JEFFREY

SEPSIS-3 ARIESTA
PUTRA
 1991 (SEPSIS-1)

Sepsis =
Infection + two
or more SIRS
criteria

Severe Sepsis =
Sepsis + Organ
dysfunction or
hypo-perfusion

Septic Shock =
Severe sepsis
with persistent
hypotension
despite adequate
fluids resus
 ‘HYPERINFLAMMATORY
RESPONSE’
SEPSIS – 1
Control inflammation – improve outcome
Multiple studies
 Steroids
 Anti TNF-α
 Anti IL-1
 Anti IL-6
 Other monoclonal antibodies
At best – no improvement
Often – increased mortality
In 2001, more detailed
categories added to
help clinicians
recognize sepsis

(Sepsis-2)

Levy MM, Fink MP, Marshall JC,

et al.
2001CCM/ESICM/ACCP/ATS/S
IS InternationalSepsis Definitions
Conference.Crit Care Med
2003;31:1250-6.
Hotchkiss 2013
• 172 ICUs in Australia and
New Zealand
• >100,000 patients
retrospectively found from
2000-2013 with SIRS and
sepsis
• SIRS missed 1 in 8
patients with sepsis!!
• No transition point in
mortality with “2 or more
SIRS criteria”!!
DEFINITION (SEPSIS-3)
Sepsis (with organ dysfunction) – now defined as
life-threatening organ dysfunction caused by a
dysregulated host response to infection. This is a
clinical diagnosis.
Septic Shock – a subset of Sepsis with circulatory
and cellular/metabolic dysfunction associated with a
higher risk of mortality.
Sepsis (with organ dysfunction) and Septic Shock
are medical emergencies and it is recommended that
treatment and resuscitation begin immediately
 Hospital Inpatient Enquiry: Crude Mortality for Inpatients
with a Diagnosis of Sepsis & Admission to Critical Care, by
Age Group, 2017
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
CBC and ABG
MAXIMUM SOFA SCORE MORTALITY
0-6 <10%
7-9 15-20%
10-12 40-50%
13-14 50-60%
15 >80%
15-24 >90%
JAMA. 2016;315(8):762-774. doi:10.1001/jama.2016.0288

Taskforce
wanted to
predict:
- Increased
mortality
- Increased ICU
length of stay
MANAGEMENT OF SEPSIS
Study Year Mortality Before (%) Mortality After (%)
EGDT 1997-2000 46.5 30.5
Ani et al (Severe) 1999-2008 40.0 27.8
Kumar (Severe) 2003-2009 39.6 27.3
Kumar (Shock) 2000-2007 47.1 36.4
Mult Observational 2001-2016 40.3 27.6
ProCESS 2008-2013 18.9 19-20
ProMISE 2011-2014 25.6 24.6
ARISE 2008-2014 18.8 18.6
Give 3 Take 3
1.OXYGEN: Titrate O2 to saturations of 1. CULTURES: Take blood cultures before
94 -98% or 88-92% in chronic lung giving antimicrobials (if no significant
disease. delay i.e. >45 minutes) and consider
source control.

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

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

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

antimicrobials according to local and consider urinary catheterisation for
antimicrobial guidelines. accurate measurement in patients with
severe sepsis/septic shock.
Risk stratification

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

guiding resuscitation to normalize lactate in
patients with elevated lactate levels as a marker of
tissue hypoperfusion.
(Weak recommendation; low quality of evidence)
 EARLY ANTIBIOTICS

Author N Setting Median time Odds ratio

(mins) for death
Gaieski 261 ED, USA 119 0.30
CCM 2010; 38;1045- (shock) (1st hour vs all times)
53

Daniels 567 Whole hospital, 121 0.62

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

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

Levy 15022 Multi-centre 0.86

CCM 2010; 38(2): 1- (1st 3 hours vs
8 delayed)
COMPLIANCE WITH SEPSIS 3
R DANIELS UK SEPSIS TRUST 2016
SOURCE CONTROL

We recommend that a specific anatomic diagnosis of infection

requiring emergent source control be identified or excluded as rapidly
as possible in patients with sepsis or septic shock, and that any
required source control intervention be implemented as soon as
medically and logistically practical after the diagnosis is made.
SEPSIS - PERIOPERATIVE
1.The first objective of fluid management: MAP≥65 mmHg, urine
output≥0.5 mL/kg per hour, arterial blood lactate<4.0 mmol/L (class
I).
2.The second objective of fluid management: ScvO2 ≥70% or
SvO2≥65% (class III).
3.Crystalloid solution such as acetated Ringer’s solution or lactated
Ringer’s solution was recommended as the first-choice fluid for
septic patients, whereas hydroxyethyl starch was not recommended as
a treatment for patients with severe sepsis during the operation. If it is
inevitable to use colloid solution, albumin is suggested as the first
choice (class II).
4.Norepinephrine is used as the first-choice vasopressor, could be used
according to the condition of septic patients (class I).
SEPSIS-PERIOPERATIVE
Fresh frozen plasma (FFP) is not applicable for the increase of blood
volume in septic patients (class II).
Platelet count should be beyond 50×109/L during the operation (class
II).
The level of hemoglobin should be beyond 7 g/dL during the
operation (class II).
Intravenous hydrocortisone at a dose of 200 mg per day is prescribled
as a treatment for septic patients when adequate fluid resuscitation
and vasopressor therapy fail to restore stable hemodynamics (class II)
 ANTIMICROBIAL THERAPY
ANTIBIOTIC STEWARDSHIP
•We recommend that empiric antimicrobial therapy be
narrowed once pathogen identification and
sensitivities are established and/or adequate clinical
improvement is noted.
•We suggest that an antimicrobial treatment duration
of 7-10 days is adequate for most serious infections
associated with sepsis and septic shock. (Weak
recommendation; low quality of evidence)
•We recommend daily assessment for de-escalation of
antimicrobial therapy in patients with sepsis and
septic shock.
•We suggest that measurement of procalcitonin levels
can be used to support shortening the duration of
antimicrobial therapy in sepsis patients. (Weak
recommendation; low quality of evidence)
 CORTICOSTEROIDS

We suggest against using intravenous hydrocortisone to treat

septic shock patients if adequate fluid resuscitation and
vasopressor therapy are able to restore hemodynamic stability.
If this is not achievable, we suggest intravenous
hydrocortisone at a dose of 200 mg per day.
(Weak recommendation; low quality of evidence)
 NUTRITION
We suggest the early initiation of enteral feeding
rather than a complete fast or only IV glucose in
critically ill patients with sepsis or septic shock who
can be fed enterally. (Weak recommendation; low
quality of evidence)
We suggest either early trophic/hypocaloric or early
full enteral feeding in critically ill patients with
sepsis or septic shock; if trophic/hypocaloric feeding
is the initial strategy, then feeds should be advanced
according to patient tolerance. (Weak
recommendation; moderate quality of evidence)
THANK YOU
 Combination therapy vs.
monotherapy for septic shock
Mortality rate *
Monotherapy Combination Rx
HR (95% CI)
(n=1223) (n=1223)
28-Day, % 36.3 29 0.77 (0.67 – 0.88)
ICU, % 35.7 28.8 0.75 (0.63 – 0.88)
Hospital, % 47.8 37.4 0.69 (0.59 – 0.81)
# deaths
All Gram + , % 39.9 30.7 0.73 (0.58 – 0.92)
All Gram - , % 34.5 28.2 0.79 (0.67 – 0.94)
* Propensity score adjusted

Crit Care Med 2010;38:1773-85

 Antibiotic review: Sepsis from
pulmonary source
Infection Example antibiotic regimens
CAP β-lactam1 + azithromycin
β-lactam1 + respiratory FQ2
HCAP antipseudomonal β-lactam3
+ aminoglycoside4 or antipseudomonal FQ5
+ vancomycin or linezolid
1 ceftriaxone, cefotaxime, ampicillin/sulbactam
2 levofloxacin, moxifloxacin
3 piperacillin/tazobactam, cefepime, meropenem, imipenem, doripenem
4 gentamicin, tobramycin, amikacin
5 levofloxacin, ciprofloxacin

Clin Infect Dis 2007;44:S27-72

Am J Respir Crit Care Med 2005;171:388-416
Antibiotic review: Sepsis from catheter-
related bloodstream infection (CRBSI)
Infection Example antibiotic regimens
CRBSI vancomycin or daptomycin1
+ antipseudomonal β-lactam2,3
+/- aminoglycoside4
Fungemia + fluconazole or echinocandin5
risk factors
1 if high rates of vancomycin MIC ≥ 2 µg/mL
2 piperacillin/tazobactam, cefepime
3 meropenem, imipenem, doripenem
4 gentamicin, tobramycin, amikacin
5 caspofungin, micafungin, anidulafungin

Clin Infect Dis 2009;49:1-45

 Antibiotic review: Sepsis from
urinary source
Infection Example antibiotic regimens
Urosepsis 3rd generation cephalosporin1
+/- aminoglycoside2 or FQ3
Urological interventions or antipseudomonal β-lactam4,5
MDR risk factors
1 ceftriaxone, cefotaxime
2 gentamicin, tobramycin, amikacin
3 levofloxacin, ciprofloxacin
4 piperacillin/tazobactam, cefepime
5 meropenem, imipenem, doripenem

Int J Urol 2013; Epub ahead of print.

 Antibiotic review: Sepsis from
unknown source
Infection Example antibiotic regimens
Unknown antipseudomonal β-lactam1,2
+ aminoglycoside or antipseudomonal FQ3
+ vancomycin
Fungemia + fluconazole or echinocandin4
risk factors
1 piperacillin/tazobactam, cefepime
2 meropenem, imipenem, doripenem
3 levofloxacin, ciprofloxacin
4 caspofungin, micafungin, anidulafungin

Clin Infect Dis 2009;48:503-35