1. ICU Presentations Vanessa Ohleyer, PGY2
Severe Sepsis
ICU Presentations
Vanessa Ohleyer, PGY2

2. Definitions
Sepsis
Severe Sepsis
Septic Shock

3. SIRS Temperature Heart Rate Tachypnea WBC Abnormalities
<96F (36C)
Heart Rate
>90-100
Tachypnea
RR >20
WBC Abnormalities
>10,000
<4,000
Tachypnea and tachycardia are the most sensitive clinical indicators of impending sepsis syndrome

4. Sepsis Severe Sepsis Septic Shock
Suspected or proven infection
>/=2/4 SIRS Criteria
Evidence of Systemic infection
Sepsis + Evidence of Organ Dysfunction(s)
Severe Sepsis + Decreased perfusion refractory to fluids
AMS (GCS dec by >2pts)
Hypotension
PaO2:FiO2 <300
Metabolic/Lactic Acidosis
Oliguria/Renal failure
Hyperbilirubinemia
Coagulopathy
Sepsis mortality = 25-30% Septic Shock mortality = 40-70%

5. Infection SIRS Sepsis Severe Sepsis Severe SIRS
MC organisms Nationally responsible for sepsis are MRSA and VRE
Lung is the most common site of infection (25-50%) Intraabdominal (25%) UTI (10%)
Severe
SIRS

6. Pathophysiology MICROORGANISM HOST High burden of infection
IMMUNE: innate/ adaptive
Superantigens
INFLAMMATORY
Resistance: to opsonization/phagocytosis and antibiotics
COAGULATION
Progression fro infection to sepsis depends on microbiological factors and inadequate/ unregulated immune response.

7. Multiorgan Dysfunction
Trigger
Innate immune and inflammatory reaction
Amplification of adaptive immunity
Disturbance of pro-anti coagulant balance
Immune suppression and apoptosis
Multiorgan Dysfunction

8. Triggers Protein/lipid/carbohydrate from microbe
Activated host compliment
Clotting cascade component
Dead host tissue
Ex: endodoxin (lipopolysaccharide of GNB), TSSST-1 of Staph aureus, BGS Toxin
Does NOT require organisms be present in bloodstream and toxins present transiently can cause sepsis (Ex: abscess/gut translocation)
Therefore, Blood cultures often negative

9. Innate Immune Reaction
Rapid response with pattern recognition
Ex: TLR2peptidoglycan of GP bacteria
Ex: TLR4 lipopolysaccharide of GN bacteria
Triggers intracellular signaling to increase transcription of proinflammatory molecules
TNFa, IL1b, IL10
Promotes upregulation of adhesion molecules in neutrophils and endothelials cells
KILLS MICROORGANISMS
INCREASES VASCULAR PERMEABILITY
RELEASES NITRIC OXIDE

10. Adaptive-Inflammatory Response
B -cells release Ig which bind microorganism then delivered by Ag presenting cells to NK cells and neutrophils
TH1: secrete proinflammatory cytokines TNFa and IL-1B
TH2: anti-inflammatory: IL4, IL10

15. Specific Organ Failures

16. Pulmonary Failure is RARELY absent
Increased work of breathing AND increased minute ventilation requirement
Usually a combination of hypoxic and hypercapnic respiratory failure
Mechanical Ventilation
Average 7-10d for survivors
½ develop ARDS (usually within the first 48H)
<5% require chronic ventilation
Severe injury reverses in 30d may take 1 yr for complete recovery
75% of severe sepsis requires mechanical ventilation

17. Sepsis Induced Hypotension
Circulatory
Sepsis Induced Hypotension
MAP<60
SBP <90
Drop in BP >40

18. Circulatory Decreased Intravascular Volume Decreased intake
Increased losses
Increased insensible losses
Increased Vascular Permeability NO

19. Circulatory Failure present at presentation in ½ Usually lasts 2-3 d
Usual vol deficit = 4-6L at presentation
Average requirement over 24H = >10L
Usually lasts 2-3 d
Pts requiring >15 DA or >7 NE  mortality of 60% (compared to 40% at lower doses)
May cause ventricle dilation and decreased contractility  decreased CO (therefore may be confused w cardiogenic shock)
SVR is increased in cardiogenic shock, decreased in Septic Shock

20. Renal
Oliguria dn modest RF (Cr 2-3) common in shock, but frank renal failure is rare
10-15% require renal replacement
Elderly pt w DM is at greatest risk
Prompt restoration of volume and avoidance of nephrotoxic drugs are essential to prevention

21. Metabolic Acidosis
Lactic Acidosis: decreased DO2 2/2 decreased PO2, anemia, decreased CO and cellular malfunction at level of O2 utilization by mitochondria
Lactic Acidosis can occur in ANBSENCE of hypotension
Resuscitation plays a much bigger role in reversal than high oxygen levels
Survival correlates best with lactate levels and NOT with pH

22. Coagulation Multifactorial
Expression of tissue factor on endothelial cells
Leukocytes and cytokine generation
Nearly 100% have some derangement in clotting factors
Full DIC present in only 10-20%
Carries a 50% mortality

23. CNS AMS is usually a later manifestation
Even minor depression in mental status is a poor prognostic indicator
Long term cognitive consequence is common among survivors
Memory, concentration and executive functioning difficulty

24. GI Ileus due to diversion of perfusion to heart and brain GI bleeding
No evidence to support delay in feeding
GI bleeding
Since EGDT, incidence has significantly decreased
Hepatocellular toxicity
shock liver elev transaminases and bilirubin, while Alk phos tends to remain NL

25. Treatment of Severe Sepsis

28. Hemodynamic Variables
Arterial Hypotension:
SBP < 90, MAP <70, SBP Decrease by >40, SBP >2 SD less than mean for age
Tissue Hypoperfusion
Hyperlactatemia (>1)
Decreased capillary refill/mottling

29. General Variables
Fever (>38.3C)
Hypothermia (core T <36C)
HR >90 or >2SD above normal value for age
Tachypnea
AMS
Significant edema or positive fluid balance (>20mL/kg over 24H)
Hyperglycemia (>140) in the absence of diabetes
Inflammatory Variables
Leukocytosis (>12)
Leukopenia (<4)
Normal WBC w >10% immature forms
Plasma CRP >2SD above normal
Plasma procalcitonin more than 2SD >mean

30. Hemodynamic Variables
Arterial Hypotension:
SBP < 90, MAP <70, SBP Decrease by >40, SBP >2 SD less than mean for age
General Variables
Fever (>38.3C)
Hypothermia (core T <36C)
HR >90 or >2SD above normal value for age
Tachypnea
AMS
Significant edema or positive fluid balance (>20mL/kg over 24H)
Hyperglycemia (>140) in the absence of diabetes
Tissue Hypoperfusion
Hyperlactatemia (>1)
Decreased capillary refill/mottling
Organ dysfunction variables
Arterial hypoxemia (Pa/FiO2<300)
Acute oliguria (UO<0.5ml/kg/hr for 2 hrs dispite fuids)
Cr increase >0.5gm/dl
Coagulation abnormalities (INR >1.5 or PTT >60)
Ileus (absent bowel signs)
Thrombocytopenia (PLT<100)
Hyperbilirubinemia (tBili >4)
Inflammatory Variables
Leukocytosis (>12)
Leukopenia (<4)
Normal WBC w >10% immature forms
Plasma CRP >2SD above normal
Plasma procalcitonin more than 2SD >mean

31. Hemodynamic Variables
Arterial Hypotension:
SBP < 90, MAP <70, SBP Decrease by >40, SBP >2 SD less than mean for age
General Variables
Fever (>38.3C)
Hypothermia (core T <36C)
HR >90 or >2SD above normal value for age
Tachypnea
AMS
Significant edema or positive fluid balance (>20mL/kg over 24H)
Hyperglycemia (>140) in the absence of diabetes
Tissue Hypoperfusion
Hyperlactatemia (>1)
Decreased capillary refill/mottling
Organ dysfunction variables
Arterial hypoxemia (Pa/FiO2<300)
Acute oliguria (UO<0.5ml/kg/hr for 2 hrs dispite fuids)
Cr increase >0.5gm/dl
Coagulation abnormalities (INR >1.5 or PTT >60)
Ileus (absent bowel signs)
Thrombocytopenia (PLT<100)
Hyperbilirubinemia (tBili >4)
Inflammatory Variables
Leukocytosis (>12)
Leukopenia (<4)
Normal WBC w >10% immature forms
Plasma CRP >2SD above normal
Plasma procalcitonin more than 2SD >mean
Yellow = new criteria for “systemic inflammatory signs
Red = not just sepsis, but severe sepsis

33. DVT Stress Ulcer Initial Resuscitation Early Goal Directed Therapy
Emergent
Initial Resuscitation
Early Goal Directed Therapy
Primary Treatment
Infection Control
Cardiovascular support
Control of Inflammation
Supportive
Respiratory
Sedation
Blood products
Renal
Nutrition
Prophylaxis
DVT
Stress Ulcer

34. kapadesigns

36. Initial Resuscitation
Within first 6 Hours
CVP 8-12
MAP >/=65
UO >/= 0.5 mL/kg/hr
SCVO2 >70%
SVO2 >65%
Normal Lactate

37. Initial Resuscitation
Despite “adequate” fluid resuscitation
SCVO2 <70% SVO2 < 65%
Transfuse if Hct <30%
Begin Dobutamine

38. Early Goal Directed Therapy

39. Initial Resuscitation Early Goal Directed Therapy
Emergent
Initial Resuscitation
Early Goal Directed Therapy
Primary Treatment
Infection Control
Cardiovascular support
Control of Inflammation

40. Antimicrobial Therapy
Administration of effective intravenous antimicrobials within the first hour of recognition
Severe infections with RF and Shock: combination therapy w ext spectrum Beta-lactam and either aminoglycoside or fluoroquinolone
Streptococcus pneumonia: beta-lactam and macrolide
Emperic Coverage 3-5 days until sourced, total typically 7-10
Cover neutropenic pts for MDR pathogens such as Acinetobacter and Pseuromonas
Cultures as clinically appropriate before antimicrobials if does not delay administration by more than 45min
Assess for de-escalation daily
Do not use low procalcitonin as a marker for discontinuation

41. Source Control Goal for ID and control of source is 12Hours
If peripancreatic necrosis is id’d as source: definitive intervention is best delayed until adequate demarcation of viable and nonviable tissues has occurred
Percutaneous rather than surgical drainage of abscesses if possible
If vascular access device suspected, should be promptly removed after alternate access est.

42. Infection Prevention
Chlorexidine gluconate for oropharyngeal decontamination to reduce risk of VAP

43. Hemodynamic Support Fluids Vasopressors Inotropic therapy
Crystalloids as initial choice in resuscitation
Minimum challenge of 30mL/kg
Do not use hydroxyethyl starches
Albumin may be used in pts who required large volumes of crystalloid
Vasopressors
Inotropic therapy
Corticosteroids

44. Hemodynamic Support Fluids Vasopressors Inotropic therapy
#1 Norepinephrine #2Epinephrine (MAP 65)
0.03 units/min Vasopressin with NE to reach MAP or to down titrate NE (do not use alone, and increase dose ONLY as salvage therapy)
DA as alternate to NE if bradycardic or LOW risk of tachyarrhythmia
Do not use Phenylepherine unless: NE causes serious arrhythmia, high CO with low BP, or as salvage
A line as soon as reasonable.
Inotropic therapy
Corticosteroids

45. Hemodynamic Support Fluids Fluid Challenge Vasopressors
Inotropic therapy
Trial of Dobutamine up to 20mcg/kg/min in presence of myocardial dysfunction or ongoing signs of hypoperfusion despite adequate volume and MAP
Corticosteroids

46. Hemodynamic Support Fluids Fluid Challenge Vasopressors
Inotropic therapy
Corticosteroids
Only use if goals cannot be met with fluids and vasopressors
Hydrocortisone IV 200mg/day as a continuous gtt; taper when vasopressors are no longer required
Do not to ACTH stim test

47. 1H 3H 6H 12H Administer 30mL/kg crystalloid Draw lactate
Draw Blood Cultures
Empiric Antibiotics 3H
Administer 30mL/kg crystalloid 6H
Apply vasopressors
CVP and SCVO2
Remeasure Lactate
12H
Source Control

48. Initial Resuscitation Early Goal Directed Therapy
Emergent
Initial Resuscitation
Early Goal Directed Therapy
Primary Treatment
Infection Control
Cardiovascular support
Control of Inflammation
Supportive
Respiratory
Sedation
Blood products
Renal
Nutrition

49. Respiratory Support Target TV of 6mL/kg PBW for sepsis induced ARDS
Upper limit goal for plateau pressure in a passively inflated lung <30
PEEP to avoid alveolar collapse
Moderate or severe ARDS higher PEEP strategies
Recruitment maneuvers for refractory hypoxemia
Prone positioning for P:F <100, where avail
Head of bed at 30-45deg
NIV for ARDS if benefits>risks
Weaning protocol with daily SBT
Do not use PA catheter in ARDS
Conservative fluid strategy for ARDS
Do not use Beta 2 agonist unless bronchospasm present

50. Sedation
Minimal continuous/intermittent sedation with specific titration endpoints
NMBA avoided in pts w/o ARDS, when used continuous infusion with train of four monitoring
Sort course NMBA (<48H) in pts w early sepsis induced ARDS and P:F <150

51. Blood Products Anemia common PRBCs when Hbg <7 to target 7-9
TNFa and IL1 b decrease expression of erythropoietin gene and protein
PRBCs when Hbg <7 to target 7-9
In absence of MI, severe hypoxemia, acute hemorrhage, ir ischemic heart disease
AFTER tissue hypoperfusion has resolved
Do not use erythropoietin for anemia
Do not use FFP to correct coagulopathy
Do not use antithrombin
PLT
<10 in absence of bleeding
<20 if significant bleeding risk
<50 if active bleeding, surgery, or invasive procedures

52. Glucose Hyperglycemia and insulin resistance are virtually universal
Acts as a procoagulant, induces apoptosis ,impairs wound healing and is associated with increased risk of death
Protocolized approach to BG when 2 consecutive levels are >180 (target <180, not <110)
Monitor glucose Q 1-2 h until stable then Q4H
POC may not be accurate

53. Renal Function
CRRT and intermittent hemodialysis are equivalent in pts w severe sepsis and acute renal failure
Use CRRT if pt is hemodynamically unstable
Do not use bicarb for the purpose of improving hemodynamics or reducing vasopressor requirement in pt w hypoperfusion-induced lactic academia with pH>7.15

54. Nutrition
Oral / enteral feedings within the first 48H rather than fasting/dextrose
Avoid mandatory full caloric feeding (500/day) and advance as tolerated
Use IV glucose and enteral nutrition over TPN
Use nutrition with no specific immunomodulating supplementation

55. Goals of Care Discuss goals and prognosis with family
Incorporate goals into treatment utilizing palliative care where appropriate
Address goals as early as possible, but no later than 72H.

56. Control of Inflammation
Do NOT use recombinant Activated Protein C
Do NOT use Immunoglobulins
Do NOT use Selenium
Do NOT use antithrombin

57. DVT Stress Ulcer Initial Resuscitation Early Goal Directed Therapy
Emergent
Initial Resuscitation
Early Goal Directed Therapy
Primary Treatment
Infection Control
Cardiovascular support
Control of Inflammation
Supportive
Respiratory
Sedation
Blood products
Renal
Nutrition
Prophylaxis
DVT
Stress Ulcer

58. Protocols
“Hospital-based performance improvement efforts in severe sepsis”
“That a weaning protocol be in place and that MV patients with severe sepsis undergo SBT regularly to evaluate the ability to discontinue…”
“A protocolized approach to blood glucose managementin ICU patients with severe sepsis”

60. 1H 3H 6H 12H Administer 30mL/kg crystalloid Draw lactate
Draw Blood Cultures
Empiric Antibiotics 3H
Administer 30mL/kg crystalloid 6H
Apply vasopressors
CVP and SCVO2
Remeasure Lactate
12H
Source Control