SEPSIS

Dr Jiss V Peter
Emergency medicine resident
 Click icon to add picture

“Except on few occasions, the

patient appears to die from the
body's response to infection
rather than from it.”
Sir William Osler –1904
The Evolution of Modern Medicine
 OLD TERMINOLOGY

• Sepsis: Systemic manifestations of infection

• Severe sepsis: Sepsis with organ dysfunction,

hypoperfusion, or hypotension

• Septic shock: Sepsis with arterial hypotension,

despite fluid resuscitation, with organ dysfunction
 SYSTEMIC INFLAMMATORY RESPONSE
SYNDROME (SIRS)

Two or more of the following:

• 1. Temperature > 38°C or < 36°C

• 2. Heart rate > 90 beats/min

• 3. Respiratory rate > 20 breaths/min or Paco2 < 32 mm Hg

• 4. White blood cell count > 12,000/mm3, < 4,000/mm3, or >

10% band neutrophilia
 LIMITATIONS OF PREVIOUS
DEFINITIONS
• An excessive focus on inflammation

• Misleading model that sepsis follows a continuum through severe

sepsis and septic shock

• Inadequate specificity and sensitivity of SIRS

• Different criteria yielding different results

 INTERRELATIONSHIP BETWEEN SYSTEMIC
INFLAMMATORY RESPONSE SYNDROME (SIRS),
SEPSIS, AND INFECTION.
PATHOPHYSIOLOGY
2016 SCCM/ESICM TASK FORCE TO RE-DEFINE
SEPSIS
• SCCM/ESICM TASK FORCE GUIDELINES :
• SEPSIS 1999 -1, 2001-2, 2016-3

• SURVIVING SEPSIS CAMPAIGN

2004/2008/2012/2018update.
 DEFINITION CHANGES IN 2016

• A task force of 19 leaders in the field of sepsis was convened by

SCCM and the European Society of Intensive Care Medicine (ESICM)

• Sepsis

A life-threatening organ dysfunction caused by a dysregulated

host response to infection
THE SIRS CRITERIA HAVE BEEN REMOVED

Reasons
• It may present in simple, non-complicated infection, or in
response to non infectious-triggers (i.e. trauma, pancreatitis,
post-cardiac arrest syndrome)

• may even be absent in critically ill patients with obvious

evidence of a life-threatening infection.

• the ability to predict death is poor

 ORGAN DYSFUNCTION

• Organ dysfunction is defined as an increase of 2 or

more points in the SOFA score.

• SOFA score is an organ dysfunction score.

 SOFA: SEQUENTIAL ORGAN FAILURE
ASSESSMENT

• SOFA uses simple measurements of major organ function

to calculate a severity score.

• The scores are calculated 24 hours after admission to the

ICU and every 48 hours thereafter.

• It helps to identify patients who potentially have a high

risk of dying from infection
 THE SOFA SEVERITY SCORE IS BASED UPON THE
FOLLOWING MEASUREMENTS OF ORGAN FUNCTION:

• Respiratory system

• Cardiovascular system

• Hepatic system

• Coagulation system

• Neurologic system

• Renal system
• Respiratory system – PaO2/FiO2

• Cardiovascular system – the amount of vasoactive medication

necessary to prevent hypotension

• Hepatic system – Serum bilirubin

• Coagulation system – Platelet count

• Neurologic system – Glasgow coma score

• Renal system – Serum creatinine or urine output

• 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
 LIMITATIONS OF SOFA

• cumbersome due to multiple variables

• not well known outside the ICU setting

• variables and cutoff values were developed by

consensus
 Q SOFA

• Early sepsis —Infection and bacteremia can progress to sepsis.

• Identification of early sepsis

• The 2016 SCCM/ESICM task force have described an assessment

score for patients outside the ICU as a way to facilitate the
identification of patients potentially at risk of dying from sepsis

quickSOFA (qSOFA)
HAT
 Q SOFA

• Respiratory rate ≥ 22/min

• Altered mentation

• Systolic blood pressure ≤ 100mmHg

• out-of-ICU patients with clinical suspicion of sepsis.

• A score ≥2 is associated with poor outcomes due to

sepsis.
 ‘SEVERE
SEPSIS’ term ‘SEPTIC
has been SHOCK’
removed.
 NEW DEFINITION….

Septic shock
• a subset of sepsis in which underlying circulatory and
cellular/metabolic abnormalities are profound enough to
substantially increase the mortality.

(2016 SCCM/ESICM task force)

 NEW DEFINITION….

• Septic shock----Clinical criteria :

• SEPSIS, plus
• despite adequate fluid resuscitation:

• The need for vasopressors to obtain a MAP≥ 65mmHg

And
• An increase in serum lactate concentration > 2mmol/L(18mg/dl)
3 variables were identified

• Presence of hypotension

• Elevated lactate level

• sustained need for vasopressor therapy

• With these criteria , hospital mortality is in excess of 40%.

• Terms like Severe Sepsis/Septicemia has been removed

SURVIVING SEPSIS CAMPAIGN
 SURVIVING SEPSIS CAMPAIGN

• collaboration between US society of critical care

medicine ,European society of Intensive care medicine and
International sepsis forum.

• Using Grades of Recommendation, Assessment,

Development and Evaluation (GRADE) system to guide
assessment of quality of evidence from high(A) to very low(D)
and to determine strength of recommendation
SURVIVING SEPSIS CAMPAIGN: INTERNATIONAL GUIDELINES
FOR MANAGEMENT OF SEVERE SEPSIS AND SEPTIC SHOCK:
2012
 DIAGNOSTIC CRITERIA FOR SEPSIS

Infection, documented or suspected, and some of the following:

• General variables

• Inflammatory variables

• Hemodynamic variables

• Organ dysfunction variables

• Tissue perfusion variables

 GENERAL VARIABLES

• Fever (> 38.3°C)

• Hypothermia (core temperature < 36°C)

• Heart rate > 90/min–1 or more than two 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 > 140 mg/dL or 7.7 mmol/L) in the absence

of diabetes
 INFLAMMATORY VARIABLES

• Leukocytosis (WBC count > 12,000 µL–1)

• Leukopenia (WBC count < 4000 µL–1) Normal WBC count

with greater than 10% immature forms

• Plasma C-reactive protein more than two sd above the

normal value

• Plasma procalcitonin more than two 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 less than two sd below normal for
age)
 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 µmol/L

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

• Ileus (absent bowel sounds)

• Thrombocytopenia (platelet count < 100,000 µL)

 TISSUE PERFUSSION VARIABLES

• Hyperlactatemia (> 1 mmol/L)

• Decreased capillary refill or mottling

MANAGEMENT OF SEPSIS AND SEPTIC
SHOCK

Surviving Sepsis Campaign: International Guidelines for

Management of Severe Sepsis and Septic Shock: 2012
 SURVIVING SEPSIS CAMPAIGN: INTERNATIONAL
GUIDELINES FOR MANAGEMENT OF SEVERE
SEPSIS AND SEPTIC SHOCK: 2012

• Initial Resuscitation and Infection Issues

• Hemodynamic Support and Adjunctive Therapy

• Supportive therapy
 INITIAL RESUSCITATION AND INFECTION
ISSUES

• 3 hr and 6hr bundles

• Screening for sepsis

• Diagnosis

• Anti microbial therapy

• Source control

• Infection prevention
 HEMODYNAMIC SUPPORT AND ADJUNCTIVE
THERAPY

• Fluid therapy

• Vasopressors

• Ionotropicc therapy

• Corticosteroids
 SUPPORTIVE THERAPY

• Blood product administration • Bicarbonate therapy

• Mechanical ventilation of • Dvt prophylaxis

sepsis-ards
• Stress ulcer prophylaxis
• Sedation/analgesics/nm
blockade • Nutrition
• Glucose control • Setting goals of care
• Renal replacement therapy
3 HR AND 6 HR BUNDLES
 GOALS OF INITIAL RESUSCITATION ( FIRST
6HRS)

• Early quantitative resuscitation of the septic patient during the

first 6 hrs after recognition.
• To prevent or limit multiple organ dysfunction, as well as to
reduce mortality

• EARLY GOAL DIRECTED THERAPY (EGDT)

 EARLY GOAL DIRECTED THERAPY (EGDT)

• Start resuscitation in patients with hypotension or elevated serum

lactate > 4mmols/l

• Resuscitation goals are

• 1.CVP 8-12mmHg
• 2. MAP ≥ 65mmHg
• 3.urine output ≥ 0.5ml/kg/hr
• 4.central venous oxygen saturation ≥ 70% or mixed venous ≥ 65%
• 5. normalise lactate levels
 DIAGNOSIS

• Obtain appropriate cultures before antimicrobial therapy is

intiated

• at least two sets of blood cultures (both aerobic and anaerobic

bottles) with at least one drawn percutaneously and one
drawn through each vascular access device

• Imaging studies to identify source of infection

 ANTIMICROBIAL THERAPY

• Effective intravenous antimicrobials within the first hour of recognition of

septic shock

• Empiric therapy include one or more drugs that have activity against all
likely pathogens (bacterial and/or fungal or viral) and that penetrate in
adequate concentrations into the tissues presumed to be the source of
sepsis

• Reassessed daily for potential de-escalation to prevent the development

of resistance, to reduce toxicity, and to reduce costs
• Use of low procalcitonin levels or similar biomarkers to
assist the clinician in the discontinuation of empiric
antibiotics in patients who appeared septic.

• Antiviral therapy should be intiated as early as possible

SOURCE CONTROL & INFECTION PREVENTION

• Source of infection identified as early as possible and source control within

12hrs

• If intravascular devices are possible source of infection they should be

removed.

• selective oral decontamination (SOD) and selective digestive decontamination

(SDD) should be introduced as a method to reduce the incidence of VAP

• Oral chlorhexidine gluconate used as a form of oral decontamination agent to

reduce risk of VAP

 FLUID THERAPY
• Using colloids or crystalloids

• Crystalloids as initial fluid for resuscitation. Initial fluid

challenge 30ml/kg in 4-6 hrs

• Incremental fluid boluses till patients improves

hemodynamically

• Albumin in patients with sepsis or shock

• Avoidance of hydroxy ethyl starch formulations

 VASOPRESSORS & INOTROPES

• Vasopressor therapy initially to target a mean arterial pressure

(MAP) of 65 mm Hg

• Norepinephrine as the first choice vasopressor (grade 1B)

• All patients requiring vasopressors have an arterial catheter

placed as soon as practical if resources are available

• Vasopressin 0.03u/min can be added to NE

 VASOPRESSIN

• VASST Trial

• Evaluated vasopressin (AVP) versus norepinephrine (NE) effect

on 28 day mortality in septic shock

• Conclusions▫ AVP significantly decreased NE doses at day 4 (p

< 0.001)▫

• AVP MAY improve mortality in patients with less severe shock

 CORTICOSTEROIDS

• Indicated with persistent hemodynamic instability

• Hydrocortisone 50mg IV every 6 hours OR Hydrocortisone 100mg

IV every 8 hours

• Corticosteroids not be administered for the treatment of sepsis in

the absence of shock

• Multiple studies have shown decreased time on vasopressors. No

mortality benefit
 MECHANICAL VENTILATION OF SEPSIS-
INDUCED ARDS

• Target a tidal volume of 6ml/kg

• PEEP be applied to avoid alveolar collapse at the end

expiration-

• Higher levels of PEEP be used

 GLUCOSE CONTROL

• IV insulin started when 2 consecutive blood glucose levels ≥

180mg/dl

• Blood glucose values monitored every 1-2hrs until glucose

values and insulin infusion rates are stable and then every 4 hrs.
 RENAL REPLACEMENT THERAPY

• Continuous renal replacement therapies and

intermittent hemodialysis in patients with
severe sepsis and acute renal failure
SURVIVING SEPSIS CAMPAIGN RESPONDS TO
SEPSIS-3
MARCH 1, 2016
• Included qSOFA
• 3 hr and 6 hr bundle to be continued
THE SURVIVING SEPSIS CAMPAIGN
BUNDLE: 2018 UPDATE
• In this revision of the SSC bundles, the 3-hour and 6-
hour bundles have been combined into a single “Hour-
1 Bundle”

• explicit intention of beginning resuscitation and

management immediately.

• This new sepsis “Hour-1 Bundle” should be introduced

to staff in the emergency department (ED), wards, and
intensive care unit.
 ATHOS-3 TRIAL

• Phase III trial evaluating AT2 for severe vasodilatory shock

• Randomized, double-blind, multicenter, placebo controlled; May

2015- January 2017

• Purpose: to determine effectiveness of AT2 for vasodilatory

shock resistant to high-dose vasopressors

• Primary Outcome: MAP response 3 hours after start of infusion

Protocolized Care Australasian Resuscitation The Protocolised
for Early Septic in Sepsis Evaluation Management in
Shock (ProCESS) – (ARISE) – 51 ED’s in Sepsis (ProMISe)
31 ED’s Australia, New Zealand, Trial – 56 ED’s in the
Finland, Hong Kong, UK
• These trials emphasize that the early recognition of sepsis,
administration of antimicrobials, adequate volume resuscitation,
and assessment of the adequacy of circulation are the important
elements that improve outcomes, not any specific path of
resuscitation.
 TAKE HOME POINTS

• SEPSIS -3 GUIDELINES 2016-

• - SEPSIS/ SEPTIC SHOCK definition/clinical criteria
• -qSOFA/ SOFA

• SURVIVING SEPSIS CAMPAIGN 2012/2018 update-

• -3hr, 6hr BUNDLES---------1 hr BUNDLE
• management steps.
THANKYOU