Sepsis and Septic Shock

Surat Tongyoo
Critical care medicine
Siriraj Hospital
 Overview
Definition
Diagnostic criteria
Clinical impact
Treatment
Hemodynamic management
Fluid resuscitation
Vasopressors & Inotropes
Tissue perfusion evaluation
Source control
Organs and metabolic support
 Overview
Surviving Sepsis Campaign: International
Guidelines for Management of Sepsis and
Septic shock: 2016
Department of Medicine, Siriraj Hospital
experience
 Diagnostic criteria

ACCP/SCCM consensus conference 1991

SCCM/ESICM/ACCP/ATS/SIS International
Sepsis Definitions Conference 2001

Surviving Sepsis Campaign: International

Guidelines for Management of Severe Sepsis
and Septic Shock: 2012
 Diagnostic criteria
SIRS :2 or more of the following conditions
Temperature > 38.5 or < 35.0 oC
Heart rate > 90 bpm
Respiratory rate > 20 /min or PaCO2 < 32 mmHg
WBC > 12,000 /ml, < 4,000 /ml or Immature > 10%

Sepsis : SIRS + Documented infection

Culture or Gram stain of blood, sputum, urine, or normally sterile body
fluid positive for pathogenic microorganism
or
Focus of infection identified by visual inspection, eg, ruptured bowel
with free air or bowel contents found in abdomen at surgery, wound
with purulent discharge
 Diagnostic criteria
Severe sepsis :Sepsis + 1 organ dysfunction
Kidney -urinary output of < 0.5 mL/kg for at least 1 h or
-renal replacement therapy or
-creatinine increase > 0.5 mg/dL
Heart -cardiac dysfunction (echocardiography)
Lung -acute lung injury/ARDS (PaO2/FiO2 < 300)
CNS -abrupt change in mental status or abnormal EEG findings
GI -bowel ileus, absent bowel sound, hyperbilirubin (total > 4mg/dL)
Skin -areas of mottled skin; capillary refilling of > 3 second
Peripheral tissue -lactate > 2 mmol/L
Blood -platelet count of < 100,000 cells/mL or
-disseminated intravascular coagulation,
-coagulopathy (INR > 1.5, aPTT > 60 sec)
 Diagnostic criteria
Septic shock
:Severe sepsis + one of the following conditions

Systemic mean BP of < 70 mm Hg (< 80 mm Hg if previous

hypertension) after 2030 mL/kg starch or 4060 mL/kg
serum saline solution or PCWP between 12 and 20 mm Hg

Need for dopamine of > 5 mcg/kg/min, or norepinephrine or

epinephrine of > 0.25 mcg/kg/min to maintain mean BP at >
70 mm Hg (80 mm Hg if previous hypertension)
Correlation of mortality rate and severity
of disease
Mortality rate
60%
Septic shock (n = 1,134)

40% Severe sepsis (n = 827)

Sepsis (n = 1,063)
20%
Infection, no SIR (n = 584)

0% Days in hospital
0 20 40 60 80

AJRCCM 2003; 168: 77-84.

 Diagnostic criteria for sepsis:
Infection, documented or suspected and some of the following:
General variables
Fever (> 38.3oC) or Hypothermia (core temp < 36oC)
Heart rate > 90/min or >2 SD over the normal value
Tachypnea
Altered mental status
Significant edema or positive fluid balance
> 20 mL/kg over 24 hr
Hyperglycemia
> 140 mg/dL in the absence of diabetes
Inflammatory variables
Leukocytosis (WBC count > 12,000 L)
Leukopenia (WBC count < 4000 L)
Normal WBC count with immature forms > 10%
Plasma C-reactive protein >2 SD above the normal
value
Plasma procalcitonin > 2 SD above the normal value
Hemodynamic variables
Arterial hypotension (SBP < 90 mm Hg, MAP < 70 mm
Hg, or an SBP decrease > 40 mm Hg in adults or <
2 SD below normal for age)
Surviving sepsis campaign 2012. Crit Care Med 2013; 41:580-637
Organ dysfunction variables
Arterial hypoxemia (Pao2/Fio2 < 300)
Acute oliguria (urine output < 0.5 mL/kg/hr for
at least 2 hrs despite adequate fluid
resuscitation)
Creatinine increase > 0.5 mg/dL or 44.2 mol/L
Coagulation abnormalities (INR > 1.5 or aPTT >
60 s)
Ileus (absent bowel sounds)
Thrombocytopenia (< 100,000 /L)
Hyperbilirubinemia (plasma total bilirubin > 4
mg/dL or 70 mol/L)
Tissue perfusion variables
Hyperlactatemia (> 1 mmol/L)
Decreased capillary refill or mottling
 Definition
Sepsis is defined as life-
threatening organ
dysfunction caused by a
dysregulated host response
to infection.
Sepsis is a life-threatening
condition that arises when the
bodys response to an
infection injures its own
tissues and organs.

JAMA. 2016;315(8):775-787
 Definition
Sepsis
Life-threatening organ dysfunction caused by a dysregulated
host response to infection.
Sepsis is a life-threatening condition that arises when the bodys
response to an infection injures its own tissues and organs.
Organ dysfunction can be identified as an acute change in
total SOFA score 2 points consequent to the infection.
The baseline SOFA score can be assumed to be zero in patients not
known to have preexisting organ dysfunction.
A SOFA score 2 reflects an overall mortality risk of
approximately 10% in a general hospital population with
suspected infection.
JAMA. 2016;315(8):801-810.
SOFA score

JAMA. 2016;315(8):801-810.
 How to make diagnosis of
sepsis/septic shock?
Sepsis
Fever or hypothermia
Documented or suspected infection
Organ dysfunction
Tachypnea, hypoxemia
Hypotension
Low platelet, elevated creatinine or bilirubin
Alteration of consciousness
SOFA score 2 or more
 Definition
Septic shock
Adult patients with septic shock can be identified
using the clinical criteria of
1. Clinical of sepsis
2. Hypotension requiring vasopressor therapy to maintain
mean BP 65 mmHg or greater
3. Having a serum lactate level greater than 2 mmol/L
after adequate fluid resuscitation.
Hospital mortality > 40%

JAMA. 2016;315(8):801-810.
 Baseline serum lactate and Hospital
mortality

An increase in serum lactate level from 2 to 10 mmol/L increased the

adjusted OR for hospital mortality from 1.4 (95%CI, 1.35-1.45) to 3.03
(95%CI, 2.68-3.45)
JAMA. 2016;315(8):775-787
 Definition
Septic shock
qSOFA should be used to identified patients at risk
1. Alteration in mental status
2. Systolic blood pressure 100 mmHg
3. Respiratory rate 22/min

JAMA. 2016;315(8):801-810.
Incidence of severe sepsis:
Age dependence

Crit Care Med 2001; 29:13031310

 9 million Thai people age > 60 years old
Estimated 100,000 septic shock patients
In the next decade, 18 million Thai people age > 60 years old
Estimated >200,000 septic shock patients
 Clinical significance

High incidence
2-5% of hospitalization patient
Incidence increasing in elderly
High mortality
30-60%
High cost
USA = 663,000 Thai baht/case
Siriraj = 240,000 Thai baht/case
 Problems
Incidence of severe sepsis and septic shock in
Siriraj hospital
Outcome of previously use treatment strategy
What is/are the prognostic determining
factors?
How can we improve our patients outcome?
Clinical significance
During 6 months period
Feb July 2550

3451 medical patients

201 were diagnosed sepsis
182 were severe sepsis
5.3 : 100 admission
78 developed septic shock

Mortality rate
Severe sepsis = 34.3%
Septic shock = 52.6%
 Septic shock management
Hemodynamic management
Fluid therapy
Vasopressors & inotrope
Hemodynamic target
Get rid of source of infection
Appropriate antibiotic
Appropriate drainage
Organs support
Metabolic supports
Ventilator support
Adjunctive therapies
Inclusion criteria
2-4 criteria for SIRS
Systolic BP <90 mmHg after 20-
30 ml/Kg crystalloid in 30 min
Blood lactate > 4 mmol/L
Achieve goal in 6 hours
CVP 8-12 mmHg
MAP 65-90 mmHg
ScvO2 > 70%
Result
28d mortality 49.2 vs 33.3%,
OR 0.58(0.39-0.87), P=0.01
60d mortality 56.9 vs 44.3%,
OR 0.67(0.46-0.96), P=0.03
Sudden cardiac death
21 vs 10.3%, P=0.02
 Siriraj septic shock
guideline
.. 2545


ICU


septic shock
% %
 The first study
Overall mortality 59%
Guideline oriented 65.4%
Better outcome in guideline
used group
Achieve goal in 6 hrs
86.8 vs 44.4%, P<0.001
Hospital mortality
41.2 vs 69.4%, P=0.008
Factors predicted outcome
Lower APACHE II score
1st hr volume > 800mL
Achieve goal in 6 hrs
Correlation of 1sthr volume and survival rate
Percent
P=0.012

Volume 1sthr
 Survival of septic shock:
Impact of rapid volume resuscitation

Odds ratio 0.28 [0.10-

0.69] P=0.006

Fluid > 800 ml

in 1st hr
Fluid < 800 ml
in 1st hr
 Can we further improve
outcome
Promote fluid
resuscitation in the 1st
hour
Problems
Complication of fluid
overload
Central venous pressure
(CVP)
Low CVP insertion rate,
only 15%
Unable to follow ScvO2
 Hemodynamic management
What is(are) our targets?
Macrocirculation
CVP target?
Blood pressure
Mean arterial pressure>65 mmHg
Microcirculation
Urine output > 0.5 mL/kg/d
ScvO2 > 70
Lactate < 2 mmol/L
Lactate clearance > 10%
 Lactate and shock management
Glucose
Blood lactate level
Pyruvate Increased serum lactate
Type A lactic acidosis
O2 Inadequate tissue O2
Shock related
Lactate
Krebs Type B lactic acidosis
cycle Metformin, methanol,
Lactate >
4mmol/l
ethylene glycol,
nucleoside reverse
transcriptase inhibitors
Gluconeogenesis
Glycogenesis
 Outcome

Include 300 severe

sepsis/septic shock patients

Intervention
EGDT: ScvO2 goal
ScvO2 > 70
EGDT: Lactate clearance
Lactate decrease > 10% in 2-6hrs

JAMA. 2010;303(8):739-746
 Lactate and shock management

The correlation of lactate and ScvO2 level

Is there any difference of lactate level in

capillary, venous and arterial blood specimen?

How often we should send the blood lactate?

Did serum lactate associate with patient

outcome?
 The 2nd study

Good correlation of
serum lactate from
capillary, venous and
arterial blood

A lactate = V lactate

C lactate = A lactate + 1
 The 3rd study
Low ScvO2
associated with high
serum lactate

However, too high

ScvO2 > 85% in
septic shock patient
associated with high
serum lactate and
very poor outcome
Goal of shock management
 Can we further improve
outcome
Promote fluid
resuscitation in the 1st
hour
We can use serum lactate
clearance as an indicator
for adequate tissue
perfusion
To use lactate clearance,
we have to send blood for
lactate level at the initial
resuscitation time and
following serum lactate
once the patients BP >
60-65 mmHg
 Can we further improve
patients outcome?

What is the most

appropriate BP goal?
MAP>65

Are current
mmHg

hemodynamic goals
good enough?

Should we admit septic

shock patient directly
into ICU for better
outcome?
 Result

Include 776 severe

sepsis/septic shock patients
Mean ABP = 74 mmHg
Mean HR = 104/min
Lactate =3.7 mmol/L
Received fluid 2,900 mL
Norepinephrine 94% Low BP VS High BP
28d mortality 34 vs 36.7, P=0.57
Randomized into 90d mortality 42.3vs43.8, P=0.74
Low mean ABP > 65 mmHg Median dose NE 0.45vs0.58, P<0.001
High mean ABP > 80 mmHg Renal replacement 35.8vs33.5, P=0.5
RRT in chronic HT 42.2vs31.7,P=0.046
 The 4th study
To evaluate the impact
of hemodynamic goals
achievement rate and
the patients outcome

Prospective study

Included 175 severe

sepsis and septic shock
patients
 Septic shock survival rate:
According to MAP at 6 hours after treatment

60-65
 Septic shock survival rate:
According to urine output at 6 hours
Initial lactate level and outcome
Goals achievement and
septic shock outcome
 Hemodynamic management
What is(are) our targets? What do we have?
Macrocirculation Intravenous fluid
CVP target? Crystalloid
Blood pressure Colloid
Mean arterial pressure>65 mmHg Albumin, starch, gelatin
Microcirculation Vasopressors
Urine output > 0.5 mL/kg/d Norepinephrine, Dopamine,
ScvO2 > 70 Adrenaline
Lactate < 2 mmol/L Inotrope
Lactate clearance > 10% Dopamine, milrinone,
levosimendan
Invasive monitoring in ICU
 Fluid management

How much volume? Which type of fluid?

Initial rate Crystalloid
Fluid challenge test Isotonic solution
Reevaluation Colloid
Albumin
Hydroxyethyl starches
(HES)
Gelatin
Dextran
EGDT (USA)
2001
263 septic shock
How much volume?
APACHE II 21.4+6.9 Initial rate
SBP 106 mmHg
Lactate 7.7 mmol/L Fluid challenge test
Usual care vs EGDT Target CVP 8-12 mmHg
-CVP 8-12 mmHg
-MAP 65-90 mmHg Reevaluation
-ScvO2 > 70%
-Hct > 30%
CVP change
Decrease mortality Fluid in 6 hrs
60 d: 56.9 vs 44.3 %
P=0.03
3.5 vs 5 L

Fluid 6hrs 3.5 vs 5 L

Vasopressor 57.3 vs 36.8%
PRC 64.5 vs 68.4%
Dobutamine 9.2 vs 15.4%
EGDT (USA) ProCESS (USA) ARISE (AUS) ProMISe (UK)
2001 2014 2014 2015
263 septic shock 1341 septic shock 1600 pts 1260 septic shock
APACHE II 21.4+6.9 20.7+7.5 15.4+6.5 18.7+7.3
SBP 106 mmHg 100 mmHg 79 mmHg 78 mmHg
Lactate 7.7 mmol/L 4.9 mmol/L 6.7 mmol/L 7 mmol/L
Usual care vs EGDT EGDT 439 EGDT 796 EGDT 625
-CVP 8-12 mmHg Standard 446 -Monitor ScvO2 -Monitor ScvO2
-MAP 65-90 mmHg -Fluid 1L in 20min Usual care 804 Usual care 626
-ScvO2 > 70% -Fluid 2L in 1 hr -No ScvO2 -No ScvO2
-Hct > 30% Usual care 456
Decrease mortality Not improve Not improve Not improve
60 d:56.9 vs 44.3 %P=0.03 60 d: 21vs18vs19% 90 d: 18.6 vs 18.9 90 d: 29.5vs29.2%

Fluid before <20mL/Kg >30mL/Kg >30mL/Kg >30mL/Kg

Fluid 6hrs 3.5 vs 5 L 4.3 vs 3.8 vs 3.3 L 4.5 vs 4.2 L 4 vs 3.8 L
Vasopressor 57.3 vs 36.8% 55 vs 52 vs 44% 66.6 vs 57.8 % 53.3 vs 46.6%
PRC 64.5 vs 68.4% 15 vs 8 vs 7% 13.6 vs 7% 8.8 vs 3.8%
Dobutamine 9.2 vs 15.4% 8 vs 2 vs 1% 15.4 vs 2.6% 18.1 vs 3.8%
 Fluid management
Current recommendation

Start with crystalloid isotonic solution

At least 30 ml/kg/hr in the 1st hour -3rd hour
4-5 L in 6 hours, following with maintenance fluid

Continue fluid therapy in fluid responsive patient

Improve BP, pulse pressure, tissue perfusion, O2
saturation
Decrease HR
 Fluid management

How much volume? Which type of fluid?

Initial rate Crystalloid
Fluid challenge test Isotonic solution
Reevaluation Colloid
Albumin
Hydroxyethyl starches
(HES)
Gelatin
Dextran
 Results
28 days mortality (Alb vs saline)
Trauma 81/596 (13.6%) vs 59/590 (10.0%)
OR 1.36 (0.99 to 1.86) P=0.06
Sepsis 185/603(30.7%) vs 217/615(35.3%)
Included 6997 critically ill pts OR 0.87 (0.74 to 1.02) P=0.09

Mean BP = 74 mmHg
43% Surgical patients
19% Severe sepsis
17% Trauma patients

Randomized to
Saline vs 4% albumin

NEJM 2004
 Outcome
28 d mortality
32% vs 31.8%, P=0.94
Subgroup
Included No septic shock (660)
32.7% vs 37%, P=0.25
1st
1818 d severe sepsis
Septic shock (1121)
SOFA score 8
49.9% vs 43.6%, P=0.03
Mean BP 74 mmHg
Lactate 2.4 mmol/L
Intervention
Crystalloid alone
20% albumin + crystalloid
To keep serum albumin >3 g/dL

N Engl J Med 2014; 370:1412-1421

 Result
6%HES vs NSS
90 d mortality 18.0% vs 17.0%
OR 1.06 (0.96 to 1.18) P=0.26
CVS failure 36.5% vs 39.9%
Randomly assigned 7000 OR 0.91 (0.84 to 0.99) P=0.03
RRT 7.0% vs 5.8%
critically ill pts to receive OR 1.21 (1.00 to 1.45) P=0.04
6%HES (Voluven) or NSS
Mean BP = 74 mmHg
45% require vasopressor
43% Surgical patients
29% Severe sepsis
8% Trauma patients

NEJM 2012
 Results
6%HES vs RLS
Dead at day 90 51% vs 43%
OR 1.17 (1.011.36) P=0.03
Bleeding 10% vs 6%
OR 1.52 (0.942.48) P=0.09
798 severe sepsis patients
RRT 22% vs 16%
OR 1.35 (1.011.80) P=0.04
Randomized to
6HES (Tetraspan) vs RLS
30% Surgical patients
55% Lung infection
33% Abdominal infection

NEJM 2012
 Results
Mortality rate
Colloid vs Crystalloid OR (95%CI)
28 d 25.4% vs 27.0% 0.96 (0.88-1.04) P=0.26
2857 shock pts (SBP 92 mmHg) 90 d 30.7% vs 34.2% 0.92 (0.86-0.99) P=0.03
ICU 25.1% vs 28.1% 0.92 (0.85-1.00) P=0.06
54% Septic shock Hospital 30.1% vs 32.6% 0.94 (0.87-1.02) P=0.07
40% Hypovolemic shock
6% Trauma
Random to received
Crystalloid
Colloid
645 Hydroxyethyl starches
281 Gelatin
80 Albumin

JAMA 2013
 Fluid management
Current recommendation

Consider colloid in non responsive patients

MAP < 65 mmHg after 30 mL/kg of crystalloid
Albumin is colloid of choice for septic shock
resuscitation
Avoid hydroxyethyl starch in septic shock patients
Avoid albumin in traumatic brain patients

Stop fluid in non responsive patient

CVP should be considered in high risk patients
 Vasopressor
Dosage
Drugs Pharmacology Effect
(mcg/kg/min)
Strongly increase
Norepinephrine >> adrenergic 0.02-0.5
BP>>HR
, Mod increase
Dopamine 3-20
dopaminergic BP & HR
Strongly increase
Adrenaline , adrenergic 0.02-0.5
BP & HR
Vasopressin 0.03-0.06
Vasopressin Increase SVR
receptor U/min
Study Vasopressors regimens Outcome
Lancet 2007 Mortality
RCT Norepinephrine + dobutamine 28 d: 34% vs 40%,P=0.31
330 septic shock vs Adrenaline 90 d: 50% vs 52%,P=0.73
MAP 69, SAPS 53 Target MAP > 70 mmHg, CI > 2.5 Arrhythmia
Lactate 3.2 Mean NE 1.1, AD 0.9 mcg/kg/min SVT 12%, VT/VF 6%
NEJM 2008 Overall mortality
RCT Norepinephrine vs Vasopressin 28 d: 39.3% vs 35.4%,P=0.26
778 septic shock Target MAP 65-75 mmHg 90 d: 43.9% vs 49.6%,P=0.11
APACHE II = 27 Less severe NE<15mcg/min
MAP 73 mmHg 28 d: 35.7% vs 26.5%,P=0.05
Lactate 3.5 90 d: 46.1% vs 35.8%,P=0.04
Arrhythmia 2%
NEJM 2010 Mortality
RCT Norepinephrine vs Dopamine 28 d: 48.5% vs 52.5%,P=0.1
1,679 shock pts Target MAP 65 mmHg Hosp:56.6% vs 59.4%,P=0.24
1,000 septic pts Arrhythmia
APACHE II = 20 12.4% vs 24%, P=0.001
MAP 58 mmHg Significant decrease
Lactate 2.2 cardiogenic shock mortality
 Dopamine vs Norepinephrine

28 days mortality 40.7% vs 38%, RR 1.07 (0.99-1.16)

Arrhythmia 17.7% vs 7.6%, RR 2.33 (1.45-3.85)
Cochrane Database of Systematic Reviews 2016

Enrolled 409 septic shock
patients
Age = 66 years(54-77)
MAP = 70 mmHg(62-77) Vasopressin vs norepinephrine
APACHE II = 24 (19-30)
Intervention
Vasopressin to 0.06 U/min
Norepinephrine to 0.12
mcg/min
Keep MAP 65-75 mmHg
Result
Survival, no renal failure
57% vs 59.2%, P=NS
Kidney failurefree days
9 vs 13 days, P=NS
RRT: 25.4% vs 35.3%, P=significant
Hospital mortality
33% vs 29.4%, P=NS
Adverse event: 10.7% vs 8.3%, P=NS
VANISH trial. JAMA. 2016;316(5):509-518
 Vasopressors
Current recommendation

Target MAP > 65 mmHg

Norepinephrine is the first-choice vasopressor
Dopamine is an alternative vasopressor
Especially in non-tachycardia patient
Vasopressin or adrenaline can be added to
norepinephrine to keep MAP in acceptable
range
 Inotrope
Dosage
Drugs Pharmacology Effect
(mcg/kg/min)
Strongly increase
Dobutamine adrenergic 0.02-0.5
BP>>HR
Increase CO via
Phosphodiesterase lower SVR
Milrinone 0.5-0.75
inhibitor type III
Mild increase HR
Strongly increase
Levosimendan , adrenergic 0.02-0.5
BP & HR
 Inotrope
Dobutamine
Standard inotrope
Evidence of inadequate tissue perfusion after
Adequate fluid resuscitation
Achieve target MAP > 65, < 90 mmHg
Evidence from EGDT 2000 study
No RCT comparing dobutamine vs placebo
 Levosimendan vs Dobutamine
A meta-analysis included 7 RCT, 246 septic
shock patients
Poor LVEF < 45%
Levosimendan (0.05-0.2mcg/kg/min) vs
Dobutamine (5-20mcg/kg/min)
Mortality 47% vs 61%
RR 0.79, 95%CI 0.63-0.98, P = 0.03
Significant decrease lactate & significant increase CI
Required higher fluid resuscitate
A. Zangrillo et al. Journal of Critical Care 2015
 Outcome

516 septic shock

Age 68
APACHE II 25
SOFA 10
Mean BP 74 mmHg
Primary outcome
HR 96/min
Levosimendan associated with
259 levosimendan higher SOFA score

256 placebo SVT 3.1% vs 0.4%, P = 0.04

Difficult weaning

N Engl J Med 2016;375:1638-48

 Inotropes
Current recommendation

Dobutamine is recommended in patients with

evidences of persistent hypoperfusion despite
adequate fluid loading and the uses of
vasopressor agents.
 The 5th study
To evaluate the impact of
direct ICU admission and
septic shock outcome
Prospective study
Included 175 severe sepsis
and septic shock patients
50 patients were
immediately admitted to
ICU
28d mortality
ICU vs Non-ICU
18 vs 25.6%, P=0.33
Can we further improve patients outcome?

Direct ICU admission may improve septic shock

patients outcome
What make it difference?
ICU admission patients received more
Fluid in 1st day 5.7+2.0 vs. 5.0+1.7 L, P = 0.04
Norepinephrine 88% vs. 68%, P = 0.007
Dobutamine 20% vs. 4.8%, P = 0.003
Renal replacement 28% vs. 5.6%, P < 0.001
 Source identification and control

Urinary tract infection: 26.9%

Pyelonephritis
Respiratory tract infection: 25.7%
Pneumonia
Intra-abdominal infection 17.1%
Hepatobiliary tract infection
Peritonitis
Perforation of holo viscous organ
Skin and soft tissue infection 8.6%
Primary bacteremia 22.9%
 Antimicrobial therapy
Current recommendation
Initiate IV antimicrobials within 1 hour after
diagnosis (after appropriate culture was send)
Empiric with one or more antimicrobials to cover
all potential pathogens (bacteria, fungus or virus)
The empiric antimicrobials should be narrowed
once pathogen was identified
Combination antimicrobial is recommended for
septic shock patient, but not for sepsis without
shock
 Antimicrobial therapy
Current recommendation
Short duration (7-10 days) of antimicrobial is
recommended in most sepsis (shock) patients
Extend antimicrobial duration in
Undrainable foci
S aureus bacteremia
Fungal infection
Immunodeficiency patients
Source control intervention as soon as possible
Remove all suspected intravascular device
infection
 Organ and metabolic support
Current recommendation
Mechanical ventilation
Renal replacement therapy
Stress ulcer prophylaxis
Venous thromboembolism prophylaxis
Sedation and analgesia
Glucose control
Early parenteral nutrition
 Continuing studies
Does early norepinephrine administration could
decrease mortality in severe sepsis and septic shock
patients compare with conventional treatment?

Efficacy of gelatin, comparing with albumin, in refractory

septic shock

Colloid versus crystalloid in shock resuscitation

Extracorporeal organ support and the outcome of septic

shock with multiple organ failure
Thank you