Sepsis, EGDT, and Source Control

Perioperative and Acute Care Surgery

Course
 Objectives

• 10 minutes for definition and clinical aspect of sepsis

– Patophysiology of sepsis
– Intervention in septic patients à SSC
• 15 minutes to explain about Early Goals Directed
therapy
– Algorithm of EGDT
– Clinical implication of EGDT
• 20 minute for source control in sepsis
 SIRS / Sepsis

Bacteremia Other
(septicemia)

SIRS Trauma
Infection Fungal Sepsis

Parasit. Burns
Vir.
Other Pancreatitis

*Severe SIRS/Sepsis includes some evidence of organ failure

 Microbial product,
trauma, ischemia
reperfusion injury, etc

Rapid activation of the innate

immune response and release of a
variety of humoral mediator
Human Immune Response to Sepsis
caused by Injury/ Infection is
orchestrated by complex interactions
of soluble mediator and cellular
elements
Process of The Inflammatory Response to Sepsis,
5 phases :

1. Recognition of microbial contamination or

tissue injury
2. Release of Signaling Molecules
3. Recruitment of Cellular Effectors
4. Destruction of Invading Microbes and
Metabolism of Injured Tissue
5. Restoration of Tissue Integrity
 Immunoglobulin,
LPS, LBP, CD14, Sepsis Mediator
complement system
Phase 1 General cellular
recognition response in sepsis

receptor
Phase 2
Phagocytosis
Signal transduction Chemo taxis

Phase 3
Secreted mediator
Cytokine receptor up
regulation

Released enzyme

Shed cytokine
receptor Adherens Shed adhesion Phase 4
molecule
 Rapid activation of host defenses expressed
by the activation of :
• Plasma Protein System / Humoral system
(coagulation cascade, complement cascade, kallikrein kinin
system)
• Cellular defense system
(phagocytes, endothelium, lymphocytes, neutrophils)

Uncontrolled activation of this protein cascades

and release of inflammatory mediators result in
systemic inflammation
Shock, Trauma, Operations, Pulmonary insufficiency,
Anesthesia, Infections, MOF

Endothelium COAGULATION
CASCADE

Tissue Factor PAI-1

Factor VIIIa
IL-6
Organisms IL-1
TNF-
Monocyte Factor Va
Suppressed
fibrinolysis

TAFI
THROMBIN

Neutrophil
Fibrin

IL-6
Fibrin clot
Tissue Factor

Inflammatory Thrombotic Fibrinolytic

Response Response Response
 cytokines

Impaired of Suppression of
Generation
anticoagulant fibrinolysis by PAI - 1
thrombin mediated
by tissue factor pathway

Formation of fibrin Attenuation of AT Inadequate

III, Protein C, removal of fibrin
TFPI

procoagulant
Anti-coagulant tendency
 Attenuate cellular Immune defense
lead to poor healing or prolonged
infection

Robust Response - may precipitate

shock and MOF

Proper balance to regulate systemic &

local immune function
Primary circulating cells that participate in septic
response : mononuclear phagocyte & neutrophils

Support the role of

T cell, B cell, and Natural Killer ( NK) cells

Produced :
Pro inflammatory mediators
Anti inflammatory mediators
Growth factors
 Pro Anti
inflammatory Initial insult inflammatory
response response

Systemic spill over Systemic spill

of pro Systemic over of anti
inflammatory reaction inflammatory
mediators SIRS mediator
CARS
Suppression of
Cardiovascular
immune system
compromised
CARS
predominate

Organ Homeostasis Apoptosis

Dysfunction CARS and death with
SIRS SIRS balance minimal
predominate inflammation
 Host Response to Injury
Inflammation
Complement activation
Endothelial activation injury
Vasodilatation
Microcirculatory leakage forming protein rich edema
1
Expression of Adhesion Molecules, cytokines,
growth factor Extravasations of PMN cells and
monocytes Respiratory
burst and phagocytosis
Removal of debris
Coagulation
Activation of Coagulation

2 Inhibition of fibrinolysis Systemic

enhancement of fibrinolysis
 Host Response to Injury
Systemic Inflammatory System
Fever
Induction of acute phase protein
Stimulation leukocyte proliferation in bone marrow
Activation and / or proliferation of B and T lymphocyte
3
depending on stimuli
Metabolic Response

Repair 4
Apoptosis of inflammatory cell
Increased cortisol production
Activation of sympathetic nervous
system Reduction of active
thyroid hormone
Regeneration of parenchyma cell
Angiogenesis
Proliferation of epithelia and fibroblasts
5
 Stress Response ( neuroendocrine response )

A. Afferent stimuli
(Shock, Trauma, Operations, Pulmonary insufficiency,
Anesthesia, Infections, MOF)
B. Transmitters
( Blood and lymphatics, peripheral nerves, CNS)

C. Effector site

Sympathetic nerv syst Hypothalamus Kidney Pancr

islets
Adrenal medula Ant pituitary Post pituitary
Renin,
Adr cortex angiotens
Epinephrn Glukagon
ADH
norepinephr Insulin
Cortison, aldostr,
G.H Aldostrn
 Approach to Management

Surviving Sepsis
Campaign
recommendations

www.ccmjournal.org - February 2013 Volume 41 Number 2

www.ccmjournal.org - February 2013 Volume 41 Number 2
 Diagnostic Criteria for Sepsis
Infection, documented or suspected, and some of the following:

General Variables
• Fever (> 38.3°C)

• Hypothermia (core temperature < 36°C)

• Heart rate > 90/min–1 or > 2 SD above the normal value for age

• Tachypnea

• Altered mental status

• Significant edema or positive fluid balance (> 20 mL/kg over 24 hr)

• Hyperglycemia (plasma glucose > 140mg/dL or 7.7 mmol/L) in the

absence of diabetes
 Diagnostic Criteria for Sepsis
Infection, documented or suspected, and some of the following:

Inflammatory Variables

• Leukocytosis (WBC count > 12000 μL–1)

• Leukopenia (WBC count < 4000 μL–1)

• Normal WBC count with greater than 10% immature forms

• Plasma C-reactive protein > 2 SD above the normal value

• Plasma procalcitonin > 2 SD above the normal value

 Diagnostic Criteria for Sepsis
Infection, documented or suspected, and some of the following:

Organ Dysfuntion 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 > 0.5mg/dL or 44.2 μmol/L

• Coagulation abnormalities (INR > 1.5 or aPTT > 60 s)

• Ileus (absent bowel sounds)

• Thrombocytopenia (platelet count < 100,000 μL–1)

• Hyperbilirubinemia (plasma total bilirubin > 4mg/dL or 70 μmol/L)

 Diagnostic Criteria for Sepsis
Infection, documented or suspected, and some of the following:

Hemodynamic Variables

• Arterial hypotension (SBP < 90mm Hg, MAP <

70mm Hg, or an SBP decrease > 40mm Hg in
adults or less than two SD below normal for age)

Tissue Perfusion Variables

• Hyperlactatemia (> 1 mmol/L)

• Decreased capillary refill or mottling

 Severe Sepsis
Severe sepsis definition =
sepsis-induced tissue hypo-perfusion or organ dysfunction

• Sepsis-induced hypotension

• Lactate above upper limits laboratory normal

• Urine output < 0.5 mL/kg/hr for more than 2 hrs despite adequate fluid resuscitation

• Acute lung injury with PaO2/FIO2 < 250 with no pneumonia as infection source

• Acute lung injury with PaO2/FIO2 < 200 with 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)

 Initial Resuscitation

• Protocolized, quantitative resuscitation of patients with

sepsis- induced tissue hypoperfusion (hypotension
persisting after initial fluid challenge or blood lactate
concentration ≥ 4 mmol/L)

• Resuscitation goals
– CVP 8–12 mm Hg
– MAP≥ 65 mm Hg
– Urine output >0.5 mL/kg/hr
– Central venous (superior vena cava) oxygen saturation 70%
or mixed venous 65%

In patients with elevated lactate levels targeting

resuscitation to normalize lactate
 Screening for Sepsis and Performance
Improvement
• Routine screening of potentially infected seriously ill
patients for severe sepsis to allow earlier
implementation of therapy (grade 1C).

• Hospital–based performance improvement efforts in

severe sepsis (UG).
 Diagnosis

• Cultures as clinically appropriate before antimicrobial

therapy if no significant delay (> 45 mins) in the start of
antimicrobial(s) (grade 1C).

• Use of the 1,3 beta-D-glucan assay (grade 2B), mannan

and anti-mannan antibody assays (2C), if available and
invasive candidiasis is in differential diagnosis of cause of
infection.

• Imaging studies performed promptly to confirm a

potential source of infection (UG).
 Antibiotic therapy

• Administration of effective intravenous antimicrobials within

the first hour of recognition of septic shock (grade 1B) and
severe sepsis without septic shock (grade 1C) as the goal of
therapy.

• Initial empiric anti-infective therapy of one or more drugs that

have activity against all likely pathogens (bacterial and/or
fungal or viral) and that penetrate in adequate concentrations
into tissues presumed to be the source of sepsis (grade 1B).

• Antimicrobial regimen should be reassessed daily for potential

deescalation (grade 1B).
 Source identification and control

• A specific anatomical diagnosis of infection requiring

consideration for emergent source control be sought and
diagnosed or excluded as rapidly as possible, and intervention
be undertaken for source control within the first 12 hr after the
diagnosis is made, if feasible (grade 1C)

• When infected peripancreatic necrosis is identified as a

potential source of infection, definitive intervention is best
delayed until adequate demarcation of viable and nonviable
tissues has occurred (grade 2B)

• If intravascular access devices are a possible source of severe

sepsis or septic shock, they should be removed promptly after
other vascular access has been established (UG).
 Fluid Therapy

• Crystalloids as the initial fluid of choice in the resuscitation of

severe sepsis and septic shock (grade 1B).

• Against the use of hydroxyethyl starches for fluid resuscitation

of severe sepsis and septic shock (grade 1B).

• Initial fluid challenge in patients with sepsis-induced tissue

hypoperfusion with suspicion of hypovolemia to achieve a
minimum of 30 mL/kg of crystalloids (a portion of this may be
albumin equivalent). More rapid administration and greater
amounts of fluid may be needed in some patients (grade 1C).
 Vasopressor
• Maintain MAP 65 mm Hg (1C)
• Norepinephrine and dopamine centrally administered are the initial
vasopressors of choice (1C)
• Epinephrine, phenylephrine, or vasopressin should not be
administered as the initial vasopressor in septic shock (2C)
• Vasopressin 0.03 units/min may be subsequently added to
norepinephrine with anticipation of an effect equivalent to
norepinephrine alone
• Use epinephrine as the first alternative agent in septic shock when
blood pressure is poorly responsive to norepinephrine or
dopamine (2B)
• Do not use low-dose dopamine for renal protection (1A)
• In patients requiring vasopressors, insert an arterial catheter as soon as
practical (1D)
 Inotropic

• Use dobutamine in patients with myocardial

dysfunction as supported by elevated cardiac filling
pressures and low cardiac output (1C)

• Do not increase cardiac index to predetermined

supranormal levels (1B)
 Steroid
• Not using intravenous hydrocortisone to treat adult septic
shock patients if adequate fluid resuscitation and vasopressor
therapy are able to restore hemodynamic stability. In case this
is not achievable, we suggest intravenous hydrocortisone alone
at a dose of 200 mg per day (grade 2C)

• In treated patients hydrocortisone tapered when vasopressors

are no longer required (grade 2D)

• Corticosteroids not be administered for the treatment of sepsis

in the absence of shock (grade 1D).
 Blood Product Administration

• Once tissue hypoperfusion has resolved and in the absence of extenuating

circumstances, such as myocardial ischemia, severe hypoxemia, acute
hemorrhage, or ischemic heart disease, red blood cell transfusion occur
only when hemoglobin concentration decreases to <7.0 g/dL to target a
hemoglobin concentration of 7.0 –9.0 g/dL in adults (grade 1B).
• Not using erythropoietin as a specific treatment of anemia associated with
severe sepsis (grade 1B).
• Fresh frozen plasma not be used to correct laboratory clotting
abnormalities in the absence of bleeding or planned invasive procedures
(grade 2D).
• Not using antithrombin for the treatment of severe sepsis and septic shock
(grade 1B).
• In patients with severe sepsis, administer platelets prophylactically when
counts are <10,000/mm3 (10 x 109/L) in the absence of apparent bleeding.
• SURVIVING SEPSIS CAMPAIGN BUNDLES
TO BE COMPLETED WITHIN 3 HOURS:
• Measure lactate level
• Obtain blood cultures prior to administration of antibiotics
• Administer broad spectrum antibiotics
• Administer 30 mL/kg crystalloid for hypotension or lactate 4mmol/L

TO BE COMPLETED WITHIN 6 HOURS:

• Apply vasopressors (for hypotension that does not respond to initial fluid
resuscitation) to maintain a mean arterial pressure (MAP) ≥ 65 mm Hg
• In the event of persistent arterial hypotension despite volume resuscitation (septic
shock) or initial lactate 4 mmol/L (36 mg/dL):
•
Measure central venous pressure (CVP)*
•
Measure central venous oxygen saturation (ScvO2)* 7) Remeasure lactate
if initial lactate was elevated*
•
*Targets for quantitative resuscitation included in the guidelines are CVP of ≥8
mm Hg, ScvO2 of 70%, and normalization of lactate.
Source Control
Historical Perspective

 Alfred Blalock (early 20th century)

shock – intravascular volume deficit
 Fleming (1920s) – penicillin
 Surgical management of infection
 Trephination – 10,000yr old skull
 Egyptians, Babylonians, Greeks, Romans
 Ambroise Pare (15th century) drainage of abcess
 Appendiceal abcess incision & drainage (1530)
 First appendectomy by Groves 1883 Canada
Scientific Basis

 Rationale for surgical intervention: unlikely

randomized controlled trial intervention vs
nonintervention is undertaken
 Source control should be individualized based on:
 Diagnostic uncertainty
 Physiologic stability
 Premorbid health status
 Previous surgical interventions
 Surgeon’s experience & skill
 Available surgical facilities
What is Source Control?

 All those physical measures that are

undertaken
 To eliminate a focus of infection
 To control ongoing contamination
 To restore premorbid anatomy &
function
What is Source Control?

 Not always surgical procedures, also

include
 Radiologically directed drainage of
intracavitary abscess
 Removal of colonized urinary or
vascular catheter
 Removal of devitalized tissue by
frequent dressing changes
Principles of Source Control

 Drainage of abscess
 Debridement of nonviable of infected tissue
 Definitive management of the anatomic
abnormality responsible for ongoing microbial
contamination à restoring normal function and
anatomy
Drainage

 Converting a contained collection to a controlled fistula

(to exterior) or sinus
 Drain must permit free flow of the abscess
 Minimum risk and physiologic derangement:
percutaneous drainage
 Modern imaging: all collections can be visualized
preoperatively
 In unstable and ill patient – surgery for controlled
sinus/fistula & removal of dead tissue only
Drainage
CT guided abcess drainage
Debridement

 The process of removing nonviable tissue

 Directed against solid components that promote
bacterial growth
 Demarcation between viable and nonviable tissue
maybe not absolute at early stage
 Gentle debridement - use wet to dry saline
dressing
Debridement
 Remove all necrotic tissue but minimize the
resulting defects for easier reconstruction
 Bleeding from viable tissue is better than fail to
debride necrotic material
Debridement
Necrotic bowel

 Excision for necrotic bowel is more complex

 The benefits of resection must be weighed against
the consequences of loss of bowel length
 The dilemma is usually best resolved by a
planned second-look laparotomy
Debridement
Retroperitoneum

 Peripancreatic retroperitoneal necrosis is well

tolerated
 Blind exploration of retroperitoneum - risk of
uncontrollable hemorrhage
 Delayed debridement is preferred for suspected
infected necrosis
Debridement
Foreign body

 Risks are minimal when urinary or vascular

catheter is infected

 Risks are high when aortic graft or heart valve is

infected
Definitive management

 The ultimate aim of therapy:

 to restore function with the least risk
 To correct the abnormality that created the infection
Biologic Rationale

 Host defenses are occasionally incapable of

combating the introduction of microbes and
establishment of infection
 When large number of microbes are present
 When host defenses are diminished
 Ongoing source of microbial contamination

 Inadequate source control increases morbidity

and mortality up to 7 folds
Drainage
 Percutaneous abscess drainage (PD) is preferred
 Indication of operative intervention
 When PD has failed
 When absolute contraindications to PD

 PD can temporize, permitting delayed definitive

management
Debridement & Peritoneal Toilet

 The degree of peritoneal contamination correlates

with the severity of infection & outcome
 The host responds to peritoneal infection by
absorbing pathogens into the bloodstream & by
mounting a local peritoneal inflammatory reaction:
kill bacteria but affect the host
 The goal of peritoneal toilet - to remove
mechanically as many contaminants as possible:
reducing infection severity
Device Removal

 Make sure the diagnosis of infection is secure

 Determine whether device removal would pose a
significant risk
 Assess complicating factors (virulence,
immunosuppression) and the history (previous
therapy failed)
 When in doubt, take it out
Definitive vs Temporizing

 The judgement to select a temporizing vs definitive

requires an integrated assessment of
 The surgeon’s knowledge about the underlying disease
 Systemic host factors
 Severity of the local inflammatory response
Extent of Surgical Therapy

 The more extensive the initial intervention, the

greater is the challenge of subsequent
reconstruction

 The optimal intervention is that which

accomplishes the source control objectives in the
simplest manner
Failed Source Control

 Failure of source control is more important than

antibiotic failure
 Cause of failure:
 Poor choice of operation
 Correct operation performed poorly
 Poor timing

 Consequences of failure:
 Nosocomial infections
 Nutritional and metabolic disorders
 Multiple organ dysfunction syndrome
Diffuse Peritonitis

 Aggressive initial surgical source control :

intraoperative lavage
 If source control not possible
 Continuous lavage
 Laparostomy
 Planned reexploration
 Or combination of above
Timing of Intervention

 As general principle: as soon as possible

 Rapid, minimally invasive, temporizing or palliative

measures - may be superior to definitive but
lengthy, more traumatizing procedures
Complications of Source Control

 Complications from
 Technical error
 Local factors that impair healing
Reconstructive Surgery after Source Control

 Reoperation should be delayed for several months

following resolution of all complications from the
source control operation
 Timing is very important
 Enter peritoneal cavity through a “virgin area” of the
abdominal wall
Evaluating Adequacy of Source Control

 No single test can measure whether adequate

source control has been achieved

 If ongoing intraabdominal infection is suspected:

CT scan before surgery
Empiric Reexploration:
Is there a role?
 The need for relaparotomy significantly worsens
the outcome
Conclusion

 The key to success when treating surgical

infections is timely intervention to stop the delivery
of bacteria and adjuvants of inflammation/infection
into the peritoneal cavity
 All others are useless if source control failed
Thank you