A ppt on Clinical features and management of sepsis according to latest protocol.

1. DR RASEENA VATTAMKANDATHIL
MEM RESIDENT

2. SEPSIS
Life-threatening organ dysfunction caused by a dysregulated host
response to infection
Criteria
- The Third International Consensus
Definition
I. Suspected or proven infection and
II. Increase in SOFA score of 2 or more from baseline

3. Septic shock
A subset of sepsis in which underlying circulatory and cellular metabolism
abnormalities are profound enough to substantially increase mortality
Criteria
Third international Consensus Definition
I. Sepsis
II. Vasopressor therapy required to maintain a MAP
of ≥65 mm Hg
III. Lactate >2 mmol/L despite adequate fluid
therapy

5. Quick Sequential Organ Failure Assessment

6. Why qSOFA?
● Rapid identification of high-risk patients immediately upon presentation
● Lower Sensitivity - Many who might benefit from early aggressive treatment
are negative according to qSOFA  So full SOFA score is to be used on
patients with infection requiring hospital admission

7. Pathology of sepsis
Imbalance in procoagulant
and anticoagulant
functioning
• DIC causes micro- and
macrovascular clot formation and
impaired microvascular tissue
perfusion.
• Microvascular ischemia adds to
organ failure
The host develops a
hyperinflammatory
response
Blunted immune
response
• Increased risk of secondary
hospital-acquired infections
• Programmed death of key
immune, epithelial, and endothelial
cells, leading to tissue injury and
multiorgan dysfunction
…….There are no current specific therapies to remedy microvascular dysfunction

8. CLINICAL FEATURES
● Vital sign abnormalities—notably fever, hypotension, and/or tachycardia—are a hint
to sepsis.
● In ED patients with undifferentiated hypotension, 40% will ultimately have an
infectious cause of symptoms.

9. ● ED patients with sepsis are often volume-depleted from decreased intake and
increased fluid losses
● Classically sepsis is distributive shock with warm peripheries
intravascular volume depletion + septic cardiomyopathy = “cold shock,”
(impaired peripheral perfusion and cool extremities)

10. PULMONARY INJURY
● Widespread inflammation secondary to sepsis can affect pulmonary function even in
the absence of pneumonia.
● Acute lung injury is common and may result in ARDS

11. ● New bilateral pulmonary infiltrates on chest
radiographs not explained by effusions, lung
collapse, or nodules and not fully explained by
heart failure or volume overload.
● Clinically, severe refractory hypoxemia,
noncompliant lungs noted on mechanical
ventilation, and a chest radiograph showing
bilateral pulmonary alveolar infiltrates suggest the
diagnosis.

12. RENAL INJURY
AKI can present with azotemia, oliguria, or anuria.
Factors increasing acute kidney injury risk:
● Pre existing kidney dysfunction
● Depth and duration of hypotension
● Dehydration
● Nephrotoxic substances .

13. HEPATIC INJURY
● Marked elevations of ALT,AST, ALP are less common unless shock is present-
consider a biliary source of infection.
● Lessor elevations in LFTs can result from hypoperfusion and ischemia or be
secondary to direct endotoxin, cytokines, or immune complex damage.
● RBC hemolysis from microvascular coagulation can cause jaundice.

14. GI CHANGES
● The most common GI manifestation of sepsis is ileus, which may persist for days
after shock resolves.
● Minor GI blood loss within 24 hours of developing severe sepsis can result from
painless erosions in the mucosal layer of the stomach or duodenum.

15. HEMATOLOGIC CHANGES
● Neutropenia or neutrophilia, thrombocytopenia, or DIC
● Neutropenia occurs rarely and is associated with increased mortality.
● Neutropenia creates a relative immunosuppression, particularly later in
patients’ course.
● Both red cell production and survival decrease

16. HEMATOLOGIC CHANGES
● Thrombocytopenia may be from DIC but is present in >30% of cases of sepsis even in
the absence of DIC.
● Lower platelet levels are associated with worse outcomes.
● Fulminant DIC ( clinical clotting and bleeding coexist) , is rare but associated with a
very poor prognosis.

17. LABORATORY STUDIES SUGGESTING DIC
● Thrombocytopenia
● Prolonged PT and aPTT
● Decreased fibrinogen and antithrombin III levels
● Increased fibrin monomer, fibrin split products, and d-dimer levels.

18. METABOLIC CHANGES
● Abnormalities in lactate metabolism come from tissue hypoperfusion
● Hyperglycemia in patients without a history of diabetes is associated with a
worse prognosis
● Hypoglycemia( uncommon) may result due to depletion of hepatic glycogen
and inhibition of gluconeogenesis or adrenal insufficiency

19. ADRENAL INSUFFICIENCY
● Hypoperfusion of the adrenal glands
● Adrenal or pituitary hemorrhage
● Cytokine dysfunction of the adrenals
● Drug-induced hypermetabolism
● Inhibition of steroidogenesis by drugs
● Desensitization of glucocorticoid responsiveness at the cellular level.

20. SKIN
● Direct bacterial involvement of the skin and underlying soft tissues
● Hematogenous seeding of the skin or the underlying tissue
● Lesions from hypotension and/or DIC (acrocyanosis and necrosis of
peripheral tissues);
● Lesions from intravascular infections (microemboli and/or immune complex
vasculitis)
● Lesions caused by toxins (toxic shock syndrome).
● Look for any necrotizing or surgical source of sepsis

21. Endocrine Disorders That Mimic Sepsis
- Adrenal insufficiency
- Thyroid storm

22. DIAGNOSIS OF SEPSIS

23. “Sepsis is a clinical diagnosis predicated on suspicion or confirmation of infection,
systemic inflammation, and evidence of new organ dysfunction and/or tissue
hypoperfusion”

24. Sepsis triggers
● Acute bacterial pneumonia(MC)
● Acute pyelonephritis
● Cholecystitis and cholangitis – Rare but severe
● Acute abdomen  perforated viscous, appendicitis, diffuse colitis, or intra-
abdominal abscesses.
● In women of childbearing age, septic abortion and postpartum endometritis
or myometritis are unusual etiologies of septic shock

25. ……Sepsis triggers
● Acute pancreatitis can result in a presentation identical to that of septic shock
due to widespread inflammation
● Necrotizing soft tissue infections can occur in immunocompromised patients,
diabetic patients, or patients with a history of poor vascular circulation
● Elderly and Bedridden  Consider decubitus ulcers and necrotizing infection
such as Fournier’s gangrene.

26. Fournier’s gangrene So that you won’t forget to
do a pelvic examination !!!!

27. …..Sepsis triggers
● In female patients, particularly those with a rash, a pelvic exam
including an assessment for a retained foreign body or tampon
responsible for
toxic shock syndrome is important
● Those without an obvious source of septic shock may have primary
bacteremia or endocarditis.

28. Sepsis source could be indwelling medical devices
Dialysis
catheters
Chemotherapy ports
Peripherally inserted central
catheters
Ventriculoperitoneal
shunts
Pacemaker/Defibrillato
rs

29. ● Acute bacterial meningitis – rare but devastating cause of septic shock.
● Brain and spinal abscesses, subdural or epidural empyemas, and viral CNS infections
are seldom associated with shock on the initial presentation.
● Shock is unusual in neurosurgical patients secondary to neurosurgical procedure or
skull fracture.

30. INVESTIGATIONS
● CBC with platelet count
● serum electrolytes (including calcium and glucose)
● RFT
● lactic acid level;
● LFT
● URE
● ABG - the metabolic, ventilatory, and oxygenation assessment in select
patients.
● ? DIC -PT, aPTT, fibrinogen, and d-dimer.

31. The cornerstones of the initial treatment and
stabilization of severe sepsis are…….
1.Early recognition
1.Early reversal of
hemodynamic
compromise
Early infection control

32. SEPTIC SHOCK RESUSCITATION
1. Administering fluids
2. Frequently assessing response
3. Adding adjunct therapies including vasopressors based on response.
 The specific method of titrating resuscitation is less important than treating
early and aggressively 
……………………do not delay vasopressors when blood pressure does not respond to volume or if volume
overload seems likely.

33. The goals of resuscitation are to improve preload, tissue perfusion, and oxygen delivery.

34. VOLUME RESUSCITATION
● First assess and replenish circulating volume, typically with an
initial 20 - 30 mg/kg crystalloid bolus.
● 1- to 2-L bolus of RL or NS in a 70-kg adult
● Give more fluids if not clinically better and there is no evidence of volume overload.
● Often, 3 to 5 L are needed in the first 6 hours.
● Use balanced fluids after 2 to 3 L when possible.

35. ● Saline can produce a hyperchloremic metabolic acidosis if used in large-volume
resuscitation.
● Balanced fluids(Like RL) is preferable, particularly among critically ill patients or
those receiving large volumes of fluids.

36. Determine whether a patient is volume responsive
● Stroke volume variation - lift the legs of a supine patient for 60 seconds 
improved blood pressure identifies a volume-responsive patient who will likely
benefit from more fluid.
● If these tools are unavailable - empiric crystalloid boluses until the patient fails to
demonstrate a response.

37. VASOPRESSORS
● Once the patient fails to respond to further IV volume expansion, aid perfusion with
vasoactive agents.
● Target a MAP goal of 65 mm Hg.
● Systolic pressure is commonly used in practice, seeking a goal of 90 mm Hg or higher.
● Administer norepinephrine as the first-line vasopressor to patients with refractory
hypotension

38. “high-dose and prolonged infusions are better deployed using a central venous line”

39. “In septic shock, norepinephrine, 0.5 to 30 micrograms/min, is the best first choice since
the dual α- and β-adrenergic effects result in peripheral vasoconstriction and cardiac
inotropy”

40. Vasopressin
● Vasopressin is a second-line agent and may allow for the down titration of
the norepinephrine dose.
● Give vasopressin as a constant infusion at a rate of 0.03 or 0.04 U/min.
● Do not titrate the dose, because higher rates are associated with vasospasm
and high morbidity.

41. ● Epinephrine at a dose of 1 to 20 micrograms/min is an option instead of
norepinephrine when dosed appropriately
● the risk of medication dosing errors related to epinephrine concentration may make
norepinephrine a superior choice.
● If tachydysrhythmias are a problem, phenylephrine is an option as a pure α-
adrenergic agonist.

42. CENTRAL VENOUS OXYGENATION
● After volume repletion and perfusion pressure optimization, if tissue perfusion is
compromised (cool extremities, poor pulses, worsening organ function), assess
oxygen balance.
● Although not needed routinely, measuring continuous SCVO2 with a catheter can aid
additional therapy
● An SCVO2 <70% implies a relative oxygen supply and demand mismatch

43. LACTATE CLEARANCE
● A decrease in lactate over time suggests a restoration of adequate tissue
perfusion.
● Measure lactate using the same method 1 to 2 hours apart
● Improvement of 10% or more is associated with improved clinical outcomes.
● Larger reductions in lactate are associated with even better outcomes

44. TREAT INFECTION
● Give broad-spectrum antibiotics as early as possible for severe sepsis.
● Combination antibiotic therapy leads to improved outcomes, potentially due to
higher rates of bactericidal activity.

45. ANTIBIOTIC OF CHOICE
In Adults (non- neutropenic) without an obvious source of infection
● Imipenem, 500 mg Q6H to 1 g IV Q8H OR
● Meropenem, 1 g IV every Q8H OR
● Doripenem, 500 mg IV Q8H OR
● Ertapenem*, 1 g IV OD
plus
● Vancomycin, 15 mg/kg loading dose

46. Adults (Nonneutropenic) - Suspected Pneumonia
● Ceftriaxone, 1–2 grams IV Q12H
● Azithromycin, 500 mg IV, then 250 mg IV OD
+
● Levofloxacin, 750 mg IV OD or moxifloxacin, 400 mg IV OD
● Vancomycin†, 15 milligrams/kg loading dose

47. Surviving Sepsis Campaign Guidelines 2021-
RECOMMENDATIONS (Adults)

48. ANTIBIOTIC
TREATMENT

49. Vasoactive Agent
Management

50.  Recommend against using qSOFA as a single screening tool for sepsis or septic
shock.
Septic shock on vasopressors an initial target MAP of 65 mm Hg is
recommended over higher MAP targets
Use crystalloids as first-line fluid for resuscitation.
Use norepinephrine as the first-line agent over other vasopressors.

51. Sepsis induced ARDS
Use a low tidal volume ventilation strategy (6 mL/kg), over a high tidal volume strategy (> 10
mL/kg
 Use an upper limit goal for plateau pressures of 30 cm H2O, over higher plateau pressures.
 For moderate-severe ARDS use prone ventilation for greater than 12 hours daily.

52. PROPHYLAXIS
 If risk factors for GI bleeding, use stress ulcer prophylaxis
 Use pharmacologic venous thromboembolism prophylaxis unless a contraindication to
such therapy exists.
 Use low-molecular-weight heparin.

53. COMORBIDITIES
● Sepsis or septic shock and acute kidney injury, use either continuous or intermittent
renal replacement therapy.
● Initiate insulin therapy at a glucose level of ≥ 180mg/dL (10mmol/L).
● For severe metabolic acidemia (pH ≤ 7.2) and acute kidney injury (AKIN score 2 or 3),
use sodium bicarbonate therapy.
● Early (within 72 hours) initiation of enteral nutrition.

54. Thank
you…..