Sepsis Education

8/6/2019 Sepsis Education

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What is Sepsis ?

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Main causative organisms

Annane D, et al. Lancet 2005;365:63-78Martin GS, et al. NEJM 2003;348:1546-54

70% Septic patients : Blood culture (-)

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Sepsis versus SIRS

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From Infection to Septic Shock

Nguyen HB, et al. AnnEmergMed 2006;48:28-545


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SIRS to Septic Shock

Insult SIRS Sepsis Severe Sepsis

2 of the following:BT >38 or 90bpmRR > 20bpm or PaCO2 12,000, 10% bands

SIRS + presumed orconfirmed infectious process

Sepsis +1 organ dysfunctionCardiovascular (Refractory low BP)

AdrenalHematologicCoagulationRenalRespiratoryHepatic

CNSUnexplained metabolic acidosisBone RC, et al. Chest 1992;101:1644

SepticShock

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Severe Sepsis

Sepsis-induced

tissue hypoperfusion or organ dysfunction

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Septic shock

Sepsis-induced hypotension persisting

despite adequate fluid resuscitation

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Epidemiology of Sepsis in US (1979-2000)

N Engl J Med 2003; 348: 1546-54.9


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Organ dysfunction is a majoroutcome parameter

Septic shock (n=1134)

Severe Sepsis (n=827)

Sepsis (n=1063)

Infection no SIRS (n584)

Total n=3608

Alberti et al. Am J Respir Crit Care Med. 2003;168:77-8410


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Crit Care Med2008; 36: 1394139611


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International Sepsis Definition:GIHOT

General variables Fever (core temperature > 38.3C) Hypothermia (core temperature < 36C)

Heart rate > 90 bpm or >2 SD above the normal value Tachypnea

Altered mental status

Significant edema or positive fluid balance (>20 mL/kgover 24 hrs)

Hyperglycemia (plasma glucose >140 mg/dL) in theabsence of diabetes

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Inflammatory variables

Leukocytosis (WBC count > 12,000/L)

Leukopenia (WBC count < 4000/L)

Normal WBC count with > 10% immature forms

Plasma C-reactive protein > 2 SD above thenormal value

Plasma procalcitonin > 2 SD above the normalvalue

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Hemodynamic variables

Arterial hypotension

SBP < 90 mm Hg,

MAP < 70 mm Hg, or

an SBP decrease > 40 mm Hg in adults or < 2 SDbelow normal for age


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Organ dysfunction variables

Arterial hypoxemia (PaO2/FiO2 < 300)

Acute oliguria (urine output < 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 or aPTT > 60 secs)

Ileus (absent bowel sounds)

Thrombocytopenia (platelet count < 100,000 /L)

Hyperbilirubinemia (plasma total bilirubin > 4 mg/dL)

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Tissue perfusion variables

Hyperlactatemia (> upper limit of lab normal)

Decreased capillary refill or mottling

2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definition Conference. CCM 2003;31:1250-125616


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Sepsis Management: VIPsSurviving Sepsis Campaign 2008 guidelines

Ventilation

InfectionPerfusion

Supportive care

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Index

Activated Protein C (rhAPC)

//

Bicarbonate

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A Problematic Measurement

It should be recognized that

systemic hypo-perfusion

usually precedeshypotension, especially in

patients with sepsis

Rackow, JAMA, 1991

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Serum Lactate as a MortalityPredictor in Severe Sepsis

1.5%

4.5%

22.4%

9.0%

28.4%

4.9%

0.0

0.1

0.1

0.2

0.2

0.3

0.3

0.0-2.4 2.5-3.9 >4.0Lactate Level ( mmol/L)

MoatyRae(%)

Death within 3 days

28 Day In-hospital Mortality

Shapiro NI, et al. Ann Emerg Med 2005;45:524-52822


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Early lactate clearance isassociated with improved outcome

Nguyen HB, et al. CCM 2004;32:1637-164223


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SvO2 versus ScvO2

Where to measure ?

Normal value ?

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What does ScvO2 mean ?

Low ScvO2 (> 70%)

Low DO2 High VO2 High DO2 Low VO2

Hypoxia, Suctioning

(low SaO2)Exercise

Hyperoxia

(high FiO2)Hypothermia

Anemia,

Hemorrhage(low Hb)

Pain

Erythrocytosis

(high Hb)

Anesthesia,

Pharmacologicparalysis

Cardiac dysfunction,Hypovolemia, Shock,

Arrythmia

(low CO)

Hyperthermia,Shivering, Seizure

Hyperdynamic state

(high CO)

Arterio-venousshunting,

Mitochondrial defect,Terminal Shock

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How do we treat global tissue hypoxiain severe sepsis/septic shock

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Approach to Hemodynamic Optimization

Hollenberg SM, et al. CCM 2004;32:1928-194827


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Oxygen Content

Contractility

AfterloadPreload

Heart Rate

DO2

Cardiac Output

Stroke Volume

Oxygen content = (1.34 x Hb x SaO2) + (0.0031 x PaO2) 28


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Early Goal-Directed Therapy

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EGDT Results

28-day Mortality

49.2%

33.3%

0

10

20

30

40

50

60

Standard Therapyn=133

EGDTn=130

P = 0.01*

Rivers E. N Engl J Med 2001;345:1368-77.30


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EGDT in ER

sepsis induced hypotension or Lactate 4 mmol/L

61. CVP: 8-12 mmHg (12-15 in ventilator pts)

2. MAP: > 65 mmHg

3. Urine output: > 0.5mL/kg/hr

4. ScvO2 or SvO2: 70%

6 PRBCHct >30%/

dobutamine (max 20g/kg/min)

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

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2

(48hr)

():

Weinstein MP. Rev Infect Dis 1983;5:35-53

Blot F. J Clin Microbiol 1999; 36: 105-109.

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1

()

Kreger BE. Am J Med 1980;68:344-355.

Ibrahim EH. Chest 2000;118:146-155.

Hatala R. Ann Intern Med 1996;124-717-725.

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48-72

Optimize efficacy

Prevent resistance

Avoid toxicity

Minimize costs

7-10

Ali MZ. Clin Infect Dis 1997;24:796-809

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Maximal efficacy & minimal physiologic upset

Jimenez MF. Intensive Care Med 2001;27:S49-S62.

Bufalari A. Acta Chir Belg 1996;96:197-200.

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/

Moss RL. J Pediatr Surg 1996;31:1142-1146.

CDC. MMWR 2002;51:1-29.

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Drainage- Intra-abdominal abscess - Septic arthritis

- Thoracic empyema - Pyelonephritis, cholangitis

Debridement

- Necrotizing fasciitis - Mediastinitis- Infected pancreatic necrosis - Intestinal infarction

Device Removal- Infected vascular catheter

- Urinary catheter

- Colonized endotracheal tube Definitive Control

- Sigmoid resection for diverticulitis

- Amputation for clostridial myonecrosis

- Cholecystectomy for gangrenous cholecystitis

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Fluid resuscitation in ICU

SAFE study. NEJM 2004;350:2247-56

Total n=6997

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:

colloidscrystalloids

(volume of distribution)

Choi PTL. Crit Care Med 1999;27:200-210.

Cook D. Ann Intern Med 2001;135:205-208.

Schierhout G. BMJ 1998;316:961-964.

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:

Goal: CVP 8 mmHg ( or 12 mmHg)

500 - 1000 mL of crystalloids over 30 mins

300 - 500 mL of colloids over 30 mins

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Goal: MAP 65 mmHg

norepinephrinedopamine

Norepinephrinedopamine Dopa ;

LeDoux D. Crit Care Med 2000;28:2729-2732. Regnier B. Intensive Care Med 1977;3:47-53.

Martin C. Chest 1993;103:1826-1831. Martin C. Crit Care Med 2000;28:2758-2765.

DeBacker D. Crit Care Med 2003;31:1659-1667. Hollenberg SM. Crit Care Med 1999; 27: 639-660.41


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dopamine

Vasopressin

: 0.01-0.04 units/min (stroke volume)

Hollenberg SM. Crit Care Med 1999; 27:639-660.Bellomo R. Lancet 2000; 356: 2139-2143.Kellum J. Crti Care Med 2001; 29: 1526-1531.

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dobutamine

dobutamine

Gattinoni L. N Eng J Med 1995;333:1025-1032.

Hayes MA. N Eng J Med 1994;330:1717-1722.

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61%

53%

0%

20%

40%

60%

80%

100%

63%

53%

0%

20%

40%

60%

80%

100%

Low-dose Steroids Placebo

(ACTH Test Non-responders)

(77%)

(ACTH Test Responders)

(23%)

P=0.04 P=0.96

N=114 N=36 N=34N=115

28-dayMortality

Annane, D. JAMA, 2002; 288 (7): 86844


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250 mcg ACTH stimulation testACTH

: Cortisol

ACTH

30-60min

>9 mcg/dL

ACTH (tapering) fludrocortisone

ACTH stimulation test Annane, D. JAMA, 2002; 288 (7): 868

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:

IV hydrocortisone 200-300mg/day * 7days in 3or 4 divided doses

Annane, D. JAMA, 2002; 288 (7): 868

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Hydrocortisone >300 mg

Bone RC. N Engl J Med 1987;653-658.

VA Systemic Sepsis Cooperative Study Group. N Engl J Med 1987;317:659-665.

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Proposed actions of Activated Protein C(PROWESS study)

Bernard GR, et al. NEJM 2001;344:699-709

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PROWESS study

ARR: 6.1%

Bernard GR, et al. NEJM 2001;344:699-709

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APC should not be used in low risk patients(Severe sepsis + APACHE II < 25 or 1 organ failure)

Abraham E, et al. (ADDRESS study). NEJM 2005:353:1332-41

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rh Activated Protein C (Xigris)

Dose: 24 g/kg/hr IV for 96 hours

Indications: >18y & infection

3 items in SIRS exp. Survival > 6m2 organ dysfunction

Hypotension

Renal Respiratory Platelet Metabolic acidosis

APACHE II 25 & 15IU/kg/hr Bleeding tendency (w/o DIC) Chr. & Severe liver disease

Platelete


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rhAPC

rhAPC (drotrecogin alfa [activated])rhAPC:

Active internal bleeding

- Recent (within 3 months) hemorrhagic stroke

- Recent (within 2 months) intracranial or intraspinal surgery, orsevere head trauma

- Trauma with increased risk of life-threatening bleeding

- Presence of an epidural catheter

- Intracranial neoplasm or mass lesion or evidence of cerebral

herniation See labeling instructions for relative contraindications (i.e. warnings)

rhAPC30,000

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< 7 g/dL

:

: Hb 7 9 g/dL

Erythropoietin(EPO)

EPO

(FFP)

Corwin HL. JAMA 2002;288:2827-2835.

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Antithrombin

High dose antithrombin in a phase III trial didnot demonstrate a beneficial effect on 28-daymortality and was associated with increasedrisk of bleeding when administered with

heparin

5000/mm3 5000 - 30,000/mm3

/ 50,000/ mm3

Warren BL. JAMA 2001;286:1869-1878.

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Lung protective ventilation

ARR: 8.8%

Traditional: 12mL/kg; Pplateau


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39.8

0

10

20

30

40

50

M

ortality(%)

ALI/ARDS

Mortality* - Low vs Traditional Tidal Volume

P=0.007

* death beforedischarge homeand breathing withoutassistance

Low Tidal

Volume

TraditionalTidal

Volume

ARDSNet. N Eng J Med 2000;342:1301-1308.

Traditional: 12mL/kg; Pplateau


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ALI/ARDS

: High tidal volumes, > 6 ml/kg

High plateau pressures, > 30 cm H2O

plateau pressure and tidal volume Hypercapnia

positive end expiratory pressure

ARDSNet. N Eng J Med 2000;342:1301-1308.

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ALI/ARDS

FiO2plateaupressure

(prone position)

(mechanical ventilation)45%,(ventilator associatedpneumonia)

Drakulovic M. Lancet 1999;354:1851-1858.

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ALI/ARDS


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ALI/ARDS

ALI/ARDS :

ALI/ARDS ALI

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ALI/ARDS


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ALI/ARDS

:

FiO2

Esteban A. Am J Respir Crit Care Med 1999;159:512-518.

Ely EW. N Engl J Med 1996;335:1864-1869.

Esteban A. Am J Respir Crit Care Med 1997;156:459-465.61


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//

(Protocols)

Brook AD. Crit Care Med 1999;27:2609-2615.

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IIT in SICU: the Leuven Study

8.00%

20.20%

10.90%

4.60%

10.60%

7.20%

0.0%

5.0%

10.0%15.0%

20.0%

25.0%

ICU ICU >5 day In-hospital

Moaty(%)

Conventional (180-200mg/dL)IIT (80-110 mg/dL)

Van den Berghe G, et al. NEJM 2001;345:1359-67

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NICE SUGAR trial:


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NICE-SUGAR trial:

Goal 150mg/dl

N Engl J Med 2009;360:1283-97

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checkq1~2 hours

< 150 mg/dL ()5% or 10% dextrose

van den Berghe G. N Engl J Med 2001;345:1359-1367.

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CVVHHD

CVVH

Mehta RL. Kidney Int 2001;60:1154-1163

Kellum J. Intensive Care Med 2002;28:29-37.

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Bicarbonate

(lactic acidosis) pH 7.15

bicarbonate

BicarbonateNS pH 7.13

Cooper DJ. Ann Intern Med 1990;112:492-498.

Mathieu D. Crit Care Med 1991;19:1352-1356.

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Better compliance Better


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Better compliance Better

outcome

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The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsisIntensive Care Med (2010) 36:222231

37% to 30.8%, P=0.001Resus. bundle: 10.9% to 31.3% (P


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Strategies to TimelyObviate the Progression

of SepsisSTOP Sepsis

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The Golden 6 hours

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The Golden 6 hours

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Goal

The Sepsis Bundles


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The Sepsis BundlesThe SSC/ICI Template: Phase III

http://www.ihi.org/IHI/Topics/CriticalCare/Sepsis/Tools/SepsisBundleIHITool.htm

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The Sepsis Bundles


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The Sepsis BundlesThe SSC/ICI Template: Phase III

http://www.ihi.org/IHI/Topics/CriticalCare/Sepsis/Tools/SepsisBundleIHITool.htm

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Heads of Sepsis


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Heads of Sepsishypotension, hypoperfusion, and organ dysfunction

Criti Care Med. 2004;32(Suppl):S595-S597

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1-2-3-4-5-6-7-8-9-10-11-12-15-30The End

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Sepsis Education

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