Sepsis, EGDT, and Source Control

Perioperative and Acute Care Surgery Course BITDEC, APRIL 2012

Objectives
15 minutes for definition and clinical aspect of sepsis
Patophysiology of sepsis Intervention in septic patients SSC

10 minutes to explain about Early Goals Directed therapy

Algorithm of EGDT Clinical implication of EGDT

10 minute for source control in sepsis 10 minutes Discussion

Stages of Sepsis Consensus Conference Definition

Systemic Inflammatory Response Syndrome (SIRS)
Two or more of the following: Temperature of >38oC or <360C Heart rate of >90 Respiratory rate of >20 WBC count >12 x 109/L or <4 x 109/L or 10% immature forms (bands)

Sepsis SIRS plus a culture-documented infection Severe Sepsis

Sepsis plus organ dysfunction, hypotension, or hypoperfusion (including but not limited to lactic acidosis, oliguria, or acute mental status changes)

Septic Shock
Hypotension (despite fluid resuscitation) plus hypoperfusion

SIRS / Sepsis

Bacteremia (septicemia)

Other

SIRS
Infection Fungal
Parasit. Vir. Other

Trauma

Sepsis
Burns Pancreatitis

*Severe SIRS/Sepsis includes some evidence of organ failure

Bone RS, 1997

Microbial product, trauma, ischemia reperfusion injury, ect

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, complement system

Sepsis Mediator Phase 1

recognition

General cellular response in sepsis

receptor

Phase 2 Chemo taxis Phase 3

Secreted mediator

Phagocytosis

Signal transduction

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
Factor VIIIa PAI-1

Tissue Factor
Organisms

IL-6 IL-1 TNF-

Monocyte

Factor Va

THROMBIN

TAFI

Suppressed fibrinolysis
Fibrin Fibrin clot

Neutrophil
IL-6
Tissue Factor

Inflammatory Response

Thrombotic Response

Fibrinolytic Response

cytokines

Generation thrombin mediated by tissue factor

Impaired of anticoagulant pathway

Suppression of fibrinolysis by PAI - 1

Formation of fibrin

Attenuation of AT III, Protein C, TFPI

Inadequate removal of fibrin

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

Local Pro inflammatory response

Initial insult

Local Anti inflammatory response

Systemic spill over of pro inflammatory mediators Cardiovascular compromised

Systemic reaction
SIRS CARS

Systemic spill over of anti inflammatory mediator Suppression of immune system CARS predominate Apoptosis death with minimal inflammation

Organ Dysfunction SIRS predominate

Homeostasis CARS and SIRS balance

Host Response to Injury

Inflammation Complement activation Endothelial activation injury Vasodilatation Microcirculatory leakage forming protein rich edema Expression of Adhesion Molecules, cytokines, growth factor Extravasations of PMN cells and monocytes Respiratory burst and phagocytosis Removal of debris

Coagulation

Activation of Coagulation 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 depending on stimuli Metabolic Response

Repair

Apoptosis of inflammatory cell Regeneration of parenchyma cell Angiogenesis Proliferation of epithelia and fibroblasts

Increased cortisol production Activation of sympathetic nervous system Reduction of active thyroid hormone

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
Adrenal medula Epinephrn norepinephr

Hypothalamus

Kidney

Pancr islets

Ant pituitary Post pituitary Adr cortex

Renin, angiotens
Glukagon Aldostrn Insulin

ADH
Cortison, aldostr, G.H

Approach to Management

Therapy Across the Sepsis Continuum

SIRS
Drainage Debridement Device removal Definitive control resection

Sepsis

Severe Sepsis

Septic Shock
62%

28%

amputation

Antibiotics and Source Control

Chest 2000;118(1):146 Chest 1992;101:1644.

Therapy Across the Sepsis Continuum

SIRS Sepsis

Severe Sepsis

Septic Shock

Early Goal Directed Therapy

Antibiotics and Source Control

Early Goal-Directed Therapy (EGDT): involves adjustments of cardiac preload, afterload, and contractility to balance O2 delivery with O2 demand

Chest 1992;101:1644.

Therapy Across the Sepsis Continuum

SIRS Sepsis

Severe Sepsis

Septic Shock

Xigris (Drotrecogin)
Early Goal Directed Therapy

Antibiotics and Source Control

Insulin and tight glucose control DVT prophylactic

Therapy Across the Sepsis Continuum

SIRS Sepsis

Severe Sepsis

Septic Shock

Steroids Drotrecogin
Early Goal Directed Therapy

Antibiotics and Source Control

Insulin and tight glucose control DVT prophylactic
Chest 1992;101:1644.

 Initial resuscitation and Infections Issues Indicates a strong recommendation we recommend Indicates a weak recommendation we suggest Initial resuscitation (first 6 hrs)

Initial Resuscitation
Begin resuscitation immediately in patients with hypotension or elevated serum lactate 4 mmol/L; do not delay pending ICU admission (1C) Resuscitation goals (1C)
CVP 812 mm Hg MAP 65 mm Hg Urine output 0.5 1 mL/kg/hr

Central venous (superior vena cava) oxygen saturation 70% or mixed venous 65% If venous oxygen saturation target is not achieved (2C)
Consider further fluid Transfuse packed red blood cells if required to hematocrit of 30% and/or Start dobutamine infusion, maximum 20g/kg/min

PROTOCOL OF EARLY GOAL-DIRECTED THERAPY

Diagnosis
Obtain appropriate cultures before starting antibiotics provided this does not significantly delay antimicrobial administration (1C)
Obtain two or more BCs One or more BCs should be percutaneous One BC from each vascular access device in place > 48 hrs Culture other sites as clinically indicated

Perform imaging studies promptly to confirm and sample any source of infection, if safe to do so (1C)

Antibiotic therapy
Begin intravenous antibiotics as early as possible and always within the first hour of recognizing severe sepsis (1D) and septic shock (1B) Broad-spectrum: one or more agents active against likely bacterial/fungal pathogens and with good penetration into presumed source (1B) Reassess antimicrobial regimen daily to optimize efficacy, prevent resistance, avoid toxicity, and minimize costs (1C) Consider combination therapy in Pseudomonas infections (2D)
Consider combination empiric therapy in neutropenic patients (2D) Combination therapy 35 days and de-escalation following susceptibilities (2D)

Duration of therapy typically limited to 710 days; longer if response is slow or there are undrainable foci of infection or immunologic deficiencies (1D) Stop antimicrobial therapy if cause is found to be noninfectious (1D)

Source identification and control

A specific anatomic site of infection should be established as rapidly as possible (1C) and within first 6 hrs of presentation (1D) Formally evaluate patient for a focus of infection amenable to source control measures (e.g. abscess drainage, tissue debridement) (1C) Implement source control measures as soon as possible following successful initial resuscitation (1C) (exception: infected pancreatic necrosis, where surgical intervention is best delayed) (2B) Choose source control measure with maximum efficacy and minimal physiologic upset (1D) Remove intravascular access devices if potentially infected (1C)

Fluid Therapy
Fluid-resuscitation using crystalloids or colloids (1B) Target a CVP of 8 mm Hg (12 mm Hg if mechanically ventilated) (1C) Use a fluid challenge technique while associated with a hemodynamic improvement (1D) Give fluid challenges of 1000 mL of crystalloids or 300500 mL of colloids over 30 mins More rapid and larger volumes may be required in sepsisinduced tissue hypoperfusion (1D) Rate of fluid administration should be reduced if cardiac filling pressures increase without concurrent hemodynamic improvement (1D)

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
Consider intravenous hydrocortisone for adult septic shock when hypotension responds poorly to adequate fluid resuscitation and vasopressors (2C) ACTH stimulation test is not recommended to identify the subset of adults with septic shock who should receive hydrocortisone (2B) Hydrocortisone is preferred to dexamethasone (2B) Fludrocortisone (50 g orally once a day) may be included if an alternative to hydrocortisone is being used that lacks significant mineralocorticoid activity. Fludrocortisone if optional if hydrocortisone is used (2C) Steroid therapy may be weaned once vasopressors are no longer required (2D) Hydrocortisone dose should be 300 mg/day (1A) Do not use corticosteroids to treat sepsis in the absence of shock unless the patients endocrine or corticosteroid history warrants it (1D)

Recombinant activated protein C

Consider rhAPC in adult patients with sepsisinduced organ dysfunction with clinical assessment of high risk of death (typically APACHE II 25 or multiple organ failure) if there are no contraindications (2B, 2C for postoperative patients). Adult patients with severe sepsis and low risk of death (typically, APACHE II 20 or one organ failure) should not receive rhAPC (1A)

OTHERS
Blood product administration Mechanical ventilation of sepsis-induced ALI/ARDS Sedation, analgesia, and neuromuscular blockade in sepsis Glucose control Renal replacement Bicarbonate therapy Deep vein thrombosis prophylaxis Stress ulcer prophylaxis Consideration for limitation of support

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 Surgeons 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

Definitions of terms
Term Source control Definition All physical measures undertaken to eliminate a source of infection, control ongoing contamination, and restore premorbid anatomy and function

Sinus
Fistula Abcess

Abnormal communication to an epithelial celllined surface

Abnormal communication between two epithelial cell-lined surfaces Fluid-filled collection of tissue fluid, tissue debris, neutrophis, and bacteria contained within a fibrous capsule Creation of a controlled sinus or fistula Removal of devitalized tissue, foreign bodies, or other areas advantageous to bacterial growth

Drainage Debridement

Principles of Source Control

Drainage of abscess Debridement of nonviable of infected tissue Definitive management of the anatomic abnormality responsible for ongoing microbial contamination 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

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
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 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 surgeons 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 inflamation/infection into the peritoneal cavity All others are useless if source control failed

Thank you