Spotting and Surviving Sepsis Thomas Koshy, Ph.D. Sr. Director, Scientific Affairs
September 12, 2012
Learning Objectives
• Discuss the scope of sepsis morbidity and mortality.
• Describe the role of sepsis biomarkers in screening, diagnosis, risk stratification, and monitoring of response to therapy in sepsis.
• List factors to be considered when evaluating sepsis testing and results.
• Identify situations where point-of-care analyte testing might benefit patients with a suspected or confirmed diagnosis of sepsis.
• Apply information to assist in the identification and treatment of patients with sepsis and improve patient outcomes.
Introduction to Sepsis
Definition, Etiology, Morbidity and Mortality
Definition of Sepsis
ACCP/SCCM Consensus Conference. Crit Care Med. 1992;20(6):864-74.
Sepsis – Systemic overwhelming immune response to infection. – Manifested by two or more Systemic Inflammatory
Response Syndrome (SIRS) criteria as a result of proven or suspected infection
Temperature ≥ 38°C or ≤ 36°C
HR ≥ 90 beats/min
Respirations ≥ 20/min
WBC count ≥ 12,000/mm3 or ≤
4,000/mm3
or > 10% bands
PaCO2 < 32 mmHg
Sepsis is Serious.
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. These conditions can also mask sepsis
http://www.nigms.nih.gov/Education/factsheet_sepsis.htm
Inflammation Procoagulants
Antifibrinolytic Events
Sepsis
“Except on few occasions, the patient appears to die from the body's response to infection rather than from it.”
Sir William Osler, 1904 “The Evolution of Modern Medicine”
Common Locations for Sepsis Infections
http://www.nigms.nih.gov/Education/factsheet_sepsis.htm
Lungs
Urinary Tract
Abdomen
Vascular Catheters
(endovascular)
Appendix
Skin and soft tissue
Clinical Manifestations of Shock Delirium and Encephalopathy
Acute Lung Injury or ARDS Oliguria
Anuria ↑ Creatinine Metabolic 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
Signs and 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: • Fever • Chills/hypothermia • Decreased
urination • Tachycardia • Nausea and
vomiting
Severe Sepsis
Bone RC, Balk RA, Cerra FB et al. Chest. 1992;101:1644-55.
Trauma
Infection
Sepsis Other
Pancreatitis
Burns
SIRS
The Relationship Between SIRS, Sepsis, and Severe Sepsis
Septic Shock
The Sepsis Continuum
Adapted from Bone RC, Balk RA, Cerra FB et al. Chest. 1992;101:1644-55.
Infection/Trauma SIRS Sepsis Severe Sepsis
Septic Shock
Systemic Inflammatory Response Syndrome 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
Severe sepsis perfusion abnormalities such as lactic acidosis, oliguria, or an acute alteration in mental status. Immediate intervention needed to prevent death: • Fluid resuscitation • Reversal of
hypotention • Antibiotics
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 infection but sepsis can also spread throughout the body.
– Bacteria (most common) – Fungi – Viruses
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 Breast Cancer
Acute Myocardial
Infarction
Multiple Sclerosis
Lung Cancer
Colon Cancer
AIDS
Inci
denc
e pe
r 100
,000
Sepsis mortality rates are higher too
Sepsis Incidence
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
Men Women
Popu
latio
n-A
djus
ted
Inci
denc
e
of S
epsi
s (N
o./1
00,0
00)
Increases in: Hospital acquired infections? Resistant bacteria? Px with compromised immune
systems? Px with indwelling devices such as
catheters or ventilators?
Sepsis Incidence (cont’d)
Sepsis Incidence Rises w/Age
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
Other Black White
Popu
latio
n-A
djus
ted
Inci
denc
e
of S
epsi
s (N
o./1
00,0
00)
500
400
300
200
100
0
Sepsis Incidence by Race
Sepsis = Longer Hospital Stays
Mortality Rates
Only 2% of hospitalizations in 2008 were for septicemia or sepsis, yet they made up 17% of in-hospital deaths.
CDC/NCHS, National Hospital Discharge Survey, 2008..
In hospital mortality Population Sepsis Other Diagnosis General 17% 2% < 65 years old 13% 1% > 65 years old 20% 3%
AIDS Severe Sepsis
Breast Cancer
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.
• Leading non-cardiac cause of death in ICUs
• Mortality rates between 28-50%!
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.
Mortality rates in floor beds is much higher than in EDs or critical
care wards.
33% of SIRS patients will develop sepsis.
25% of septic non-ICU patients and 50% of septic ICU patients develop severe sepsis
This is ~11% of all in-hospital patients and ~25% of ICU patients
25% of patients with severe sepsis develop septic shock
Sepsis Morbidity and Mortality
In severe cases, one or more organs fail. • Worst case scenario:
o Blood pressure drops o Septic shock o Multiple organ system failure o Death
• The number of sepsis cases per year has been on the rise: o 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.
http://www.nigms.nih.gov/Education/factsheet_sepsis.htm
How Do I Decide Who is Really Sick With an Infection?
Sepsis Biomarkers
Use in Diagnosis, Risk, and Response
Utility of Biomarkers
Diagnosis/ Differentiation
Prognostication • Value of baseline • Value of change
over time
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.
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.
Time is vital. Every hour of delayed
diagnosis decreases survival by 7.6% (Kumar, et al. Crit
Care Med. 2006;34(6):1593.)
Sepsis Biomarkers: Screening
Lever A, Mackenzie I. Br Med J. 2007;335:879–83.
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:
WBC Lactate Procalcitonin
Interleukins and other cytokines
C-reactive protein (CRP)
Procoagulant factors
Biomarker Performance in Severe Sepsis With or Without Septic Shock
Linder A, Christensson B, Herwald H et al. Clin Infec Dis. 2009;49(7):1044-50.
HBP Procalcitonin IL-6 Lactate CRP WBC
Sens
itivi
ty
1-Specificity
0.0 0.2 0.4 0.6 0.8 1.0
1.0
0.8
0.6
0.4
0.2
0.0
Procalcitonin Accuracy
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
Sens
itivi
ty
0.00 0.25 0.50 0.75 1.00
Clinical model with PCT AUC: 0.94
Clinical model without PCT AUC: 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.
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 2
CR
P m
g/dL
CR
P m
g/dL
CRP Day 0 CRP Day 2 Non-Survivors
Survivors
p = 0.002 p = 0.001
Survivors vs. Non-Survivors
Global Tissue Hypoxia: A More Sensitive Measure of Shock
Oxygen Balance
Global Tissue Hypoxia
Lactic Acid > 4 mM/L
Lactic Acidosis
Mizock BA, Falk JL. Crit Care Med. 1992;20:80-95.
Glycogen Glucose Pyruvate
Lactate
Citric Acid Cycle
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
http://www.uic.edu/classes/bios/bios100/lecturesf04am/lect12.htm
http://www.uic.edu/classes/bios/bios100/lecturesf04am/lect12.htm
Lactic Acidosis
Mizock BA, Falk JL. Crit Care Med. 1992;20:80-95.
Glycogen Glucose Pyruvate
Lactate
Citric Acid Cycle
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
X X X X
Lactate and Prognosis
Auden J, Bernsein WK, Khastgir T et al. J Am Med Assoc. 1994;272:1678-85.
Lactate
There is evidence that serum lactate levels may carry prognostic value in sepsis. Risk-stratification based on serum lactate levels.
o Patients with a lactate of > 4 mmol/L had a mortality of > 40%, compared with under 15% for patients with a lactate of < 2 mmol/L.1
Other studies have shown lactate to be predictive of critical care admission.2
1 Drumheller B, Goyal M, Pines J et al. Ann Emerg Med. 2007;50:S21-2. 2 Chan YL, Tseng CP, Tsay PK et al. Crit Care Med. 2004;8:R12-20.
38-40%
28 day in-hospital mortality Death within 3 days
Lactate1
30
25
20
15
10
5
0 0-2.4 2.5-3.9 > 4.0
% o
f Mor
talit
y R
ate
% o
f Mor
talit
y R
ate
0-2.4 2.5-3.9 > 4.0 N = 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%
Serum Lactate and Mortality in Severe Sepsis
Initial serum lactate evaluated in 839 adults admitted with severe sepsis. High initial serum lactate
associated with ↑ mortality regardless of presence of shock or MODS.
Mikkelsen ME, Miltiades AN, Gaieski DF et al. Crit Care Med. 2009;37:1670-7.
Low Int High
Shock Non-Shock
28-D
ay M
orta
lity
(%)
50 45 40 35 30 25 20 15 10 5 0
p < 0.001
p = 0.001
p = 0.022
p = 0.024
Low Int High
MODS=Multiple Organ Dysfunction Syndrome, also MSOF; Multisystem Organ Failure.
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 La
ctat
e Le
vel (
mm
ol/L
) 7
6
5
4
3
2
1
0
Arrival Scene (T1) Emergency Department (T2)
Non-survival Survival
p = 0.001 p < 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%)
Mortality p < 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%)
Mortality p < 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.
Lactate, SBP, and Mortality
Mor
talit
y (%
)
SBP (mmHg) Lactate (mmol/l)
< 100 > 100
> 3.5
< 3.5
60
50
40
30
20
10
0
Lactate May Predict Mortality in Sepsis
Hermans MAW, Leffers P, Jansen LM et al. Emerg Med J. 2011;Epub.
Sens
itivi
ty
1-Specificity 0.0 0.2 0.4 0.6 0.8 1.0
1.0
0.8
0.6
0.4
0.2
0.0
Predictor AUC (95% CI) MEDS 0.81 (0.73-0.88)
CRP 0.68 (0.58-0.78)
Lactate 0.75 (0.60-0.90)
MEDS (n = 331) Lactate (n = 47) CRP (n = 326)
Mortality in Emergency Department Sepsis
Improving Lactate a Good Prognostic Sign
Bakker J, Gris P, Coffernils M et al. Am J Surg. 1996;171:221-6.
INITIAL +8h +16h +24h FINAL
8
6
4
2
0
Time
Lact
ate
(mm
ol/L
)
Survivors
Non-survivors p < 0.05 p < 0.05
p < 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%
Mortality Risk
Sepsis Biomarkers: Monitoring Response to Therapy
1 Nguyen HB, Rivers EP, Knoblich BP et al. Crit Care Med. 2004;32(8):1637-42. 2 Becker KL, Snider R, Nylen ES. Crit Care Med. 2008;36(3):941-52. 3 Nguyen HB, Loomba M, Yang JJ et al. J Inflam. 2010;7:6.
Lactate levels are particularly useful when measured serially, to guide response to resuscitation and fluid therapy.
Lactate clearance (≥ 10% decrease in lactate concentration between initial and repeat measurements) has been shown to be a better prognostic factor than a single lactate determination.1,2
Early goal-directed therapy targeting global tissue hypoxia may be more effective than standard care in decreasing lactate during the first six hours of intervention.3
12-Month Survival Based on Lactate Clearance Quartile
Nguyen HB, Loomba M, Yang JJ et al. J Inflam. 2010;7:6. *During the first 6 hours in the emergency department (p < 0.01).
Mor
talit
y Pr
obab
ility
Lactate Clearance Quartiles*
0 2 4 6 8 10 12
1.0
0.8
0.6
0.4
0.2
0.0
Time (Months)
1 (-24.3 ± 42.3%) 2 (30.1 ± 7.5%) 3 (53.4 ± 6.6%) 4 (75.1 ± 7.1%)
Sepsis Testing and Results
Guidelines, Algorithms, and Protocols
Blood gases Electrolytes Glucose Hematocrit Lactate
Factors to Consider When Evaluating Sepsis
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.
© Surviving Sepsis Campaign and the Institute for Healthcare Improvement 56
1
Evaluation for Severe Sepsis Screening Tool
1. Is the patient’s history suggestive of a new infection?
Pneumonia, empyema Skin/soft tissue infection
Endocarditis
UTI Bone/joint infection Implantable device infection
Acute abdominal infection
Wound infection Other ____________
Meningitis Bloodstream catheter infection
57
Yes No
© Surviving Sepsis Campaign and the Institute for Healthcare Improvement
58
1
2
Yes
No
© Surviving Sepsis Campaign and the Institute for Healthcare Improvement
Evaluation for Severe Sepsis Screening Tool
2. Are any of the following signs and symptoms of infection both present and new to the patient?
Hyperthermia > 38.3 ºC Tachypnea > 20 bpm Leukopenia (WBC count < 4000 ul-1
Hypothermia < 36 ºC Acutely altered mental status
Hyperglycemia (plasma glucose > 120 mg/dL) in the absence of diabetes
Tachycardia > 90 bmp Leukocytosis (WBC count > 12,000 uL-1)
59
Note: Laboratory values may have been obtained for inpatients but may not be available for outpatients
© Surviving Sepsis Campaign and the Institute for Healthcare Improvement
Yes No
60
1
2
3
Yes*
Yes*
No
No STOP *If the answer is yes to either 1 or 2, suspicion of infection is present. • Obtain lactate, blood cultures, CBC with
differential, basic chemistry labs, bilirubin • At the physician’s discretion obtain: UA, chest X-
ray, amylase, lipase, ABG, CRP, CT scan
© Surviving Sepsis Campaign and the Institute for Healthcare Improvement
Evaluation for Severe Sepsis Screening Tool
3. Are any of the following organ dysfunction criteria present at a site remote from the site of the infection that are not considered to be chronic conditions?
SBP < 90 mm Hg or MAP < 65 mm Hg
Bilateral pulmonary infiltrates with PaO2/FiO2 ratio < 300
Platelet count < 100,000
SBP decrease > 40 mm Hg from baseline
Creatinine > 2.0 mg/dL or urine output <0.5 mL/kg/hour for >20 hours
Coagulopathy (INR >1.5 or aPTT > 60 sec)
Bilateral pulmonary infiltrates with a new (or increased) oxygen requirement to maintain SpO2 > 90%
Bilirubin > 2 mg/dL Lactate > 2 mmol/L
61
Note: The remote site stipulation is waived in the case of bilateral pulmonary infiltrates
Yes No
© Surviving Sepsis Campaign and the Institute for Healthcare Improvement
Evaluation for Severe Sepsis Screening Tool
62
1
2
3
STOP
Sepsis Resuscitation
Bundle
Sepsis Management
Bundle
Severe Sepsis
ASAP and scored over first 6 hours
ASAP and scored over first 24 hours
Yes*
Yes*
Yes No
No
No
*If the answer is yes to either 1 or 2, suspicion of infection is present. • Obtain lactate, blood cultures, CBC with
differential, basic chemistry labs, bilirubin • At the physician’s discretion obtain: UA, chest X-
ray, amylase, lipase, ABG, CRP, CT scan
© Surviving Sepsis Campaign and the Institute for Healthcare Improvement
Sepsis Resuscitation Bundle To be accomplished as soon as possible and scored over the first 6 hours
© Surviving Sepsis Campaign and the Institute for Healthcare Improvement
Serum lactate measured
Blood cultures obtained prior to antibiotic administration
From the time of presentation, broad-spectrum antibiotics administered within 3 hours for ED admissions and 1 hour for non-ED ICU admissions
In the event of hypotension and/or lactate > 4 mmol/L •Deliver an initial minimum of 20 mL/kg of crystalloid (or colloid equivalent) •Apply vasopressors for hypotension not responding to initial fluid resuscitation to maintain MAP > 65 mm Hg
In the event of persistent hypotension despite fluid resuscitation (septic shock) and/or lactate > 4 mmol/L •Achieve central venous pressure of > 8 mm Hg •Achieve central venous oxygen saturation of > 70%
Sepsis Treatment Guidelines
Antibiotic therapy Begin intravenous antibiotics as early as possible
• Always within the first hour of recognizing severe sepsis and septic shock.
Broad-spectrum
• One or more agents active against likely bacterial/fungal pathogens and with good penetration into presumed source.
Reassess antimicrobial regimen daily to optimize efficacy, prevent resistance, avoid toxicity, & minimize costs.
Consider combination therapy in Pseudomonas infections.
Surviving Sepsis Campaign. http://ssc.sscm.org.
Sepsis Treatment Guidelines
Antibiotic therapy Consider combination empiric therapy in
neutropenic patients. Combination therapy no more than 3-5 days and
de-escalation following susceptibilities Duration of therapy typically limited to 7-10 days
• Longer if response slow, undrainable foci of infection, or immunologic deficiencies.
Stop antimicrobial therapy if cause is found to be non-infectious
Surviving Sepsis Campaign. http://ssc.sscm.org.
Sepsis Treatment Guidelines
Fluid therapy Fluid-resuscitate using crystalloids or colloids. Target a CVP of ≥ 8 mmHg (≥ 12 mmHg if mechanically
ventilated). Use a fluid challenge technique while associated with a
hemodynamic improvement. Give fluid challenges of 1000 mL of crystalloids or 300–500 mL
of colloids over 30 minutes. • More rapid and larger volumes may be required in sepsis-
induced tissue hypoperfusion. Rate of fluid administration should be reduced if cardiac filling
pressures increase without concurrent hemodynamic improvement.
Surviving Sepsis Campaign. http://ssc.sscm.org.
Sepsis Treatment Guidelines
Inotropic therapy Use dobutamine in patients with myocardial
dysfunction • Supported by elevated cardiac filling
pressures and low cardiac output.
Do not increase cardiac index to redetermined supranormal levels.
Surviving Sepsis Campaign. http://ssc.sscm.org.
Sepsis Treatment Guidelines
Vasopressors – Maintain MAP ≥ 65 mmHg. – Norepinephrine or dopamine centrally administered
are the initial vasopressors of choice. – Epinephrine, phenylephrine, or vasopressin should
not be administered as the initial vasopressor in septic shock. Vasopressin use may be considered in patients
with refractory shock despite adequate fluid resuscitation and high-dose conventional vasopressors.
Surviving Sepsis Campaign. http://ssc.sscm.org.
Sepsis Management Bundle
To be accomplished as soon as possible and scored over the first 24 hours
© Surviving Sepsis Campaign and the Institute for Healthcare Improvement
Low-dose steroids administered for septic shock in accordance with standardized ICU policy
Drotecogin alfa (activated) administered in accordance with standardized ICU policy
Glucose control maintained > lower limit of normal but < 150 mg/dL
Inspiratory plateau pressures maintained < 30 cm H2O for mechanically ventilated patients.
Is it Working?
15,775 patients at 252 participating Surviving Sepsis
sites1
Unadjusted hospital mortality
decreased from 37% to 30.8% over a 2 year
period
1. Intensive Care Med (2010) 36:222-231, 2. Crit Care Med (2011) 39:252-258, 3. Ann Pharmacother (2010) 44:1733-1738
Is it Working?
15,775 patients at 252 participating Surviving Sepsis
sites1
Unadjusted hospital mortality
decreased from 37% to 30.8% over a 2 year
period
33-month study period at Mayo-
MN2
Bundle compliance rose from
12.7% to 52.7%
Mortality declined from 30.3% to 22%
1. Intensive Care Med (2010) 36:222-231, 2. Crit Care Med (2011) 39:252-258, 3. Ann Pharmacother (2010) 44:1733-1738
Is it Working?
15,775 patients at 252 participating Surviving Sepsis
sites1
Unadjusted hospital mortality
decreased from 37% to 30.8% over a 2 year
period
33-month study period at Mayo-
MN2
Bundle compliance rose from
12.7% to 52.7%
Mortality declined from 30.3% to 22%
Medical City Plano (TX) evaluation3
Mortatility in the non-bundle
group: 61.1%
Mortality in the bundle group:
20%
1. Intensive Care Med (2010) 36:222-231, 2. Crit Care Med (2011) 39:252-258, 3. Ann Pharmacother (2010) 44:1733-1738
Is it Working?
15,775 patients at 252 participating Surviving Sepsis
sites1
Unadjusted hospital mortality
decreased from 37% to 30.8% over a 2 year
period
33-month study period at Mayo-
MN2
Bundle compliance rose from
12.7% to 52.7%
Mortality declined from 30.3% to 22%
Medical City Plano (TX) evaluation3
Mortatility in the non-bundle
group: 61.1%
Mortality in the bundle group:
20%
1. Intensive Care Med (2010) 36:222-231, 2. Crit Care Med (2011) 39:252-258, 3. Ann Pharmacother (2010) 44:1733-1738
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
Turnaround Time
Serum lactate must be available with rapid turnaround time (within minutes) to effectively treat severely septic patients.
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.
http://www.survivingsepsis.com/bundles/individual_changes/serum_lactate. www.emcrit.org/wp-content/uploads/lactate-faq.pdf.
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 came to the emergency department since he could not see his dentist until the morning. 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’s been started on antibiotics.
• 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
BP 128/88
Respiratory Rate 22
Serum Lactate
1) Does Mr. Z have signs of sepsis? Yes
2) What blood test would be useful? Lactate
Case Study: Mr. Z
Admission After 20 mg/kg normal saline (10 minutes)
Heart Rate 111 104
Temperature 38.7 38.6
SPO2 0.96 0.96
BP 128/88 130/88
Respiratory Rate 22 22
Serum Lactate 4.0
75 kg = 165 lbs » » Me! 20 mg/kg = 1.5 L!
Case Study: Mr. Z
Admission After 20 mg/kg normal saline (10 minutes)
After 4 Hours
Heart Rate 111 104 88
Temperature 38.7 38.6 38.1
SPO2 0.96 0.96 0.98
BP 128/88 130/88 133/78 (94)
Respiratory Rate 22 22 17
Serum Lactate 4.0 1.8
• A decrease in lactate shows improved perfusion. • If the lactate had remained elevated, more fluids could have been given. • The use of the lactate allowed the clinician to better evaluate the severity
of the situation. • Often, vital signs are normal when lactates are elevated
Applications
Identification, Treatment, and Outcomes
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 mmHg if 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
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.
Lactate clearance is associated with improved patient outcome. Lactate measurement is associated with increased risk of death
independent of other aspects of sepsis bundle guidelines. Point-of-care measurements of lactate are faster than
central laboratories.
– May be beneficial for serial measurements.
Questions?
Thank You!
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