Assessing Treatment of Severe
Sepsis and Septic Shock: How Are
We Performing?
A Case-Comparison Study to Evaluate the Treatment of
Severe Sepsis and Septic Shock in Critical Care Patients at
Sisters of Charity Hospital in Buffalo, NY
Erik Diringer, DO
Mentor: Thomas Brewer, DO
Background
• Severe sepsis and septic shock are complex
disease states that carry high rates of mortality.
– 28.6% overall and 38.4% in those >85 yrs. old1
• International efforts, such as the Surviving
Sepsis Campaign, have been made to define,
diagnose and treat sepsis in attempts to
improve morbidity and mortality2.
Background
• Evidence suggests that early goal-directed
therapy (EGDT) contributes to a significant
improvement in morality in severe sepsis and
septic shock3.
• On December 1, 2008, the Catholic Health
System released a new clinical standards order
set for the septic patient. This order set is
designed to utilize recommendations from the
Surviving Sepsis Campaign.
Introduction
• Definitions4:
– Systemic inflammatory response syndrome (SIRS)
– Sepsis is comprised of SIRS with a known source of
infection.
– Severe sepsis involves dysfunction in one or more
vital organs with hypotension that is responsive to
adequate fluid resuscitation.
– Septic shock is comprised of the same criteria,
however, it is not responsive to fluid resuscitation.
Introduction
• As a result of global tissue hypoxia, these
conditions can quickly progress to multiorgan
dysfunction syndrome (MODS), multiorgan
failure (MOF) and death5.
– Global tissue hypoxia is difficult to evaluate using
traditional hemodynamic measurements, such as
physical findings, vital signs, central venous
pressure (CVP), and urinary output.
Introduction
• The Cost of Sepsis
– Despite major advances in medicine and
technology, mortality rates remain high.
– In the United States, treatment of sepsis costs
$16.7 billion annually and is projected to increase
by 1.5% per year1.
Early Goal-Directed Therapy in the
Treatment of Severe Sepsis and
Septic Shock
Emanuel Rivers, M.D., M.P.H., Bryant Nguyen, M.D., Suzanne Havstad,
M.A., Julie Ressler, B.S., Alexandria Muzzin, B.S., Bernhard Knoblich, M.D.,
Edward Peterson, Ph.D., Michael Tomlanovich, M.D., for the Early GoalDirected Therapy Collaborative Group
November 8, 2001
SCVO2 Monitoring6
• Surrogate of global tissue hypoxia
– Sepsis results in increased metabolic stress at the
tissue level
– Response is to increase cardiac output and/or O2
utilization
– When O2 supply is overwhelmed by the disease,
SCVO2 continues to decrease (O2 demand > supply)
– Thus, SCVO2 is proposed to be a marker of
adequate O2 utilization at the tissue level as a
response to metabolic stress
EGDT Treatment
EGDT Results
• Significant (P=0.009) decrease in in-hospital
mortality from 46.5 to 30.5% when EGDT was
used over of standard therapy
– significant decrease in 28-day mortality
• Rapid identification and treatment
– These results were seen when therapy was
initiated immediately and continued for at least
six hours.
12/01/08 – CHS Sepsis Order Set
• 3 page admission order set
• Provides option to initiate EGDT
– Access: CVC, arterial line
– Monitoring: CVP/MAP monitoring, I/O
– Treatment: fluids, transfusions, vasopressors,
inotropic therapy
Study Objective
• The goal of this study is compare set
outcomes in patients at Sisters of Charity
Hospital (SOCH) in Buffalo, NY diagnosed with
severe sepsis and/or septic shock prior to and
following the release of the new sepsis order
set.
Study Design
• A case-comparison study of 100 ICU patients
with the diagnosis of severe sepsis and/or
septic shock prior to and following the release
of the sepsis standardized order set.
Methods
• Approved by SOCH Institutional Review Board
• Using December 1, 2008 as a reference, a
chart review of SOCH ICU patients with the
diagnosis of severe sepsis and/or septic shock
was performed until 100 charts that met
inclusion criteria were reviewed prior to and
following the release of the CHS sepsis order
set
Methods
• Inclusion criteria: similar to EGDT
– fulfillment of two of four criteria for SIRS
– systolic blood pressure no higher than 90 mm Hg
(after a crystalloid-fluid challenge) or a blood
lactate concentration 36 mg/dL
Methods
• Exclusion criteria:
–
–
–
–
–
–
age <18 years
pregnancy
CVA
ACS
Acute pulm. edema
Cardiac dysrhythmias (as
a primary diagnosis)
– active gastrointestinal
hemorrhage
– seizure/drug overdose
– contraindication to CVC
– burn injury/trauma
– requirement for
immediate surgery
– uncured cancer (during
chemotherapy)
– immunosuppression
– do-not-resuscitate status
Methods
• Data collection
– Hemodynamic parameters at 0, 4, 8, 12, 16, 20, 24h
• Temp, HR, input, output (when available), systolic
pressure, diastolic pressure, MAP (calculated)
– Age, sex, weight, APACHE II score
– Sepsis order set used?
– LOS in ED, ICU
– Mortality (all-cause, in-hospital)
Methods
• Statistical analysis
– Unpaired, two-tailed t-test
– Chi-square test
Results
213 charts reviewed
(12/24/0710/10/09)
100 charts met
inclusion criteria
50 charts prior to
12/01/08
50 charts on or after
12/01/08
Baseline Characteristics
Pre-SOS
Post-SOS
P value
65
68
0.67
Female
52
54
0.89
Male
48
46
Weight (kg)
83.4
80.0
0.4
APACHE II
21.9
22.2
CVP line (%)*
22
20
0.9
0.83
SOS used (%)
-
14
-
Age
Sex (%)
SOS = sepsis order set
APACHE II = Acute Physiologic and Chronic Health Evaluation II, scale range from 0 to 71, with higher values
indicating more severe disease.
CVP = central venous pressure
*Average time to CVP placement 10.17h
Results
0h
4h
8h
12 h
16 h
20 h
24 h
Pre-SOS
100.0
100.8
97.8
98.1
98.3
99.0
99.3
Post-SOS
100.3
101.1
98.3
98.4
98.5
99.3
99.2
P value
0.69
0.76
0.34
0.52
0.64
0.64
0.67
Pre-SOS
112.5
111.8
98.6
100.2
99.8
99.2
93.5
Post-SOS
114.8
114.8
102.8
106.2
103.4
101.8
97.8
P value
0.55
0.41
0.31
0.15
0.39
0.43
0.21
Temperature
Heart Rate
SOS = sepsis order set
Results
0h
4 h*
8h
12 h
16 h
20 h
24 h
Pre-SOS
-
1336.8
1240.9
1195.6
1061.2
930.2
940.5
Post-SOS
-
1311.5
1045.6
1135.1
1083.3
948.8
882.4
P value
-
0.88
0.27
0.78
0.89
0.85
0.55
Pre-SOS
-
112.5
45.9
135.1
247.4
254.3
429.2
Post-SOS
-
87.5
39.0
94.8
196.3
222.4
404.4
P value
-
0.69
0.78
0.25
0.29
0.46
0.74
Input
Output
SOS = sepsis order set
*Urine output available 0-4h in 24% of patients
Results
0h
4h
8h
12 h
16 h
20 h
24 h
Pre-SOS
116.7
75.0
76.2
87.7
98.7
93.7
91.6
Post-SOS
111.7
73.8
79.1
88.9
99.2
94.5
89.1
P value
0.43
0.67
0.40
0.66
0.91
0.66
0.40
Pre-SOS
58.9
37.4
36.5
39.1
45.4
50.5
51.1
Post-SOS
54.9
35.8
37.7
40.7
45.1
50.0
49.1
0.35
MAP (calculated)
0.42
0.55
0.51
0.93
0.86
0.39
Pre-SOS
78.2
50.2
49.7
55.1
62.5
64.5
64.3
Post-SOS
73.1
48.5
51.5
56.8
63.2
64.8
60.8
P value
0.27
0.37
0.43
0.46
0.81
0.90
0.24
Systolic BP
Diastolic BP
P value
SOS = sepsis order set
MAP = mean arterial pressure
Results
Pre-SOS
Post-SOS
P value
ED LOS (h)
8.31
8.51
ICU LOS (d)
7.52
6.94
0.71
0.70
Lactate (mg/dL)*
55.54
51.14
0.59
32
36
0.63
Mortality (%)
SOS = Sepsis order set
LOS = Length of stay
*Lactate available within 24h in 50% of patients pre-SOS and 68% post-SOS
Discussion
• No significant difference in hemodynamic parameters
• SOCH mortality rate similar to those reported
nationally1
• CVP lines placed in 21% of pts
– Average time to line was 10.17h
• Average IVF in 1324ml in first 4h; 2467ml in first 8h
– EGDT averaged 4981ml in first 6h3
• Urine output only available in 24% of pts in first 4h
• Sepsis order set only used in 14% of pts
Can EGDT be done in real-world
clinical practice?
Discussion
• A 1-Year Experience With Implementing Early
Goal-Directed Therapy for Septic Shock in the
Emergency Department7
– Academic center in Camden, NJ
– 22 pts treated with EGDT protocol in ED
• Executed by ED/ICU physicians and nurses as part of regular
duties
– ED physicians identify and initiate
– ICU physicians ensure outcomes are achieved
– Required no extra staffing or modification to physical
plant
Discussion
• Future consideration
– Early identification of severe sepsis and septic shock
• Hemodynamic parameters, lab values
• “Door-to-EGDT” <60min in original trial3
– In-hospital mortality in STEMI 3% with door-to-balloon time
<90min8
– Collaboration between ED and ICU teams
– Modification of sepsis order set
• “Sepsis bundles”9
– Modification of EGDT?
Discussion
• Role of the resident
– Diagnosis of severe sepsis and septic shock
– EGDT
– Procedural competency
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe
sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. CritCare
Med. 2001; 29: 1303-1310.
Surviving Sepsis Campaign®. http://www.survivingsepsis.org. 2009.
Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis
and septic shock. N Engl J Med 2001; 345: 1368–1377.
Marino P. The ICU Book, Third Edition. Philadelphia: Lippincott Williams & Wilkins, 2007.
Beal AL, Cerra FB. Multiple organ failure syndrome in the 1990s: systemic inflammatory response
and organ dysfunction. JAMA 1994; 271: 226-233.
Pinsky R, Brochard L, Mancebo J. Applied Physiology in Intensive Care Medicine. Springer-Verlag
Berlin Heidelberg 2006
Trzeciak JES, Dellinger RP, Abate NL, Cowan RM, Stauss M, Kilgannon JH, Zanotti S. A 1-Year
Experience With Implementing Early Goal-Directed Therapy for Septic Shock in the Emergency
Department. Chest. 2006; 129: 225-232.
McNamara RL, Wang Y, Herrin J, Curtis JP, Bradley EH, Magid DJ, Peterson ED, Blaney M, Frederick
PD, Krumholz HM. Effect of door-to-balloon time on mortality in patients with ST-segment elevation
myocardial infarction. J Am Coll Cardiol. 2006. Jun 6;47 (11): 2180-6.
Institute for Health Care Improvement. http://www.ihi.org/IHI/Topics/CriticalCare/Sepsis. Accessed
May 2010.
ProCESS Study
•
•
•
•
Protocolized Care for Early Septic Shock
Funded by NIH, coordinated by UPMC
24 US sites
3-pronged
– Clinical efficacy
• Do we need SCVO2, blood transfusions?
– Mechanism of action
• Trend markers of cellular hypoxia, oxidative stress,
inflammation, and coagulation/thrombosis
– Costs and cost-effectiveness
Baseline Characteristics
No SOS (n = 93)
SOS (n = 7)
P value
66
58
0.47
Female
52.7
57.1
0.53
Male
47.3
42.9
Weight (kg)
82.0
77.3
0.55
APACHE II
22.2
18.1
22
14.3
0.28
0.20
Age
Sex (%)
CVP line (%)*
SOS = sepsis order set
APACHE II = Acute Physiologic and Chronic Health Evaluation II, scale range from 0 to 71, with higher values
indicating more severe disease.
CVP = central venous pressure
*Average time to CVP placement 10.17h
Results
0h
4h
8h
12 h
16 h
20 h
24 h
No SOS
100.0
100.9
98.0
98.1
98.4
99.1
99.3
SOS
101.4
101.7
99.1
99.6
98.6
99.2
98.9
P value
0.33
0.61
0.31
0.20
0.85
0.92
0.57
No SOS
113
113
100
102
101
100
96
SOS
122
121
114
116
112
107
99
P value
0.22
0.24
0.09
0.09
0.15
0.30
0.64
Temperature
Heart Rate
SOS = sepsis order set
Results
0h
4h
8h
12 h
16 h
20 h
24 h
No SOS
0
1357
1190
1184
1080
959
927
SOS
0
1021
528
964
830
695
751
P value
-
0.31
0.06
0.61
0.44
0.15
0.31
No SOS
0
107
45
119
228
244
429
SOS
0
200
58
81
146
164
264
P value
-
0.42
0.81
0.58
0.38
0.35
0.24
Input
Output
SOS = sepsis order set
Results
0h
4h
8h
12 h
16 h
20 h
24 h
No SOS
114
75
77
88
98
94
91
SOS
124
73
87
91
113
98
86
P value
0.41
0.74
0.12
0.65
0.07
0.21
0.32
No SOS
58
37
37
40
46
51
51
SOS
46
29
39
34
37
44
46
0.06
0.68
0.17
0.17
0.23
0.26
Systolic BP
Diastolic BP
P value
0.18
MAP (calculated)
No SOS
76
50
50
56
63
65
63
SOS
72
44
55
53
62
62
59
0.67
0.12
0.31
0.45
0.92
0.47
0.48
P value
SOS = sepsis order set
MAP = mean arterial pressure
Results
No SOS
SOS
P value
ED LOS (h)
8.43
9.03
ICU LOS (d)
7.12
5.86
0.54
0.62
Lactate (mg/dL)*
53.07
39.92
0
Mortality (%)
37
SOS = Sepsis order set
LOS = Length of stay
*Lactate available within 24h in 50% of patients pre-SOS and 68% post-SOS
0.44
0.00