severe sepsis and septic shock

SEPSIS

DEFINITIONS
microbes involves a
rapidly amplifying
polyphony of signals
and responses that
may spread beyond
the invaded tissue.
 1.
1.
1.1


(systemic inflammatory response
syndromeSIRS)
1.2
1.2.1 38C36C
1.2.2 90
1.2.3 20
1.2.4 120004000
10(bands)
 ETIOLOGY
gram-negative and gram-
positive bacteria
fungi,
mycobacteria,
rickettsiae,
viruses,
or protozoans

Positive blood cultures :

30 to 60 % of patients with sepsis
60 to 80 % of patients with septic
shock
Sepsis
 Definitions Used to Describe
the Condition of Septic Patients
Bacteremia Presence of bacteria in blood

Systemic inflammatory Fever, tachypnea, tachycardia,

response syndrome (SIRS) leukocytosis/leukopenia

Sepsis SIRS has a proven or suspected

microbial etiology

Severe sepsis Sepsis with 1 signs of organ

dysfunction

Septic shock Sepsis with hypotension or need

for vasopressor

Multiple-organ dysfunction Dysfunction of 1 organ

syndrome (MODS)
Epidemiology of Sepsis in the
United States from 1979-2000

N Engl J Med 2003; 348: 1546-54.

 EPIDEMIOLOGY

2/3: in hospitalized patients.

Risk Factors to GNB bacteremia

diabetes mellitus
lymphoproliferative diseases
cirrhosis of the liver
burns
invasive procedures or devices
drugs that cause neutropenia
 EPIDEMIOLOGY
Risk factors for GPC bacteremia
vascular catheters,
indwelling mechanical devices,
burns,
intravenous drug injection.

Fungemia :
immunosuppressed patients
neutropenia
broad-spectrum antimicrobial therapy
TPN
Intestinal perforation
 PATHOPHYSIOLOGY
Endotoxin

Gram negative bacilli

Lipopolysaccharide (LPS, also called
endotoxin)
 PATHOPHYSIOLOGY
Microbial signals

Gram positive cocci

peptidoglycan and lipoteichoic acids
extracellular enzymes

Fever or hypothermia (low body temperature)
Hyperventilation
Chills
Shaking
Warm skin
Skin rash
Rapid heart beat
Confusion or delirium
Decreased urine output
 CLINICAL MANIFESTATIONS

S/S:
fever, chills, tachycardia, tachypnea, altered mental
status, and hypotension.

afebrile
common in neonates, in elderly patients
and in persons with uremia or alcoholism.
 CLINICAL MANIFESTATIONS

Llaboratory finding:
C-reactive protein
fibrinogen
complement components
transferrin
inhibits albumin synthesis
Leukocytosis, left shift
 LABORATORY FINDINGS

Early sepsis
leukocytosis with a left shift
Respiratory alkalosis
Thrombocytopenia
Hyperbilirubinemia
proteinuria.
neutrophils may contain toxic granulations, Dohle
bodies, or cytoplasmic vacuoles
 LABORATORY FINDINGS

Progressing of sepsis:
thrombocytopenia worsens
prolongation of the thrombin time
decreased fibrinogen
presence of D-dimers, suggesting DIC)
Azotemia, hyperbilirubinemia become prominent
Elevated GOT GPT
 LABORATORY FINDINGS
Progressing sepsis:
hyperventilation induces respiratory alkalosis.
accumulation of lactate,
metabolic acidosis (with increased anion gap)
hyperglycemia, severe infection may precipitate
diabetic ketoacidosis(DKA)
 Multiple organ dysfunction
syndrome
MOF:
Dysfunction or failure of multiple organs
reflecting widespread vascular endothelial
injury
associated with high fatality rates.
Mortality and morbidity correlate with the
number of organs affected.
 DIAGNOSIS

S/S --Progressing sepsis

tachypnea,
tachycardia,
altered mental status,
The septic response can be quite variable
systemic inflammatory response syndrome
SIRS
 DIAGNOSIS

Definitive diagnosis
isolation of the microorganism from blood or a local
infected site
Gram's stain
culture of the primary site of infection.
 TREATMENT

Sepsis may be fatal quickly.

Successful management
urgent measures to treat the local site of infection,
hemodynamic and respiratory support
eliminate the offending microorganism
Therapy of acidosis and DIC, other complications
 TREATMENT

Outcome
influenced by the patient's underlying disease
aggressively treated.
Antimicrobial agents
 PROGNOSIS
Mortality:
More than 25 %
1/3 within the first 48 h
mortality can occur 14 or more days later.
Late deaths
poorly controlled infection
complications of intensive care
multiple organs failure
 2.
2.1


2.1.1 8-12mmHg
2.1.2 65 mmHg
2.1.3 0.5
2.1.4 70
 2.
2.2
2.2.123
2.2.2

2.2.3

2.2.4

 2.
2.2
2.2.5
2.2.6
2.2.7

2.2.8
2.2.9
 3.
3.1
3.2
()
3.3
(
)
3.3.1
3.3.2
3.3.3

 3.
3.44872

3.4.1
3.4.2
3.4.3

3.4.47-10
3.4.5

 4
4.1
4.1.1
4.1.2

 5
5.1
5.1.1
5.1.2303001000
30300500
5.1.3
5.1.4
5.2

 6
6.1

6.2

6.3 Nor-epinephrinedopamine
6.4
6.5 Nor-epinephrine0.010.04 units/
6.6 Cardiac index2.5 L.min-1.m2

 7 (Dobutamine)
7.1


 8
8.1

8.2 hydrocortisone20030034
7
8.3 ATCHdexamethasone
hydrocortisonecortisol
8.4
 9 C
9.1

APACHEII score>=25
C(rhAPC)
 10
10.1 7.0g/dl

10.2 7.09.0g/dl
10.3

10.4
5000/mm3(510-9/L)
 11
11.1

12

12.1

12.2

 13
13.1
13.2 200 mg/dl(
140 mg/dl)
13.3
 14
14.1

14.2 pH7.3
14.3

14.4
 15
15.1
15.2 H2 receptor

 16
16.1
16.2
16.3
 Epidemiology of Sepsis in the
United States from 1979-2000

Causative Organisms

Gram-positive bacteria 52.1%

Gram-negative bacteria 37.6%
polymicrobial infections 4.7%
anaerobes 1.0%
fungi 4.6%

Specific organisms causing sepsis were recorded in

51% of all discharge records over the 22-year period.

N Engl J Med 2003; 348: 1546-54.

 Antimicrobial Agents in the
Management of Sepsis
Two blood culture
- one percutaneous
- one from each vascular
access >48 hrs

- one or more drugs active against

Begin IV antibiotics within likely bacterial or fungal pathogens
the first hr of recognition - consider microbial susceptibility
of severe sepsis patterns

- microbial and clinical data

Reassess antimicrobial - narrow-spectrum antibiotics
regimen at 48-72 hrs - non-infectious cause identified
- prevent resistance, reduce toxicity
Evaluate patient for a and reduce cost
focused infection
Crit Care Med 2004; 32: 858-73.
 Vasopressor and Inotropics
Norepinephrine 4 mg/4 ml/amp (diluted by D5W)
- 0.03~3.3 g/kg/min (2~200 g/kg/hr)

Epinephrine 1 mg/1 ml/amp

- 0.06~0.47 g/kg/min (3.6~30 g/kg/hr)

Dopamine 200 mg/5 ml/amp

-2~55 g/kg/min (0.12~3.3 mg/kg/hr)

Dobutamine 250 mg/20 ml/amp

- 2~28 g/kg/min (0.12~1.68 mg/kg/hr)

Vasopressin 20 U/1 ml/amp

- 0.01~0.04 U/min (0.6~2.4 U/hr)
Crit Care Med 2004; 32: 1928-48.
 Role of Corticosteroid in the
Management of Septic Shock

Treat patients who still require vasopressors despite

fluid replacement with hydrocortisone 200-300 mg/day
for 7 days divided in 3-4 doses or by continuous
infusion

(Grade C)

High dose of corticosteroids (> 300 mg/day) should

NOT be used in severe sepsis or septic shock.

(Grade A)

Crit Care Med 2004; 32: 858-73.

 Role of Corticosteroid in the
Management of Septic Shock
In the absence of shock, corticosteroids should NOT
be administrated for the treatment of sepsis

(Grade E)

The use of ACTH stimulation test to identify responders

(>9 g/ml increase in cortisol 30-60 mins post-ACTH
administration) and to continue therapy is optional.

Should NOT wait for ACTH stimulation results to

administer corticosteroids

(Grade E)
Crit Care Med 2004; 32: 858-73.
 Mechanical Ventilation of
Sepsis-induced ALI/ARDS

High tidal volume that are coupled with high plateau

pressures should be avoided in ALI/ARDS.

- reduce tidal volume over 1-2 hrs to 6 ml/kg predicted

body weight
- maintain inspiratory plateau pressure <30 cmH2O
- maintain SaO2/SpO2 88-95%
- anticipated PEEP settings at various FiO2 requirements

FiO2 0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7 0.7 0.8 0.9 0.9 0.9 1.0
PEEP 5 5 8 8 8 10 10 12 14 14 14 16 18 20-24

(Grade B)
Crit Care Med 2004; 32: 858-73.
 Intensive Insulin in Critical
Ill Patients

After initial stabilization of patients with severe sepsis

- maintain glucose <150 mg/dl by continuous infusion of

insulin
- monitor blood glucose every 30-60 mins and then q4h

(Grade D)

In patients with severe sepsis, a strategy of glycemic

control should include a nutrition protocol with the
preferential use of the enteral route.

(Grade E)
Crit Care Med 2004; 32: 858-73.
 Intensive Insulin in Critical
Ill Patients
- prospective, randomized, controlled trial
- adults admitted to SICU (N= 1,548) who were receiving MV
adults admitted to MICU (N= 1,200) who were considered
to need ICU care for at least 3 days

- 50 IU actrapid HM/ 50 ml NS infused by pump (max. dose

50 IU/hr)
- intensive insulin (blood glucose ~80-110 mg/dl)
conventional treatment (blood sugar ~180-200 mg/dl)
- primary endpoint: ICU mortality/in-hospital mortality

N Engl J Med 2006; 354: 449-61.

 Intensive Insulin in Critical
Ill Patients
Mortality RRR ARR NNT P value
Surgical ICU
ICU death 8.0% vs 4.6% 42.5% 3.4% 29 <0.04

In-hospital 10.9% vs 7.2% 33.9% 3.7% 27 0.01

death
Medical ICU

ICU death 26.8% vs 24.2% 9.7% 2.6% - 0.31

38.1% vs 31.3%* 17.8% 6.8% 14 0.05

In-hospital 40.0% vs 37.3% 6.8% 2.7% - 0.33

death 52.5% vs 43.0%* 18.1% 9.5% 10 0.009
N Engl J Med 2001; 345: 1359-67.
* patients who stayed in the ICU 3 days N Engl J Med 2006; 354: 449-61.
 Advances in Therapy for
Severe Sepsis and Septic Shock
Time-sensitive intervention Mortality reduction (ARR)

Early goal-directed therapy 16% (P= 0.009), NNT= 6

Drotrecogin alfa (activated) 13% (P= 0.001), NNT= 8
for high-risk patients

Low-dose steroids 10% (P= 0.023), NNT= 10

Low tidal volume ventilation 10% (P= 0.005), NNT= 10
Tight blood sugar control 3.4% (P= 0.005), NNT= 29

JAMA 2002; 288: 862-71.

N Engl J Med. 2001; 345: 1368-77. N Engl J Med. 2000; 342: 1301-8.
N Engl J Med. 2001; 344: 699-709. N Engl J Med. 2001; 345: 1359-67.
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