Update on Sepsis Management

Update on Sepsis

Kristopher R. Maday, MS, PA-C, CNSCUniversity of Alabama at Birmingham

Objectives• Identify the sign and symptoms of

sepsis• Describe the common complications of

sepsis• Introduce the new Sepsis-III definition• Critically evaluate landmark Early Goal

Directed Therapy study• Appraise current literature on sepsis

management

Sepsis Statistics

Me

Mostof

you

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.

2000-2008 CDC Data

Hall MJ. NCHS Data Brief. 2011;62.

2000-2008 CDC Data


2000-2008 CDC Data


2000-2008 CDC Data


2000-2008 CDC DataDisposition

Sepsis All Other Diagnoses

PercentRoutine 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.

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.

What Exactly Is “Sepsis”?

sipsi

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

Angus DC. NEJM. 2013;369(9):840-851

…that triggers inflammation…

Systemic Inflammatory Response Syndrome

Marino PL. Infection, Inflammation, and Multiorgan Injury. In: The ICU Book. 4e. 2013.

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

Angus DC. NEJM. 2013;369(9):840-851

…that leads to hypoperfusion…

…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

Multiple Organ Dysfunction Syndrome

• Altered Mental Status

• Hyperglycemia

• Lactic Acidosis

• Hypoxemia

• Acute Kidney Injury

• Coagulopathy

• Paralytic Ileus

• Hyperbilirubinemia

• Elevated troponin

• Hypotension

Howell MD. Intensive Care Medicine. 2007;33:1892-1899

InfectionSystemic

Inflammatory

ResponseSyndrome

SEPSIS

Severe

Shock

The Sepsis Spectrum

Brown T. Journal of Critical Care. 2015;30:71-77

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

What if we miss it?

5.3% increase in mortality EVERY HOUR

Bai X. Critical Care. 2014;18:532

Sepsis-III Definition• No more “severe sepsis”• Sequential Organ Failure Assessment

Score

Singer M and Sepsis-3 Group. JAMA. 2016;315(8):801-810

Singer M and Sepsis-3 Group. JAMA. 2016;315(8):801-810

qSOFARR ≥ 22/minGCS ≤ 13SBP ≤ 100 mmHg

Sepsis Trials

Early

Goal

Directed

Therapy

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

Rivers E. NEJM. 2001;345(19):1368-1377

Rivers E. NEJM. 2001;345(19):1368-1377

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

Levy MM. Critical Care Medicine. 2015;43(1):3-12

Ani C. Critical Care Medicine. 2015;43(1):65-77

Since 2001, Early Goal Directed Therapy

has become the …

StandardOf

Care for sepsis management

But… a lot happened in 2014/2015

The Sepsis Trilogy

TRISS Trial

SEPSISPAM Trial

ProCESS

ARISE ProMISe

Sepsis Trilogy

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

STRIKE ONE!!!

ARISE Trial• 1600 patients across 51 international

hospitals• Intervention Group– EGDT protocol

• Control Group– Usual resuscitation care


• Results– No difference in mortality

The ARISE Investigators. NEJM. 2014;371:1496-1506

STRIKE TWO!!!

ProMISe Trial• 1260 patients across 56 UK hospitals• Intervention group– EGDT protocol

• Control group– Usual care

• Primary Outcome– All-cause 90-day mortality


The ProMISe Investigators. NEJM. 2015;371:1496-1506

EGDT

ISOUT

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%

TRISS Trial• 998 patients across 32 Scandinavian ICUs• Treatment– Transfusion threshold ≤ 7mg/dL

• Control– Transfusion threshold ≤ 9mg/dL



Holst LB. NEJM. 2014;371:1381-1391

SEPSISPAM Trial• 776 patients across 29 French hospitals• Treatment Group– Target MAP 80-85

• Control Group– Target MAP 65-70



Asfer P. NEJM. 2014;370:1583-1593

Sepsis Management in 2016

• http://www.emdocs.net/the-dangers-of-over-resuscitation-in-sepsis/

Sepsis Management in 2016• 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

Three “T’s” of Shock Management

• 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

The Tubing

Norepinephrine for MAP 65-80 mmHg


Dobutamine for lactate clearance or CI > 2.5 L/min/m2


The Ticker

Sepsis Management in 2016

• Hydrocortisone 200mg if refractory hypotension after norepinephrine

• Transfusion only if Hgb < 7.0 mg/dL

• Transfer to ICU


2015 CMS Sepsis Core Measures

Sepsis Septic Shock

Performed by hour 3

1)Initial lactate level2)Blood cultures

3) Broad spectrum antibiotics

Performed by hour 6

1) Repeat lactate if initial lactate > 2 mmol

1) Resuscitation with 30cc/kg crystalloid2) Vasopressors if hypotension is refractory to fluids

or initial lactate ≥ 4 mmol:a) Repeat volume status and tissue perfusion

assessment consisting of:a) Focused physical examb) Any 2 of the following:

i. CVPii. ScVO2iii. CV USiv. Passive leg raise or fluid challenge

So The Next Time You See This…

BP – 102/65

Temp – 102.3o

HR - 114

RR - 22

O2 – 92%

SEPT IC

end Lactic Acidarly Antibioticsressorsransfernfusionsultures

Thank You!

w w w . p a i n e p o d c a s t . c o m

Health & Medicine

Update on Sepsis Management