Kathleen M. Vollman RN, MSN, CCNS, FCCM Clinical Nurse Specialist/Educator/Consultant ADVANCING...

Kathleen M. Vollman RN, MSN, CCNS, FCCMClinical Nurse Specialist/Educator/Consultant

ADVANCING [email protected]

Northville, Michiganwww.vollman.com

Nurse’s role In Nurse’s role In Comprehensive Comprehensive Sepsis ManagementSepsis Management

Nurse’s role In Nurse’s role In Comprehensive Comprehensive Sepsis ManagementSepsis Management

© Vollman 2009

Overview

• Significance of the Problem• Defining the continuum• Brief overview of Pathophysiologic

derangements• Prevention• Early Recognition & Resuscitation

* Based on data for septicemia †Reflects hospital-wide cases of severe sepsis as defined by infection in the presence of organ dysfunction

1 Sands KE, et al. JAMA 1997;278:234-40.2 National Vital Statistics Reports. 2005.3 Angus DC, et al. Crit Care Med 2001;29:1303-10.

Severe Sepsis: A Significant Healthcare Challenge

• Major cause of morbidity and mortality worldwide– Leading cause of death in noncoronary

ICU (US)1

– 10th leading cause of death overall (US)2*• More than 750,000 cases of severe sepsis

in the US annually3

• In the US, more than 500 patients dieof severe sepsis daily3†

Severe Sepsis Is Common

• 1 in 10 patients admitted to the ICU has severe sepsis.*

• 2.26% of total hospital discharges nationally

• Incidence is expected to increase by nearly 17% by 2014.

•All analyses were performed using the 2000 MEDPAR Hospital Discharge Database. The information presented represents national averages, and similar analyses performed at an individual institution may provide different results.

1. Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome and associated costs of care. Crit Care Med. 2001;29(7):1303-1310. 2. Data of file, Eli Lilly and Company: XIG20070405b.

Severe Sepsis Is Common

AIDS1 Colon Cancer2

Breast Cancer2

CHF3 Severe Sepsis4

Cas

es/1

00,0

00

Incidence

1. National Center for Health Statistics, 2001. 2. American Cancer Society, 2001. 3. American Heart Association. 2000. 4. Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome and associated costs of care. Crit Care Med. 2001;29(7):1303-1310.

Severe sepsis is more common than AIDS, colon cancer, and breast cancer combined.

Begin Proven Care Strategies

• Early appropriate antibiotic use

• EGDT: Early Goal-Directed Therapy

• Low-tidal volume ventilation/ARDS/ALI

• Xigris if not contraindicated

• Tight glycemic control

• Low-dose steroid administration for refractory septic shock particularly in patients with relative adrenal insufficiency

Implementation Through Proven Implementation Through Proven Change StrategiesChange Strategies

IHI/VHA Change Strategy• Care Bundles

– Grouping of care elements for particular symptoms, procedures or treatments

– Strong science, good methodology, poor process

– Bundle characteristics• Solid evidence• Relatively easy & inexpensive• Individual components defined

well• Process not defined well

How Does Severe Sepsis Compare to Your Current Care Priorities?

Quality Projects

US Incidence

# of Deaths Mortality Rate

AMI1 895,000 171,000 19%

Stroke1 700,000 157,800 23%

Pneumonia2 1,300,000 61,800 4.8%

Severe Sepsis3 751,000 215,000 29%

Why do you think that severe sepsis has not received the same focus as these other common disease states?

1. American Heart Association. Heart Disease and Stroke Statistics 2006 Update. 2. National Center for Health Statistics. Available at: www.cdc.gov/nchs/fastats/pneumonia.htm. Accessed February 4, 2005. 3. Angus DC, et al. Crit Care Med 2001;29(7):1303-1310.

Organizational Consensus that Severe SepsisMust be Managed Early and Aggressively

Early Screening with Tools and Triggers

Implementation of the Sepsis Bundle

Measuring Success

4-Tier Process for Severe Sepsis Program Implementation

* All analyses were performed using the 2004 through 2006 MEDPAR Hospital Discharge Databases. Cost and charge data are reported in year-appropriate US Dollars.† Severe sepsis patients were identified by looking for combinations of ICD-9-CM codes indicating infection and new onset of acute organ failure following SCCM/ACCP

guidelines as described in Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome and associated costs of care. Crit Care Med. 2001;29 (7):1303-1310.‡ Average total hospital costs for patients treated in the ICU.

2004-2006 Severe Sepsis ReportNational-All Hospital, Medicare Reporting-3670

Copyright © 2007, Eli Lilly and Company. All rights reserved

Top Ten Severe Sepsis Diagnosis-Related Groups *†

(53.5% of all cases with severe sepsis fell within 10 DRGs)

Severe Sepsis Cases

(average)

All Others

(average)

Mortality 27% 7%

Ventilator Use 30% 2%

Hospital Length of Stay 11.1 days 7.2 days

ICU Length of Stay 6.5 days 4.2 days

Cost per Case‡ $22,000 $12,000

Payment-to-Cost Ratio -24% 8%

(costs exceeds payment)

Organization Support

Executive management at hospital actively supports the program

Managing severe sepsis is aligned with hospital ‘s current year goals

Willingness to align resources with programUnderstanding that this is a 2-3+ year program to make

this the standard of practice for this patient populationExisting culture that supports change

• Successfully implemented other major change programs—eg: vent bundle, tight glucose control, CR-BSI

Established team in place with ICU physician and nurse champion, ED physician and nurse champion that are respected by staff

Building a Severe Sepsis Tool Kit:Project Team Charter

Severe Sepsis is Common and Deadly Problem Statement::

Team Members

ED, ICU, Patient Care Unit ED, ICU, Patient Care Unit Representatives, Administration, Representatives, Administration,

Medical Staff, Nursing, Medical Staff, Nursing, Pharmacy, Performance Improvement, Pharmacy, Performance Improvement,

Case Management, LaboratoryCase Management, Laboratory

Business Case

In comparison to other ICU patients, In comparison to other ICU patients, severe sepsis patients have a higher severe sepsis patients have a higher mortality rate, increased LOS, and an mortality rate, increased LOS, and an

increased need for a ventilatorincreased need for a ventilator

Benefits

Potential to improve outcomesPotential to improve outcomes

Goals

Reduce severe sepsis mortality (make Reduce severe sepsis mortality (make the goal specific and measurable)the goal specific and measurable)

Scope

Severe sepsis patients in the ED, ICU, Severe sepsis patients in the ED, ICU, and patient care unitsand patient care units

Milestones

Implementation of tiers 1, 2, 3, and 4Implementation of tiers 1, 2, 3, and 4

The Team is KEY!!Can Be Major Barrier If Not Functioning

Well• Must have nurse and physician champions from

ED and ICU (need at least one physician at all meetings)

• Must be linked in the organization’s quality or operational structure

• Must meet at least 2 times per month• Team members must be well educated on the

evidence and armed with tools and knowledge to change behavior at the bedside

• MUST have bedside nurses on team—provide reality check and best knowledge of barriers

Severe Sepsis: Defining a Disease Continuum

SIRS with a

presumed or confirmed infectious

process

SepsisSIRSInfection orTrauma

Severe Sepsis

Sepsis with 1 sign of organ

dysfunction, hypoperfusion or

hypotension.

Examples:• Cardiovascular (refractory hypotension)

• Renal• Respiratory• Hepatic• Hematologic• CNS• Unexplained metabolic acidosis

Adult CriteriaA clinical response arising from a nonspecific insult, including ≥ 2

of the following:

Temperature:> 38°C or < 36°CHeart Rate: > 90 beats/minRespiration:> 20/minWBC count: > 12,000/mm3,

or < 4,000/mm3,or > 10% immature

neutrophils

SIRS = Systemic Inflammatory Response SyndromeBone et al. Chest.1992;101:1644-1654.

Shock



Severe Sepsis

Adult CriteriaA clinical response arising from a nonspecific

insult, including ≥ 2 of the following:

Temperature:> 38°C or < 36°CHeart Rate: > 90 beats/minRespiration: > 20/minWBC count: > 12,000/mm3,

or < 4,000/mm3,or > 10% immature neutrophils


Signs & Symptoms of Sepsis

PlateletsBandsSkin perfusion Urine outputSkin mottlingPoor capillary refillHyperglycemiaPurpura/petechia

31

ChillsAlteration in LOCTachypneaUnexplained metabolicacidosisHeart rateAltered blood pressure

Levy M, et al. Crit Care Med 2003;31:1250-6.


SIRS with a

presumed or confirmed infectious

process


Severe Sepsis




Severe Sepsis

.

Examples:

• Cardiovascular (refractory hypotension)• Renal• Respiratory• Hepatic• Hematologic• CNS• Unexplained metabolic acidosis


Shock

Sepsis with 1 sign of organ

dysfunction, hypoperfusion or hypotension

Identifying Acute Organ Dysfunction as a Marker of Severe

SepsisTachycardiaSBP<90mmHgMAP < 70mmHg (despite fluid)Need for Vasopressors

Unexplained metabolic acidosis•Lactate > 1.5 times upper normal

PaO2/FiO2 200 if lung only dysfunction/site of infectionPaO2/FiO2 250 with other organ dysfunction/lung not site of infection UO <0.5 ml/kg per hr

(despite fluid)

Platelets <80,000/mm3

Decline in platelet count of 50% over 3 days

RespiratoryRespiratory

MetabolicMetabolic

CardiovascularCardiovascular

RenalRenal

HematologicHematologic

21

Deterioration of Cardiovascular Function on Day 1 was Associated with Increased Mortality in Placebo Patients

* 28-day mortality for standard therapy patients enrolled in PROWESS and a Phase II study of an investigational anti-sepsis drug.† Vasopressor requirement at study entry through day 1. Based on the Sequential Organ Failure Assessment (SOFA) score, low dose was defined as dopamine 6-15 µg/kg/min, epinephrine 0.1 µg/kg/min, or norepinephrine 0.1 µg/kg/min. High dose was defined as dopamine

> 15 µg/kg/min, epinephrine > 0.1 µg/kg/min, or norepinephrine >0.1 µg/kg/min.

Levy, M., Macias, W., Vincent, J., et al. Early changes in organ function predict eventual survival in severe sepsis. Crit Care Med. 2005; 33:1-8.

Change in Vasopressor Dose on Day 1*†

54%58%

37%

20%

No Vasopressor No Vasopressor to Low Dose

No Vasopressor to High Dose

CV SOFA Increased by 1

% M

orta

lity

n=294 n=41 n=36 n=46

P<0.0001

40

50

60

70

0

20

30

PaO2/FiO2 Ratio

• User friendly tool

• Crude assessment of the severity of lung injury

• May be used in the assessment of Acute Respiratory Dysfunction due to Severe Sepsis

• Also used in the definition of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS)

PaOPaO22 = 70 torr = 70 torr

FiOFiO22 = 60% or .60 = 60% or .60

P/F RatioP/F Ratio = 70/.60 = 70/.60

Answer:Answer: 117 117

24

Respiratory Dysfunction (Mortality by Change in SOFA Score) in Placebo Patients

57%

30%27%

0%

10%

20%

30%

40%

50%

60%

IMPROVED BY DAY1

UNCHANGED ATDAY 1

WORSENED BY DAY1

N=355 N=398 N=94

Levy, M., Macias, W., Vincent, J., et al. Early changes in organ function predict eventual survival in severe sepsis. Crit Care Med. 2005; 33:1-8.

Severe sepsis mortality predictors (Baseline to Day 1)Severe sepsis mortality predictors (Baseline to Day 1)Population-based outcomes observed in severe sepsis patientsPopulation-based outcomes observed in severe sepsis patients

p=0.0004

26

Renal Dysfunction (Mortality by Change in Serum Creatinine) in Placebo Patients

† Renal SOFA Score = 2 equivalent to creatinine range 2.0 - 3.4 mg/dL.‡ APACHE (Acute Physiology And Chronic Health Evaluation). For more information on using the APACHE II scoring system, please see http://www.sfar.org/scores2/scores2.html.

Levy, M., Macias, W., Vincent, J., et al. Early changes in organ function predict eventual survival in severe sepsis. Crit Care Med. 2005; 33:1-8.Data on file, Eli Lilly and Company: XIG20060922a.

0

10

20

30

40

50

60

70

CMH Trend TestP<0.0001

19%

35%

61%

1.2 TO 1.9 mg/dLTO< 1.2 mg/dL

1.2 TO 1.9 mg/dLTO1.2 TO 1.9 mg/dL

1.2 TO 1.9 mg/dLTO> 1.9 mg/dL

Severe sepsis mortality predictors (Baseline to Day 1)Population-based outcomes observed in severe sepsis patientsIn PROWESS, patients with chronic kidney failure on dialysis were excluded. The following was observed in patients with acute kidney dysfunction at baseline (renal SOFA = 2)†‡

N=129 N=109 N=38

Homeostasis

Homeostasis Is Unbalanced in Severe Sepsis

Carvalho AC, Freeman NJ. J Crit Illness 1994;9:51-75.Kidokoro A, et al. Shock 1996;5:223-8.Vervloet MG, et al. Semin Thromb Hemost 1998;24:33-44.

COAGULATIONCOAGULATIONINFLAMMATIONINFLAMMATION

FIBRINOLYSISFIBRINOLYSIS

SEVERE SEPSIS

PATHOPHYSIOLOGY

Microvascular dysfunction

Inflammation Coagulation Fibrinolysis

Hypoperfusion/hypoxiaMicrovascular thrombosisEndothelial dysfunction

Organ dysfunctionGlobal tissue hypoxiaDirect tissue damage

Inflammation, Coagulation and Impaired Fibrinolysis In Severe Sepsis

Adapted from Bernard GR, et al. N Engl J Med. 2001;344:699-709.

Endothelium

Neutrophil

Monocyte

IL-6IL-1TNF-

IL-6

Inflammatory Responseto Infection

Thrombotic Responseto Infection

Fibrinolytic Responseto Infection

PAI-1

Suppressedfibrinolysis

Factor VIIIaTissue Factor

COAGULATION CASCADE

Factor Va

THROMBIN

Fibrin

Fibrin clotTissue Factor

The Role Of Endogenous Activated Protein C In Severe Sepsis

Adapted from Bernard GR, et al. N Engl J Med. 2001;344:699-709

Endothelium

Neutrophil

Monocyte

IL-6

IL-6

Activated Protein C

Inactivation

Inactivation

Inactivation

Activated Protein CPAI-1

SuppressedfibrinolysisActivated

Protein C

Reduction

of Rolling

Inhi

bitio

nIn

hibi

tion

Activated Protein C

Factor VIIIaTissue Factor

Factor Va

THROMBIN

Fibrin

Fibrin clotTissue Factor

Organisms

Inflammatory Responseto Infection

Thrombotic Responseto Infection

Fibrinolytic Responseto Infection

COAGULATION CASCADE

Pathophysiologic Characteristics in Severe

Sepsis

• Maldistribution of blood flow

• Imbalance of oxygen supply & demand

• Metabolic alterations & activation of the stress response

© Vollman 2001

Maldistribution of Blood Flow• Mechanical obstruction

– Micro-emboli– Increased blood viscosity– Compression

• Systemic & local mediator & ion influence– Constriction vs. dilation

• Loss of regulatory activities/endothelial cell injury– Reactive hyperemia

– Anticoagulation © Vollman 2001

Imbalance of Oxygen Supply & Demand

SUPPLY

DEMAND© Vollman 2001

OXYGEN SUPPLY/DEMAND OXYGEN SUPPLY/DEMAND DYNAMICSDYNAMICS

ScvO2CVP, CO, CI, SV, SVI

O 2 Supply/Demand Compensatory Mechanisms

Improve pulmonary gas exchange

Increase oxygen delivery

Alter the distribution of blood flow

O2 Supply Debt

Metabolic Alterations & The Stress Response

Initiation of the Stress Response

Sympathetic Nervous Sympathetic Nervous System ActivationSystem Activation

Hypothalamus Activation

Metabolic Alterations & The Stress Response

• SNS Activation• Gut hypothesis• BMR• Inhibition of

insulin secretion• Inhibition of

glucose uptake by the tissues

• Hypothalamus Activation• Adrenal cortex

stimulation• Changes in

carbohydrate, protein & fat metabolism resulting in glucose concentration

Except on few occasions, Except on few occasions, the patient appears to die from the patient appears to die from the body's response to infection the body's response to infection rather than from it."rather than from it."

Sir William Osler – 1904The Evolution of Modern Medicine

The Nurse’s Role

• Prevention of infection

• Early recognition of patients with signs of sepsis

• Early initiation of evidence-based practice therapies appropriate for your area of practice (antibiotics, fluids/blood, and vasopressors)

• Swift disposition to care areas where the rest of the bundle can be started

Prevention of Infection

• Ventilator-associated pneumonia

• Hospital acquired pneumonia

• Bloodstream infection related to an invasive catheter

• Are you currently working on strategies to prevent infections?

PREVENTING THE INVASION

© Vollman 2001

Oral careOral care

Line care Line care

HandwashingHandwashing

HOBHOB

EARLY MANAGEMENT

Early RecognitionEarly Recognition

ICU/Additional EvidenceICU/Additional Evidence

Based TherapiesBased Therapies

Early AntibioticsEarly Antibiotics

Prompt/Aggressive Prompt/Aggressive ResuscitationResuscitation


Screens and triggers developed to ID Severe Sepsis

patients in the ED, ICU, and on patient care units

2nd-Tier Implementation of Early Screening

Tools and Triggers

Early Recognition: A Screening Process

• TIME IS TISSUE!! – If you identify patients early then you can

intervene and prevent further tissue damage

• To screen effectively, it must be part of the nurses’ daily routine

• Must define a process for what to do with the results of the screen

If you don’t screen you will miss patients that could have benefited from the interventions

Make it Process Dependent

• Weave into fabric of current practice

• Assess for daily

• Identify strategies for initiation of therapy response once patient is identified

Location/Trigger Type

Standard Procedure Manual Alert MessageComputerized Alert Message

Emergency Department

• Triage: Criteria-Based Early Response

• Concurrent coder or case manager

• Upon pharmacy entry of vasopressor/antibiotic

• Lactate drawn as a screen

• Order sheets antibiotic/vasopressor

• Upon withdrawal of med from Automated Dispensing Cabinet

• Change in lactate • Change in lab values (lactate)

• Upon scanning of medication at bedside

“Triggers” for Identifying Severe Sepsis




ICU

• Upon admission• From concurrent

coder or case manager

• Upon pharmacy entry of vasopressor/antibiotic

• By nurse at shift change

• Nurse MAR review (for antibiotic/vasopressor)

• In note field on computerized MAR

• Change in lactate• During MD, RN, RPh,

rounds• Change in lab values

(lactate)

• In note field of vasopressor computerized label

• Criteria-Based Early Response

• Place on all ICU charts (daily) • Upon withdrawal of

med from Automated Dispensing Cabinet





Patient Care Units

• Upon admission• From concurrent

coder or case manager

• Upon pharmacy entry of antibiotic

• During MD, RN, RPh, rounds

• Nurse MAR review for antibiotic

• In note field on computerized MAR

• Criteria-Based Early Response teams

• Change in patient hemodynamics

• In note field of vasopressor computerized label

• Need to mobilize MET

• Upon withdrawal of med from Automated Dispensing Cabinet

• Change in lab values (e.g., elevated WBC, decreased platelet count)


Reaching Outside the ICU: Early Recognition Models

• Shock Program

• Medical Emergency Response Team (MET)

• Critical Care Nurse Consultant Service

Screening: Barriers/Strategies

BarriersTime for nurses to do it (perception vs reality)Screening is not sensitive only for severe sepsisPositive screen is not a diagnosis of severe sepsis

StrategiesMust assign responsibility and hold them accountable--Perform audits to measure compliance and identify problemsRound on unit and ask nurses how it is going and discuss

issues

Screening: Barriers/Strategies

• Lesson Learned: Bedside nurse must do Lesson Learned: Bedside nurse must do screeningscreening

• Education/Simulation/EducationEducation/Simulation/Education- Every 6 monthsEvery 6 months- Build into orientationBuild into orientation- Must be part of their documentation structureMust be part of their documentation structure- Practice-Practice-PracticePractice-Practice-Practice

The END RESULT—anytime patient has 2 or more SIRS—will think that this patient might have sepsis and can screen at that time

EARLY MANAGEMENT








Implementation of the Sepsis Bundle with protocol & order sets

3rd-Tier Implementation of Evidence-Based Sepsis

Bundles

The Severe Sepsis Bundles: Surviving Sepsis Campaign/IHI

Bleeding is the most common adverse effect associated with Xigris therapy.See Important Safety Information in this presentation.

Management Bundle(To be accomplished as soon as possible

and scored over first 24 hours):

Low-dose steroids administered for septic shock in accordance with a standardized ICU policy. (Given to patients who respond poorly to fluids or vasopressors) (2C)

Drotrecogin alfa (activated) administered in accordance with a standardized ICU policy. (Given to patients with sepsis induced organ dysfunction at high risk of death (2B)

Glucose control maintained to < 150 mg/dL (8.3 mmol/L). (2C)

Tidal volume 6 ml/kg (1B) Inspiratory plateau pressures < 30 cmH2O for mechanically ventilated patients. (1C)

Resuscitation Bundle(To be accomplished as soon as possible and scored over first 6 hours):

Serum lactate measured.Blood cultures obtained prior to antibiotics

administered. (1C)Perform imaging studies promptly to fine source

(1C)From the time of presentation, broad- spectrum

antibiotics within 3 hours for ED admissions and 1 hour for non-ED ICU admissions. (1D/1B)

For hypotension and/or lactate > 4 mmol/L: Deliver an initial minimum of 20 mL/kg of

crystalloid (or colloid equivalent) (1C)Apply vasopressors for hypotension not

responding to initial fluid resuscitation to maintain MAP > 65 mmHg.

For persistent hypotension despite initial fluid resuscitation (septic shock) and/or lactate > 4 mmol/L: 1CAchieve CVP > 8 mmHg & MAP > 65 mmHg &

UO >0.5mL/kg/hrAchieve ScvO2 of > 70% or SvO2 > 65%.

if ScvO2 not > 70% blood or dobutamine (2C)

Adapted from the revised guidelines: CCM 2008;36:296-327.

SURVIVING SEPSIS GUIDELINES 2008

• The GRADE system is based on a sequential assessment of the quality of evidence, followed by assessment of the balance between benefits versus risks, burden, and cost and, based on the above, development and grading of a management recommendations.

• Keeping the rating of quality of evidence and strength of recommendation explicitly separate constitutes a crucial and defining feature of the GRADE approach.

• This system classifies quality of evidence as high (Grade A), moderate (Grade B), low (Grade C), or very low (Grade D).

• The GRADE system classifies recommendations as strong (Grade 1) or weak (Grade 2).

• The grade of strong or weak is considered of greater clinical importance

than a difference in letter level of quality of evidence.

1. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36:296-327.

Strength of the Science:Part 1 of Grading System

A. Supported by at least two level I investigations

B. Supported by one level I investigation

C. Supported by level II investigations only

D. Supported by at least one level III investigation

E. Supported by level IV or V evidence

Grading of Recommendations:

Dellinger RP, et al. Crit Care Med. 2008;36:296-327.

Recommendations are published in groups by category and not by hierarchy

New Grading System• Quality of the evidence process = no change

• Recommendation process = new

Which components of the bundle do you

believe will encounter the most resistance?

““Early Goal Directed Therapy”Early Goal Directed Therapy”

PROMPT AGGRESSIVE PROMPT AGGRESSIVE RESUSCITATIONRESUSCITATION

Sepsis Resuscitation Bundle(To be accomplished as soon as possible over first 6 hours):

1. Serum lactate measured.2. Blood cultures obtained prior to antibiotic administration.3. From the time of presentation, broad-spectrum antibiotics administered within 3 hours for ED admissions and 1 hour for non-ED ICU admissions.4. In the event of hypotension and/or lactate > 4 mmol/L (36 mg/dl):a) Deliver an initial minimum of 20 ml/kg of crystalloid (or colloid equivalent*).b) Apply vasopressors for hypotension not responding to initial fluid resuscitation tomaintain mean arterial pressure (MAP) > 65 mm Hg.5. In the event of persistent hypotension despite fluid resuscitation (septic shock) and/orlactate > 4 mmol/L (36 mg/dl):a) Achieve central venous pressure (CVP) of > 8 mm Hg.b) Achieve central venous oxygen saturation (ScvO2) of > 70%.**

Early Goal Directed Therapy

• Early Goal-Directed Therapy (EGDT)• Continuous ScvO2

monitoring & tx with fluids, blood, inotropes &/or vasoactives to maintain:ScvO2 >70%, SaO2 > 93%, Hct > 30%, CI/VO2CVP > 8-12MAP > 65UO > .5ml/kg/hr

• Standard Therapy• CVP > 8-12• MAP > 65• UO > .5ml/kg/hr

Rivers et. al. N Engl J Med. 2001;345;19:1368-1377.

Methodology: 263 severe sepsis patients

49.2%

33.3%

0

10

20

30

40

50

60

Standard Therapy n=133

EGDTn=130

P = 0.01*

*Key difference was in sudden CV collapse, not MODS

28-day Mortality

Rivers E. N Engl J Med 2001;345:1368-77.

Early Goal-Directed Therapy Results

NNT = 7-8

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11794169

Evidence of Early Goal Directed Therapy

• First 6 hours of EGDT:– 1500cc more fluid – 64% received blood products vs. 18.5%– 13.7% received inotropes vs. 0.8%– No difference in vasopressor use or

mechanical ventilation

Rivers et. al. N Engl J Med. 2001;345;19:1368-1377.

Protocolized resuscitation should begin as soon as sepsis induced tissue hypoperfusion is recognized

or Elevated Serum lactate identifies tissue

hypoperfusion in patients at risk who are not hypotensive

Initial fluid challenges be started at > 1000 mL/kg or 300-500 mL of colloid over 30 minutes (1C)

Rivers E. N Engl J Med 2001;345:1368-77.

Initial Resuscitation (1C)

Dellinger, et. al. Crit Care Med 2008, 36:296-327.

-


Early Goal-Directed Therapy:SSC Recommendations

• Goals of therapy within first 6 hours are: (1C)

• Central Venous Pressure 8 - 12 mmHg

• Mean arterial pressure 65 mmHg

• Urine output 0.5 mL/kg/hr

• ScvO2 70%; if not achieved with fluid resuscitation during first 6 hours (2C)

- Transfuse PRBC to hematocrit >27% and/or

- Administer dobutamine (max 20 mcg/kg/min) to goal


Potential Emergency Department Challenges

• Screening in Triage• Drawing lactic acid level with less than one

hour turn around time• When and who will place the central line?

Physician skill level ?• Monitoring CVPs and ScvO2-nurses skill level

and available resources?• When to transfer to ICU? ED-ICU handoff• If long ED LOS---does the ED implement both

resuscitation and management bundles

EGDT: Revisited

Outcomes Survey: 12 programs 1,298 patients with severe sepsis and septic

shock Treated with EGDT and/or the sepsis bundles Pre implementation mortality: 44.8 + 7.8% Post implementation mortality: 24.5 + 5.5 %

Otero RM. et al Chest; 2006:130:1579-1595

20.3% Reduction in Mortality, NNT 5

EGDT: Revisited

Cost Effectiveness of EGDT/Guideline Based Care (ED, ICU or RRT initiated)23.4% reduction in hospital cost (incorporated

additional training, personnel and equipment) Huang et al Crit Care Med 2003:7(suppl S116)

Henry Ford Hospital: 4 day Hospital LOS (32.6% reduction)

Reduction in hospital charges from $135,199 to $82,233 (39.2% reduction) Trzeciak S et al, Chest 2006:129:225-232

Otero RM. et al Chest; 2006:130:1579-1595

BeforeBefore 11041104 AfterAfter 11751175

Peer Review Publications

Favors EGDT

Favors No EGDT

0 10 20 30 40 50

Rivers, 2001Gao, 2005

Sebat, 2005Kortgen, 2006Shapiro, 2006

Trzeciak, 2006Micek, 2006

Shu-Min Lin, 2006Qu, 2006

Nguyen, 2007Jones, 2007Sebat, 2007Chen, 2007

Abstracts

Absolute Risk Reduction (%)

0.00 0.25 0.50 0.75 1.00

Rivers, 2001Gao, 2005

Sebat, 2005Kortgen, 2006Shapiro, 2006

Trzeciak, 2006Micek, 2006

Shu-Min Lin, 2006Qu, 2006

Nguyen, 2007Jones, 2007Sebat, 2007Chen, 2007

Abstracts

Relative Risk Reduction (%)

3311 3311 BeforeBefore

3223 3223 AfterAfter

Abstracts and Publications

0.0 2.5 5.0 7.5 10.0

Abstracts

Publications

Rivers, 2001

Number Need To Treat

1 of every 6 Patients

Abstracts and Publications

4125 4125 BeforeBefore

3328 3328 AfterAfter

Vasopressors

• Recommend that MAP be maintain > 65 mmhg (1C)

• Ideally adequate fluid resuscitation should be achieved before vasopressors and inotropes are used, but use early in septic shock may need to occur. When it does the goal should be to try and wean with continuing fluid resuscitation.

• Norepinephrine or dopamine as first choice. (1C)

• Epinephrine, phenylephrine or vasopression should not be used as the initial vasopressor. (2C) Vasopresion may be added to norepinephrine at 0.03 units/min.

• Suggest that epinephrine be the first chosen alternative. (2B)

• Low dose dopamine not be used for renal perfusion. (1A)

Dellinger RP, et al. Crit Care Med. 2008;36:296-327

Vasopressin vs Norepinephrine Infusion in Septic Shock

VASST Study• Design: Multicenter, randomized, double-

blinded• Population: 778 patients with septic shock and

were receiving a minimum of 5mcq/min of norephinephrine (or equivalent) for 6 hours (excluded pts with underlying heart disease)

• Methods: Received either low dose vasopressin (0.01-0.03U per minutes) or norepinephrine in addition to open-label vasopressors

• End point: 28 day mortality

Russell et al NEJM, 2008; Vol. 58, No 9

VASST Study Results

• No significant difference in 28 day or 90 day mortality between the two groups– Among patients who had less severe septic shock(on

norepinephrine between 5-15 mcq/min) there was a trend toward improved mortality with vasopressin (hypothesis generating)

• No significant difference in rates of organ dsyfunction between the two groups

• No significant difference in overall rates of serious adverse events between the two groups– Trend toward higher rate of cardiac arrest in norepinephrine

group– Trend toward higher rate of digital ischemia in the vasopressin

group


Additional Findings

• Vasopressin infusion allowed a rapid decrease in the total norepinephrine dose while maintaining mean arterial pressure

• Overall rates of serious adverse events were approximately 10% each in the vasopressin and norepinephrine groups.

• The MAP at baseline was 72-73mmHg—essentially making this a study of the effects of low dose vasopressin as a “catecholamine-sparing drug” not an evaluation of vasopressin in patients with catecholamine-unresponsive refractory shock


EARLY MANAGEMENT






• Start intravenous antibiotic therapy within the first hour of recognition of severe sepsis after obtaining appropriate cultures (1D) for Septic shock (1B)

• Board spectrum: include one or more agents active against likely bacterial/fungal pathogens, & with good penetration into presumed source (1B)

• Reassess regimen daily to optimize efficacy, prevent resistance, avoid toxicity & minimize costs. (1C)

Kreger BE. Am J Med 1980;68:344-355. Ibrahim EH. Chest 2000;118:146-155. Hatala R. Ann Intern Med 1996;124-717-725.

Antibiotic Therapy

Dellinger, et. al. Crit Care Med 2008, 36: 296-327.





Mortality as a Function of Adequacyof Empiric Antimicrobial Therapy

Ho

sp

ita

l Mo

rta

lity

(%

)

All causes Infection-related

P<0.001Inadequate Therapy

Adequate Therapy60

50

40

30

20

10

0

P<0.001

Kollef MH, et al. Chest 1999;115:462-74.

Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in

human septic shock

*Effective antimicrobial administration within the 1st hour of documented hypotension was associated with increased survival in patients with septic shock.

*Each hour of delay over the next 6 hours was associated with an average decrease in survival of 7.6% (range 3.6-9.9%)

CCM 2006 Vol. 34 No.6

Antibiotic ChallengesAppropriate selection – determined based upon

consensus guidelines and pathogen sensitivity at your institution

Timing issues How? Delivery time challenges of

antibiotics Possible solutions

Case Study

• Disclaimer:– This is intended for education purposes

– Judgment of physician/clinician should always be the deciding factor

– The following case represents individual experience that are specific to these patients and may not reflect the typical course of recovery

Clinical Scenario 2 : Early Identification and Intervention

• 88 year old, 51.6kg,white, female presented to ED at 1345 from ECF

• History: CAD, COPD, dementia, Alzheimer disease, depression, SVT

• Chief Complaint: rib pain, chest congestion and SOB

• Awake, alert and oriented, slight combative (history of combative behavior)

Case Study 2: Early Identification and Intervention

• Initial VS: – Temp: 101.6 F– RR: 31– HR: 109, atrial fib with occasional SVT– B/P: 79/51– 2L of O2, O2 sat of 96%

• Positive Screen for severe sepsis:– SIRS: HR >90; RR> 20; Temp > 38– Organ dysfunction: SBP<90mmHg

• Early Treatment– IV started– Received 500cc NS bolus over 30 minutes– Labs drawn

Advanced Treatment Guidelines

Department of Emergency Services

PURPOSE: To provide prompt, consistent nursing interventions for the patient with SIRS or sepsis prior to physician evaluation, to enable rapid diagnosis and slow the progression of illness.

IMPLEMENTATION:

The nursing staff may implement these interventions for patients who present with all three of the following criteria. The nurse should take into consideration the patient’s baseline vital signs when evaluating as a potential candidate. Also, these interventions should not conflict with the patient/family goals. (i.e. DNR, comfort care)

1. Clinical suspicion of systemic infection

2. At least two of the following:

» Hyperthermia :Temperature greater than 38 °C (100.4 °F)» Hypothermia: Temperature less than < 36 °C (96.8 °F)» Tachycardia Pulse > 90 bpm» Tachypnea RR > 20

3. SBP < 90

– Patients who meet all three criteria will be placed in a room immediately after consultation with charge nurse and/or attending.

Advanced Treatment GuidelinesDepartment of Emergency Services

TREATMENT

1. Notify Physician 2. Place Intermittent Infusion Device (large bore catheter) in 2 sites3. Place on cardiac monitor4. Continuous pulse oximetry5. Vital signs every 15 minutes6. Administer oxygen at 2 L/min per nasal cannula if O2 sat <92%7. Draw and hold blood cultures x 2, Type & screen8. Draw tube for serum lactate and place on ice.9. Collect CCMS urine sample in the non-menstruating patient. Send for

Urinalysis and urine culture.10. Portable CXR11. Intravenous hydration: Administer 500ml bolus of normal saline

over 15 minutes.


• Labs:– WBC: 11.5– Hgb: 15.8– Hct: 47.4– BUN: 28 Creatinine:1.6– Glucose:158– BNP:78 (moderate CHF); troponin:0.03– Lactic acid: 4.6– U/A: positive for bacteria– ScvO2: 49.1%– Blood cultures X 2 drawn


• CXR: RLL consolidation

• Additional Interventions:– Broad spectrum antibiotics given within 3 hours of

presentation– Lactic acid >4mmol/L so CVP inserted– Fluid resuscitation continued – Foley inserted

• Received total of 3 Liters of NS during 3 hour ED stay

• ED diagnosis: Severe sepsis, Pneumonia , UTI, CHF

• Transferred to MICU

Case Study 2 : Early Identification and Intervention--MICU

• Additional Interventions: Day 1– Continued fluid resuscitation—7 L– Low dose vasopressor– Low dose steroids– Remained on 2 L nasal canula– Not eligible for Xigris (renal failure resolved and

vasopressor weaned off within 12hours after ICU admission)

• Labs:– ScvO2: 72.8 (after resuscitation)– Lactic acid: 4 hours after ICU admission: 6.7

12 hours after ICU admission: 3.0

Bleeding is most common adverse effect associated with Xigris therapy, please see important safety information in this presentation


• Day 2:– Vasopressor weaned off– Lasix to assist with fluid mobilization– Lactic acid: 3.0

• Day 3: – Lactic acid: 1.2– O2 sat 93% on room air– Central line discontinued

• Transferred to intermediate care on Day 3• Discharged from hospital on day 7

EARLY MANAGEMENT






Management Bundle Components

• Recombinant human Activated Protein C [Drotrecogin alfa (activated)] is recommended in patients at a high risk of death (APACHE II score 25, or Sepsis-induced multiple organ failure) if there are no contraindications.

• Within 30 days of surgery with the above indications (2C)

• Drotrecogin alfa (activated) is not indicated in adult patients with severe sepsis and lower risk of death. (1A)

• Relative contraindications/warnings should be consider

Recombinant human Activated Protein C (2B)

Dellinger, et. al. Crit Care Med 2008, 36: 296-327.

*as defined by APACHE II 25†relative risk reduction at 28 daysData on file, Eli Lilly and Company.

PROWESS 28-Day Mortality – High Risk of Death Patients*

44%

31%

0%

10%

20%

30%

40%

50%

60%

Placebo Drotrecogin alfa

(activated)

Absolute Risk Reduction

= 13%M

orta

lity

Rat

e

Drotrecogin Alfa (Activated) In Severe Sepsis: PROWESS Results

29% reduction in relative risk of death with Xigris†

See important safety information in this presentation.

Survival Benefit Consistent across

High-risk Severe Sepsis Patients

The 95% relative risk confidence interval for each subgroup included the point estimate for the overall PROWESS population (0.80). The point estimate of relative risk of death in each subgroup is indicated by a solid circle, and the 95% confidence interval is indicated by the horizontal lines. Note the consistency between the overall trial result and the subgroup analyses.

*APACHE (Acute Physiology And Chronic Health Evaluation). For more information on using the APACHE II scoring system, please see http://www.sfar.org/scores2/scores2.html †Nonprospectively defined population 1. Barie P, et al. Am J Surg. 2004; 188:212-220. 2. Dhainaut JF MD, PhD, et al. For the PROWESS Study Group. Intensive Care Med. 2003;29(6):894-903.3. Laterre P-F et al. Crit Care Med. 2005;33(5):952-961. 4. Data on file, Eli Lilly and Company. 6. Dhainaut JF, Yan SB, Joyce DE, et al. J Thromb Haemost 2004; 2:1924-33.

Xigris® (drotrecogin alfa [activated]) benefits consistent

See Important Safety Information in this presentation.

0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 Relative Risk of Death (95% CI)

FAVORS XIGRIS FAVORS PLACEBO TOTAL RELATIVE RISK XIGRIS PLACEBO(CONFIDENCE

INTERVAL)

APACHE II* ≥ 251 817 0.70(0.59 - 0.85) 30.9 43.7

ORGAN DYSFUNCTION ≥ 22 1271 0.78(0.66 - 0.93) 26.5 33.9

CAP WITH APACHE II ≥ 253 321 0.60(0.44 - 0.82) 26.2 43.5

CAP S. PNEUMONIAE 92 0.40(0.20 - 0.78) 18.0 45.2WITH APACHE II ≥ 254

INTRA-ABDOMINAL SURGERY 116 0.60(0.36 - 1.00) 26.8 45.0WITH APACHE II ≥ 251

OVERT DIC6 454 0.71(0.55 - 0.91) 30.5 43.0

28-DAY MORTALITY

6

Fine-Tuning Xigris Therapy in Adult High-Risk Severe Sepsis Patients

Right Patient, Right Drug, Right Time

New: Clinical trials to help advance care of adultpatients with severe sepsis at high risk of death:

Contact 1-800-LILLY-RX for more information.

RESPOND Targeted Enrollment = 500 RESPOND Targeted Enrollment = 500 Enrollment started in Nov. 2006Enrollment started in Nov. 2006

Phase 2 trial investigating a biomarker (Protein C) to help guide Phase 2 trial investigating a biomarker (Protein C) to help guide Xigris therapy in adult patients with severe sepsis at high risk of death.Xigris therapy in adult patients with severe sepsis at high risk of death.

NEW Placebo Controlled Trial NEW Placebo Controlled Trial in Adult High-Risk Severe Sepsisin Adult High-Risk Severe Sepsis

Help clinicians better identify patients who are most likely to benefit Help clinicians better identify patients who are most likely to benefit from Xigris, as well as to further clarify the benefit/risk profile of the drug.from Xigris, as well as to further clarify the benefit/risk profile of the drug.

Please see Important Safety Information in this presentation and accompanying full Prescribing Information.Bleeding is the most common adverse effect associated with Xigris therapy.

• Concerns about risk of bleeding

• Restrictive order set

• Inconsistent screening process

• Cost issues

What are the Challenges to Appropriate Screening and Administration

of Xigris® (drotrecogin alfa [activated])?

Safety Profile Low incidence of serious bleeding events* Rate of serious bleeding events during infusion in high-risk

patients:PROWESS: 2.2% (9 of 414) in drotrecogin alfa (activated)

patients vs 0.7% (3 of 403) in standard therapy patients Rate of ICH in high-risk patients during infusion:

PROWESS: 0.2% (1 of 414) in drotrecogin alfa (activated) patientsAssociated with severe thrombocytopenia (platelet count

< 30,000/mm3)†

Not associated with other adverse events

*Serious bleeding events were defined as any intracranial hemorrhage, any life-threatening bleeding, any bleeding event requiring the administration of ≥3 units of packed red blood cells per day for 2 consecutive days, or any bleeding event assessed as a serious adverse event.

†At the time of enrollment in the PROWESS study, the patient had a platelet count above 30,000/mm 3. The patient’s platelet count fell to less than 30,000/mm3 after drotrecogin alfa (activated) therapy was initiated.

Data on file, Eli Lilly and Company

See important safety information and full prescribing information in this presentation.

Drotrecogin Alfa (Activated) Has a Favorable Risk/Benefit Profile 8 times more likely to save an additional life than observe an additional serious bleeding event *

* Based on a 13% 28-day survival benefit and a serious bleeding rate during infusion attributable to Xigris of 1.5% (13% ÷ 1.5% = 8.7) in patients with an APACHE II score > 25.Data on file, Eli Lilly and Company.

CONTRAINDICATIONS

– Active internal bleeding– Recent (within 3 months) hemorrhagic stroke– Recent (within 2 months) intracranial or intraspinal surgery, or

severe head trauma– Trauma with an increased risk of life-threatening bleeding– Presence of an epidural catheter– Intracranial neoplasm or mass lesion or evidence of

cerebral herniation

See full Prescribing Information available at this presentation.

Important Safety InformationImportant Safety Information

Drotrecogin alfa (activated) increases the risk of bleeding. Drotrecogin alfa (activated) is contraindicated in patients with the following clinical situations in which bleeding could be associated with a high risk of death or significant morbidity.

Drotrecogin alfa (activated) is contraindicated in patients with known Drotrecogin alfa (activated) is contraindicated in patients with known hypersensitivity to drotrecogin alfa (activated) or any component of this product.hypersensitivity to drotrecogin alfa (activated) or any component of this product.

WARNINGSBleeding• Bleeding is the most common serious adverse effect associated with drotrecogin alfa (activated) therapy. Each

patient being considered for therapy with drotrecogin alfa (activated) should be carefully evaluated and anticipated benefits weighed against potential risks associated with therapy

• Certain conditions, many of which led to exclusion from the Phase 3 trial, are likely to increase the risk of bleeding with drotrecogin alfa (activated) therapy. For individuals with one or more of the following conditions, the increased risk of bleeding should be carefully considered when deciding whether to use drotrecogin alfa (activated) therapy:

– Concurrent therapeutic dosing of heparin to treat an active thrombotic or embolic event– Platelet count < 30,000 x 106/L, even if the platelet count is increased after transfusions– Prothrombin time-INR > 3.0– Recent (within 6 weeks) gastrointestinal bleeding– Recent administration (within 3 days) of thrombolytic therapy– Recent administration (within 7 days) of oral anticoagulants or glycoprotein IIb/IIIa inhibitors– Recent administration (within 7 days) of aspirin > 650 mg per day or other platelet inhibitors– Recent (within 3 months) ischemic stroke– Intracranial arteriovenous malformation or aneurysm– Known bleeding diathesis– Chronic severe hepatic disease– Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its

location

See full Prescribing Information available at this presentation.

Important Safety InformationImportant Safety Information

Additional Management Bundle Components

Low Tidal Volume Ventilation: SSC Recommendations

• Target tidal volumes to < 6 mL/kg (predicted body weight) in patients with ALI/ARDS (1B)

• Initial upper limit goal for plateau pressures in a passively inflated patient be < 30 cm H2O (1C)

• Hypercapnia can be tolerated in patients with ALI/ARDS if required to minimize plateau pressures and tidal volumes (1C)

• Recommend that positive end expiratory pressure be set as to avoid extensive lung collapse at end-expiration (1C)

• Suggest prone positioning in ARDS patients requiring potentially injurious levels of FiO2 or plateau pressures in facilities that have experience with the practice (2C)

Dellinger RP, et al. Crit Care Med. 2008;36;296-327.

ARDS Network ALI/ARDS Ventilator Study

Methodology:– Inclusion criteria: p/f ratio < 300, bilateral

infiltrates, no cardiac cause, receiving mechanical ventilation

–Outcomes: mortality/VFD–841 patients randomized–12 ml/kg TV group – Plat < 50 cm H2O–6 ml/kg TV group - Plat < 30 cm H2O

ARDS Network, N Engl J Med 2000;342:1301-8.

ARDS Network ALI/ARDS Ventilator Study

Results:PEEP: no difference in average amount usedPEEP: no difference in average amount usedMortality: 31% ( 6 ml/kg TV) vs. 40% (12 ml/kg Mortality: 31% ( 6 ml/kg TV) vs. 40% (12 ml/kg

TV) p=0.007TV) p=0.007VFD: 12+ 11 vs. 10+11 (p=0.007)VFD: 12+ 11 vs. 10+11 (p=0.007)Greater organ failure free days in protective Greater organ failure free days in protective groupgroupReduction in IL-6 levels by day 3Reduction in IL-6 levels by day 3Difficulty with agitation/high rates in the 6 ml/kg Difficulty with agitation/high rates in the 6 ml/kg

groupgroupARDS Network, N Engl J Med 2000;342:1301-ARDS Network, N Engl J Med 2000;342:1301-

8.8.

Additional Mechanical Ventilation Recommendations

• Unless contraindicated, maintain HOB elevated to limit aspiration and prevent VAP (1B). Elevation should be 30 to 45 degrees (2C)

• Non-invasive mask ventilation only be considered in that minority of mild to moderate hypoxemic respiratory failure patients who are able to protect their airway & are hemodynamically stable. A low threshold for intubation should be maintain (2B)

Dellinger RP, et al. Crit Care Med. 2008;36;296-327

Additional Mechanical Ventilation Recommendations

• Weaning protocol in place where patients undergo SBT if the satisfy criteria (1A)

• Recommend against the routine use of PA catheters (1A)

• Recommend a conservative fluid strategy for patients with established ALI/ARDS who do not have evidence of tissue hypoperfusion (1C)

Dellinger RP, et al. Crit Care Med. 2008;36;296-327

• Intravenous corticosteroids should only be given to adult septic shock patients after it has been confirmed that their blood pressure is poorly responsive to fluid resuscitation and vasopressor therapy

• Suggest that the ACTH stimulation test should NOT BE used to identify the subset of adult with septic shock who should receive hydrocortisone. (2B)

• We suggest that patients with septic shock should not receive dexamethasone if hydrocortisone is available. (2B)

– Administer intravenous hydrocortisone <300 mg daily (1A)

– Fludrocortisone is optional if hydrocortisone is used (2C)


Corticosteroids In Septic Shock:SSC Recommendations (2C)

Hydrocortisone Therapy for Patients with Septic Shock

• Design: Multicenter, randomized, double-blind, placebo-controlled trial

• Population: 499 patients with septic shock—BP<90 systolic despite adequate fluid replacement or vasopressors for at least one hour (onset of shock within previous 72 hrs)

• Method: 2 groups: one group received 50mg hydrocortisone every 6 hrs for 5 days, then tapered; other group received a placebo.

• End Point: 28 day mortality

Sprung, NEJM,2008; Vol 358 No 2

Hydrocortisone Therapy for Patients with Septic Shock--Results

• No significant difference between 2 study groups in rate of death at 28 days (no matter if responded or not to corticotropin)

• Duration of time to reversal of shock was significantly shorter among all pts receiving hydrocortisone (3.3 days vs 5.8 days; p<0.001)

• Pts in this study who has a SBP of< 90mmHg at 1 day after fluid and vasopressor resuscitation had mortality of 56% if received placebo and mortality of 44.9 if received hydrocortisone (difference of 11.4%)—similar to Annane et al results.

• In hydrocortisone group there was an increased incidence of superinfections, including new episodes of septic shock

Sprung, NEJM,2008; Vol 358 No 2

• Initial stabilization of patients with severe sepsis and hyperglycemia who are admitted to the ICU receive IV insulin therapy to reduce blood glucose levels. (1B)

• Use of a validated protocol and target glucose levels to < 150 mg/dL range. (2C)

• All patients receiving IV insulin should receive a glucose calorie source and blood glucose values should be initially assesses every 1-2 hrs, then q 4 hours after stabilization. (1C)

• Low glucose levels obtained by Point of Care testing should be interpreted with caution (1B)


Glucose Control: SSC Recommendations

NICE Study• 6104 Critically Ill Patients within 24 hrs

of admission to ICU randomized• Data evaluated on 3010 pts in

intensive control group (target 81-108 mg/dL) & 3012 pts to conventional group (target < 180 mg/dL)

• Similar characteristics at baseline

• Results: • Conventional group has

significantly lower number of deaths

• Severe hypoglycemia (blood glucose < 40mg per dL greater in intensive control group (6.8% vs. .5% (p<0.001

NICE-SUGAR Investigators, N Engl J Med;2009:1283-97.

27.5% vs. 24.9% (p =0.02)

Procedure or Population Breakdown

NICE-SUGAR Investigators, N Engl J Med;2009:1283-97.

What to Do Now?

Continue to Optimize Management of Glucose to Prevent Hyperglycemic & Hypoglycemic Events…range target to < 180 mg/dL, stop infusion at 140 mg/dL

Do NOT Return to Sliding Scale Inzucchi SE, Siegel MD. N Engl J Med;2009;360(13):1346-48.

Additional Management Bundle Components Barriers

• TGC:• Lack of tested nomogram• What target range to pick?• Evaluating success• Increase nursing time• Not enough monitors

• Low TV ventilation• Lack of knowledge of research by physicians,

RT and nursing• No defined policy• Lack of accountability• Identifying patients who have ALI or ARDS?

Sepsis Evidence Sepsis Evidence ImplementationImplementation

Making it a RealityMaking it a RealitySepsis BundleSepsis Bundle

Sepsis BundlesScreen for Severe SepsisYes No

Management Sepsis Bundle (24 hour)

• Maintain serum glucose levels on Maintain serum glucose levels on average < 150 mg/dl. (8.3 mmol/L )average < 150 mg/dl. (8.3 mmol/L )

• Drotrecogin alfa (activated) Drotrecogin alfa (activated) administered in accordance with administered in accordance with hospital guidelineshospital guidelines

• Steroids given for septic shock Steroids given for septic shock requiring continued use of requiring continued use of vasopressors for equal to or greater vasopressors for equal to or greater than 6 hoursthan 6 hours

• Adoption of a lung protective strategy Adoption of a lung protective strategy (tidal volumes (tidal volumes < < 6ml/kg) with plateau 6ml/kg) with plateau pressures of 30 cm H2O for pressures of 30 cm H2O for mechanically ventilated patientsmechanically ventilated patients

Resuscitation Sepsis Bundle (6-Hour) •Obtain Cultures before antibiotic administrationObtain Cultures before antibiotic administration•Lactate LevelLactate Level•In the event of hypotension (SBP < 90, MAP < 70) or lactate > In the event of hypotension (SBP < 90, MAP < 70) or lactate > 4 mmol/L, begin initial fluid resuscitation with 20-40 ml of 4 mmol/L, begin initial fluid resuscitation with 20-40 ml of crystalloid (or colloid equivalent) per estimated kg of body crystalloid (or colloid equivalent) per estimated kg of body weightweight•Vasopressors employed for hypotension ((MAP) Less than 65 Vasopressors employed for hypotension ((MAP) Less than 65 mm Hg) during and after initial fluid resuscitationmm Hg) during and after initial fluid resuscitation•Board spectrum antibiotics administered Within 3 hours of Board spectrum antibiotics administered Within 3 hours of presentationpresentation•In the event of septic shock or lactate > 4 mmol/L, CVP and In the event of septic shock or lactate > 4 mmol/L, CVP and ScvO2 or SVO2 measured. ScvO2 or SVO2 measured. •In the event of septic shock or lactate > 4 mmol/L, CVP In the event of septic shock or lactate > 4 mmol/L, CVP maintained 8-12 mmhgmaintained 8-12 mmhg•Inotropes (and/or PRBC’s if hematocrit <= 30 percent) Inotropes (and/or PRBC’s if hematocrit <= 30 percent) delivered for ScvO2 < 70 percent or SVO2 < 65 percent if CVP delivered for ScvO2 < 70 percent or SVO2 < 65 percent if CVP >= 8 mmhg>= 8 mmhg

Standard careStandard care

If on Antibiotic, then Monitor Q24H FL Monitor Per shift ICU

Develop Protocols & Order Sets to Implement

Resuscitation in Medical-Surgical Area

• Draw blood– Lactate Level– Obtain blood cultures before administration of

antibiotic• In the event of hypotension (SBP < 90, MAP < 70) or

lactate > 4 mmol/L, begin initial fluid resuscitation with 20-40 ml of crystalloid (or colloid equivalent) per estimated kg of body weight

• Vasopressors employed for hypotension ((MAP) Less than 65 mm Hg) during and after initial fluid resuscitation

• Broad spectrum antibiotics administered within three hours of presentation

www.ihi.org

Within 6 hrs (Transport to the ICU is Key)

• In the event of septic shock or lactate > 4 mmol/L, CVP and ScvO2 or SVO2 measured. (line inserted)

• In the event of septic shock or lactate > 4 mmol/L, CVP maintained 8-12 mmhg

• Inotropes (and/or PRBC’s if hematocrit <= 30 percent) delivered for ScvO2 < 70 percent or SVO2 < 65 percent if CVP >= 8 mmhg

www.ihi.org

Adoption of a lung protective strategy (tidal volumes < 6ml/kg) with plateau pressures of 30 cm H2O for mechanically ventilated patients with ALI/ARDS

Drotrecogin alfa (activated) administered in accordance with hospital guidelines

Maintain serum glucose levels on average < 150 mg/dl. (8.3 mmol/L)

Consider steroids given for septic shock requiring continued use of vasopressors and fluid resuscitation and remains unstable

Develop Protocols & Order Sets to Implement Management 24-Hour Severe Sepsis Bundles

www.IHI.org

http://www.ihi.org/



Implementation of the Sepsis Bundle

Measuring Success

Fourth Tier: Measuring Process and Outcomes

Changes

Sepsis Measurement tool found at www.ihi.org & www.survivingsepsis.org

http://www.ihi.org/

Data Collection

• Outcome– Mortality (ICU and Hosp)– Hosp LOS– Cost per case (total and direct)

• Process– SSC database– Data elements that measure implementation

of resuscitation and management bundle

Role of Data

• Outcome data– Share with staff and administration to keep

momentum going– Helps convince/move skeptics

• Process data– Celebrate small successes– Helps identify where opportunities for

improvement still exist

Implementation• Hospital resources often focused on planning

phase and then back off after implementation.• The implementation phase is the most critical• Frequent rounds recommended on unit by project

champion to support staff and answer questions.• Defined resources for bedside nurse-IE:

– Project champion has pager to be available 24/7 initially

– Clinical nurse champions identified on each ICU unit and ED to be resources to bedside staff (these staff should be a member of the sepsis team/committee from the beginning)

Severe Sepsis Bundle Implementation Results

• Loma Linda, California

• England

• Germany

• St. Louis, Missouri

Surviving Sepsis Campaign

• 252 hospitals in 18 countries• Data from January 2005-March 2008• Observational; time series• Baseline is first quarter data was

collected• Use of standardized screening tool• Excluded site if less than 20 patients or

less than 3 months of results

M Levy, presented at SCCM 02/2009 Nashville

Surviving Sepsis CampaignResults

• Final Sample Size: 15,022 patients from 166 sites (95% of total) – North America: 58%– Europe: 31%– South America: 10%


Surviving Sepsis Campaign Results

Entry Point Subjects Mortality (hosp)

ED 52% 27.6

ICU 12.8% 41.3

Ward 34.8% 46.8

Hospital mortality went from 37% to 30%7% ARR; 19% RRR; p< 0.007


Surviving Sepsis CampaignBundle Compliance

Bundle Baseline 2 year

Resuscitation 10.9 % 31.3 %

Management 18 % 36 %

Risk Adjusted Hospital Mortality decreased by 5.4%20 % improvement in compliance with bundles


A Prospective Multi-Center Collaborative A Prospective Multi-Center Collaborative StudyStudy

Before and After Implementation of anBefore and After Implementation of anEarly Sepsis InitiativeEarly Sepsis Initiative

The Multi-Center Severe Sepsis & Septic Shock Collaborative Group

Presented by Emanuel Rivers at the World Federation of Critical care Medicine, Florence Italy 08/09

Methods Pre-implementation analysis occurred from

2003-2005 with post-implementation observation from 2005-2008.

11 centers ranging from community (N=6) to academic tertiary care (N=5) settings were included in the study.

In this intention-to-treat evaluation, all patients including DNR were examined.


http://www.henryford.com/

http://www.centracare.com/hospitals/sch/index.html

http://www.sjmercyhealth.org/default.cfm

http://www.porterhealth.com/default.aspx

0

2

4

6

8

10

12

PRE-Implementation POST-Implementation

2.5 2.82.5 2.3

10.4

11.2

Flu

id V

olu

me

(L)

Fluid AdministrationPre- & Post Sepsis Initiative Implementation

Fluids admin. 0-6 hours, L




In-Hospital Mortality: M SS/SS C vs. SSC

PRE % POST % ARR % RRR %

M SS/SS C 39.1 28.9 10.2 26.0

1st Q Last Q

SSC 37.0 30.0 7.0 19.0


Mortality by Lactate & SBP Subsets

PRE- POST-

Lactate > 4 Only 40.4 32.9

SBP < 90 Only 42.4 30.9

Lactate > 4 & SBP < 90

57.3 39.5


Bundle Implementation: Decreased Mortality

• 2 year prospective study in academic tertiary care facility, with majority of care delivered in the ED

• 330 patient enrolled

• Measured 5 quality indicators related to management of Severe sepsis & septic shock population. CVP/ScvO2 by 2 hrs, antibiotics by 4 hours, EGDT completed at 6 hours, appropriate steroids, lactate clearance

Nguyen et al CCM, 2007 Vol 35, No. 4,

Methodology

Bundle Implementation: Decreased Mortality

• In hospital mortality in patients who completed the bundle was significantly lower then those who did not complete the bundle (20.8 vs 39.5; p<0.01)

• 14% of patients that completed the bundle received rhAPC.

• Completing EGDT in 6 hours was the only quality indicator with a significant odds ratio for decreased mortality using multivariate regression analysis

• After 2 years, achieved 51% compliance with all five indicators

Nguyen et al CCM, 2007 Vol 35, No. 4,

Results:

Bundle Component Compliance and Impact on Mortality

Nguyen et al CCM, 2007 Vol 35, No. 4

Prospective External Validation of Effectiveness of EGDT

• Prospective interventional study conducted over 2 years

• Compared 79 patients in pre-intervention year and 77 patients in post intervention year

• Intervention group received significantly more fluid (2L), less vasopressors

• Mortality 18% vs. 27%

Jones AE, et al. Chest, 2007;132:425-432

Source: Gao F, Melody T, Daniels D, et al. The impact of compliance with 6-hour and 24-hour sepsis bundle on hospital mortality in patients with severe sepsis: A prospective observational study. Crit Care Med. 2005;9(6):R764-R770.

Is a two-fold mortality improvement a possibility in your institution?

Sepsis Bundles: Significant Impact on Hospital Outcomes

• Two acute National Health Service Trust Teaching Hospitals in England performed a prospective observational study with 101 adult patients with severe sepsis or septic shock

• Outcomes measures– Rate of compliance with 6-hour and 24-hour bundles adapted from 2004

SSC guidelines– Hospitality mortality between compliant and noncompliant groups

Compliance with Bundles6-hour bundle 52%24-hour bundle 30%

Bundle MortalityNoncompliant 49% (p=.001)Compliant 23% (p=.001)

More than two-fold increase in hospital mortality associated with noncompliant group

Assessed compliance as “all or none” for the bundle elements

Compliance with 6hr Bundle Gao F, et al. Critical Care, 2005;9:R764-770

0%

20%

40%

60%

80%

100%

lactate blood culture antibiotics fluid+/-vasopressors

Hb 7-9g/dl

52%

74% 74%

84%

70%

6hr Bundle & Hosp Mortality Gao F, et al. Critical Care, 2005;9:R764-770

0%

10%

20%

30%

40%

50%

6hr Bundle Yes

6hr Bundle No

N=12/52

N=24/49

RR=2.12 (1.2-3.8)

NNT = 3.9

23%

49%

Mo

rtal

ity

P=0.01

Compliance with 24hr Bundle Gao F, et al. Critical Care, 2005;9:R764-770

0%

20%

40%

60%

80%

100%

Glucose < 8.3 Steroids Pp < 30 RhAPC

64%

43%

85%

30%

24hr Bundle & Hosp Mortality Gao F, et al. Critical Care, 2005;9:R764-770

0%

10%

20%

30%

40%

50%

24hr Bundle Yes

24hr Bundle No

N=6/21

N=24/48

RR=1.75(0.84-3.6)

NNT = 4.829%

50%

Mo

rtal

ity

P=0.16

Severe Sepsis Protocol in Use Germany

• Retrospective cohort study in 10 bed mixed ICU in Germany

• 60 patients (30 consecutive receiving SOP severe sepsis management compared to historical controls)

• Measured: Primary endpoint 28 day mortality

• Measured: Secondary endpoints; ABG’s, lactate, glucose, creat, WBC, Plat, time to dx & 7am on day 2 & 4 SOFA scores

• Results: In SOP group: ↑ use of dobutamine, glucose control, steroids & rhAPC

• Mortality: Control vs SOP (53% vs. 27% p <.05)

• Independent predictors of survival: lactate on admission, age, gender, blood glucose < 150 mg/dl, adm of rhAPC & steroids

Kortgen A et al. Crit Care Med, 2006:34:943-949

Standardized Order Set-Sepsis Bundles

St. Louis, Missouri• Before-after study design with prospective consecutive

data collection of 120 patients

• 1,200 bed academic medical center

• Primary endpoint: 28 day mortality

• Other measures: hospital LOS, IV fluid intact for shock, appropriate antibiotic

• Results: after group: received more IV fluids in ED (p=0.002); more likely to receive >20ml/kg of fluid prior to vasopressors; had lower risk of mortality (48.3% vs 30%, p=0.04); lower hospital LOS (12.1 vs 8.9 days, p=0.038)

• Independent predictors of survival: increased pt age and not receiving >20 ml/kg of IV fluid prior to vasopressors

Micek, Scott et al., Critical Care Medicine, 2006; 34:2707-2714

Standardized Order Set-Sepsis Bundles Decreases Cost

St. Louis, Missouri• Before-after study design with prospective consecutive

data collection of 120 patients to determine financial impact of sepsis protocol

• 1,200 bed academic medical center

• Primary endpoint: Overall Hospital costs

• Secondary endpoint: Hospital LOS

• Results: after group: Hospital costs $16,103 vs. $21,985, p = .008; LOS 5 days less in the protocol group (p= .023)

• Use of protocol independently associated with less per patient cost.

Shorr AF, et al. Critical Care Medicine, 2007; 35:1257-1262

Case Study

• Disclaimer:– This is intended for education purposes

– Judgment of physician/clinician should always be the deciding factor

– The following case represents individual experience that are specific to these patients and may not reflect the typical course of recovery


• 63 year old white female directly admitted to a med-surg floor from a free standing urgent care at 2130

• Hx: NIDDM, COPD, HTN• Chief complaint: pain right lower sternal

border times 2 days, worse with deep breath, SOB.

• CXR: right pleural effusion• Orthostatic hypotension, renal insufficiency

(creatinine 3.4—previously 1.2)

Case Study 3: Early Identification And Intervention

• Initial VS: stable BP, HR-102, RR-WNL

• On 2L nasal cannula, IV at 150/hr

• Labs: WBC-7.5, plat 197, D-dimer: 273

• Resp distress at 0600 next am

• Transferred to MICU

• Possible PE—heparin gtt started

• Broad spectrum antibiotics started


• ICU course:– 2000: BP: 79/34, HR: 123 , WBC: 3.3– Dx of severe sepsis at 2000– 2 liter fluid bolus– Intubated and ventilated– Lactic acid 0.9– Levophed started, heparin gtt d/c’d– CVP inserted


• ICU course-continued:– Xigris started at 0600 (still on vasopressors,

vent, creat-3.9)– 1000: Stopped Xigris for CT guided pleural

aspirtation– 1200: CT- 2 loculated cavities in right lung;

Cardio thoracic surgery consulted– OR at 1700 for drainage of empyema

• Right mini-thorocotomy, empyema drainage, decortication and bronchoscopy. CT (2) inserted


• Post-op– Temp-97, HR: 84, BP-139/69 on levophed and vasopressin

and bicarb gtt.– Xigris restarted

• Post-op Day 1– Levophed off at 0400– Bicarb gtt off at 0400– Vasopressin gtt off at 1000– Vent FiO2 decreased to 55% @ 0800

• Full course of Xigris• Off vent/extubated in 6 days (hx of COPD)• Transfer out of ICU- post-op day 11• Discharge home- post-op day 25

The Nurses Role• Early recognition of patients

with signs of sepsis• Early initiation of evidence

based practice therapies appropriate for your area of practice (antibiotics, fluids/blood & pressors)

• Swift disposition to care areas where the rest of the bundle can be started.

Kathleen M. Vollman RN, MSN, CCNS, FCCM Clinical Nurse Specialist/Educator/Consultant ADVANCING...

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Transcript of Kathleen M. Vollman RN, MSN, CCNS, FCCM Clinical Nurse Specialist/Educator/Consultant ADVANCING...