SEPSIS Recognition,

Treatment and
Referral
Dr. Vida Hamilton
National Clinical Lead Sepsis
www.hse.ie/sepsis
 Sepsis - 2

A dysregulated immune response to infection

Regulated
o 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 inflammation
o Vasodilation, capillary leak

Systemic inflammation
o SIRS, CARS
Bone 1996
 Hyperinflammatory response
Sepsis 1

Control inflammation improve outcome

Multiple studies
o Steroids
o Anti- TNF
o Anti-IL1
o Anti-IL6
o Other monoclonal antibodies
At best no improvement
Often increased mortality
NEJM
 Actors
Micro-organism
o Virulence
o Innoculation dose
o Multi-drug resistance

Host
o Genetic polymorphisms
o 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 score
o Respiration: PaO2/FiO2 or SaO2/FiO2
o Coagulation: Platelets
o Liver: Bilirubin
o Cardiovascular: Hypotension or vasopressor
o CNS: GCS
o Renal: Creatinine or urinary output
qSOFA
o 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 = 8,770
o Number of bed days = 220,288
2013 2012 2011
o In-hospital mortality 28.8% 31.3% 32.4%
 Reality of Sepsis
2013 Without With

ALOS Sepsis 5.59 26

ALOS Infection 5.59 10

ALOS Maternity 2.61 5.47

ALOS 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 survivors

o Anxiety, depression, post-traumatic stress
o Musculo-skeletal, immune suppression
o Shortened life expectancy
 Cognitive impairment

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

Sepsis Severe Sepsis Septic Shock

SIRS
Sepsis plus Sepsis-induced
Infectious & SIRS plus
Sepsis-induced hypo-perfusion or
non infectious Presumed hypotension
causes or organ
dysfunction or persisting despite
Clinical confirmed 30 mls/kg fluid
response arising infection tissue
hypoperfusion rescusitation
from a non
specific insult
 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 parameters
o Mottling, capillary refill, lactate
Haemodynamic variables
o 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 3
1.OXYGEN: Titrate O2 to saturations 1. CULTURES: Take blood cultures
of 94 -98% or 88-92% in chronic lung before giving antimicrobials (if no
disease. significant delay i.e. >45 minutes)
and consider source control.

2. FLUIDS: Start IV fluid 2.BLOODS: Check point of care

resuscitation if evidence of lactate & full blood count. Other
hypovolaemia. 500ml bolus of tests and investigations as per
isotonic crystalloid over 15mins & history and examination.
give up to 30ml/kg, reassessing for
signs of hypovolaemia, euvolaemia,
or fluid overload.

3. ANTIMICROBIALS: Give IV 3. URINE OUTPUT: Assess urine

antimicrobials according to local output and consider urinary
antimicrobial guidelines. 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-patient
ED Ward
Community Hospital acquired
acquired Co-morbidities
Less co-morbidities Second Hit
Generalised training Specialist training
Mortality 20% 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 good
Author N Setting Median Odds ratio
time (mins) for death
Gaieski 261 ED, USA 119 0.30
CCM 2010; 38;1045- (shock) (1st hour vs all
53 times)

Daniels 567 Whole hospital, 121 0.62

Emerg Med J 2010; UK (1st hour vs all
doi:10.1136 times)

Kumar 2154 ED, Canada 360 0.59

CCM 2006; 34(6): (shock) (1st 3 hours vs
1589-1596 delayed)

Appelboam 375 Whole hospital, 240 0.74

CCM 2010; UK (1st 3 hours vs
14(Suppl 1):50 delayed)

Levy 15022 Multi-centre 0.86

CCM 2010; 38(2): 1- (1st 3 hours vs
8 delayed)
Management of sepsis in
adult in-patient
 Start Smart
9-fold increase in mortality with
inappropriate antibiotics
Independent risk factors
o COPD
o Immunocompromised
o Chronic dialysis
 Then Focus
Daily patient review
o Investigations
o Culture results
Five options
o Continue current antimicrobial
o Change antimicrobial
o Change iv to oral
o Stop
o OPAT
Risk stratification

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

 Fluid resuscitation and
Mortality

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, 2013

http://www.atsjournals.org/doi/abs/10.1513/AnnalsATS.201304-099OC
 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 6
R Daniels UK Sepsis Trust 2011
 Severe sepsis audit SSC
Inital Sepsis Bundle
100

90

80

70
Percent in Compliance

60

50

40

30

20

10

0
Oct-14 Nov-14 Dec-14 Jan-15 Feb-15 Mar-15 Apr-15 May-15 Jun-15

Serum lactate within 3 Hrs Blood Culture before Antibiotics

Antibiotic Compliance Fluids for hypotension or elevated lactate
 Fluid resuscitation trials
Antibioti Pre- EGDT Usual Protocol Mort Mort
c randomis Care Standar 28-day 90 day
mins ation dCare (60 day in
ProCESS)
(mls/kg) UC/EGD
UC/EGD
T
T
ProCES 76 30 2.8 2.3 3.3 18.9/21/ 33.7/31.9
S +/- 1.9 +/- 1.9 +/- 1.7 18.2 /30.8

ARISE 70 34 1.96 1.7 14.8/15.9 18.6/18.8

+/-1.4 +/-1.4

ProMis 70 2 litres 2.0 1.78 24.5/24.8 29.2/29.5

e +/- 1.0 +/- 1.0
 Impress Sept 2014

Mortality
US 24%
Europe 28%
Bundle compliant 20%
Non-bundle compliant 30% p=0.026
 HIPE: Diagnosis of Sepsis, Severe Sepsis
or Septic Shock in 2015
Crude
Number of Number of Mortality
Diagnosis Inpatients Deaths 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
Number of Number of Crude Mortality
Diagnosis Admission to Crit Inpatients Deaths Rate
Yes 2542 680 26.8%
Sepsis No 6697 1076 16.1%
Total 9239 1756 19.0%
Yes 73 29 39.7%
Severe Sepsis No 38 9 23.7%
Total 111 38 34.2%
Yes 372 153 41.1%
Septic Shock No 137 64 46.7%
Total 509 217 42.6%
Yes 2987 862 28.9%
Total Sepsis, Severe
No 6872 1149 16.7%
Sepsis & Septic Shock
Total 9859 2011 20.4%
 Hospital Inpatient Enquiry: Crude Mortality for
Inpatients with a Diagnosis of Sepsis & Admission to
Critical Care, by Age Group, 2015
50.0%

45.0%

40.0%

35.0%
Mortality Rate

30.0%

25.0%

20.0%

15.0%

10.0%

5.0%

0.0%

0-14 15-34 35-44 45-54 55-64 65-74 75-84 85+

Years Years Years Years Years Years Years Years
 OECD Health Care Quality Indicators
National Healthcare Quality Reporting System
March 2015

Number per Mortality Change in

annum 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?
Dont 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 Education
o Audit
 Audit
HIPE Metadatasheet
o Mortality
o ICU admission
o Median LOS

Compliance (> 95% form in chart)

o All ED patients admitted with sepsis
o All NEWS > 4 with infection
 Summary

Recognise, Resuscitate, Refer

Sepsis 6 in the 1st hour
Risk stratify and document
Review
Thank you
www.hse.ie/sepsis