrated to maintain glucose between 80 to 110 mg/dL .
 This approach necessitates frequent (eg, q 1 to 4 h) glucose
measurement.

36.  Intermittent haemodialysis and continuous
veno venous haemofiltration (CVVH) are
considered equivalent. CVVH offers easier
management in haemodynamically unstable
patients.

37.  Use either low-dose unfractionated heparin
or low-molecular weight heparin.
 Use a mechanical prophylactic device, such
as compression stockings or an intermittent
compression device, when heparin is
contraindicated.
 Use a combination of pharmacologic and
mechanical therapy for patients who are at
very high risk for DVT.

38.  Discuss advance care planning with patients
and families.
 Describe likely outcomes and set realistic
expectations.

44.  As sepsis progresses to septic shock,the risk
of dying increases substantially.
 Sepsis is usually reversible whereas patients
with septic shock often succumb despite
aggressive therapy.
 So prevention offers the best oppurtunity to
reduce mortality and morbidity.

45.  Special consideration must be given to
neonates, infants, and small children with
regard to fluid resuscitation, appropriate
antibiotic coverage, intravenous (IV)
access, and vasopressor therapy.