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New Trends in

Management of Severe Sepsis

Dr. M. HELMI AFIFI(MBBCh, MSc, MD, DHA)

Prof. of Anesthesia & Intensive Care

Menoufiya Faculty of Medicine, Egypt

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Sepsis: common, lethal, and expensive

• Major cause of morbidity and mortality

worldwide

• Kills ~ 1,400 people worldwide every day

• 400 000 ICU admission /y in USA

• Mortality rate 30–40%

• $50 billion per year in health care costs in USA

Angus DC et al, Crit Care Med 2001; 29[Suppl.]:S109

American Heart Association. Heart Disease and Stroke statistics 2006

Update

Severe Sepsis:

Comparative Incidence and Mortality

†National Center for Health Statistics, 2001. §American Cancer Society, 2001. *American Heart

Association. 2000. ‡Angus DC et al. Crit Care Med 2001

Incidence Mortality

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Infection

“A microbial phenomenon

due to invasion of host

tissue by microorganisms”

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Sepsis

“ Systemic host response to

invasive infection”

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"Except on few occasions,

the patient appears to die

from the body's response to

infection rather than from

it."

Sir William Osler – 1904

The Evolution of Modern Medicine

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Widespread inflammatory response to a

variety of severe clinical insults

Systemic Inflammatory Response Syndrome

(SIRS)

Others

Pancreatitis

Trauma

Burn

INFECTION

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Widespread inflammatory response to a

variety of severe clinical insults

Clinically recognized by the presence of

two or more of the following:

1. Temperature >38°C or <36°C

2. Heart rate > 90/min

3. RR > 20/min or PaCO2 <32 mmHg

4. WBC >12,000 cells/mm3, <4000 cells/mm3

Systemic Inflammatory Response Syndrome

(SIRS)

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SIRS + Evidence of infection

Sepsis

INFECTION SIRS

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Severe SepsisSepsis + Organ dysfunction

Infection SIRS

Acute Organ Dysfunction

Tachycardia

Hypotension

CVP

PAOP

Jaundice

Enzymes

Albumin

PT

Altered

Consciousness

Confusion

Psychosis

Tachypnea

PaO2 <70 mm Hg

SaO2 <90%

PaO2/FiO2 300

Oliguria

Anuria

Creatinine

Platelets

PT/APTT

Protein C

D-dimer

Balk. Crit Care Clin 2000;16:337-52

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Septic shock

Sepsis

+

Hypotension despite adequate fluid resuscitation

+

Hypoperfusion

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Septicemia

Sepsis that has an infection

in the bloodstream

itself

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1. Systemic Inflammatory Response Syndrome

(SIRS)

2. Sepsis (SIRS + infection)

3. Severe Sepsis (sepsis + end-organ damage)

4. Septic Shock (severe sepsis + hypotension

despite a fluid bolus)

ACCP/SCCM Consensus Conference 1991

Definitions

Bone RC, et al: Chest 1992; 101:1644 –1655

Crit Care Med 1992; 20:864

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Sepsis: Progressive Disease

Infection Sepsis Severe Sepsis Septic Shock

Microbiological

Phenomenon

Infection

+

SIRS

Sepsis

+

End-Organ

Damage

Severe Sepsis

+

Refractory

Hypotension

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Sepsis: Pathophysiology

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Systemic

InflammationCoagulation

Impaired

Fibrinolysis

Sepsis: A complex disease

Sepsis

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Hemostasis is unbalanced in

severe sepsis

Hemostasis

Coagulation

InflammationFibrinolysis

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Sepsis: Pathophysiology

Micro-organism

Microbial Products

Host Inflammatory Mediators

Inflammation Coagulation

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Sepsis: PathophysiologyFinal Common Pathway

Endothelial Cell Injury &

Microvascular Thrombosis

Hypoperfusion/Ischemia

Acute Organ Dysfunction

Death

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Surviving Sepsis Campaign

Crit Care Med 2008 Reprint

Also published in Intensive Care Medicine

(January 2008)

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Management of Severe Sepsis :

Antibiotics

Source control

Hemodynamic support

Mechanical ventilation

Nutritional support

Renal replacement Rx

Activated Protein C

(Xigris)

Fluid resuscitation

Intensive

Insulin Tx

Low Dose

Steroids

Early

Goal-Directed Rx

Initial Resuscitation

• Fluid resuscitation as soon as sepsis suspected

• Should not wait until ICU admission

• Elevated lactate identifies tissue

hypoperfusion in at-risk patients who are not

hypotensive

• Resuscitation goals: EGDT

Rivers et al. NEJM 2001;345:1368-77

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SIRS

Sepsis Septic ShockSevere Sepsis

Golden hours

Early goal-directed therapy in severe

sepsis & septic shock

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From Dellinger RP. Cardiovascular management of septic shock. Crit Care Med 2003;31:946-955.

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• Involves manipulation of cardiac preload, afterload, and contractility to achieve a balance between systemic oxygen delivery and oxygen demand

• Resuscitation end points: CVP, BP, venous oxygen saturation, arterial lactate concentration

Early goal-directed therapy in severe

sepsis & septic shock

N Engl J Med 2001;345:1368-77

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Central venous and

arterial catheterization

CVP

8 -12 mm Hg

MAP

65 and 90 mm Hg

ScvO2

70%

Goals achieved

Hospital admission

Protocol for Early Goal-Directed Therapy

Crystalloid

Colloid

Vasoactive

agents

Transf. of RBC

until Hct 30%

Inotropic agents

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49.2%

33.3%

0

10

20

30

40

50

60

Standard Therapyn=133

EGDTn=130

P = 0.01*

28-day Mortality

Rivers E. N Engl J Med 2001;345:1368-77.

Early Goal-Directed Therapy Results

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Fluid Therapy

• Colloid or crystolloid resuscitation is considered equal

– Natural or artificial colloids (less peripheral edema)

– Crystalloids (less cost)

• Fluid challenge over 30 min

– 500-1000 ml crystalloid

– 300–500 ml colloid

• Target CVP 8 mm Hg (12 mm Hg in mechanically ventilated patients)

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Vasopressors

• Norepinephrine or dopamine through a central

catheter is the initial vasopressor of choice.

– Failure of fluid resuscitation

– During fluid resuscitation attempts

• Do not use low-dose dopamine for renal protection

• In patients requiring vasopressors, place an arterial

catheter as soon as possible

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Vasopressin and Septic Shock

•• Decreases or eliminates requirements of

traditional pressors

• As a pure vasopressor, expected to decrease

cardiac output

• Consider in refractory shock despite high dose

conventional vasopressors

• 0.01-0.04 units/minute in adults

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Inotropic Therapy

• Consider dobutamine in patients with measured

low cardiac output despite fluid resuscitation.

• Continue to titrate vasopressor to mean arterial

pressure of 65 mm Hg or greater.

• Do not increase cardiac index to achieve an

arbitrarily predefined elevated level of oxygen

delivery.

Corticosteroids

• IV hydrocortisone 200-300 mg/d for 7 days

– recommended in patients with septic shock

who, despite adequate fluid replacement,

require pressors to maintain adequate BP

– Decreased mortality in patients with relative

adrenal insufficiency

Annane et al. JAMA 2002;288:862-71

Briegel et al. Crit Care Med 1999;27:723-32

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Controversies and Future Directions

1. How generalizable is EGDT to other populations?

2. How cost-effective is EGDT?

3. How are time and resources utilized so that the

EGDT protocol is accomplished?

4. Which components of EGDT actually make a

difference in outcomes?

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Mortality Reduction

• 2006 analysis of available randomized and observational data from 12 centers, totaling 1,298 patients, yielded similar results

– Mortality was reduced from 44.8% in the control group to 24.5% in the EGDT group

• This is better than aspirin + streptokinase for MI 5-week mortality (NNT=19) or tPA for acute ischemic stroke within 4.5 hours (NNT=15)

CHEST 2006; 130; 1579-1595.

for every 5 EGDT patients, one life was

saved

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EGDT decreases health care resource

consumption

• Decrease in vasopressor use, hospital and

ICU LOS, and MV days

• With a long ED wait time for an ICU bed,

there are few options other than making this

an ED intervention

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Take home message

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Employ EGDT & Sepsis Bundles in the

treatment of severe sepsis and septic

shock

• if you want to save lives,

• save your institution money,

• improve your department’s

standing in the house of medicine

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Thank You