Transcript
Page 1: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Diagnosing & Managing Sepsis Syndrome: 

The Emerging Role of Bedside Analyte Testing

Page 2: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Continuing Education Credit

Date of Release: 6/29/2011

Date of Expiration: 6/29/2013

Estimated time to complete this educational activity: 1 hour

Page 3: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Continuing Education Credit

• Nursing - Educational Review Systems is an approved provider of continuing education in nursing by ASNA, an accredited provider by the ANCC/Commission on Accreditation. Provider #5-115. This program is approved for one (1.0) hour. Educational Review Systems is also approved for nursing continuing education by the State of California and the District of Columbia.

• Physicians - This program has been reviewed and is acceptable for up to one (1.0) prescribed credit hour by the American Academy of Family Physicians. AAFP prescribed credit is accepted by the AMA as equivalent to AMA PRA Category I for the AMA Physicians‘Recognition Award. When applying for the AMA PRA, prescribed hours earned must be reported as prescribed hours, not as Category I.

• Respiratory Therapy - This program has been approved for 1 contact hours Continuing Respiratory Care Education (CRCE) credit by the American Association for Respiratory Care, 9425 N. MacArthur Blvd. Suite 100 Irving TX 75063 Course # 213078000

Page 4: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Statement of Need

Sepsis kills more than 210,000 Americans each year and is becoming more common, especially in the hospital. Sepsis is a medical emergency that can be difficult to define, diagnose, and treat, but every minute counts in the effort to save lives. This learning activity will describe how bedside analyte testing could aid therapeutic decision making and improve the prognosis for patients with sepsis.

Page 5: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Intended Audience

The primary audience for this learning activity are health care professionals (physicians and nurses) who are involved in the testing, diagnosis, treatment, and management of sepsis and are interested in the role of biomarkers to improve the care forthese patients.

Page 6: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Learning Objectives

1. Discuss the scope of sepsis morbidity and mortality.

After completing this activity, the participant should be able to:

2. Describe the role of sepsis biomarkers in screening, diagnosis, risk stratification, and monitoring of response to therapy in sepsis.

3. List factors to be considered when evaluating sepsis testing and results.

4. Identify situations where point-of-care analyte testing might benefit patients with a suspected or confirmed diagnosis of sepsis.

5. Apply information to assist in the identification and treatment of patients with sepsis and improve patient outcomes.

Page 7: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Medical Advisement

We would like to acknowledge the following medical expertswho served as advisors to this educational program:

Emanuel P. Rivers, MD, MPH

Thomas Ahrens, DNS, RN, PhD Arthur P. Wheeler, MD

Jill A. Sellers, BSPharm, PharmD

Page 8: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Disclosures

Thomas Ahrens, DNS, RN, PhD No financial relationships to disclose.

Emanuel P. Rivers, MD, MPH No financial relationships to disclose.

Jill A. Sellers, BSPharm, PharmD No financial relationships to disclose.

Arthur P. Wheeler, MD No financial relationships to disclose.

Page 9: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Introduction to Sepsis

Definition, Etiology, Morbidity and Mortality

Page 10: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Definition of Sepsis

• Sepsis

ACCP/SCCM Consensus Conference. Crit Care Med. 1992;20(6):864-74.

– Systemic response to infection

– Manifested by two or more SIRS criteria as a result of proven or suspected infection

• Temperature ≥ 38C or ≤ 36C

• HR ≥ 90 beats/min

• Respirations ≥ 20/min

• WBC count ≥ 12,000/mm3 or ≤ 4,000/mm3

or > 10% bands

• PaCO2 < 32 mmHg

Page 11: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Case Study

Page 12: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Case Study: Mr. Z

• He tells you “My tooth is killing me! You can pull it if you need to. I feel like it is going to explode.”

• His tooth pain is severe and he cameto the emergency department since he could not see his dentist until themorning. He has drainage from tooth #20, for which a culture has been obtained and sent to the lab.

• Mr. Z is a 47 year-old male who was admitted to the emergency department. He is complaining of a toothache that has been present for 7 days.

Page 13: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Case Study: Mr. Z

• He is started on Cefoxitin (Mefoxin®) 2 g IV q6h.

• Mr. Z is alert and oriented.

• He has a history of hypertension and had a hemorrhagic stroke 10 years ago but has had no major health issues since this time.

• His heart and lung sounds are normal and his skin is cool and moist. He has good capillary refill, abdomen soft and non-tender.

Page 14: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Case Study: Mr. Z

Admission

Heart Rate 111

Temperature 38.7

SPO2 0.96

NIBP 128/88 (101)

Respiratory Rate 22

Questions

1) Does Mr. Z have signs of sepsis? Yes

2) What is a blood test that would be useful? Lactate

SPO2: Pulse oximetry oxygen saturation; NIBP: Non-invasive blood pressure

Page 15: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Case Study: Mr. Z

AdmissionHeart Rate 111

Temperature 38.7

SPO20.96

NIBP 128/88 (101)

Respiratory Rate 22

Serum Lactate 3.5

After 20 mg/kg normal saline (10 minutes)

Heart Rate 104

Temperature 38.6

SPO20.96

NIBP 130/88 (102)

Respiratory Rate 22

Page 16: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Case Study: Mr. Z

After 4 Hours

Heart Rate 88

Temperature 38.1

SPO2 0.98

NIBP 133/78 (94)

Respiratory Rate 17

Serum Lactate 1.8

• Often, vital signs are normal when lactates are elevated.

• The use of the lactate allowed the clinician to better evaluate the seriousness of the situation.

• If the lactate had remained elevated, more fluids could have been given.

• A decrease in lactate shows improved perfusion.

Page 17: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Sepsis is Serious.

• Sepsis is a serious medical condition caused by an overwhelming immune response to infection.

http://www.nigms.nih.gov/Education/factsheet_sepsis.htm

• Complex chain of events:

– Inflammatory and anti-inflammatory processes

– Humoral and cellular reactions

– Circulatory abnormalities

• Results in impaired blood flow, which damages organs by depriving them of nutrients and oxygen.

Page 18: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

The Intracellular Immune Response to Infection

Adapted from Holmes CL, Russell JA, Walley KR. Chest. 2003;124:1103-15.

Page 19: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Symptoms of Sepsis

• Sepsis can begin in different parts of the body and can have many different symptoms.

• Rapid breathing and a change in mental status, may be the first signs of sepsis.

• Other symptoms include:

– Chills/hypothermia

– Decreased urination

– Tachycardia

– Nausea and vomiting

– Fever

Page 20: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Clinical Manifestations of Shock

Delirium and Encephalopathy

Acute Lung Injury or ARDS Oliguria

Anuria CreatinineMetabolic acidosis

Platelets PT/APTT Protein C D-dimer

Adrenal Dysfunction

Altered Glucose Metabolism

Jaundice Enzymes Albumin PT

Gut Dysfunction

Hyperpyrexia or Hypothermia

ARDS: Acute respiratory distress syndrome; PT: Prothrombin time; APTT: Activated partial thromboplastin time

Page 21: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

The Sepsis Continuum

Adapted from Bone RC, Balk RA, Cerra FB et al. Chest. 1992;101:1644-55.

Infection/Trauma

SIRS SepsisSevere Sepsis

A clinical response arising from a nonspecific insult, including ≥ 2 of the following:

• Temperature > 38ºC or < 36ºC

• Heart rate > 90 beats/min

• Respiratory rate > 20 breaths/min or PaCO2 < 32 Torr

• WBC > 12,000 cells/mm3, < 4,000 cells/mm3, or > 10% immature

SIRS with a presumed or confirmed infection

Sepsis with ≥ 1 sign of organ failure:

• Cardiovascular (refractory hypotension)

• Renal

• Respiratory

• Hepatic

• Hematologic

• CNS

• Unexplained metabolic acidosis

Local or systemic infection or traumatic injury

Page 22: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

SevereSepsis

Bone RC, Balk RA, Cerra FB et al. Chest. 1992;101:1644-55.

Trauma

Infection

SepsisOther

Pancreatitis

Burns

SIRS

The Relationship Between SIRS, Sepsis, and Severe Sepsis

Page 23: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Locations for Common Infection

Lungs

Urinary Tract

Abdomen

Vascular Catheters(endovascular)

Appendix

http://www.nigms.nih.gov/Education/factsheet_sepsis.htm

Skin and soft tissue

Page 24: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Microbes

• Many different types of microbes can cause sepsis:

http://www.nigms.nih.gov/Education/factsheet_sepsis.htm

CDC/ Matthew J. Arduino CDC/ Robert Simmons

Staphylococcus sp. (Bacteria) Aspergillus sp. (Fungi) Influenza (Virus)

CDC/ Erskine. L. Palmer, PhD; M. L. Martin

• Severe cases often result from a localized infectionbut sepsis can also spread throughout the body.

– Bacteria (most common)

– Fungi

– Viruses

Page 25: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Mortality Rates

• Sepsis remains the leading cause of death in critically ill patients in the United States.

• Each year 750,000 people will develop sepsis.

Angus DC, Linde-Zwirble WT, Lidicker J et al. Crit Care Med. 2001;29(7):1303-10.

National Center for Health Statistics, 2001. American Cancer Society, 2001.

0

50,000

100,000

150,000

200,000

250,000

Dea

ths

Per

Year

AIDS SevereSepsis

Breast Cancer

Page 26: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Sepsis Incidence in Men and Women

Martin GS et al. N Engl J Med. 2003;348:1546-54.

1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001

300

200

100

0

MenWomen

Po

pu

lati

on

-Ad

just

ed I

nci

den

ce

of

Sep

sis

(No

./10

0,00

0)

Page 27: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Martin GS, Mannino DM, Eaton S et al. N Engl J Med. 2003;348:1546-54.

1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001

OtherBlackWhite

Po

pu

lati

on

-Ad

just

ed I

nci

den

ce

of

Sep

sis

(No

./10

0,00

0)

500

400

300

200

100

0

Sepsis Incidence by Race

Page 28: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Sepsis Incidence in the United States: 2000

Martin GS, Mannino DM, Eaton S et al. N Engl J Med. 2003;348:1546-54. SEER Cancer Statistics Review. National Cancer Institute. www.cancer.gov. 2007. HIV/AIDS Surveillance Report. Centers for Disease Control. 2001;11.Incidence & Prevalence: 2006 Chart Book on Cardiovascular and Lung Diseases. NHLBI, NIH. 2006. Turabelidze G. J Neurol Sci. 2008;269:158-62.

0

50

100

150

200

250

Sepsis BreastCancer

AcuteMyocardial

Infarction

MultipleSclerosis

LungCancer

ColonCancer

AIDS

Inci

den

ce p

er 1

00,0

00

Page 29: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Sepsis Morbidity and Mortality

• In severe cases, one or more organs fail.

http://www.nigms.nih.gov/Education/factsheet_sepsis.htm

• Worst case scenario:– Blood pressure drops

– Septic shock

– Multiple organ system failure

– Death

• The number of sepsis cases per year has been on the rise:

– Aging population, the increased longevity of people with chronic diseases, the spread of antibiotic-resistant organisms, an upsurge in invasive procedures and broader use of immunosuppressive and chemotherapeutic agents.

Page 30: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

How Do I Decide Who is Really Sick With an Infection?

Page 31: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Sepsis Biomarkers

Use in Diagnosis, Risk, and Response

Page 32: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Utility of Biomarkers

1. Diagnosis/differentiation

– Value of baseline

2. Prognostication

– Value of change over time

3. Following success/failure of therapy

Page 33: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Diagnosis of Sepsis

• Bacteria in the blood or other body fluids

– Source of the infection

– A high or low white blood cell count

– A low platelet count

– Low blood pressure

– Too much acid in the blood (acidosis)

– Altered kidney or liver function 

• Biomarkers

Page 34: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

• Diagnosis of sepsis and evaluation of its severity is complicated by the highly variable and non-specific nature of signs and symptoms.

Sepsis Biomarkers: Screening

Lever A, Mackenzie I. Br Med J. 2007;335:879–83.

• Distinguishing patients with localized infections or SIRS from those with sepsis is challenging.

• SIRS is not specific to sepsis and can result from other conditions such as acute pancreatitis and immunodeficiencies.

• Biomarkers of sepsis may improve diagnosis and therapeutic decision making.

Page 35: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Sepsis Biomarkers

• More than 170 biomarkers have been assessed for sepsis prognosis and diagnosis

Pierrakos C, Vincent JL. Crit Care. 2010,14:R15.

• Some common biomarkers include:

– White blood cell count

– Procalcitonin (PCT)

– Procoagulant factors– Lactate

– Interleukins and other cytokines

– C-reactive protein (CRP)

Page 36: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Procalcitonin and Accuracy of Diagnosis

Harbarth S, Holeckova K, Froidevaux C et al. Am J Respir Crit Care Med. 2001;164:396-402.

1 - Specificity

1.00

0.75

0.50

0.25

0.00

Sen

siti

vity

0.00 0.25 0.50 0.75 1.00

Clinical model with PCTAUC: 0.94

Clinical model without PCTAUC: 0.77

Page 37: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Procalcitonin Reference Range

Normal subjects < 0.5 pg/ml

Chronic inflammatory processes and autoimmune diseases

< 0.5 pg/ml

Viral infections < 0.5 pg/ml

Mild to moderate localized bacterial infections

< 0.5 pg/ml

SIRS, multiple trauma, burns 0.5 – 2 pg/ml

Severe bacterial infections, sepsis, multiple organ failure

> 2 pg/ml(often 10 – 100 pg/ml)

ACCP/ Society of Critical Care Medicine Consensus Conference. Crit Care Med. 1992;20:864-74. Harbarth S, Holeckova K, Froidevaux C et al. Am J Respir Crit Care Med. 2001;164:396-402. Christ-Crain M, Jaccard-Stolz D, Bingisser R et al. Lancet. 2004;363:600-7.

Page 38: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Annane D, Sebille V, Troche G et al. J Am Med Assoc. 2000;283:1038-45.

Survival Curves in Severe Sepsis and Septic Shock: Baseline Cortisol and Post-ACTH

Pro

bab

ility

of

Su

rviv

al

0

Basal Plasma Cortisol Level 34 g/dL, max > 9 g/dL

Basal Plasma Cortisol Level 34 g/dL, max 9 g/dL orBasal Plasma Cortisol Level > 34 g/dL, max > 9 g/dL

Basal Plasma Cortisol Level > 34 g/dL, max 9 g/dL

1.00

0.80

0.60

0.40

0.20

0 7 14 21 28

Time (Days)

Page 39: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Lobo SM, Lobo FR, Bota DP et al. Chest. 2003;123:2043-9.

CRP Levels Correlate With Mortality and Organ Failure in Sepsis

30

20

10

0

30

20

10

0

*

* p < 0.05

Number of Organ Failures

0 1 2 3 > 4(116/115) (111/110) (56/56) (20/19) (4/4)

Day 0 Day 2C

RP

mg

/dL

CR

P m

g/d

L

CRP Day 0

CRP Day 2 Non-Survivors

Survivors

p = 0.002

p = 0.001

Survivors vs. Non-Survivors

Page 40: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Lactic Acidosis

Mizock BA, Falk JL. Crit Care Med. 1992;20:80-95.

Glycogen

Glucose Pyruvate

Lactate

CitricAcidCycle

CO2

H2O

(Cytoplasm) (Mitochondria)

Anaerobic Glycolysis

1 Glu + 2 ADP + 2 Pi

2 Lactate + 2 ATP

1 Glu + 6 O2 + 38 ADP + 38 Pi

6 CO2 + 6 H20 + 38 ATP

O2

Aerobic Glycolysis

Page 41: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Diagnostic and Therapeutic Markers

SvO2

60-80% Normal

50% Lactic Acidosis (≥ 4 mmol/L)

80

60

40

Page 42: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

38-40%

28 day in-hospital mortality Death within 3 days

Lactate1

30

25

20

15

10

5

00-2.4 2.5-3.9 > 4.0

% o

f M

ort

alit

y R

ate

% o

f M

ort

alit

y R

ate

0-2.4 2.5-3.9 > 4.0N = 827 N = 238 N = 112

Initial Lactate (mmol/L)2

50

40

30

20

10.0

0.0

Serum Lactate as a Predictor of Mortality

1 Trzeciak S, Dellinger RP, Chansky ME et al. Intensive Care Med. 2007;33:970-7.2 Shapiro NI, Howell MD, Talmor D et al. Ann Emerg Med. 2005; 45:524-8.

28%

Page 43: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Jansen TC, van Bommel J, Mulder PG et al. Crit Care. 2008,12:R160.

Prognostic Value of Serum Lactate

Page 44: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Jansen TC, van Bommel J, Mulder PG et al. Crit Care. 2008,12:R160.

Serum Lactate as a Predictor of Mortality

Mea

n L

acta

te L

evel

(m

mo

l/L)

7

6

5

4

3

2

1

0

Arrival Scene (T1) Emergency Department (T2)

Non-survival

Survival

p = 0.001p < 0.001

Page 45: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Adapted from Jansen TC, van Bommel J, Mulder PG et al. Crit Care. 2008,12:R160.

8/66 (12%)

Mortality

24/58 (41%)

Mortalityp < 0.001

7 Missing (4 Died)

11 Missing (0 Died)

First Lactate Measurement

Second Lactate Measurement

N = 55

8/54 (15%)

Mortality

0/1(0%)

Mortality

p = 1.00

N = 51

2/14 (14%)

Mortality

18/37(49%)

Mortality

p = 0.025

N = 106

10/68 (15%)

Mortality

18/38 (47%)

Mortalityp < 0.001

N = 124

< 3.5 mmol/l ≥ 3.5 mmol/l

< 3.5 mmol/l ≥ 3.5 mmol/l < 3.5 mmol/l ≥ 3.5 mmol/l

< 3.5 mmol/l ≥ 3.5 mmol/l

Second Lactate Cumulative

Value of Blood Lactate Levels

Page 46: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Jansen TC, van Bommel J, Mulder PG et al. Crit Care. 2008,12:R160.

Mo

rtal

ity

(%)

SBP (mmHg)

Lactate (mmol/l)< 100

> 100

> 3.5

< 3.5

60

50

40

30

20

10

0

Lactate, SBP, and Mortality

Page 47: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Serum Lactate and Mortality in Severe Sepsis

• Initial serum lactate evaluated in 839 adults admitted with severe sepsis.

Mikkelsen ME, Miltiades AN, Gaieski DF et al. Crit Care Med. 2009;37:1670-7.

Low Int High

ShockNon-Shock

28-D

ay M

ort

alit

y (%

)

50

45

40

35

30

25

20

15

10

5

0

p < 0.001

p = 0.001

p = 0.022

p = 0.024• High initial serum

lactate associated with ↑ mortality regardless of presence of shock or MODS.

Low Int High

Page 48: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Improving Lactate a Good Prognostic Sign

Bakker J, Gris P, Coffernils M et al. Am J Surg. 1996;171:221-6.

8

6

4

2

0

INITIAL +8h +16h +24h FINAL

Time

La

cta

te (

mm

ol/L

)

Survivors

Non-survivorsp < 0.05

p < 0.05p < 0.01

Page 49: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Sepsis is No Longer Just an ICU Disease

Levy MM, Dellinger RP, Townsend SR et al. Crit Care Med. 2010;38:367-74.

Page 50: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

You have to go to the disease instead of waiting for it to come to you!

Hospital Origin and Mortality

Origin Mortality

Surviving Sepsis Campaign. http://ssc.sscm.org.

ED 52.4% 27.6%

ICU 12.8% 41.3%

Wards 34.8% 46.8%

Page 51: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Risk Stratification of Sepsis

Surviving Sepsis Campaign. http://ssc.sscm.org.

Hypotension, vasopressors 36.7%

Lactate > 4 mmol/L only 30.0%

SBP < 90 mmHg and lactate > 4 mmol/L 46.1%

Page 52: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Sepsis Testing and Results

Guidelines, Algorithms, and Protocols

Page 53: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

• Blood gases

Factors to Consider When Evaluating Sepsis

• Electrolytes

• Glucose

• Hematocrit

• Lactate

Page 54: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Sepsis Resuscitation Bundle

The Sepsis Resuscitation Bundle is published by the Surviving Sepsis Campaign and is used by multiple hospitals across the country.

The goal is to perform all indicated tasks 100% of the time within the first 6 hours of identification of severe sepsis.

Surviving Sepsis Campaign. http://ssc.sscm.org.

Page 55: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Sepsis Resuscitation Bundle

Surviving Sepsis Campaign. http://ssc.sscm.org.

3. Administer broad-spectrum antibiotic, within 3 hours of emergency department (ED) admission and within 1 hour of non-ED admission.

2. Obtain blood cultures prior to antibiotic administration.

1. Measure serum lactate.

4. In the event of hypotension and/or a serum lactate > 4 mmol/L:a. Deliver an initial minimum of 20 ml/kg of crystalloid or an equivalent.

b. Apply vasopressors for hypotension not responding to initial fluid resuscitationto maintain mean arterial pressure (MAP) > 65 mmHg.

5. In the event of persistent hypotension despite fluid resuscitation (septic shock) and/or lactate > 4 mmol/L:a. Achieve a central venous pressure (CVP) of > 8 mmHg.

b. Achieve a central venous oxygen saturation (ScvO2) > 70% or mixed venous oxygen saturation (SvO2) > 65%.

Page 56: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

1. Administer low-dose steroids for septic shock in accordance with a standardized ICU policy. If not administered, document why the patient did not qualify for low-dose steroids based upon the standardized protocol.

Sepsis Management Bundle

Efforts to accomplish these goals should begin immediately, but these items may be completed within 24 hours of presentation for patients with severe sepsis or septic shock.

The tasks are:

2. Administer recombinant human activated protein C (rhAPC) in accordance with a standardized ICU policy. If not administered, document why the patient did not qualify for rhAPC.  

3. Maintain glucose control > 70 mg/dL, but < 150 mg/dL.

4. Maintain a median inspiratory plateau pressure (IPP) < 30 cm H2O for mechanically ventilated patients.

Surviving Sepsis Campaign. http://ssc.sscm.org.

Page 57: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Point-of-Care Analyte Benefits

• A 2010 study published in the Journal of Emergency Medicine found that point-of-care testing provided a reliable and feasible way to measure serum lactate at the bedside.1

1 Shapiro NI, Fisher C, Donnino M et al. J Emerg Med. 2010;39:89-94.2 Montassier E, Batard E, Segard J et al. Am J Emerg Med. 2010. Epub ahead of print.3 Martin MJ, FitzSullivan E, Salim A et al. Am J Surg. 2006;191:625-30.4 Moore CC, Jacob ST, Pinkerton R et al. Clin Infect Dis. 2008;46:215-22.

• Point-of-care lactate is useful in the diagnosis of sepsis at the bedside

– Recommended for institutions where clinical decisions are limited by lack of laboratory infrastructure or reliability.4

• Base excess (BE)

– Some studies suggest BE is an accurate marker for the prediction of elevated lactate in the emergency department (ED).2

– Some studies also show poor correlation due to effects of other conditions.3

Page 58: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

• pH, pCO2, pO2, lactate, Na, K, iCa, Glu, Hct (plus calculated values TCO2, HCO3, BE, sO2, Hb)

• Single-use, self-calibrating, 100-150 uL WB sample

Point-of-Care Analyte Testing

*unique market features

• Requires only room temperature storage*

• Analytes on a single test card

• Bar-coded for patient safety

• Low-cost test cards

– Cant use expired cards*

– Smart card technology

– < $ than benchtop systems

Page 59: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Turnaround Time

• Serum lactate must be available with rapid turnaround time (within minutes) to effectively treat severely septic patients. 

http://www.survivingsepsis.com/bundles/individual_changes/serum_lactate.www.emcrit.org/wp-content/uploads/lactate-faq.pdf.

• An arterial blood gas analyzer located in the clinical laboratories usually accomplishes this. 

• Hospitals should invest in adequate equipment in to meet present standards of care for septic patients.

• If a central analyzer is not efficient in a particular hospital setting, point-of-care analyzers should be evaluated for faster turnaround time.

Page 60: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Time and Cost for Measuring Blood Lactate

Chiron Accusport® Central Laboratory

Time of transportation (min) -- -- 9.6 ± 3.8

Time for results (min) 1 1 85 ± 35

Time for results (range) 1-10 1 45-168

Hardware Electrodes: 4 x $134Total: $536 Device: $156 --

Reagents --Test strip: $1.22Quality Control Bottle: $11.10

--

Costs for 197 samples $536 $248 $493

Costs of transportation of one sample -- -- $3.61

Boldt J, Kumle B, Suttner S et al. Acta Anaesthesiol Scand. 2001;45:194–9.

Page 61: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Sepsis Treatment Guidelines

• Antibiotic therapy

Surviving Sepsis Campaign. http://ssc.sscm.org.

– Begin intravenous antibiotics as early as possible

• Always within the first hour of recognizing severe sepsis (1D) and septic shock. (1B)

– Broad-spectrum

• One or more agents active against likely bacterial/fungal pathogens and with good penetration into presumed source. (1B)

– Reassess antimicrobial regimen daily to optimize efficacy, prevent resistance, avoid toxicity, & minimize costs. (1C)

– Consider combination therapy in Pseudomonas infections. (2D)

Page 62: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Sepsis Treatment Guidelines

• Antibiotic therapy

Surviving Sepsis Campaign. http://ssc.sscm.org.

– Consider combination empiric therapy in neutropenic patients. (2D)

– Combination therapy no more than 3-5 days and de-escalation following susceptibilities. (2D)

– Duration of therapy typically limited to 7-10 days

• Longer if response slow, undrainable foci of infection, or immunologic deficiencies. (1D)

– Stop antimicrobial therapy if cause is found to be non-infectious. (1D)

Page 63: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Glycemia Control 80-110

Semi-recumbent

Position

Lactate POC (< 15’) Fluid Bolus

SIRS 2 Criteria• T > 38° or < 36°• HR > 90• RR > 20 or PaCO2 32 mmHg• WBC > 12 K or < 4 K; Bands > 10%

SepsisNo

Yes

CVP < 8

CVP > 15 + MAP > 110

MAP > 110

MAP < 65

No

NS 500 cc IVB until CVP > 8

NTG 10-60 mcg/min until CVP < 12 or MAP < 110

Norepinephrine 2-20 mcg/min or Dopamine 5-20 mcg/kg/min

NTG 10-60 mcg/min until MAP < 90 or Hydralazine 10-40 mg IV

Transfuse PRBC

Dobutamine 2.5-20 mcg/kg/min

ScvO2 < 70% Hgb < 10

ScvO2 < 70%

• CVP 8-12• MAP 65-110• ScvO2 > 70%• Lactate improved

Iden

tifi

cati

on

A

bs

Rap

id

CV

EG

DT

Bu

nd

led

Th

erap

ies

Preload

Afterload

Central Venous Oxygen

Content

Goals Achieved

?

APACHE III > 25

Activated Protein C

Organic Dysfunction

SBP < 90 p bolus Lactate > 4

Central Venous Arterial Line Access (< 2°)

Initiate Sepsis Bundle

Mechanical Ventilation

Labs Cultures

Antibiotics (< 4°)

Severe Sepsis/ Septic Shock

SIRS + Suspected Infection

ScvO2

Hgb

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

CCF Sepsis Flowchart

Page 64: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Applications

Identification, Treatment, and Outcomes

Page 65: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Are any two of the following SIRS criteria present and new to the patient?

Heart rate > 90 beats/min Respiratory rate > 20/min

Temperature < 36.0 or > 38.3C Acutely altered mental state

Blood glucose > 7.7 mmol/L (in absence of diabetes) White cell count < 4 or > 12 x 109/L

Is there a clinical suspicion of new infection?

Cough/sputum/chest pain Dysuria

Abdominal pain/distension/diarrhea Headache with neck stiffness

Line infection Cellulitis/wound/joint infection

Endocarditis

Is there evidence of any organ dysfunction?

Systolic BP < 90/mean < 65 mmHg Urine output < 0.5 mL/kg/h for 2 h

Lactate > 2 mmol/L after initial fluids Creatinine > 177 umol/L

INR > 1.5 or aPTT > 60 s Platelets < 100 x 109/L

Bilirubin > 34 umol/L SpO2 > 90% unless O2 given

Identification of Sepsis

If YES, patient has SIRS

If YES, patient has Sepsis

If YES, patient has Severe Sepsis

Daniels R. J Antimicrob Chemother. 2011;66(Suppl 2):ii11–ii23.

Page 66: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Treatment of Patients With Sepsis

• Early goal-directed therapy: standard operating procedure– Apply with critical care/sepsis team if patient remains hypotensive

or lactate remains high following fluid challenges

Daniels R. J Antimicrob Chemother. 2011;66(Suppl 2):ii11–ii23.

1. Site central venous catheter using ultrasound guidance where practicable, according to proper procedures for infection control

2. If central venous pressure (CVP) < 8 mmHg, give further fluid challenges to achieve a target CVP of > 8 mmHg (> 12 mmHgif ventilated) unless the patient shows signs of fluid overload

3. If patient remains hypotensive, start a norepinephrine infusion to target SBP > 90 mmHg or MBP > 65 mmHg.

Page 67: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Improve Patient Outcomes

• Lactate clearance is associated with improved patient outcome.

Nguyen HB, Rivers EP, Knoblich BP et al. Crit Care Med. 2004;32(8):1637-42.Afessa B, Keegan MT, Schramm GE et al. Crit Care Med. 2011;15(Suppl 1): P286. Boldt J, Kumle B, Suttner S et al. Acta Anaesthesiol Scand. 2001;45:194–9.

• Point-of-care measurements of lactate are faster than central laboratories.

– May be beneficial for serial measurements.

• Lactate measurement is associated with increased risk of death independent of other aspects of sepsis bundle guidelines.

Page 68: Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing

Conclusion


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