1. SEPSIS
Stephanie Tang

2. Page #1:
 10:40pm:
“Patient Chen spiked fever to 38.7oC.
Other vitals are BP 100/60, HR 110, RR
20, SaO2 95% on RA”

3. Fever
 work up should include (at least) the following:
 blood cultures
 at least two with one being peripheral
 if pt has central access, must culture each port
 UA and urine culture
 CXR
 a careful exam

4. Page #2
 12:15am:
“Patient Peterson spiked fever to 38.7oC.
Other vitals are BP 92/55, HR 120, RR
24, SaO2 95% on RA”

5. SIRS sepsis
severe
sepsis
septic
shock
multiple
organ
dysfunction
syndrome
(MODS)

6. Systemic Inflammatory Response
Syndrome (SIRS)
 T >38.3oC OR T <36oC
 HR >90/min
 RR >20/min OR PaCO2 <32mmHg
 WBC >12,000 OR <4,000
OR >10% immature forms
American College of Chest Physicians & Society of Critical Care Medicine 1991

7. Systemic Inflammatory Response
Syndrome (SIRS)
 dysregulated inflammatory response to
an insult
 autoimmune disorder
 pancreatitis
 vasculitis
 thromboembolism
 burns
 surgery

8. Sepsis
 SIRS + source of infection
(probable or documented source)

9. Severe Sepsis
 sepsis + evidence of hypoperfusion
 oliguria or acute renal failure
 encephalopathy
 coagulopathy
 acute respiratory failure
 ischemic hepatopathy
 skin mottling
 elevated lactate
 low central venous saturation

10. Septic Shock
 severe sepsis refractory to fluid resuscitation
of 30mL/kg
- ex. 70 kg  2.1 L of IVF
 distributive shock

11. Why Do We Care about Sepsis?
 1,665,000 cases in the United States each year
Chest. 2011;140(5):1223-1231

12. In-hospital mortality
N Engl J Med. 2003;348(16):1546

13. Long term Mortality
Crit Care Med. 1995 Jun;23(6):1040-7.

14. Long term Mortality
Crit Care Med. 1995 Jun;23(6):1040-7.

15. WHAT HAPPENS?

16. Normally…
proinflammatory
mediators
TNFα, IL-1
anti-inflammatory
mediators
IL-10, transforming growth factor
β, IL-1 receptor antagonist

17. Sepsis
 occurs these responses to an infection
exceeds the boundaries of the local
environment, leading to a more
generalized response

18. Mitochondrial Dysfunction
 Peripheral blood
monocytes in
sepsis
 Assay membrane
potential at
admission, 3 days
and at hospital
discharge
Christophe et al. Am. J. Respir. Crit. Care Med 2001 164: 389-395

19. Circulatory Failure
↑ nitric oxide
↑ prostacyclin
(improve metabolic
autoregulation)
hypotension
(high CO, low SVR state)

20. Endothelial Damage
Mutunga et al. Am. J. Respir. Crit. Care Med., Volume 163, 2001, 195-200

21. Myocardial Dysfunction
 circulating depressant factors
Parrillo. J Clin Invest. 1985;76:1539–1553

22. Myocardial Dysfunction
 reduced
ventricular
function
 even in setting of
elevated CO
 reversible (usually
7-10 days)
Kumar et al J Exp Med 1996;183:949-953
TNF
IL-1

23. Coagulopathy
 Endothelial
expression of
Tissue Factor
 Decreased
endothelial
expression of
thrombomodulin
Marshall Nature Rev Drug Disc 2003;2-391-405.

24. Coagulopathy of Sepsis
 In-situ thrombosis
 Skin biopsy in meningococcal sepsis
Faust et al.N Engl J Med 345 (6): 408, August 9, 2001

25. In Summary…
Riedemann et al, Novel strategies for the treatment of sepsis, Nat Med, 9(5):517-524

26. TREATMENT OF SEVERE
SEPSIS

27. Monitoring
 close monitoring of heart rate and blood pressure
 foley (to monitor urine output)
 frequent clinical reassessments

28. Goals
fluid
resuscitation
stabilize
breathing
source
control
SEPSIS

29. Resuscitation
 Fluids should be bolused
 Large bore IVs are best
 22g IV = max 35 ml/minute
 20g IV = max 60 ml/min
 18g IV = max 105 ml/min
 16g IV = max 205 ml/min
 14g IV = max 333 ml/min
rate ∞
length
radius4

30. Resuscitation
 crystalloid
 lactated ringers
 normal saline
 nongap (hyperchloremic) acidosis
 hypokalemia
 colloid
 blood
 albumin
130 109
154 154
4
+ lactate 28
HCO3
(by liver)

31. Respiratory Status
oxygenation ventilation airway

32. Respiratory Status
oxygenation
pulmonary edema
ARDS
ventilation airway

33. Respiratory Status
oxygenation ventilation
primary respiratory alkalosis
↑ work of breathing ↔ ↑ O2 consumption
airway

34. Respiratory Status
oxygenation ventilation airway
altered mental status

35. Source Control
 appropriate antibiotic coverage
 abscesses or closed space infections
 ascending cholangitis
 obstructive pyelonephropathy

36. Early Goal-Directed Therapy in the Treatment of
Severe Sepsis and Septic Shock
Emanuel Rivers, M.D., M.P.H., Bryant Nguyen, M.D., Suzanne Havstad, M.A., Julie Ressler, B.S.,
Alexandria Muzzin, B.S., Bernhard Knoblich, M.D., Edward Peterson, Ph.D., Michael Tomlanovich,
M.D., for the Early Goal-Directed Therapy Collaborative Group
N Engl J Med 2001;345: 1368-1377

37. Early Goal-Directed Therapy
 Rationale: early hemodynamic assessment
(physical findings, vital signs, CVP, UOP) fail to
detect persistent global tissue hypoxia
 Goal: resuscitation strategy targeted to
optimize cardiac preload, afterload, and
contractility to achieve balance between
systemic oxygen delivery and oxygen demand
 Endpoints: mixed venous O2 sat, arterial
lactate, base deficit, pH

38. Early Goal-Directed Therapy
 n = 263
 In ED:
SIRS +
sBP< 90 or lactate >4
 after 30cc/kg fluid bolus
 Randomized to:
usual care
vs.
early goal-directed
therapy protocol

39. In-hospital mortality
 Mortality: 30.5% vs. 46.5% (p=0.009)
 ARR 16%, NNT 6.3
 Larger initial fluid resuscitation in EGDT arm
 4.9L vs. 3.5L (p<0.001)

40. Lessons from EGDT
 up front aggressive monitoring for
hypoperfusion is critical
 early aggressive IVF is beneficial
 clinical markers are important but we need to
also track markers for occult hypoperfusion
(mixed venous sat, lactate)