update on sepsis management
TRANSCRIPT
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Update on Sepsis Management
Kristopher R. Maday, MS, PA-C, CNSCUniversity of Alabama at Birmingham PA Program
Pegasus Emergency Group
Is Early Goal Directed Therapy Septic and Dying?
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@PA_Maday #AAPA15
Follow Along at……
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Objectives• Identify the sign and symptoms of
sepsis• Describe the common complications
of sepsis• Critically evaluate landmark Early
Goal Directed Therapy study• Appraise current literature on sepsis
management
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Sepsis Statistics
Me
Mostof
you
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Sepsis Incidence and Cost• 2-4% of all diagnoses– 6th most common principle reason for
hospitalization
• Single most expensive condition treated – $15.4 billion spent on sepsis in 2009• $18,500-33,900 per case
Hall MJ. NCHS Data Brief. 2011;62. Elixhauser A. HCUP Statistical Brief. 2011;112.
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2000-2008 CDC Data
Hall MJ. NCHS Data Brief. 2011;62.
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2000-2008 CDC Data
Hall MJ. NCHS Data Brief. 2011;62.
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2000-2008 CDC Data
Hall MJ. NCHS Data Brief. 2011;62.
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2000-2008 CDC Data
Hall MJ. NCHS Data Brief. 2011;62.
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2000-2008 CDC DataDisposition
Sepsis All Other Diagnoses
Percent
Routine 39 79
Transfer to other short-term facility 6 3
Transfer to long-term care facility 30 10
In-hospital mortality 17 2
Other or not stated 8 6
Total 100 100
Hall MJ. NCHS Data Brief. 2011;62. Elixhauser A. HCUP Statistical Brief. 2011;112.
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Surviving Sepsis Campaign • Initiated in 2002• International joint collaborative
between:– Society of Critical Care Medicine– European Society of Intensive Care
Medicine• Mission Statement– “reducing mortality from severe sepsis
and septic shock worldwide”• Developed guidelines and bundles
for sepsis managementSurviving Sepsis Campaign. Accessed February 17, 2015, from http://www.survivingsepsis.org/Pages/default.aspx.
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What Exactly Is “Sepsis”?
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It starts with an infection…
Infectious Source Total (%)
Urinary Tract 34.5
Respiratory Tract 28.7
Gastrointestinal Tract 5
Soft Tissue 6.6
Other 25.2
Ani C. Critical Care Medicine. 2015;43(1):65-77
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Angus DC. NEJM. 2013;369(9):840-851
…that triggers inflammation…
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Systemic Inflammatory Response Syndrome
Marino PL. Infection, Inflammation, and Multiorgan Injury. In: The ICU Book. 4e. 2013.
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Systemic Inflammatory Response Syndrome
Temperature> 38o C (100.4o F)
or< 36o C (96.8o F)
Heart Rate> 90 beats/minute
Respiratory Rate>20 breaths/minute
orPaCO2 < 32 mmHg
Prognosis Mortality2 Criteria 5%3 Criteria 10%4 Criteria 20%
Chen CL. Patient Safety. In: Schwartz’s Principles of Surgery. 10e. 2014.
White Blood Cell Count> 12,000
or< 4,000
or> 10% bands
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Angus DC. NEJM. 2013;369(9):840-851
…that leads to hypoperfusion…
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…that causes organ dysfunction
• Multiple Organ Dysfunction Syndrome– Acute reversible physiologic
derangement of at least 1 organ system
0 1 2 3 4 5 60
20
40
60
80
100
Qureshi K. BJMP. 2008;1(2):7-12
# of Organ Systems Affected
% M
orta
lity
Marshall J. Critical Care Medicine. 1995;10:1638-1652
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Multiple Organ Dysfunction Syndrome
• Altered Mental Status
• Hyperglycemia
• Lactic Acidosis
• Hypoxemia
• Acute Kidney Injury
• Coagulopathy
• Paralytic Ileus
• Hyperbilirubinemia
• Elevated troponin
• Hypotension
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Howell MD. Intensive Care Medicine. 2007;33:1892-1899
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InfectionSystemic
Inflammatory
ResponseSyndrome
SEPSIS
Severe
Shock
The Sepsis Spectrum
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Brown T. Journal of Critical Care. 2015;30:71-77
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Kumar A. Critical Care Medicine. 2006;34:1589-1596
What if we miss it?
7.6% increase in mortality PER HOUROdds Ratio < 1 if antibiotics started within 1st hr
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What if we miss it?
5.3% increase in mortality EVERY HOUR
Bai X. Critical Care. 2014;18:532
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Sepsis Trials
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Early
Goal
Directed
Therapy
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Early Goal Directed Therapy• Published in 2001 by Dr. Emanuel
Rivers• Single academic tertiary hospital• EGDT vs Standard Care• Primary Outcome– In-hospital mortality
• Secondary Outcome– 28-day and 60-day mortality
Rivers E. NEJM. 2001;345(19):1368-1377
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Rivers E. NEJM. 2001;345(19):1368-1377
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Rivers E. NEJM. 2001;345(19):1368-1377
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Results of EGDT
• Fluid difference• Transfusion difference• Vasopressor difference
Outcome EGDT Usual Care ARR 95% CI p
In-hospital Mortality 30.5% 46.5% 15.13
%3.62-
26.64% 0.015
28-day Mortality 33.3% 49.2% 15.1% 3.33-26.3% 0.017
60-day Mortality 44.3% 56.9% 14.2% 2.1-25.6% 0.029
Rivers E. NEJM. 2001;345(19):1368-1377
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Levy MM. Critical Care Medicine. 2015;43(1):3-12
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Ani C. Critical Care Medicine. 2015;43(1):65-77
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Since 2001, Early Goal Directed Therapy
has become the …
StandardOf
Care for sepsis management
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But… a lot has happened in past year
The Sepsis Trilogy
TRISS Trial
ALBIOS Trial
SEPSISPAM Trial
Well …. %$#! you, too
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ProCESS
ARISE ProMISe
Sepsis Trilogy
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ProCESS Trial• 1351 patients across 31 academic US
hospitals• 2 Intervention Groups– EGDT protocol– Protocol-based standard therapy
• Control Group– Usual care
• Primary Outcome– 60-day mortality
• Results– No difference in mortality between all groups
The Process Investigators. NEJM. 2014;370:1683-1693
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STRIKE ONE!!!
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ARISE Trial• 1600 patients across 51 international
hospitals• Intervention Group– EGDT protocol
• Control Group– Usual resuscitation care
• Primary Outcome– 90-day mortality
• Results– No difference in mortality
The ARISE Investigators. NEJM. 2014;371:1496-1506
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STRIKE TWO!!!
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ProMISe Trial• 1260 patients across 56 UK hospitals• Intervention group– EGDT protocol
• Control group– Usual care
• Primary Outcome– All-cause 90-day mortality
• Results– No difference in mortality
The ProMISe Investigators. NEJM. 2015;371:1496-1506
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EGDT
ISOUT
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Comparison of EGDT StudiesEGDT (Rivers) ProCESS ARISE ProMISe
Location US US Australasia UKPatient # 263 1351 1600 1260
SEPSIS DEFINITIONSuspected/
Actual Infection
Yes Yes Yes Yes
≥ 2 SIRS Criteria Yes Yes Yes Yes
SBP < 90 or lactate > 4 Yes Yes Yes Yes
PROTOCOLFluid before
randomization 20-30 mL/kg ~20-30 mL/kg 1000 mL 1000 mL
Intervention EGDT 6 hours EGDT 6 hours EGDT 6 hours EGDT 6 hours
Control Usual therapy1) Protocol usual
support2) Usual therapy
Usual therapy Usual therapy
Primary Outcome
In-hospital mortality 60-day mortality 90-day
mortality 90-day mortality
PRIMARY OUTCOMEIntervention 30.5% 21% 18.6% 29.5%
Control 46.5% 1) 18.2%2) 18.9% 18.8% 29.2%
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TRISS Trial• 998 patients across 32 Scandinavian ICUs• Treatment– Transfusion threshold ≤ 7mg/dL
• Control– Transfusion threshold ≤ 9mg/dL
• Primary Outcome– 90-day mortality
• Results– No difference in mortality
Holst LB. NEJM. 2014;371:1381-1391
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ALBIOS Trial• 1818 patients across 100 Italian ICUs• Treatment Group– 20% albumin daily to maintain ≥ 30 g/L– Crystalloid at MD’s discretion
• Control Group– Crystalloid at MD’s discretion
• Primary Outcome– 28-day mortality
• Results– Improved hemodynamic indices– No difference in mortality
Caironi P. NEJM. 2014;370:1412-1421
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SEPSISPAM Trial• 776 patients across 29 French hospitals• Treatment Group– Target MAP 80-85
• Control Group– Target MAP 65-70
• Primary Outcome– 28-day mortality
• Results– No difference in mortality
Asfer P. NEJM. 2014;370:1583-1593
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Sepsis Management in 2015
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Sepsis Management in 2015• Vigilant early identification of sepsis
• Baseline lactic acid
• Antibiotics within 1st hour of hypotension
• Identify infectious source (cultures, imaging)
Keegan J. Emerg Med Clin N Am. 2014;32:759-776 Marik P. CHEST. 2014;145(6):1407-1418
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• 20-30 cc/kg initial crystalloid bolus• 500cc bolus thereafter
Keegan J. Emerg Med Clin N Am. 2014;32:759-776 Marik P. CHEST. 2014;145(6):1407-1418 Raghunathan K. Critical Care Medicine. 2014;42:1585-1591
The Tank
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The Tubing
Norepinephrine for MAP 65-80 mmHg
Keegan J. Emerg Med Clin N Am. 2014;32:759-776 Marik P. CHEST. 2014;145(6):1407-1418 Raghunathan K. Critical Care Medicine. 2014;42:1585-1591
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Dobutamine for lactate clearance or CI > 2.5 L/min/m2
Keegan J. Emerg Med Clin N Am. 2014;32:759-776 Marik P. CHEST. 2014;145(6):1407-1418 Raghunathan K. Critical Care Medicine. 2014;42:1585-1591
The Ticker
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Sepsis Management in 2015
• Hydrocortisone 200mg if refractory hypotension after norepinephrine
• Transfusion only if Hgb < 7.0 mg/dL
• Transfer to ICU
Keegan J. Emerg Med Clin N Am. 2014;32:759-776 Marik P. CHEST. 2014;145(6):1407-1418 Raghunathan K. Critical Care Medicine. 2014;42:1585-1591
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Surviving Sepsis Campaign Bundles
• To be completed within 3 hours:–Measure lactate level– Cultures then broad spectrum antibiotics– 30 ml/kg crystalloid bolus
• To be completed within 6 hours:– Vasopressors for MAP > 65 mmHg– Recheck lactate– Re-evaluate volume status
http://www.survivingsepsis.org/bundles/Pages/default.aspx
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Is EGDT Septic and Dying?
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Dr. Rivers is the “Wright Brothers of
Sepsis”
We don’t do it that way now, but he got us flying
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So The Next Time You See This…
BP – 102/65
Temp – 102.3o
HR - 114
RR - 22
O2 – 92%
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IsThisPatient….
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SEPT IC
end Lactic Acidarly Antibioticsressorsransfernfusionsultures