Survival benefits and policy conflicts in

SepsisAmith Shetty

SMEDSA studyWestmead

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

The Challenge

CEC Sepsis kills programhttp://www.cec.health.nsw.gov.au/programs/sepsis

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

Program focus

Initiate sepsis pathway based on suspected infection + 2 SIRS criteria

Up-triaging to ATS category 2 Sepsis bomb

RECOGNISE

Oxygen Blood cultures Lactate Intravenous fluids – 20ml/kg crystalloid

bolus Antibiotics <60 minutes

◦ Based on clinician predicted source◦ Antibiotic stewardship program and guidelines

Monitoring

RESUSCITATE – SEPSIS SIX

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

REFER

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

Westmead achievements

Retrospective evaluation of prospectively identified patients presenting to ED with sepsis

Multicentre approval◦ Westmead ◦ Concord ◦ RPA

Single centre data collection and analysis

The SMEDSA initiative

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

Westmead hospital

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

Interventions

~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)

Demographics

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 (IQR27.5-43.5)

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)

Exclusions

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)

Inclusions

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

Triage guideline

492/590 (83.4% 95%CI 80.2-86.2) 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

Lactate testing

484/505 patients had blood cultures collected

95.8% adherence (95% CI 93.7-97.3) 94 /484 (19.4%) positive BC, 13/94 (13.8%

contamination rates) → 81/ 484 (16.7% 95%CI 13.7-20.3) significant results

26.5% BC + for severe sepsis group versus 13.4% BC + in plain sepsis group

Blood culture testing

329/505 Urine cultures – 62/329 positive results

193/ 505 other cultures – 100/193 positive results

Other cultures

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

Antibiotic guidance and stewardship

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)

Severe sepsis criteria (SSC 2012)

Age – 58 (IQR 38-75) versus 67 (49-80) Lactate value → 1.5 (1.1-2.2) v 2.2 (1.4-3.8) 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)

Plain sepsis versus Severe Sepsis

Time to antibiotics →69 minutes (IQR 42-126.5) 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 (107.5-403.5) v 249 minutes (136-489)

Time to antibiotics / IV fluids

no sepsis

severe sepsis/ septic shock

Plain sepsis

SIRS 0 17 6 14 37

SIRS 1 14 28 55 97

SIRS 2 28 46 116 190

SIRS 3 18 57 78 153

SIRS 4 6 42 34 82

SIRS 5 2 16 8 26

SIRS 6 0 5 0 5

total 85 200 305 590

SIRS characterisation

Sensitivity 0.80 95%CI 0.76- 0.83 Specificity 0.36 95%CI 0.27- 0.48 Positive predictive value = 0.88 Negative predictive value = 0.25 Patients with severe sepsis more likely to

have >3 SIRS criteria (p<0.001)

SIRS >2 criteria

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 42.3-

54.1) versus 68/231 (29.4% 95% CI 23.9-35.6) (p<0.01)

◦ MEDS score 9 vs 3 (MD 5 p<0.01)◦ Mortality (51/231 22.1% 95%CI 17.2-27.9%)

versus (6/231 2.6% 95% CI 1.2-5.5%)

Mode of arrival statistics

478/ 505 (94.7%) concurrence of clinician prediction of presumed source of diagnosis when compared to final discharge diagnosis

Clinician predicted source vs final diagnosis

Final diagnosesSource 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

Mortality rates – in-hospital, 30-day or 90-day

Hospital LOS Discharge location Occurrence of severe sepsis or septic shock

Outcome measures

Time to antibiotic

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 x

> 3 hours 86 47 39 x

Total 501 302 199 x

Time to antibiotic 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 35 30 X

>2 to ≤ 3 hours

76 46 30 X

>3 hours 279 177 102 X

Total 455 271 184 x

Time to intravenous fluid analysis

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

Future focus

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

Conclusions