Update in Sepsis Care

Report
Update in Sepsis
David Wyler, DO
January 16, 2014
Patient #1
58 year old diabetic male presents with
AMS and decreased urine output
About 2-3 weeks of increasing flank pain
Initial heart rate in the 120s. Respiratory
rate in the mid 20s. Temperature of 39.0C
BP 70s/40s. Lactate 4.5
Subsequent imaging demonstrated renal
calculi with obstruction and severe
pyelonephritis
Epidemiology
1979 estimated 164,000 cases per year1
1. “The epidemiology of sepsis in the United States from 1979 through 2000.” Martin GS, Mannino DM, Eaton S, Moss M. N Engl J Med.
2003;348(16):1546.
Fig 1. “Septicemia in U.S. Hospitals, 2009.” Anne Elixhauser, Ph.D., Bernard Friedman, Ph.D., Elizabeth Stranges, M.S. October 2011.
http://www.hcup-us.ahrq.gov/reports/statbriefs/sb122.pdf. Downloaded 12/2014.
The increased rate of sepsis is thought to be
a consequence of:
 Advancing age
 Immunosuppression
 Multidrug-resistant infection
 Awareness, screening, reimbursement, coding?
3. “Extending international sepsis epidemiology: the impact of organ dysfunction.” Esper AM, Martin GS Crit Care. 2009;13(1):120.
Baby Boomers age 50-68 in 2014
“Inpatient Care for Septicemia or Sepsis: A Challenge for Patients and Hospitals.” Margaret Jean Hall, Ph.D.; Sonja N. Williams, M.P.H.;
Carol J. DeFrances, Ph.D.; and Aleksandr Golosinskiy, M.S. NCHS Data Brief. Number 62, June 2011.
CDC lists septicemia as the 11th
leading cause of death.
Only 2% of hospitalizations in 2008
were for septicemia or sepsis, yet they
made up 17% of in-hospital deaths.
5. “Deaths: Preliminary Data for 2010.” National Vital Statistics Reports. Volume 60, Number 4. January 11, 2012.
http://www.cdc.gov/nchs/data/nvsr/nvsr60/nvsr60_04.pdf. Downloaded 12/2014.
 Most expensive condition treated in
U.S. hospitals.
 More than $20 billion in 2011.6
 Congestive heart failure. 5.1 million
people with $32 billion per year,
including inpatient/outpatient and loss
of work and productivity.7
6. “Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project Statistical Brief No. 160 August 2013. National inpatient
hospital costs: the most expensive conditions by payer, 2011.” http://www.hcup-us.ahrq.gov/reports/statbriefs/sb160.pdf. Downloaded 12/2014.
7. “Centers for Disease Control and Prevention. Heart Failure Fact Sheet.”
http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/docs/fs_heart_failure.pdf. Downloaded 12/2014.
From: Mortality Related to Severe Sepsis and Septic Shock Among Critically Ill Patients in Australia and New
Zealand, 2000-2012
JAMA. 2014;311(13):1308-1316. doi:10.1001/jama.2014.2637
Figure Legend:
Mean Annual Mortality in Patients With Severe SepsisError bars indicate 95% CI.
Date of download: 12/27/2014
Copyright © 2014 American Medical
Association. All rights reserved.
St Luke’s Treasure Valley
N=144
St Luke’s Treasure Valley
 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis
Definitions Conference
 Early Goal-Directed Therapy in the Treatment of Severe Sepsis
and Septic Shock
Emanuel Rivers, M.D., et al. N Engl J Med 2001
 2001 Surviving Sepsis Campaign. Phase I.
Rivers, 2001 NEJM
9. “Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock.” Emanuel Rivers, M.D., M.P.H., et. Al. N Engl J Med
2001; 345:1368-1377November 8, 2001DOI: 10.1056/NEJMoa010307.
Surviving Sepsis Guidelines
2004-2008,
Grade B to C
10. “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.” Dellinger RP, et al. Crit Care Med. 2004
Mar;32(3):858-73.
11. “Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008.” R. Phillip Dellinger, et al.
Intensive Care Med. Jan 2008; 34(1): 17–60.
12. “Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.” Dellinger RP. Crit Care Med.
2013 Feb;41(2):580-637.
Critiques of Rivers study
 Higher than typical death rate in standard
care group
 25 patients excluded after randomization
 Possible conflict of interest with links to
industry
 Does not indicate what parts of bundle are
beneficial
13. “Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference
Committee. American College of Chest Physicians/Society of Critical Care Medicine.” Bone RC. Chest. 1992 Jun;101(6):1644-55.
Septic shock — Septic shock is defined as sepsis-induced hypotension
persisting despite adequate fluid resuscitation.
Questioning parameters
Central Venous Pressure
Survey of Canadian intensivists in 2007
showed 90% used CVP to guide fluid
Merick et al. in 2008 and in 2013
published meta-analysis.
14. “A survey of Canadian intensivists’ resuscitation practices in early septic shock.” McIntyre LA, Hebert PC, Fergusson D, Cook DJ, Aziz A:
Crit Care 2007, 11:R74.
15. “Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares.” Marik PE,
Baram M, Vahid B. Chest. 2008 Jul;134(1):172-8. doi: 10.1378/chest.07-2331.
Area under the receiver operating characteristic curve (AUC)
between the central venous pressure and change cardiac performance
following an intervention that altered cardiac preload.
 From 191 articles screened, 43 studies met inclusion criteria
and were included for data extraction.
Healthy controls (n = 1) and ICU (n = 22) and operating room (n = 20)
The summary AUC was 0.56 (95% CI, 0.54–0.58)
16. “Hemodynamic parameters to guide fluid therapy.” Marik et al. Annals of Intensive Care 2011, 1:1.
Fluid Responsiveness
16. “Hemodynamic parameters to guide fluid therapy.” Marik et al. Annals of Intensive Care 2011, 1:1
ScVO2%?
17. “High central venous oxygen saturation in the latter stages of septic shock is associated with increased mortality.” Textoris et al. Critical Care
2011, 15:R176.
Lactate v ScVO2%
From: Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy: A
Randomized Clinical Trial
JAMA. 2010;303(8):739-746. doi:10.1001/jama.2010.158
Multicenter randomized, noninferiority trial involving patients with severe sepsis and evidence of
hypoperfusion or septic shock who were admitted to the emergency department from January
2007 to January 2009 at 1 of 3 participating US urban hospitals.
Date of download: 12/27/2014
Copyright © 2014 American Medical
Association. All rights reserved.
From: Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy: A
Randomized Clinical Trial
JAMA. 2010;303(8):739-746. doi:10.1001/jama.2010.158
Multicenter randomized, noninferiority trial involving patients with severe sepsis and evidence of
hypoperfusion or septic shock who were admitted to the emergency department from January
2007 to January 2009 at 1 of 3 participating US urban hospitals.
Date of download: 12/27/2014
Copyright © 2014 American Medical
Association. All rights reserved.
Lower versus Higher
Hemoglobin Threshold for
Transfusion in Septic Shock
19. Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock. Lars B. Holst, M.D, et al. N Engl J Med 2014; 371:13811391October 9, 2014.
Primary and Secondary Outcome Measures
Outcome
Lower
Hemoglobin
Threshold
Higher
Hemoglobin
Threshold
Relative Risk
(95% CI)
P Value
Primary outcome: death by day 90 – no./total no/ (%)
216/502 (43.0)
223/496 (45.0)
0.94 (0.78-1.09)
0.44
At day 5
278/432 (64.4)
267/429 (62.2)
1.04 (0.93-1.14)
0.47
At day 14
140/380 (36.8)
135/367 (36.8)
0.99 (0.81-1.19)
0.95
At day 28
53/330 (16.1)
64/322 (19.9)
0.77 (0.54-1.09)
0.14
35/488 (7.2)
39/489 (8.0)
0.90 (0.58-1.39)
0.64
0/488
1/489 (0.2)
-
1.00
Alive without vasopressor or inotropic therapy –
mean % of days
73
75
-
0.93
Alive and out of the hospital – mean % of days
30
31
-
0.89
Second outcomes
Use of life support- no./total no/ (%)
Ischemic event in the ICU – no./total no. (%)
Severe adverse reaction – no./total no. (%)
Choice of Fluids
20. “Albumin versus Other Fluids for Fluid Resuscitation in Patients with Sepsis: A Meta-Analysis.” Jiang L. PLoS One. 2014 Dec
4;9(12):e114666.
Chloride
760 patients admitted consecutively to the
intensive care unit (ICU) during the control
period (February 18 to August 17, 2008)
Compared with 773 patients admitted
consecutively during the intervention period
(February 18 to August 17, 2009)
Single center University-affiliated hospital in
Melbourne, Australia
21. Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in
Critically Ill Adults. JAMA. 2012;308(15):1566-1572. doi:10.1001/jama.2012.13356
From: Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration
Strategy and Kidney Injury in Critically Ill Adults
JAMA. 2012;308(15):1566-1572. doi:10.1001/jama.2012.13356
Figure Legend:
Stage 2 or 3 defined according to the Kidney Disease: Improving Global Outcomes clinical practice guideline.
Date of download: 12/27/2014
Copyright © 2014 American Medical
Association. All rights reserved.
Rivers, 2001 NEJM
Do we continue with EGDT?
Do we continue with EGDT?
ARISE
ProCESS
PROMISE (ongoing)
ARISE trial
Goal-Directed Resuscitation for Patients
with Early Septic Shock
51 center Australia/New Zealand
1600 enrolled patients assigned to EGDT
or “usual-care.”
22. “Goal-Directed Resuscitation for Patients with Early Septic Shock.” The ARISE Investigators and the ANZICS Clinical Trials Group. N Engl
J Med 2014;371:1496-506.
ProCESS trial
A Randomized Trial of Protocol-Based
Care for Early Septic Shock
31 tertiary US emergency departments
1341 enrolled patients assigned to EGDT,
protocol based standard therapy, or
“usual-care.”
23. “A Randomized Trial of Protocol-Based Care for Early Septic Shock.” The ProCESS Investigators. N Engl J Med. 2014;370:1683-93.
Back to the 90s?
Something is working
Surviving Sepsis Campaign
Response
(CVP) and central venous oxygen saturation (ScvO2) via a central venous
catheter as part of an early resuscitation strategy does not confer survival
benefit.
Requiring measurement of CVP and ScvO2 in all patients who have lactate
results >4 mmol/L and/or persistent hypotension after initial fluid challenge
and who have received timely antibiotics is not supported by the available
scientific evidence.
The results of the ProCESS and ARISE trials have not demonstrated any
adverse outcomes in the groups that utilized CVP and ScvO2 as end points
for resuscitation. Therefore, no harm exists in keeping the current SSC
bundles intact until a thorough appraisal of all available data has been
performed.
In light of the evidence from the ProCESS and ARISE trials, the SSC
guidelines committee will immediately review the evidence and assess
whether the guidelines need to be updated now.
Surviving Sepsis compliance
mortality association
PURPOSE: To determine the association between compliance with the Surviving Sepsis Campaign (SSC)
performance bundles and mortality.
DESIGN: 29,470 subjects entered into the SSC database from January 1, 2005, through June 30, 2012. Two
hundred eighteen community, academic, and tertiary care hospitals in the United States, South America, and
Europe.
Mortality rate decreased 4% (95% CI: 1% - 7%; p = 0.012) for every 10% increase in site compliance with the
resuscitation bundle.
24. “Surviving sepsis campaign: association between performance metrics and outcomes in a 7.5-year study.” Levy MM. Crit Care Med. 2015
Jan;43(1):3-12.
What has lead to improved
mortality?
Recognition as medical emergency
– Surviving sepsis campaign
– Screening protocols
Early antibiotics
Training
Tracking and reporting quality
Treatment
Screening/early recognition
Broad spectrum antibiotic based on suspected
source and local antibiogram
Initial fluid administration 30ml/kg
Lactate
Cultures
Vasopressors – adequate perfusion pressure
Assess fluid responsiveness and response to
treatment
References
1. “The epidemiology of sepsis in the United States from 1979 through 2000.” Martin GS, Mannino DM, Eaton S, Moss M. N Engl J Med. 2003;348(16):1546.
2. Fig 1. “Septicemia in U.S. Hospitals, 2009.” Anne Elixhauser, Ph.D., Bernard Friedman, Ph.D., Elizabeth Stranges, M.S. October 2011. http://www.hcupus.ahrq.gov/reports/statbriefs/sb122.pdf. Downloaded 12/2014.
3. “Extending international sepsis epidemiology: the impact of organ dysfunction.” Esper AM, Martin GS Crit Care. 2009;13(1):120.
4. Fig. 2. “Inpatient Care for Septicemia or Sepsis: A Challenge for Patients and Hospitals.” Margaret Jean Hall, Ph.D.; Sonja N. Williams, M.P.H.;
Carol J. DeFrances, Ph.D.; and Aleksandr Golosinskiy, M.S. NCHS Data Brief. Number 62, June 2011.
5. “Deaths: Preliminary Data for 2010.” National Vital Statistics Reports. Volume 60, Number 4. January 11, 2012. http://www.cdc.gov/nchs/data/nvsr/nvsr60/nvsr60_04.pdf.
Downloaded 12/2014.
6. “Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project Statistical Brief No. 160 August 2013. National inpatient
hospital costs: the most expensive conditions by payer, 2011.” http://www.hcup-us.ahrq.gov/reports/statbriefs/sb160.pdf. Downloaded 12/2014.
7. “Centers for Disease Control and Prevention. Heart Failure Fact Sheet.”
http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/docs/fs_heart_failure.pdf. Downloaded 12/2014.
8. Mortality Related to Severe Sepsis and Septic Shock Among Critically Ill Patients in Australia and New Zealand, 2000-2012.” JAMA. 2014;311(13):1308-1316.
9. “Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock.” Emanuel Rivers, M.D., M.P.H., et. Al. N Engl J Med 2001; 345:1368-1377.
10. “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.” Dellinger RP, et al. Crit Care Med. 2004 Mar;32(3):858-73.
11. “Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008.” R. Phillip Dellinger, et al. Intensive Care Med. Jan 2008; 34(1): 17–60.
12. “Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.” Dellinger RP. Crit Care Med. 2013 Feb;41(2):580-637.
13. “Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest
Physicians/Society of Critical Care Medicine.” Bone RC. Chest. 1992 Jun;101(6):1644-55.
14. “A survey of Canadian intensivists’ resuscitation practices in early septic shock.” McIntyre LA, Hebert PC, Fergusson D, Cook DJ, Aziz A: Crit Care 2007, 11:R74.
15. “Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares.” Marik PE, Baram M, Vahid B. Chest. 2008 Jul;134(1):172-8.
16. “Hemodynamic parameters to guide fluid therapy.” Marik et al. Annals of Intensive Care 2011, 1:1.
17. “High central venous oxygen saturation in the latter stages of septic shock is associated with increased mortality.” Textoris et al. Critical Care 2011, 15:R176.
18. “Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy: A Randomized Clinical Trial.” JAMA. 2010;303(8):739-746.
19. “Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock.” Lars B. Holst, M.D, et al. N Engl J Med 2014; 371:1381-1391October 9, 2014.
20. “Albumin versus Other Fluids for Fluid Resuscitation in Patients with Sepsis: A Meta-Analysis.” Jiang L. PLoS One. 2014 Dec 4;9(12):e114666.
21. “Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in Critically Ill Adults.” JAMA. 2012;308(15):15661572.
22. “Goal-Directed Resuscitation for Patients with Early Septic Shock.” The ARISE Investigators and the ANZICS Clinical Trials Group. N Engl J Med 2014;371:1496-506.
23. “A Randomized Trial of Protocol-Based Care for Early Septic Shock.” The ProCESS Investigators. N Engl J Med. 2014;370:1683-93.
24. “Surviving sepsis campaign: association between performance metrics and outcomes in a 7.5-year study.” Levy MM. Crit Care Med. 2015 Jan;43(1):3-12.

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