1. SEPSIS Recognition, Treatment and Referral
Dr. Vida Hamilton
National Clinical Lead Sepsis

2. SEPSIS – a dysregulated response to infection
Gary Larson
SEPSIS – a dysregulated response to infection

3. What is regulated? Skin/ Mucosal barrier Dendritic cells Innate
pH, commensals
Dendritic cells
TLR, PAMPs, DAMPs
Innate
White blood cells, complement
Cytocines, chemokines, iNOS
Adaptive
T-cell, B-cells

6. Immune response Local inflammation Systemic inflammation
Vasodilation, capillary leak
Systemic inflammation
Pro-inflammatory phase
‘Modulate response improve outcome’

8. Dysregulated? Multi-organ dysfunction then failure
Little necrosis more like ‘hibernation’
Apoptosis of the cellular immune system
D4 persistent lymphopenia
‘Stimulate immune system improve outcome’

9. Hotchkiss Nature 2013

10. Sepsis Definition Infection causing a systemic inflammatory response
A process not an event
Severe sepsis
Tissue hypo-perfusion and/or new onset organ dysfunction
Septic shock
Haemodynamic instability and/or tissue hypo-perfusion that persists after fluid resuscitation to address hypovolaemia

11. Systemic Inflammatory Response (SIRS)

12. Actors Micro-organism Host Virulence Innoculation dose
Genetic polymorphisms
Co-morbidities
Age
Chronic health status
Immuno-modulatory medications

13. The Burden International estimates
Severe sepsis: 330 per 100,000 per annum
AMI: 208 per 100,000 per annum
Mortality: %
Mortality from sepsis today is the same as that for AMI in the 1960s
More than breast cancer, bowel cancer and HIV/AIDS combined
Sepsis incidence is rising internationally
Most expensive since condition being managed in the US healthcare system
25,000 euros per patient

14. UK Sepsis Trust
Bowel cancer
Breast cancer
Annual UK sepsis deaths

15. The Burden in Ireland HIPE data:
60% all in-hospital deaths has a sepsis or infection diagnosis
Number of sepsis cases = 8,770
Number of bed days = ,288
In-hospital mortality 28.8% % %
Sepsis not routinely documented in case notes rather site of infection. Percentage of deaths with sepsis code 16.3%, with sepsis or infection 60.3%

16. Reality of Sepsis 2013 Without With ALOS Sepsis 5.59 26 ALOS Infection10
ALOS Maternity
2.61
5.47
ALOS Paediatrics
3.08
22.19

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

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

19. Sepsis 2013 National Average Sepsis cases as % of all cases 1.44
Sepsis as % of all bed days
6.8
Sepsis + Infection as % of all cases
20.22
Sepsis + Infection as % of all bed days
42.3

20. Costs Sepsis acute care Eur 25,000
Sepsis consumes 30% of the UK critical care budget
£2.5 billion annually

21. Chronic health burden for survivors
Anxiety, depression
Post traumatic stress disorder
Chronic lung disease
Immune suppression
Shortened life expectancy

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

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

24. 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

25. National Sepsis Guidelines
20% decrease in mortality over 5 years
Care pathway for every patient diagnosed with sepsis in Ireland
Recognition, Resuscitation, Referral
Education, audit

26. Diagnostic criteria for sepsis
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

27. SIRS Criteria T > 38.3oC, < 36oC HR > 90 beats/min
RR > 20 breathes/min
WCC > 12, < 4
BSL > 7.7 mmol/l in non-diabetic
Altered mental status

28. SIRS criteria continued
Inflammatory parameters eg CRP, PCT
New organ dysfunction
Hypoxia, Oliguria, Creatinine, Coag, Platelet, Bilirubin, Ileus
Inadequate tissue perfusion
Mottling, capillary refill, lactate
Haemodynamic instability
BP <90, MAP < 70, SBP  > 40mmHg from baseline

29. Common sources of sepsis Impress 2014
Respiratory 38%
Urinary tract 21%
Intra-abdominal 16.5%
CRBSI 2.3%
Device 1.3%
CNS %
Others %

30. 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

31. Patient demographics Emergency Department Ward in-patient
Community acquired
Less co-morbidities
Mortality 20%
Hospital acquired
Co-morbidities
Second – Hit
Mortality ??? Higher

33. Sepsis 6 in the Ist hour Give 3 Take 3 1.OXYGEN:
Titrate O2 to saturations of % or 88-92% in chronic lung disease.
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 lactate & full blood count. 
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.

35. Management of sepsis in adult in-patient
Identify yourself, Situation, Background, assessment, recommendation

37. Prompt treatment Sepsis is a time-dependent medical emergency
Mortality increases by 7.6% for each hour delay to appropriate antibiotics (Kumar CCM 2006)

38. Early antibiotics are good
Author N
Setting
Median time (mins)
Odds ratio for death
Gaieski
CCM 2010; 38;
261
ED, USA
(shock)
119
0.30
(1st hour vs all times)
Daniels
Emerg Med J 2010; doi:
567
Whole hospital, UK
121
0.62
Kumar
CCM 2006; 34(6):
2154
ED, Canada
360
0.59
(1st 3 hours vs delayed)
Appelboam
CCM 2010; 14(Suppl 1):50
375
240
0.74
(1st 3 hours vs delayed)
Levy
CCM 2010; 38(2): 1-8
15022
Multi-centre
0.86

39. Start Smart
9-fold increase in mortality with inappropriate antibiotics
Independent risk factors
COPD
Immunocompromised
Chronic dialysis

40. Then Focus Daily patient review Five options Investigations
Culture results
Five options
Continue current antimicrobial
Change antimicrobial
Change iv to oral
Stop
OPAT

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

43. UK Sepsis Trust

44. 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%
Daniels et al, Emergency medicine journal 2011

45. Compliance with Sepsis 6 R Daniels UK Sepsis Trust 2011

46. Fluid resuscitation trials
Antibiotic
mins
Pre-randomisation
(mls/kg)
EGDT
Usual Care
Protocol
StandardCare
Mort
28-day
(60 day in ProCESS)
UC/EGDT
90 day
ProCESS 76 30
2.8
+/- 1.9
2.3
3.3
+/- 1.7
18.9/21/
18.2
33.7/31.9/30.8
ARISE 70 34
1.96
+/-1.4
1.7
14.8/15.9
18.6/18.8
ProMise
2 litres
2.0
+/- 1.0
1.78
24.5/24.8
29.2/29.5

47. Impress Sept 2014 Mortality US 24% Europe 28% Bundle compliant 20%
Non-bundle compliant
30% p=0.026

48. 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

50. Niccolo Machiavelli, The Prince, 1513
“….as the physicians say it happens in hectic fever, that in the beginning of the malady it is easy to cure but difficult to detect, but in the course of time, not having been either detected or treated in the beginning, it becomes easy to detect but difficult to cure.”
Niccolo Machiavelli, The Prince, 1513

51. UK Sepsis trust

52. Audit
NOCA Metadatasheet
Mortality
ICU admission
aLOS

53. Barriers to implementation
Lack of awareness, Lack of agreement
Lack of self-efficacy
Perception – Reality gap, Education, Audit
Lack of outcome expectancy
Audit
Inertia of previous practice
Lactate, Audit, Discussion forums, Bottom-up/ Top-down
Perception – reality gap

54. External barriers Guideline related Patient related
Poor specificity of SIRS criteria
Patient related
Late presentation, co-morbidities
Environment related
Lack of resources

55. Summary Recognise, Resuscitate, Refer Sepsis 6 in the 1st hour
Risk stratify and document
Reassess at 3 hours
Haemodynamic stabilisation by 6 hours
If possible
Review

56. Thank you