SEPSIS Recognition,

Treatment and Referral

Dr. Vida HamiltonNational Clinical Lead Sepsis

www.hse.ie/sepsis

Sepsis - 2

• A dysregulated immune response to infection

• Regulatedo Innate & Adaptive

• Cellular: Dendritic cells, T-cells, B-cells• PAMPs that bind TLR 2,3,4, Mannin-binding lecithin

receptors• (DAMPs)• Molecular: complement, acute phase, cytokines• Anti-viral: Interfon, local cellular immunity, apoptosis

Regulated?

• Local inflammationoVasodilation, capillary leak

• Systemic inflammationo SIRS, CARS

Bone 1996

‘Hyperinflammatory response’ Sepsis – 1

• Control inflammation – improve outcome• Multiple studies

o Steroidso Anti- TNFo Anti-IL1o Anti-IL6 o Other monoclonal antibodies

• At best – no improvement• Often – increased mortality

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NEJM

Actors• Micro-organism

o Virulenceo Innoculation doseo Multi-drug resistance

• Hosto Genetic polymorphismso Co-morbidities

• Age• Chronic health status• Immuno-modulatory medications

More pathophysiology

• Hotchkiss 2013

Dysregulated?

• Multi-organ dysfunction then failure

o Little necrosis• Apoptosis of the cellular immune system• Anti-inflammatory phase ‘ immunoparalysis’• D4 persistent lymphopenia• ‘Stimulate immune system improve

outcome’

Sepsis-3: A life threatening organ dysfunction caused by a dysregulated host

response to infection

• SOFA scoreo Respiration: PaO2/FiO2 or SaO2/FiO2o Coagulation: Plateletso Liver: Bilirubino Cardiovascular: Hypotension or vasopressoro CNS: GCSo Renal: Creatinine or urinary output

• qSOFAo RR> 22, Altered Mental status, SBP <100

1o outcome: increased specificity in predicting Mortality > 10%; ICU LOS > 3 days

The Burden

• Common

• Sepsis: 330 per 100,000 per annum• AMI: 208 per 100,000 per annum

• Mortality: 20 - 55%

The Burden in Ireland• HIPE data:

o 60% all in-hospital deaths has a sepsis or infection diagnosis

o Number of sepsis cases = 8,770o Number of bed days = 220,288

2013 2012 2011o In-hospital mortality 28.8%

31.3% 32.4%

Reality of Sepsis

2013 Without With

ALOS Sepsis 5.59 26ALOS Infection 5.59 10

ALOS Maternity 2.61 5.47ALOS Paediatrics

3.08 22.19

Age standardised hospital discharge rate for medical septic shock, 2005 - 2012

Age standardised hospital discharge rate for surgical septic shock, 2005 - 2012

Costs

• 25,000 euro per acute presentation

• Chronic health burden for survivorsoAnxiety, depression, post-traumatic

stress oMusculo-skeletal, immune suppressiono Shortened life expectancy

Iwashyna et al: Long-term cognitive impairment & functional disability among survivors of severe sepsis. JAMA, 2010.

Cognitive impairment

Issues

• 90% of cases with poor outcome in the Australian sepsis database, inadequate recognition was found to be the most common feature

An Irish Report

• The categorisation of the severity of a patients illness

• The early detection of that deterioration• The use of a standardised and structured

communication tool such as ISBAR• Early medical review that is prompted by

evidence based trigger points• A definite escalation plan that is monitored and

audited on a regular basis

National Sepsis Guidelines

• Aim for decrease in in-hospital mortality by 20% for severe sepsis

• Care pathway for every patient diagnosed with sepsis in Ireland

• Recognition, Resuscitation, Referral• Education, audit

SIRS•Infectious & non infectious causes•Clinical response arising from a non specific insult

Sepsis•SIRS plus•Presumed or confirmed infection

Severe Sepsis•Sepsis plus•Sepsis-induced organ dysfunction or tissue hypoperfusion

Septic Shock•Sepsis-induced hypo-perfusion or hypotension persisting despite 30 mls/kg fluid rescusitation

Diagnostic criteria for sepsis

SIRS Criteria• T > 38.3, < 36• HR > 90• RR > 20• WCC > 12, < 4• BSL > 7.7 mmol/l in non-diabetic• Altered mental status

Common mistake - 1• Other inflammatory parameters

o CRP, PCT• Organ dysfunction parameters

o Hypoxia, Oliguria, Creatinine, Coag, Platelet, Bilirubin, Ileus

• Tissue perfusion parameterso Mottling, capillary refill, lactate

• Haemodynamic variableso BP <90, MAP < 70, SBP > 40mmHg from

baseline

Sources of sepsis• Respiratory 38%• Urinary tract 21%• Intra-abdominal 16.5%• CRBSI 2.3%• Device 1.3%• CNS 0.8%• Others 11.3%

Give 3 Take 31.OXYGEN: Titrate O2 to saturations of 94 -98% or 88-92% in chronic lung disease.

1. CULTURES: Take blood cultures before giving antimicrobials (if no significant delay i.e. >45 minutes) and consider source control. 

2. FLUIDS: Start IV fluid resuscitation if evidence of hypovolaemia. 500ml bolus of isotonic crystalloid over 15mins & give up to 30ml/kg, reassessing for signs of hypovolaemia, euvolaemia, or fluid overload.

2.BLOODS: Check point of care lactate & full blood count. Other tests and investigations as per history and examination.

3. ANTIMICROBIALS: Give IV antimicrobials according to local antimicrobial guidelines.

3. URINE OUTPUT: Assess urine output and consider urinary catheterisation for accurate measurement in patients with severe sepsis/septic shock.

Sepsis screening• Early recognition• 2% of all ED referrals are due to sepsis • NSW audit of NEWS: sepsis is the cause of

30% of triggered reviews• UK: NEWS > 5; 52% sepsis

ED vs In-patientED Ward

• Community acquired

• Less co-morbidities• Generalised

training• Mortality 20%

• Hospital acquired• Co-morbidities• Second – Hit• Specialist training• Mortality ???

Higher

Prompt treatment• Sepsis is a time-dependent medical

emergency

• Mortality increases by 7.6% for each hour delay to appropriate antibiotics (Kumar CCM 2006)

Early antibiotics are goodAuthor N Setting Median

time (mins)

Odds ratio for death

GaieskiCCM 2010; 38;1045-53

261 ED, USA(shock)

119 0.30(1st hour vs all times)

DanielsEmerg Med J 2010; doi:10.1136

567 Whole hospital, UK

121 0.62(1st hour vs all times)

KumarCCM 2006; 34(6): 1589-1596

2154 ED, Canada(shock)

360 0.59(1st 3 hours vs delayed)

AppelboamCCM 2010; 14(Suppl 1):50

375 Whole hospital, UK

240 0.74(1st 3 hours vs delayed)

LevyCCM 2010; 38(2): 1-8

15022 Multi-centre 0.86(1st 3 hours vs delayed)

Management of sepsis in adult in-patient

Start Smart• 9-fold increase in mortality with

inappropriate antibiotics• Independent risk factors

o COPDo Immunocompromisedo Chronic dialysis

Then Focus• Daily patient review

o Investigationso Culture results

• Five optionso Continue current antimicrobialo Change antimicrobialo Change iv to oralo Stop o OPAT

Trzeciak, S et al. Int Care Med 2007; 33(6):870-7. n-=1177

Risk stratification

Figure 3. Mean hospital mortality among patients with decreased lactate within 8 hours of index test, stratified by total fluid received in increments of 7.5 ml/kg based on medication administration record.

Annals ATS, 2013http://www.atsjournals.org/doi/abs/10.1513/AnnalsATS.201304-099OC

Fluid resuscitation and Mortality

Cultures – common mistake 2

Compliance with sepsis 6

• Reduces the relative risk of death by 46.6%

• 1 additional life saved for every 5 care episodes

• Mortality reduced from 44% to 20%o Daniels et al, Emergency medicine journal 2011

Compliance with Sepsis 6R Daniels UK Sepsis Trust 2011

Oct-14 Nov-14 Dec-14 Jan-15 Feb-15 Mar-15 Apr-15 May-15 Jun-150

10

20

30

40

50

60

70

80

90

100

Inital Sepsis Bundle

Serum lactate within 3 Hrs Blood Culture before AntibioticsAntibiotic Compliance Fluids for hypotension or elevated lactate

Perc

ent

in C

ompl

ianc

e

Severe sepsis audit – SSC

Fluid resuscitation trialsAntibioticmins

Pre-randomisation(mls/kg)

EGDT Usual Care

ProtocolStandardCare

Mort28-day(60 day in ProCESS)UC/EGDT

Mort90 day

UC/EGDT

ProCESS

76 30 2.8+/- 1.9

2.3+/- 1.9

3.3+/- 1.7

18.9/21/18.2

33.7/31.9/30.8

ARISE 70 34 1.96+/-1.4

1.7+/-1.4

14.8/15.9

18.6/18.8

ProMise

70 2 litres 2.0 +/- 1.0

1.78+/- 1.0

24.5/24.8

29.2/29.5

Impress Sept 2014

MortalityUS 24%

Europe 28%

Bundle compliant 20%

Non-bundle compliant 30% p=0.026

HIPE: Diagnosis of Sepsis, Severe Sepsis

or Septic Shock in 2015

DiagnosisNumber of Inpatients

Number of Deaths

Crude Mortality

Rate

Sepsis 9239 1756 19.0%

Severe Sepsis 111 38 34.2%

Septic Shock 509 217 42.6%

Total 9859 2011 20.4%

HIPE: Inpatients with a Diagnosis of Sepsis, Severe Sepsis or Septic Shock in 2015

Diagnosis Admission to CritNumber of Inpatients

Number of Deaths

Crude Mortality Rate

Sepsis

Yes 2542 680 26.8%

No 6697 1076 16.1%

Total 9239 1756 19.0%

Severe Sepsis

Yes 73 29 39.7%

No 38 9 23.7%

Total 111 38 34.2%

Septic Shock

Yes 372 153 41.1%

No 137 64 46.7%

Total 509 217 42.6%

Total Sepsis, Severe Sepsis & Septic Shock

Yes 2987 862 28.9%

No 6872 1149 16.7%

Total 9859 2011 20.4%

0-14 Years

15-34 Years

35-44 Years

45-54 Years

55-64 Years

65-74 Years

75-84 Years

85+ Years

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%

35.0%

40.0%

45.0%

50.0%

Hospital Inpatient Enquiry: Crude Mortality for Inpatients with a Diagnosis of Sepsis & Admission to Critical Care, by Age Group,

2015

Mor

talit

y R

ate

OECD Health Care Quality IndicatorsNational Healthcare Quality Reporting

System March 2015

Number per annum

Mortality Change in Mortality 2004 - 2013

AMI 6125 6.4% 40%

H. Stroke 1456 26%

I. Stroke 4485 10% 13.6%

Sepsis 9859 20.4% ?

Reassess• Is your patient responding to treatment?• After an initial response have they deteriorated

again?• Are they having a prolonged static period?• Don’t forget recent travel, seasonal outbreaks,

risk factors for MDRs

Barriers to implementation

• Lack of awareness, Lack of agreement• Lack of self-efficacy

o Perception – Reality gap, o Educationo Audit

Audit• HIPE Metadatasheet

o Mortalityo ICU admissiono Median LOS

• Compliance (> 95% form in chart)o All ED patients admitted with sepsiso All NEWS > 4 with infection

Summary

• Recognise, Resuscitate, Refer• Sepsis 6 in the 1st hour• Risk stratify and document• Review

Thank youwww.hse.ie/sepsis