1. Intern’s Guide to: Sepsis Spectrum
Adam Hayek PGY 3

2. Objective Identification Classification Management Escalation of care
Importance of timely delivery of care
Escalation of care
Importance of early goal directed therapy (EGDT)

3. Sepsis Spectrum SIRS SEPSIS (SIRS+ proven/probable infection)
SEVERE SEPSIS (SEPSIS + acute organ dysfunction)
SEPTIC SHOCK (SEPSIS + hypotension not reversed with fluid resuscitation)
DEATH (25%)

4. What is sirs?

5. 1992 Identify: SIRS Systemic Inflammatory Response System
Fever
>38°C(100.4°F)
<36°C(96.8°F)
Heart Rate
>90 BPM
Tachycardia
RR >20
pCO2 <32 mmHg
WBC
>12,000 cells/mm³
<4000 cells/mm³
> 10% bands
2 or More SIRS Criteria= Go hunting for infection
BCx2, CXR, UA/UC
If infection found or suspected= SEPSIS

7. Who Are We Missing? 2012 Surviving Sepsis Campaign Updates
1992 criteria was not sensitive enough
Allows physician to account for more variables
Patients don’t always decompensate in linear fashion
Importance of early detection
Early goal directed therapy
Allowed more variables to consider when deciding SEPSIS
Patient “Toxic Appearing”
Definitions
“Sepsis is the clinical syndrome that results from a dysregulated inflammatory response to an infection”
Probable or documented infection with SOME of the following:

9. General variables Fever (> 38.3°C) (>100.9°F)
Hypothermia (core temperature < 36°C)
Heart rate > 90/min OR 2 SD above age normal
Tachypnea
Altered mental status
Significant edema or positive fluid balance
> 20 mL/kg over 24 hr
Hyperglycemia > 140 mg/dL without diabetes

10. Inflammatory variables
Leukocytosis (WBC count > 12,000 µL–1)
Leukopenia (WBC count < 4000 µL–1)
Normal WBC count with greater than 10% immature forms
CRP > 2SD above normal
PCT > 2SD above normal

11. Hemodynamic variables
Arterial hypotension
SBP < 90 mm Hg, MAP < 70 mm Hg Or
SBP decrease > 40 mm Hg in adults
< 2SD below normal

12. Organ dysfunction variables
Arterial hypoxemia (Pao2/Fio2 < 300)
Acute oliguria
UO < 0.5 mL/kg/hr for at least 2 hrs
Despite adequate fluid resuscitation
Creatinine increase > 0.5 mg/dL
Coagulation abnormalities INR > 1.5, aPTT > 60s
Ileus (absent bowel sounds)
Thrombocytopenia (platelet count < 100,000 µL–1)
Hyperbilirubinemia (Total bilirubin > 4 mg/dL

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

14. You’ve Determined probable Sepsis
Now What?

15. Initial Screening Routine screening for potential infection (1C)
Draw appropriate cultures (antibiotics can be delayed only up to 45 min for this) (1C)
Draw 2 sets of BC ( at least one peripheral and one central if line placed >48 hrs ago)
If invasive candidiasis suspected: 1,3 B glucan (2B) and galactomannan antibodies (2 C)
Prompt imaging studies to confirm source of infection (UG)
Allows earlier implementation of therapy

16. Time-bound delivery care
Get good PIV access 2 < 18 gauge

17. Which Antibiotic?
Administration of antibiotics within 1 hour of onset of severe sepsis (1C) and septic shock (1B)
One or more antibiotics that will have activity and penetration against likely pathogens (1B)
Reassess antibiotic regimen for de-escalation (1B)
Use Procalcitonin to guide de-escalation (2C)

18. Special Antibiotics Consideration
Combination antibiotics therapy (2B) for :
Neutropenic patients
Multidrug resistant bacteria
High risk of resistant
gram negatives, acinetobacter, pseudomonas
Pseudomonas bacteremia
B lactam + Aminoglycoside or fluoroquinolone ( 2B)
Strep pneumonia bacteremia
B lactam + macrolide (2B)

19. Duration of antibiotics
Continue combination for 3-5 days then de-escalate to appropriate (2 B)
Total antibiotics 7-10 days, except: (2C)
Unresolved clinically
S.aureus bacteremia
undrainable focus of infection
viral/fungal sepsis
immunocompromised or neutropenic
Initiate antivirals as early as possible when indicated (2C)

20. Source control
Establish anatomic diagnosis of infection source and intervene <12 hours (1C)
Infected peripancreatic necrosis- delay intervention till demarcation develops (2B)
Intervention should be percutaneous when possible ( IR instead of surg) (UG)

21. Where does the patient belong
General Medical Floor vs
Medical Intensive Care Unit

22. Severe Sepsis

23. Initial Resuscitation
Central venous pressure 8-12 cm
Mean arterial pressure ≥ 65 mm
Urine output > 0.5 ml/kg/hr
Central venous saturation > 70% or mixed venous saturation > 65% (1C)
If lactate elevated: normalize lactate

24. Fluid therapy Crystalloids are initial therapy (1B)
Do not use Hydroxyethyl starches (1B)
Use albumin only when substantial amounts of crystalloids are needed (1C)
Minimum of 30 ml/kg bolus of crystalloids initially
Continue fluid administration until hemodynamic improvement occurs (UG)

25. INITIAL RESUSCITATION: EGDT
Rivers, E, et al. NEJM 2001

26. EGDT

27. Vasopressors Target mean arterial pressure of 65(1C)
Norepinephrine is first choice of vasopressors(1B)
Add epinephrine when additional agent required (2B)
Vasopressin can be added at 0.03 units/min for raising MAP or reducing dose of NE (UG)

28. Vasopressors Do not use vasopressin as single agent (UG)
Vasopressin dose more than 0.04 units/min not recommended (UG)
Dopamine used only in selected patients- bradycardia and low risk for tachyarrhythmias (2C)
Phenylephrine to be used as salvage therapy, serious tachyarrhythmias, good cardiac output (1C)

29. Vasopressors
Low dose dopamine should not be used for “renal protection” (1A)
Place an arterial catheter as soon as practical in patients requiring vasopressors (UG)
Trial of dobutamine up to 20 mcg/kg/min in patients with documented low cardiac output/high filling pressures
First 6 hours with hypoperfusion despite adequate fluids and MAP (1C)

30. Steroids in shock
Use hydrocortisone if persistent hemodynamic instability despite fluids and vasopressors (2C)
Do not use the ACTH stimulation test (2B)
Taper steroids when off the vasopressors (2D)
Steroids should not be used in the absence of shock (2D)

31. So much more to know… Transfusion in Sepsis
Mechanical Ventilation Management
Sedation and NM blockade
Glucose Control
Renal Replacement therapy
Nutrition
Stress ulcer prophylaxis
Discuss goals of care

32. Questions? Have fun Ask questions Keep reading
Don’t accept anecdotes at face value
Look up
Find supporting literature

33. Transfusion in severe sepsis
In first 6 hours ( EGDT) if ScvO2 <70 despite adequate MAP and CVP, and HCT <30
In absence of active bleeding, active myocardial ischemia, transfuse only if Hb <7 gm/dl to target of 7-9 gm /dl (1B)
Do not use erythropoietin (1B) in severe sepsis to treat anemia
Do not use blood products ( FFP) to treat lab abnormalities ( prolonged INR) in absence of bleeding or planned procedures (2D)

34. Transfusion in severe sepsis
Platelet transfusion (2D):
Plt count <10,000 /mm3
Plt count <20,000 /mm3 and risk for bleeding is high
Plt count <50,000 and bleeding or needs procedures
Do not use: antithrombin (1B), activated protein C, iv immunoglobulins (2b)

35. Mechanical Ventilation
6 ml/kg predicted body weight tidal volume (1A)
Maintain plateau pressures ≤ 30 cm in ARDS(1B)
Apply PEEP to avoid alveolar collapse (1B)
Head of bed elevation degrees (1B)
Appropiate use of NIPPV in acute hypoxic respiratory failure (2B)

36. Mechanical Ventilation
Severe ARDS ( PaO2/FiO2 <100 mm Hg)
Recruitment manouver (2 C)
Prone positioning (2B) in experienced facilities
Avoid
Pulmonary artery catheters (1A)
Liberal fluid strategy(1C) in absence of hypoperfusion
B2 agonists in absence of bronchospasm (1B)

37. ARDS-NET protocol

38. Mechanical Ventilation
Weaning protocols in place for SBT (1A):
Arousable
Hemodynamically stable
No new potentially serious condition
Low ventilatory and FiO2 requirements
Consider extubation if above conditions are met

39. Sedation and NM blockade
Minimize sedation targeting specific titration endpoints (1B)
Avoid neuromuscular blocking agents in absence of ARDS (1C)
For severe ARDS short course of NMB agents may be used for upto 48 hours for hypoxia (2C)

40. Glucose control Protocolized approach (1A):
When 2 consecutive BS >180
Target upper BS level ≤ 180
Check BS 1-2 hrs till BS and insulin infusions are stable , then q 4 hours (1C)
Point of care BS may not be as accurate as plasma glucose (UG)

41. Renal replacement therapy
Continuous renal replacement therapy and intermittent hemodialysis are equivalent (2B)
Use continuous renal replacement therapy for better fluid management in hemodynam ically unstable patients (2D)

42. Stress Ulcer Prophylaxis
H2 blockers or proton pump inhibitors should be used in patients at risk for Upper GI bleeding (1B)
Proton pump inhibitors used rather than H2 blockers (2D)
In absence of risk factors, do not use prophylaxis (2B)

43. Prophylaxis Daily pharmacoprophylaxis in sepsis against VTE (1 B)
Daily sc low molecular weight heparin (1B)
Unfractionated heparin sc bid (1C) or tid
If creatinine clearance <30 ml/min, use deltaparin (1A) or Unfractionated heparin (1C)
Severe sepsis: combination of pharmacological therapy and intermittent pneumatic compression devices (2C)

44. Prophylaxis Contraindications to use of pharmacological prophylaxis:
Intracerebral hemorrhage
Active bleeding
Severe coagulopathy
Thrombocytopenia
Use intermittent pneumatic compression devices (2C)

45. Nutrition
Start oral or enteral ( if necessary) feeding within 48 hours for patients admitted with severe sepsis (2C)
Avoid full dose feeding in first week, use low dose (500 cal/day advancing only as tolerated) (2B)
Use iv glucose or enteral feeding instead of total parental nutrition in first week (2B)
Do not use specific immunomodulating supplementation (2C)

46. Goal clarification
Discuss goals of care and prognosis with patients and families (1B)
Incorporate goals of care and end of life care planning into treatment
Use palliative care when appropriate (1B)
Address goals of care within 72 hours of ICU admission (2C)