Ricard Ferrer Intensive Care Department

Mutua Terrassa University Hospital Barcelona. SPAIN

Edusepsis: Un Projecte per Millorar

els resultats clínics a la Septicemia

La sepsis es una de las enfermedades más frecuentes pero menos reconocidas del

mundo

1. INTRODUCCIÓN MEDICINA INTENSIVA

Su incidencia está aumentando de

forma exponencial.

Los hospitalizados por sepsis se han duplicado en los últimos 10 años.

1. INTRODUCCIÓN MEDICINA INTENSIVA

Entre 20-30 millones de

personas en todo el mundo son

afectadas cada año. De las cuales

8 millones mueren.

1. INTRODUCCIÓN MEDICINA INTENSIVA

Cada 4 segundos

alguien muere por sepsis en el

mundo

1. INTRODUCCIÓN MEDICINA INTENSIVA

Use of Retrospective Administrative Data

Epidemiology of sepsis

Evolución Mortalidad Sepsis Grave CMBD Cataluña

Ferrer R et al. SCCM Congress 2014

Evolución Mortalidad Sepsis Grave CMBD Cataluña

Ferrer R et al. SCCM Congress 2014

• 42 ICUs in Spain.

• All episodes of severe sepsis or septic shock in two periods of time.

– 2 months in 2005, before EDUSEPSIS intervention.

– 3 months in 2011, before ABISS intervention.

• 2011 patients were:

– Older: 62.1±16.7 vs 64.9±14.9 years; p=0,023

– More severe: APACHE II 20.7±7.2 vs 22.4±7.9; p=0,001

Evolution of Sepsis care and mortality in Spain

ESICM Congress 2013

Evolution of Sepsis Mortality in Spain

p< 0.001

Adjusted mortality: OR 0.638 (0.49-0.831); p=0,001

ESICM Congress 2013

Crit Care Med 2010; 38(2):367-374

n= 15.022

Mortality: Site Quarter

• Mortality over 4 year

study period

–36.7% to 27.5%

• ARR: 9.2%

• RRR: 25.0% – P=0.005

DOI: 10.1097CCM.0000000000000026

Control group in 36 RCT vs Administrative data

RCT

Angus

Martin

Australian and New Zealand Intensive Care Society adult ICU patient database

Australian and New Zealand Intensive Care Society adult ICU patient database

Crit Care Med 2009; 37: 1268–1274

Mortality (%)

ICU 15.5

Hospital 28.3

1 Year 40.9

2 Year 44.9

Quality of life (EuroQol-5D)=

Crit Care Med 2009; 37: 1268–1274

Crit Care Med 2009; 37: 1268–1274

Pillars of Sepsis Treatment

ABX Source Control EGDT

Lactate Radiology

YOUR speed is LIFE!

EDUSEPSIS es una organización independiente de profesionales que

atienden al paciente crítico, tanto adulto como pediátrico, cuyo objetivo es reducir la

mortalidad de la sepsis grave y el shock séptico mediante la evaluación de la

eficacia y eficiencia de los tratamientos y la transferencia del conocimiento científico.

Acciones

• Intervenciones de Transferencia del Conocimiento en Sepsis. – Adultos

– Pediatría

• Evaluaciones de la efectividad de los tratamientos de la sepsis. – Nacional

– Internacional: SSC

• Evaluaciones de costes y Coste-Efectividad.

PRE-INTERVENTION PROCESS-OF-CARE MEASURES

POST-INTERVENTION PROCESS-OF-CARE MEASURES

IMPROVE KWONLEDGE

CHANGE BEHAVIOUR

IMPROVE OUTCOME

EDUCATIONAL

STRATEGIES STRUCTURE AND

ORGANIZATIONAL

STRATEGIES

Performance Improvement Interventions

EDUCATIONAL

PROGRAMME

POST-EDUCATION

DATA COLLECTION

OCT-DEC JAN-FEB MAR-JUN

2005 2006

BASELINE

DATA COLLECTION

a before-and-after intervention study

2007

LONG-TERM

FOLLOW-UP

MAR-JUN

JAMA 2008;299(19):2294-2303

Study Timeline

PE

RC

EP

TIO

N

Multifaceted Intervention

PI

Hospital

Manager

Interview

Physicians

Nurses

ICU

ED

Medical Ward

Surgical Ward

Graphic material:

distribution and display

Clinical training

Resuscitation Bundle (6H)

0

10

20

30

40

50

60

70

80

90

% C

om

plia

nc

e

Lactate Blood Cultures Antibiotics Fluids +

Vasopresors

CVP>8 SvcO2>70 All

Preintervention Intervention

* p<0.05

*

*

*

*

* *

Management Bundle (24h)

0

10

20

30

40

50

60

70

80

90

% C

om

plia

nc

e

Steroids APC Glucose IPP All

Preintervention Intervention

* p<0.05

* * *

*

Educational Program and Mortality

4439,7

36,4

31,1

0

10

20

30

40

50

%

Hospital Mortality ICU Mortality

Preintervention Intervention

p= .036 p= .01

Absolute reduction: 4.3%

Relative reduction 10%

28d Mortality: Kaplan-Meier curve

Absolute reduction: 4.3%

Relative reduction 10%

SSC objective was 25%!

Impact of Baseline Compliance

0

5

10

15

20

25

30

Pre-Intervention Post-Intervention

%

Cat 1 Cat 2 Cat 3

0

5

10

15

20

25

30

Pre-Intervention Post-Intervention

%

Cat 1 Cat 2 Cat 3

20

25

30

35

40

45

50

Pre-Intervention Post-Intervention

%

Cat 1 Cat 2 Cat 3

Resuscitation Bundle Management Bundle

Mortality

* p<0.05

*

* *

*

*

Cat 1: < 4 tasks (n= 20)

Cat 2: 4-5 tasks (n= 19)

Cat 3: > 5 tasks (n= 20)

Resuscitation Bundle (6H)

0

10

20

30

40

50

60

70

80

90

% C

om

plia

nc

e

Lactate Blood Cultures Antibiotics Fluids +

Vasopresors

CVP>8 SvcO2>70 All

Preintervention Intervention Long-term

Long-term follow up (23 centers) * p<0.05

* *

*

*

*

Time to Treatment

0

50

100

150

200

250

Min

ute

s

Lactate Blood culture Antibiotics PVC >8 ScvO2>70

Preintervention Intervention Long-term

* p<0.05

*

Long-term follow up (23 centers)

Educational Program and Mortality

42,538,7

0

10

20

30

40

50

%

Hospital Mortality

Preintervention Intervention Long-term

38,0

Long-term follow up (23 centers)

PRE-INTERVENTION GUIDELINE IMPLEMENTATION

POST-INTERVENTION GUIDELINE IMPLEMENTATION

IMPROVE KWONLEDGE

IMPROVE OUTCOME

EDUCATIONAL STRATEGIES

Continuous Performance Improvement

ABISS Edusepsis Study Antibiotic Intervention in Severe Sepsis

Objectives

• Efficacy:

– Reduce time to empiric antibiotic in severe sepsis.

– Increase appropriateness of antibiotic treatment

– Reduce hospital mortality.

• Safety:

– Increase antibiotic deescalation.

By a multifaceted quality-improvement intervention in patients with severe sepsis/septic shock admitted to the Spanish ICUs.

Multifaceted Intervention

• Audit and Feed-back.

• Educational meetings: PP presentation.

• Interactive Sepsis simulation on-line.

• Posters and pocket material about initial TTM.

• Support for antibiotic prescription.

• Remainders by mail and SMS to all staff assisting to educational meetings.

Remainders: SMSs

Audit and Feed-Back

120 hospitals were invited to participate and received the educational material: -Poster “La Sepsis Mata”: 360 -Poster “Pilares del tratamiento de la Sepsis”: 360 -Poster “Juego interactivo”: 360 -Triptics “Pilares del tratamiento de la Sepsis”: 6000 Educational intervention: -80 hospitals complete the educational intervention -4567 doctors and nurses attend to the meetings and provide a email address and/or mobile phone for remainders.

Educational Meetings

Educational Material

Prescription Support

• Local Guidelines of empiric antibiotic treatment • Spanish Society of Intensive Care Guidelines of empiric antibiotic treatment

Gamification

Remainder. SMSs

• En sepsis la administración del antibiótico adecuado es una emergencia.Consulta tu guia local de tto antibiotico empirico.TU VELOCIDAD ES VIDA.

• Los pilares del tratamiento de la sepsis son:antibióticoterapia, control del foco y resucitación hemodinámica.¡COMPLETALOS RAPIDAMENTE!

• Tardamos 3 horas en administrar antibiótico empírico en sepsis con mortalidad 33%. Administrado en 1h la mortalidad sería inferior!.

• Antes del tto antibiótico, recuerda tomar hemocultivos + cultivos adicionales según foco de sepsis, después podrás ajustar tu tto empírico!.

Results

• 72 hospitals in Spain.

• 2576 patients: PRE 1,325, POST: 1,251

• Age 64.1 ± 15.1 years, 54.1% male.

• CHARLSON 2.7 ± 2.2

• Septic Shock 67.6%, 32.4% severe sepsis.

• Bacteriemia: 33%

• APACHE-II 22 ± 8.

• SOFA 9 ± 3

• PCT 25 ± 35

Results: Antibiotics

p< 0.001 p= 0.020

Results

p= 0.002 p= 0.001

Results

p= 0.422 p= 0.182

ABISS Edusepsis

Pediatric

ABISS pediatric net

PICUs ABISS: 33

ABISS pediatric

ABISS PICUs characteristics:

• Total: 380 PICU beds

• Total admissions/month: 1460

• 100% of PICU with residents

• 94% public

• 83.3% medical and surgical, 25% pediatrics-

neonatal

• Protocols for sepsis management 100%

• Use of biomarkers: PCR 100%, PCT 64%

• Hemofiltration: 50%; ECMO: 20%

Preintervention results

• 198 cases

• 118 ♂ (59.6%)

• Median age (years) 2.9 ±4.6 ( 7 days-17.8 ys)

• Underlying diseases: 88 (44,4%)

• SOFA 6,74±3.71

• PRISM3 10.71± 7.21

• Biomarkers:

– PCT 36.97±52.25 ng/ml

– CRP 19.60±21.66 mg/dl

Preintervention results

• Global Mortality 15.6%

–Mortality Septic shock 26.2%

• Days of mechanical ventilation: 13.6±42.6

• Days of inotropic support: 5.77± 8.43

• PICU length of stay (days): 12.02±35.03

• Hospital length of stay (days): 26±45.09

Preintervention results

• Antibiotics previous to the onset of sepsis: 46

(23,2%)

• Evaluation of treatment: Change of ATB at 72

hs:

Objective: To analyze the impact on hospital

mortality of severe sepsis treatments

included in the SSC guidelines in a

prospective multicenter observational

study (n= 2,796 adult patients with

severe sepsis in 77 Spanish ICUs).

Method: The effectiveness of each sepsis

treatment was estimated by using PS.

AJRCCM 2009;180:861–866.

TREATMENTS and MORTALITY

• Adjust for possible confounders:

–Clinical risks factors for mortality

–Other treatments and therapeutic

goals

–Propensity Score

Propensity Score. Antibiotics.

0,4 0,6 0,8 1 1,2 1,4 1,6 1,8

Odds ratio

OR and 95% CI

Broad spectrum AB:

Fluid challenge#

0-1 Hour 1-3 Hour 3-6 Hour Previous AB No AB first 6H

Steroids in septic shock

APC in MOF

Fluid challenge, only severe sepsis

Ferrer R et al. AJRCCM 2009;180:861–866

Effectiveness of APC in MOF

Final Model: All risk factors + Other TTMs + PS

CCM 2014, in press

Predicted hospital mortality and 95% CIs for time to first antibiotic administration

Results adjusted by the sepsis severity score, ICU admission source ([ED], ward, vs ICU),

and geographic region (Europe, United States, and South America)

Cox proportional hazard regression of PP < 30 cm H2O in patients without ALI

Cox proportional hazard regression of PP < 30 cm H2O in patients with ALI

Coste y Coste-Efectividad

Can it work? Efficacy

Does it work? Effectiveness

Efficiency Is it worth it?

Life year gained (LYG)

Quality adjusted life year (QALY)

60.000 euros/LYG

30.000 euros/LYG

rechazo

?

adopción ADOPTION

+ EFFECTIVENESS

+ C

OS

T

Cost-Effectiveness

Cost-Effectiveness Analysis

• Ratio of the cost of the intervention to a

relevant measure of its effect.

THERAPEUTIC

INTERVENTION

Expenditures Outcome

Improvement in Health Costs

Incremental Cost-Effectiveness Ratio (ICER)

Incremental Cost-Utility Ratio (ICUR)

16935

18671

15000

16000

17000

18000

19000

20000

Eu

ros

Hospital Costs

Preintervention Intervention

5.445.98

3.75 4.12

0

1

2

3

4

5

6

7

Years

LYG QALY

Preintervention Intervention

Adjusted ICER 4,435 euros per LYG

Adjusted ICUR 6,428 euros per QALY

Distribution of mean costs per patient

1296314018

3100

3773820

826

54

52

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

Control group Treatment group

Co

st

per

pati

en

t (E

uro

s 2

006)

ICU Ward SSC protocol interventions Emergy Department

60.000 euros/LYG

30.000 euros/LYG

rechazo

?

adopción ADOPTION

+ EFFECTIVENESS

+ C

OS

T

SSC

Cost-Effectiveness

Conclusions

1. La sepsia greu continua teneint una elevada incidència i mortalitat. El reconeixement social encara és escàs.

2. La sepsia greu és una emergencia mèdica. Cal que rebi una atenció multidisciplinar, coordinada i precoç.

3. Pla Nacional de Sepsis. Indicadors de Qualitat.

4. Codi de Sepsis

rferrer@mutuaterrassa.es

Ricard Ferrer Intensive Care Department

Mutua Terrassa University Hospital Barcelona. SPAIN