Severe Sepsis & Septic Shock Sepsis: the 1 st 6 hours. Objectives. What would you do? Case #2. What would you do? Case #1. What would you do?

(1)

Sepsis: the 1

st

_{6 hours}

Identification

&

Initial Management

Chris Fee, MD

UCSF Division of Emergency Medicine

2007 Topics in Emergency Medicine

Severe Sepsis & Septic Shock

• Gain respect for severe sepsis/septic shock

• Utilize lactate to identify high risk patients &

monitor resuscitation

• Understand & implement the 6 hour sepsis

bundle

Objectives

What would you do?

Case #1

• 66 yo man presents with anterior CP

What would you do?

Case #2

• 19 yo woman with abdominal pain after a

motor vehicle collision

HR 120, BP 80/50

After 1.5 L NS IV

HR 90, BP 126/76

What would you do?

Case #3

• 66 yo woman with R weakness & aphasia

What would you do?

Case #4

• 58 yo man with cough, fever, SOB

T 38.3

°

C

HR 106

BP 110/62

RR 22

O2 sat 98% on 4L/min

Lactate 4.4 mmol/L

(2)

Cases: Common Themes

• 1. Acute anterior wall STEMI

• 2. Isolated blunt abdominal trauma

• 3. Acute ischemic L MCA CVA

• 4. Severe sepsis due to community

acquired pneumonia

Door to lytics (30 mins)/balloon time (90 mins)

“Golden Hour of Trauma”

3 Hour window for lytics

Mortality

10%

8%

10%

30%

6 Hour Sepsis Bundle of Care

Antibiotics within 4 Hours???

Now what would you do?

Case #4 (same but different)

• 58 yo man with cough, fever, SOB

T 38.3

°

C

HR 126

BP 60/46

RR 22

O2 sat 98% on 4L/min

76/52

2L NS IV

Se

ptic

Sh

ock

Outline

• Surviving Sepsis Campaign

Definitions & Epidemiology

Evidence-Based Recommendations

Implementation strategies

• Controversies

• Future Directions

Dellinger RP, et al.

Intensive Care Med

. 2004;30:536-555.

Osborn TM, et al.

Ann Emerg Med

2005;46:228-31.

• Surviving Sepsis Campaign

Definitions & Epidemiology

Evidence-Based Recommendations

Implementation strategies

• Controversies

• Future Directions

SIRS

Systemic Inflammatory Response Syndrome (SIRS) (

≥

2)

• T > 38 °C or < 36 °C

• HR > 90

• RR > 20 or PaCO2 < 32mmHg

• WBC > 12, < 4, or > 10% bands

Pancreatitis Trauma Burns Other

Infection

Sepsis

Severe

Sepsis

Sepsis +

≥

1 organ dysfunction or

lactate

≥

4mmol/L

Bone RC, et al.

Chest

1992:1644-55. Vincent JL.

Crit Care Med

1997;25:372-4.

Septic

Shock

Sepsis + hypotension (after 20mL/kg IVF)

Organ Dysfunction

• Cardiovascular

SBP< 90 mmHg

MAP< 65

SBP decrease > 40 mmHg

from baseline

• Renal

Creatinine > 2

UOP < 0.5ml/kg/hr for > 2

hrs

• Heme

Platelets < 100,000

• Metabolic

Lactate > 2.0 once CVP >

8-12 mmHg

• Respiratory

Bilateral pulmonary

infiltrates with

a new (or increased) O2

requirement to maintain

SpO2>90%

PaO2/FiO2 <300

• Hepatic

INR > 1.5

aPTT > 60 secs

Total bili > 2 mg/dL

At least 7 different definitions

(3)

Pathogenesis

Organism

Global Tissue Hypoxia &

Organ Dysfunction

Severe Sepsis

Multiple Organ Dysfunction &

Refractory Hypotension

Septic Shock

Systemic Inflammation or

Inflammatory Response

Diffuse Endothelial Disruption

& Microcirculation Defects

Nguyen HB, et al.

Ann Emerg Med

2006;48:28-54.

QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture.

Death

Pathogenesis

QuickTime™ and a TIFF (Uncompressed) decompressor

are needed to see this picture.

Death

Organism

Global Tissue Hypoxia &

Organ Dysfunction

Severe Sepsis

Multiple Organ Dysfunction &

Refractory Hypotension

Septic Shock

Systemic Inflammation or

Inflammatory Response

Diffuse Endothelial Disruption

& Microcirculation Defects

Nguyen HB, et al.

Ann Emerg Med

2006;48:28-54.

How many patients with severe sepsis/septic

shock are seen in your workplace each year?

A. <5

B. 6-10

C. 11-15

D. 16-20

E. >20

Incidence of Severe Sepsis

Cas

es

/10

0,

00

0

300

250

200

150

100

50

0 AIDS

*

_Colon

CA

§

Breast

CA

§

CHF

†

_Severe

Sepsis

‡

*_{Karon JM, et al.}_{Am J Public Health}_{. 2001;91:1060-1068}§_{American Cancer Society, 2001} ‡Angus, et al. Crit Care Med. 2001;29:1303-10 †American Heart Association, 2001

Mortality of Severe Sepsis

250,000

200,000

150,000

100,000

50,000

0 D

eat

hs

/Y

ear

AIDS

*

_Breast

CA

§

Acute

MI

†

Severe

Sepsis

‡

*_{Karon JM, et al.}Am J Public Health. 2001;91:1060-1068 §_{American Cancer Society, 2001} ‡_{Angus, et al.}_{Crit Care Med}_{. 2001;29:1303-10}†_{American Heart Association, 2001}

Probability of Death

Days in Hospital

60%

40%

20%

0%

0 ₂₀

₄₀

60

80 M

o

rt

alit

y

Alberti C, et al.

AJRCCM

2003;168:77-84.

Infection no SIRS

(n=584)

Sepsis (n=1063)

Severe Sepsis

(n=827)

Septic Shock

(n=1134)

QuickTime™ and a TIFF (Uncompressed) decompressorare needed to see this picture.

(4)

Severe Sepsis-Associated

Mortality

Angus

0%

20%

40%

60%

80%

M

o

rt

alit

y

Number of Dysfunctional Organ Systems

Vincent

One

Two

Three

≥

Four

Vincent JL, et al. Crit Care Med1988;21:1793-800. Angus DC, et al. Crit Care Med2001;29:1303-10.

Newer Diagnostic Criteria

for Sepsis

• General variables

Temp > 38.3 or < 36C

HR > 90

Tachypnea

Altered mental status

Significant edema or positive fluid balance (>20ml/kg/24hrs) Glucose > 120 (no DM)

• Inflammatory variables

WBC >12 or < 4 or > 10% bands CRP > 2 SD above normal Procalcitonin > 2 SD above normal

• Hemodynamic variables

SBP < 90, MAP < 70 or SBP decrease > 40 SvO2< 70%

Cardiac index > 3.5 L/min/m2

• Organ Dysfunction variables

PaO2/FiO2< 300 Acute oliguria Creatinine increase > 0.5 INR > 1.5 or aPTT > 60s Ileus Platelets < 100,000 Total bilirubin > 4

• Tissue perfusion variables

Hyperlactatemia

Decreased cap refill or mottling

Infection (documented or suspected) and SOME of the following:

Levy MM, et al.

Crit Care Med

2003;31:1250-6.

• Surviving Sepsis Campaign

Definitions & Epidemiology

Evidence-Based Recommendations

Implementation strategies

• Controversies

• Future Directions

Identification

(2 Step Process)

• Step 1.

Is the patient septic?

≥

2 SIRS criteria + suspected infection

z

Step 2.

Does the patient have severe sepsis

/septic shock?

Any one of the following:

1. Persistent hypotension (after 20mL/kg IVF)

2. 1 or more organ system dysfunction

3. Lactate > 4mmol/L

_Why???

Do You Currently Order Lactate Levels on

Patients with Suspected Sepsis?

A. Yes

B. No, it’s not going to change my

management

C. No, the lab turnaround makes it

essentially useless to me

D. No, it’s not available where I work

E. No, other reason

Lactate

M

o

rt

alit

y R

at

e

0%

5%

10%

15%

20%

25%

0 - 2.4

2.4 – 3.9

≥

4 Death within 3 days

28-day in-hospital mortality

(5)

Lactate

“Cryptic Shock”

• Tissue hypoperfusion without

hypotension

• On the brink of cardiovascular collapse

↓

Myocardial contractility & compliance

If not treated aggressively, leads to multiple

organ failure & mortality

Lactate

Resuscitation

• Lactate clearance

inversely related to

mortality (measured at 6

hrs from initiation)

• Best available marker

for need of ongoing

resuscitation

Nguyen HB, et al.

Crit Care

Med

2004;32:1637-42.

So You Can Identify Severe

Sepsis/Septic Shock, Now What?

• Step 3

Source control

Early cultures & antibiotics

Early goal-directed therapy

Protective ventilation strategies

Activated protein C

Intensive insulin therapy

Low dose steroids

Narrowing antibiotic spectrum once sensitivities

available

Grade of Recommendation

B

D

C/E?

E

D&E

B

ED

ICU

Early Goal-Directed Therapy

Physical exam, vitals, urine output,

CVP, mental status are

UNRELIABLE

indicators

of perfusion

Early Goal-Directed Therapy

• Inadequate O

2 delivery = key to progression

Surrogate measure of cardiac output & oxygen extraction

at the tissue level

Mixed venous (S

v

O

2

) and central venous (S

cv

O

2

) O

2

saturation

• Manipulate preload, afterload, contractility

Goal: balance O

2

demand & delivery

Rivers E, et al.

NEJM

2001;345:1368-77.

Early Goal-Directed Therapy

Sedation, paralysis (if intubated), or both

Central venous ±

arterial catheterization

1. SIRS + suspected infection & 2. SBP < 90 (after 20mL/kg IVF)

or lactate ≥4 or multiorgan dysfunction

Supplemental O2 ±

endotracheal intubation & mechanical ventilation

(6)

Early Goal-Directed Therapy

CVP

Colloid <8 mm Hg Crystalloid 8-12 mm Hg

Central venous ±

Supplemental O2 ±

endotracheal intubation & mechanical ventilation

Rivers E, et al.

NEJM

2001;345:1368-77.

Early Goal-Directed Therapy

MAP CVP

Colloid <8 mm Hg Crystalloid 8-12 mm Hg

Central venous ±

Supplemental O2 ±

endotracheal intubation & mechanical ventilation Vasoactive agents <65 mm Hg >90 mm Hg

Norepinephrine

pressor of choice

Rivers E, et al.

NEJM

2001;345:1368-77.

>65 and <90 mm Hg

Early Goal-Directed Therapy

ScvO2 <70% Transfusion of red cells _{until hematocrit > 30%} ≥70% Sedation, paralysis (if

intubated), or both CVP Colloid <8 mm Hg Crystalloid 8-12 mm Hg Central venous ± arterial catheterization

Supplemental O2 ±

endotracheal intubation & mechanical ventilation MAP >65 and <90 mm Hg Vasoactive agents <65 mm Hg >90 mm Hg

Norepinephrine

pressor of choice

<70% ≥70% Inotropic agents

Dobutamine

Rivers E, et al.

NEJM

2001;345:1368-77.

Early Goal-Directed Therapy

Sedation, paralysis (if intubated), or both CVP Colloid <8 mm Hg Crystalloid 8-12 mm Hg Central venous ± arterial catheterization

Supplemental O2 ±

endotracheal intubation & mechanical ventilation MAP >65 and <90 mm Hg Vasoactive agents <65 mm Hg >90 mm Hg

Norepinephrine

pressor of choice

ScvO2 <70% Transfusion of red cells _{until hematocrit > 30%} ≥70% <70%

≥70%

Inotropic agents

Dobutamine

Rivers E, et al.

NEJM

2001;345:1368-77.

Goals

achieved?

No

Hospital admission Yes

Early Goal-Directed Therapy

Central venous ±

arterial catheterization Sedation, paralysis (if intubated), or both CVP MAP ScvO2 Goals achieved? Colloid <8 mm Hg Crystalloid 8-12 mm Hg >65 and <90 mm Hg

Transfusion of red cells until hematocrit > 30% <70% ≥70%

No

Hospital admission Yes

Supplemental O2 ±

Norepinephrine

pressor of choice

Dobutamine

Rivers E, et al.

NEJM

2001;345:1368-77.

Early Goal-Directed Therapy

• ↓

In-hospital mortality 16%

46.5% controls vs 30.5% in EGDT group

Relative risk of death = 0.58

(7)

Does Your ED/Practice Currently

Utilize an EGDT Protocol?

A. Yes

B. No, lack of specialized monitoring

equipment

C. No, too many ED resources required

D. No, need for central venous cannulation

E. No, other reason(s)

• Surviving Sepsis Campaign

Definitions & Epidemiology

Evidence-Based Recommendations

Implementation strategies

• Controversies

• Future Directions

Concept of the “Bundle”

• Institute for Healthcare Improvement

(www.ihi.org)

Bundle: group of interventions that, when

implemented together, result in better

outcomes than individually

Institute for Healthcare Improvement website: as accessed on 9/2/2007.

Concept of the “Bundle”

The Acute MI Model

Angiotensin-converting enzyme (ACE) inhibitors, lipid-lowering agents (statins), additional antihypertensive agents

Secondary prevention strategies

Percutaneous transluminal coronary angioplasty (PTCA), stenting, coronary artery bypass grafting (CABG)

Invasive procedures for tissue reperfusion and vessel revascularization

Angiography, intravascular ultrasound, vascular catheterization

Invasive procedures for diagnosis/monitoring

ASA, glycoprotein (GP) IIb/IIIa inhibitors, adenosine diphosphate-(ADP) receptor blockers Antiplatelet therapies

Heparin, low-molecular-weight heparins Anticoagulants

Streptokinase, urokinase, alteplase, retaplase, tissue plasminogen activator (tPA)

Fibrinolytics

Echocardiography Cardiac monitoring

Nitrates, analgesics (opioids), oxygen therapy, fluid resuscitation

Acute management

www.survivingsepsis.org

6 Hour (Resuscitation) Bundle

Steps 1-3 (ED Care)

• Prompt identification

Includes lactate measurement

• Early cultures & appropriate antibiotics

• EGDT

Includes measurement of CVP & S

_cv

O

₂

Severe sepsis (2001-2004): 2/3 present via ED

Average ED length of stay: 4.7 hours (20% spent >6 hours)

Which Antibiotics to Give?

Carbapenem + vancomycin or third- or

fourth-generation cephalosporin, piperacillin/tazobactam, or

ticarcillin/clavulonate + gentamicin

Unknown

Vancomycin

Catheter

Piperacillin/tazobactam or ticarcillin/clavulonate or

carbapenem or ampicillin + gentamicin or

fluorquinolone

Urinary tract

Carbapenem or ampicillin + metronidazole +

gentamicin/tobramycin or fluoroquinolone

Abdomen

Carapenem +/- fluoroquinolone or Cefepime or

piperacillin/tazobactam +/- fluoroquinolone

Health care-associated

pneumonia

3rd generation cephalosporin + azithromycin or

fluoroquinolone

Community-acquired

pneumonia

Antibiotic

Source

54%

20%

10%

(8)

24 Hour (Management) Bundle

The 4th Step (ICU Care)…

• Source control

• Protective ventilation strategies

• Low dose steroids (???)

• Intensive insulin therapy (???)

• Activated protein C (???)

• Narrowing of antibiotic spectrum

Example Sepsis Bundles

♦

MUST (Multiple Urgent Sepsis Therapies)

♦

www.mustprotocol.com

♦

STOP (Strategies to Timely Obviate the

Progression of Sepsis in the ED)

♦

www.llu.edu//llumc/emergency/patientcare

♦

UCSF

♦

Included with syllabus

Strategies for Initiating EGDT

• ED-based

Henry Ford Hospital, MUST protocol

• Rapid response team-based

Good Samaritan Hospital (community)

• ICU-based

UCSF

If you do utilize EGDT, what

model do you use?

A. ED-based

B. Rapid Response Team-based

C. ICU-based

D. Not sure

E. Don’t utilize EGDT where I work

• Surviving Sepsis Campaign

Definitions & Epidemiology

Evidence-Based Recommendations

Implementation strategies

• Controversies

• Future Directions

n

(9)

Controversies

Lactate & “Cryptic Shock”

• Subgroup in River’s EGDT study

20% (EGDT) vs 60.9% (control) mortality

• MUST Protocol Implementation

37/116 in protocol had

“cryptic shock”

Donnino MW.

Chest

2003;90S.

Shapiro NI, et al.

Crit Care

Med

2006;34:1025-1032.

Controversies

When to Order a Lactate?

• “Blood culture = lactate”

• ≥

2 SIRS criteria & suspected

infection (i.e. septic)

Controversies

EGDT

1st 6 Hours – Was it the volume?

3.5 ±

2.4L

18.5%

60%

0.8%

Control

EGDT

P<0.001

5 ±

3L

64%

95%

13.7%

Fluids

Red Cell

Transfusion

Dobutamine ScvO2

≥

70%

Rivers E, et al.

NEJM

2001;345:1368-77. (see accompanying

Letters to the Editor.

NEJM

2002;346:1025-1026.)

Controversies

EGDT

Central venous ± arterial catheterization CVP MAP ScvO2 Goals achieved Colloid <8 mm Hg Crystalloid

No

Supplemental O2 ±

Norepinephrine

pressor of choice

<70% Inotropic agents

Dobutamine

Sedation, paralysis (if intubated), or both CVP

Dobutamine-induced

hypotension vs

unmasks volume

depletion

35.9%

50.4%

13.7%

27.4%

Controversies

EGDT

1st 6 Hours – Was it the volume?

3.5 ±

2.4L

18.5%

60%

0.8%

Control

EGDT

P<0.001

5 ±

3L

64%

95%

13.7%

Fluids

Red Cell

Transfusion

Dobutamine ScvO2

≥

70%

Controversies

Standardized Order Sets

• Cookbook or evidence-based medicine??

• Significantly reduced mortality & length

of stay

(10)

Controversies

Single Center & Small n

• Review of all published EGDT data

12 trials (1298 patients)

Aggregate risk reduction of 20.3%

Did not use formal methods for meta-analyses

Otero RM, et al.

Chest

2006 Nov;130:1579-95.

Controversies

High Cost / Resource Utilization

• 23.4% reduction in hospital costs

• Most cost effective if >16 patients/year

• True for all models (ED-, Rapid Response

Team-, and ICU-based care)

Huang DT, et al.

Crit Care

2003;7(suppl):S116.

Controversies

Proprietary Equipment

• PreSep catheter & Vigilance monitor

(Edwards Lifesciences)

• Can use central line (in RA) & draw

blood gases for serial ScvO2 levels

instead

Controversies

Pharma Support of SSC Guidelines

• Lilly & Edwards funded Surviving Sepsis

Campaign

? overstated benefits of activated protein C

No mention of ADDRESS/RESOLVE trial data

• Guidelines from other unbiased sources

are similar

Eichacker PO, Natanson C, Danner RL.

NEJM

2006;355:1640-2.

• Surviving Sepsis Campaign

Definitions & Epidemiology

Evidence-Based Recommendations

Implementation strategies

• Controversies

• Future Directions

Future Directions

Diagnostics

• More specific markers for bacterial sepsis

Procalcitonin???

Soluble Flt-1???

• Predicting who may progress from severe

sepsis to septic shock

(11)

Future Directions

Case #4 (same but more different)

• 58 yo man with cough, fever, SOB.

Lactate 4.4 mmol/L

T 38.3

°

C

HR 106

BP 110/62

RR 22

O2 sat 98% on 4L/min via NC

Future Directions

Diagnostics

• Blood/urine/CSF cultures negative

• 3 days in ICU with broad-spectrum

antibiotics

• Clostridium dificile

colitis

• Rash

• $$$

• Influenza A positive nasal wash

Future Directions

Diagnostics

• Identification of bacteria causing severe

sepsis/septic shock in patients using a

16S microarray

10ml blood

Compares rDNA in sample to microarray of

rDNA from known bacteria (internal library)

In theory: obtain rapid speciation of any

bacteria in the bloodstream

Future Directions

Diagnostics

Future Directions

Refinements to EGDT?

Central venous ±

arterial catheterization Sedation, paralysis (if intubated), or both CVP MAP ScvO2 Goals achieved Colloid <8 mm Hg Crystalloid 8-12 mm Hg >65 and <90 mm Hg

No

Supplemental O2 ±

Norepinephrine

pressor of choice

Dobutamine

Future Directions

Treatments

• Statins

• Drugs designed against superantigen &

mannose

• Inhibition of tissue factor

• Interferon gamma to boost macrophage

function

(12)

Mortality Reductions:

Sepsis vs. Acute Coronary Syndromes

A

b

so

lu

te

M

o

rt

al

ity

Re

d

u

ct

io

n

16%

12%

8%

4%

0%

Cardiology Trials

Sepsis Trials

GP

II

b/

II

Ia

in

hi

bi

to

rs

St

re

pt

ok

in

as

e i

n M

I

APC

, al

l co

mer

s

APC

, A

PAC

H

E

II

>

2

5 EGDT

Low

do

se

s

ter

oid

s

AR

D

Sn

et

ve

nt

Ti

gh

t gl

yc

em

ic

co

ntr

ol

An

tib

iot

ic

s

(< 4 hr s for pneu moni a)

51 >100

16

10

11

29

6

8

NNT to prevent 1 death

Agarwal R, Singh N.

Acad Emerg Med

. 2005;12:912.

166

Long Way To Go…

• 2004 survey of academic EDs in 18 states

7% reported use of EGDT

Barriers

75%: lack of specialized monitoring equipment

43%: too many ED resources required

36%: need for central venous cannulation

Jones AE, Kline JA.

Crit Care Med

2005;33:1888-9.

Take Home Points

• Early identification paramount

SIRS criteria, lactate levels

• Concept of “cryptic shock”

“Blood culture = lactate”

• Establish sepsis bundles of care in your

workplace

Physician champion, interdepartmental/

multidisciplinary collaboration

Thank You

• Any Questions?

UCSF Sepsis Bundle

Step 1: Recognize Sepsis

TIME 0 hours

Triage:

1. Vital Signs (Temp, HR, RR, BP) 2. History of Illness If ≥2 SIRS criteria: 1. Temp > 38.3C or <36.0C 2. HR > 90 3. RR > 20 or PaCO2<32mmHg 4. WBC >12K, <4K or > 10% bands AND

Suspected Bacterial Infection

ED RN: if obtaining blood cultures prior to pt seen by MD, send CBC c diff and lactate level or discuss with

Attending If < 2 SIRS or no Suspected Bacterial Infection NOT SEPTIC EXIT PROTOCOL NOW!

UCSF Sepsis Bundle

Step 2: Assess for Severe Sepsis/Shock

Assess appropriateness of EGDT: 1. Obtain WBC

2. Obtain VBG, lactate, electrolytes 3. Administer fluid bolus 4. Obtain appropriate cultures 5. Assess organ function 6. Initiate antibiotic therapy

2 hours 4 hours If SBP, lactate, organ function within normal limits

NOT SEVERE SEPSIS/ SEPTIC SHOCK

Reassess in 1 hour If one or more of: 1. SBP < 90 after 20mL/kg fluid administration 2. Lactate ≥4mmol/L 3. ≥1 organ dysfunction*

PATIENT HAS SEVERE SEPSIS/SEPTIC SHOCK: 1. CONSULT ICU FELLOW r.e. EGDT 2. MOVE PATIENT TO ICU, IF POSSIBLE 3. INITIATE EARLY GOAL DIRECTED THERAPY

(13)

4 hours Initiate Early Goal Directed Therapy Orders: 1. Place central line for CVP/ScvO2 monitoring 2. Begin broad spectrum antibiotics

CVP? If < 8mmHg 500mL crystalloid bolus over 30 min

If ≥ 8 MAP? If < 65mmHg Titrate vasopressors** ScvO2? If < 70% Hgb? If ≥ 65 6-8 hours If ≥ 70%

EARLY GOAL DIRECTED THERAPY TARGETS ACHIEVED:

1.) REASSESS ANTIBIOTIC THERAPY 2.) CONSIDER ADDITIONAL THERAPIES 3.) IF ScvO2 STILL < 70%, CONSIDER INTUBATION, MECHANICAL VENTILATION, PARALYSIS, AND SEDATION TO DECREASE O2 CONSUMPTION

If ≥ 10 Titrate inotropic agent If < 10mg/dL Transfuse

UCSF Sepsis Bundle

Step 4: ICU Care

1.) ASSESS PATIENT FOR APPROPRIATENESS OF ADDITIONAL THERAPIES#

Calculate APACHE II score Measure rise in cortisol after ACTH-stim test*** Measure blood glucose Assess for ALI or ARDS If ≥ 25 Give APC If < 9mcg /dL Give Steroids If ≥ 140 mg/dL Maintain serum glucose btwn 80-120 mg/dL If resp. failure Ventilate with low tidal volume protective mechanical ventilation

Selected References

• Surviving Sepsis Campaign

Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med2004;32:858-873.

Osborn TM, Nguyen HB, Rivers EP. Emergency medicine and the Surviving Sepsis Campaign: an international approach to managing severe sepsis and septic shock. Ann Emerg Med2005;46:228-31.

www.survivingsepsis.org • Early Goal-Directed Therapy

Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. NEJM2001;345:1368-77.

Accompanying Letters to the Editor. NEJM2002;346:1025-1026.

• Treatment Bundles

www.ihi.org(Institute for Healthcare Improvement)

www.mustprotocol.com www.llu.edu//llumc/emergency/patientcare • Review

Nguyen HB, Rivers EP, Abrahamian FM, et al. Severe sepsis and septic shock: review of the literature and emergency department management guidelines. Ann Emerg Med2006;48:28-54.

Otero RM, Nguyen HB, Huang DT, et al. Early goal-directed therapy in severe sepsis and septic shock revisited: concepts, controversies, and contemporary findings. Chest2006 Nov;130:1579-95.

Russell JA. Management of sepsis. NEJM2006;355:1699-42.