Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing.
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Transcript of Diagnosing & Managing Sepsis Syndrome: The Emerging Role of Bedside Analyte Testing.
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
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
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.
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.
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.
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
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.
Introduction to Sepsis
Definition, Etiology, Morbidity and Mortality
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
Case Study
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.
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.
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
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
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.
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.
The Intracellular Immune Response to Infection
Adapted from Holmes CL, Russell JA, Walley KR. Chest. 2003;124:1103-15.
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
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
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
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
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
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
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
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)
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
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
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.
How Do I Decide Who is Really Sick With an Infection?
Sepsis Biomarkers
Use in Diagnosis, Risk, and Response
Utility of Biomarkers
1. Diagnosis/differentiation
– Value of baseline
2. Prognostication
– Value of change over time
3. Following success/failure of therapy
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
• 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.
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)
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
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.
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)
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
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
Diagnostic and Therapeutic Markers
SvO2
60-80% Normal
50% Lactic Acidosis (≥ 4 mmol/L)
80
60
40
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%
Jansen TC, van Bommel J, Mulder PG et al. Crit Care. 2008,12:R160.
Prognostic Value of Serum Lactate
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
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
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
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
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
Sepsis is No Longer Just an ICU Disease
Levy MM, Dellinger RP, Townsend SR et al. Crit Care Med. 2010;38:367-74.
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%
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%
Sepsis Testing and Results
Guidelines, Algorithms, and Protocols
• Blood gases
Factors to Consider When Evaluating Sepsis
• Electrolytes
• Glucose
• Hematocrit
• Lactate
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.
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%.
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.
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
• 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
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.
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.
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)
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)
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
Applications
Identification, Treatment, and Outcomes
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.
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.
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.
Conclusion