1. Survival benefits and policy conflicts in Sepsis
Amith Shetty
SMEDSA study
Westmead

2. The Challenge
Sepsis noted as leading cause for SAC 1 incidents and RCAs in NSW
A process for early recognition, review and resuscitation of septic patients
Timely early interventions – antibiotics and intravenous fluids

3. CEC Sepsis kills program

4. Program focus RECOGNISE - risk factors, signs and symptoms of sepsis
RESUSCITATE with rapid intravenous fluids and antibiotics within the first hour of recognition of sepsis
REFER to senior clinicians and specialty teams, including retrieval as required

6. RECOGNISE
Initiate sepsis pathway based on suspected infection + 2 SIRS criteria
Up-triaging to ATS category 2
Sepsis bomb

7. RESUSCITATE – SEPSIS SIX
Oxygen
Blood cultures
Lactate
Intravenous fluids – 20ml/kg crystalloid bolus
Antibiotics <60 minutes
Based on clinician predicted source
Antibiotic stewardship program and guidelines
Monitoring

8. REFER Early senior review and assessment
Early referral to intensive care services
Inpatient sepsis management pathway being launched soon
24-48 hr sepsis management tool in pipeline

9. CEC sepsis kills achievements
Improvement in time to antibiotics to 60 minutes in last three years
>18000 patients registered on CEC sepsis archive
Crude patient level data available on archive – time to antibiotics , lactate level, SIRS data

10. Westmead achievements

11. The SMEDSA initiative
Retrospective evaluation of prospectively identified patients presenting to ED with sepsis
Multicentre approval
Westmead
Concord
RPA
Single centre data collection and analysis

12. Westmead hospital 850 bed tertiary hospital
45 treatment space Emergency department
>65000 annual census ED presentations
35-40% ED to ward admission rates

13. Interventions Sepsis kills pathway
ATS category 2 for suspected infection + 2 SIRS criteria
Clinicians encouraged to report
Sepsis pathway antibiotic guidelines
Antibiotic stewardship guidance
Patient safety officer and audits

14. Demographics ~1200 patients recorded at Westmead in past 24 months
Interim analysis at 590 patients
Median age of patients = 59.5 (IQR 36-75)
Females = 306 median age 54.5 (IQR 32-76)
Males = 284 median age 63 (IQR 46-75)

15. Exclusions
Antibiotics ceased or not given in 48 hours – non bacterial etiology, DNR
Exclusions (no antibiotics 9 + antibiotics ceased <48 hours 76) 85
Median age of female (44 exclusions) = 33 (IQR )
Median age for males (41 exclusions) = 49 (IQR 26-68)
Mann-Whitney U test comparing Age in inclusions versus exclusions Median difference = -17 (CI: -24 to -11) (p<0.001)

16. Inclusions Total number of inclusions = 505
Median age of patients = 63 (IQR 42-78)
Females = 262 median age 59.5 (IQR 35-78)
Males = 243 median age 64 (IQR 50-77)

17. Triage guideline 507/ 590 patients triaged to ATS category 2
85.9% adherence to guideline
Median time to clinician 36 mins (IQR 16-73)
ATS<2 versus >2
Time to clinician– 35 versus 84 minutes (p<0.001)
Time to antibiotics – 66.5 versus 129 minutes (p<0.001)
Time to 2nd L fluids – 99.5 versus 228 minutes

18. Lactate testing
492/590 (83.4% 95%CI ) underwent lactate testing
Exclusions vs inclusions – median 1.4 v 1.8 (p<0.01)
Sepsis versus severe sepsis/ septic shock – median 1.5 v 2.2 (p<0.01)
Dead versus alive – 2.8 v 1.7 (p<0.001)
But significant overlap of tails

19. Blood culture testing 484/505 patients had blood cultures collected
95.8% adherence (95% CI )
94 /484 (19.4%) positive BC, 13/94 (13.8% contamination rates) → 81/ 484 (16.7% 95%CI ) significant results
26.5% BC + for severe sepsis group versus 13.4% BC + in plain sepsis group

20. Other cultures 329/505 Urine cultures – 62/329 positive results
193/ 505 other cultures – 100/193 positive results

21. Antibiotic guidance and stewardship
297/ 505 (58.8%) received appropriate antibiotics according to guidelines
192 / 505 (38.0%) received at least one antibiotic as per guidelines
16 / 505 (3.2%) received antibiotics not according to guidelines

22. Severe sepsis criteria (SSC 2012)
Severe sepsis definition = sepsis-induced tissue hypoperfusion or organ dysfunction (any of the following thought to be due to the infection)
Sepsis-induced hypotension
Lactate above upper limits laboratory normal (>2)
Urine output < 0.5 mL/kg/hr for more than 2 hrs despite adequate fluid resuscitation
Acute lung injury with Pao2/Fio2 < 250 in the absence of pneumonia as infection source
Acute lung injury with Pao2/Fio2 < 200 in the presence of pneumonia as infection source
Creatinine > 2.0 mg/dL (176.8 μmol/L)
Bilirubin > 2 mg/dL (34.2 μmol/L)
Platelet count < 100,000 μL
Coagulopathy (international normalized ratio > 1.5)

23. Plain sepsis versus Severe Sepsis
Age – 58 (IQR 38-75) versus 67 (49-80)
Lactate value → 1.5 ( ) v 2.2 ( )
Total MEDS score → 5 (3-9) v 8 (6-12)
Charlson score → 3 (0-7) v 5 (2-9)
Hospital LOS → 4 (2-8.5) v 7 (3-13)

24. Time to antibiotics / IV fluids
Time to antibiotics →69 minutes (IQR ) in patients with plain sepsis versus 67 minutes (IQRR 49-80) in patients with severe sepsis or septic shock
Time to second litre fluids → 196 minutes ( ) v 249 minutes ( )

25. SIRS characterisation
no sepsis
severe sepsis/ septic shock
Plain sepsis
SIRS 0 17 6 14 37
SIRS 1 28 55 97
SIRS 2 46
116
190
SIRS 3 18 57 78
153
SIRS 4 42 34 82
SIRS 5 2 16 8 26
SIRS 6 5
total 85
200
305
590

26. SIRS >2 criteria Sensitivity 0.80 95%CI 0.76- 0.83
Specificity %CI
Positive predictive value = 0.88
Negative predictive value = 0.25
Patients with severe sepsis more likely to have >3 SIRS criteria (p<0.001)

27. Mode of arrival statistics
AMBULANCE vs PRIVATE transport 274 vs 231 (Mann-Whitney)
Median age 74 versus 48 (MD 23 p<0.01)
>SIRS 3 vs 2 (MD 1 p<0.01)
Higher lactate 2.2 vs 1.5 (MD 0.6 p<0.01)
Severe sepsis rates 132/274 (48.2% 95% CI ) versus 68/231 (29.4% 95% CI ) (p<0.01)
MEDS score 9 vs 3 (MD 5 p<0.01)
Mortality (51/ % 95%CI %) versus (6/ % 95% CI %)

28. Clinician predicted source vs final diagnosis
478/ 505 (94.7%) concurrence of clinician prediction of presumed source of diagnosis when compared to final discharge diagnosis

29. Final diagnoses Source Number Chest/ respiratory 219 Urine 84
Skin/ soft tissue/ Orthopedic 44
Abdominal / biliary 41
PUO/ unknown 51
Neuro/ CNS 6
Bloodstream 10
Oral/ Dental 22
Mixed / others 28
Total
505

30. Outcome measures Mortality rates – in-hospital, 30-day or 90- day
Hospital LOS
Discharge location
Occurrence of severe sepsis or septic shock

31. Time to antibiotic analysis
Total patients
Plain sepsis
Severe sepsis and septic shock
Mortality
≤ 1 hour
224
127 97 X
>1 to ≤ 2 hours
134 95 39 x
> 2 to ≤ 3 hours 57 33 24
> 3 hours 86 47
Total
501
302
199

32. Time to intravenous fluid analysis
Time to second litre fluids
Total patients
Plain sepsis
Severe sepsis and septic shock
In-hospital mortality
≤ 1 hour 35 13 22 X
>1 to ≤ 2 hours 65 30
>2 to ≤ 3 hours 76 46
>3 hours
279
177
102
Total
455
271
184 x

33. Future focus
More clinical trials needed on sepsis patients not just focus on severe sepsis and septic shock – ED from ICU shopfront
Overall benefit of bundles care – risk versus benefit
? RCT on antibiotics after source identification versus clinician prediction based – stratified risk tool development
Risk factors for progression to severe sepsis

34. Conclusions
Bundled care can lead to significant improvements in delivery of care to sepsis patients
Ambulance cohort significantly more unwell – focus for future studies
Senior clinicians are able to reliably predict source of infection