Sepsis and Septic Shock

guidelines
DR MAHESH KUMAR
• Sepsis is a medical emergency that describes the body’s
systemic immunological response to an infectious process
that can lead to end-stage organ dysfunction and death.
• There has been a significant evolution in the definition and
management of sepsis over the last three decades. This is
driven in part due to the advances made in our
understanding of its pathophysiology.
 SEPSIS -1
• An earlier sepsis definition, Sepsis-1, was
developed at a 1991 consensus conference in
which SIRS criteria were established|

• Four SIRS criteria were defined, namely

• Tachycardia (heart rate >90 beats/min),
• Tachypnea (respiratory rate >20 breaths/min),
• Fever or hypothermia (temperature >38 or <36
℃), and
• leukocytosis, leukopenia, or bandemia (white
blood cells >1,200/mm3, <4,000/mm3 or
bandemia ≥10%).
• Patients who met two or more of these criteria
fulfilled the definition of SIRS, and
• Sepsis-1 was defined as infection or
suspected infection leading to the onset of
SIRS
• Sepsis complicated by organ dysfunction was
termed severe sepsis, which could
progress to septic shock, defined as
“sepsis-induced hypotension persisting despite
adequate fluid resuscitation.”
 Sepsis-2
• A 2001 task force recognized the limitations with
these definitions, but did not offer alternatives due to a
lack of supporting evidence.
• However, they did expand the list of diagnostic
criteria, resulting in the introduction of Sepsis-2.
Therefore, in order to be diagnosed with sepsis under
the Sepsis-2 definition, as with Sepsis-1,
• An individual must have at least 2 SIRS criteria and a
confirmed or suspected infection (4-6). In effect, the
definitions of sepsis and septic shock remained
unchanged for more than two decades.
 Definition Changes in 2016
• “life threatening organ dysfunction caused by a
dysregulated host response to infection”
• Infection: the invasion of normally sterile tissue by
organisms resulting in infectious pathology
• Organ Dysfunction: Increase of 2 or more points in SOFA
Score (Sepsis-related/Sequential Organ Failure
Assessment)
• Recognizing the practical limitations,
• the 2016 SCCM/ESICM task force described a
simplified method termed “quick SOFA” to facilitate
easier identification of patients potentially at risk of
dying from sepsis .
• This score is a modified version of the Sequential
(Sepsis-related) Organ Failure Assessment score
(SOFA). qSOFA consists of only three components
that are each allocated one point
qSOFA score of ≥2 points indicates
organ dysfunction
FLUID RESUSCITATION/ACUTE KIDNEY
INJURY
• An important component for the management of sepsis
is fluid resuscitation.
• Several recent trials investigated crystalloid
administration. As with any therapeutic, there are
hazards and benefits to fluid administration. Excess
negatively impacts cardiac and renal physiology. During
resuscitation, when a patient’s circulation is no longer
fluid responsive, hazard outweighs benefit
• Cardiac myocytes overstretch, resulting in worsening
myocardial performance. Pulmonary edema affects
arterial oxygenation, and interstitial edema impairs
cellular oxygenation
• 2016 Society of Critical Care Medicine( SCCM)
guidelines support conservative fluid management
in acute respiratory syndrome (ARDS) with
resolution of shock, and after resolution of shock
• There is evidence for conservative fluid
management during organ dysfunction, and lower
cardiac filling pressures result in improvements in
lung function for patients in shock
• Many experts suggest a cautious approach to fluid
resuscitation in sepsis, and an emphasis on late
conservative fluid management with timely
‘deresuscitation’ .
• OUR BODY PLASMA HAS chloride
concentration ranging from 94 to 111mmol/l,
whereas the 0.9% normal saline has a
concentration of 154mmol/l,
• Lactated Ringers 109mmol/l, and Plasma-Lyte
98mmol/l. Chloride rich saline may produce
detrimental effects on renal function and
worsening effects on mortality
• High chloride concentration leads to renal
vasoconstriction in animal models
 STEROIDS IN CRITICAL ILLNESS

• Administration of steroids in sepsis is a common, but

largely unsettled, practice. Although it is clear that
mineralocorticoid and glucocorticoid secretion,
disposition, and response are altered during sepsis,
• There are arguments for and against administration
• Steroids reduce vasoconstrictor use and improve SOFA
scores and might improve mortality in septic shock
• They also lead to hypernatremia, hyperglycemia, and
neuromuscular weakness
• Among concerns is the identification of patients likely to
benefit
• The specific role of mineralocorticoids in combination
with glucocorticoids, an ideal diagnostic approach, and
translation of reversal of shock to more patient
important outcomes remain unresolved.
• Mortality may not be the best investigational endpoint ,
as mechanisms underlying steroid benefit remain
unclear.
• The SCCM guidelines continue to recommend IV
hydrocortisone for septic shock unresponsive to fluid
resuscitation
 ANGIOTENSIN II
• After judicious resuscitation, the primary
approach to maintaining arterial pressure in
septic shock is through the use of vasoactives,
ostensibly to reverse pathologic vasodilation.
• Vasoconstrictors can normalize what is measured
(arterial pressure), but mixed evidence
repeatedly suggests that this metric is imperfect
• Currently, norepinephrine, vasopressin, and
epinephrine are recommended
vasoconstrictors in septic shock
• The prospect of another agent, acting by a
separate mechanism, might improve
resuscitation ,particularly in patients refractory
to traditional medications and in extreme,
refractory shock states.
• Angiotensin II was awarded Food and Drug
Administration (FDA) approval with a caution
regarding increased venous and arterial
thromboembolic events . vs. 5%) And a
statement that it should be used with
concurrent venous thromboembolism
prophylaxis
• Sepsis frequently includes a hypercoagulable
state, so that there may be real risks to
administering a potentially prothrombotic
drug.
 VITAMIN C/THIAMINE
• Vitamin C and thiamine enjoy renewed interest
as therapies for sepsis.
• Vitamin C is thought to play an integral role for
maintenance of the endothelium, and depletion may
contribute to capillary leak .
• Its administration may be beneficial in burns,
trauma, and sepsis
• Thiamine (vitamin B1) depletion appears to be
common in sepsis and deficiencies may contribute to
mitochondrial metabolic impairments, and cause
lactic acidosis . Repletion may increase lactate
clearance
• New data suggest that IV vitamin C,
hydrocortisone, and IV thiamine
synergistically improve metabolic and functional
circulatory impairments in septic SHOCK.
 PROCALCITONIN
• Early administration of antibiotics decreases
mortality in sepsis.
• Delays in therapy for septic shock patients can lead
to mortality rates as high as 7% per hour for the first
6h
• De-escalation of therapy at the time of clinical
improvement is less clear, and clinicians frequently
rely on judgment.
• Procalcitonin(PCT )levels, produced predominately
by the thyroid gland but also the lungs and intestines,
rise during acute tissue inflammation and tissue
injury .
• PCT levels may prove to be a more accurate
biomarker that can distinguish between nonspecific
inflammation and bacterial infection.
• SCCM guidelines endorse the use of the PCT
assay to limit antibiotic exposure in patients
with sepsis, and de-escalation of antibiotic
therapy in patients originally presumed to have
sepsis
• Although this assay is another added tool to
limit antibiotic exposure and a trigger to treat
infection prospectively, it should not replace
clinician judgment. The Infectious Disease
Society of America recommends clinical criteria
alone in diagnosis, but follow-up in treatment
can be accompanied by PCT to guide therapy
 CONCLUSION
• Clinical approaches to sepsis continue to advance.
• A dysregulated host response to infection causing organ
damage now helps to further define the disease.
• Sepsis-3 provides a framework for asking scientific
questions and separating noninfectious inflammation from
an infectious source.
• New evidence revisits established therapies for sepsis
such as IV fluid administration and steroids, and new
treatments including angiotensin II, vitamin C, thiamine,
and the role of PCT as guide for antimicrobial therapy.
• Balanced crystalloids appear to be superior to
hyperchloremic solutions. Steroid use has been
controversial; however, early use in sepsis reverses shock
• Angiotensin II is a new vasoconstrictor to raise
blood pressure, but may risk a prothrombotic
state.
• Vitamin C and thiamine may improve metabolic
abnormalities, but need further validation before
routine use.
• PCT assays reduce antibiotic exposure and may
help discern between sepsis and non sepsis
inflammation
 Surviving Sepsis Campaign:
International Guidelines for
Management of Sepsis and Septic
Shock: 2016
Surviving Sepsis Campaign Bundle
• Initial Resuscitation Bundle
To Be Completed in 3 hours
1 Measure lactate level
2 Obtain cultures prior to administration of
antibiotics
3 Administer broad spectrum antibiotics
4 Administer 30ml/kg crystalloid for
hypotension or lactate greater than or equal to
4mmol/kg
 Septic Shock Bundle
• To be Completed Within 6 Hours
• 1 Apply vasopressors (for hypotension that does not
respond to initial fluid resuscitation) to maintain a mean
arterial pressure (MAP) greater than or equal to 65mmHg
• 2 In the event of persistent arterial hypotension despite
volume resuscitation (septic shock) or initial lactate
greater than or equal to 4mmol/L
a. Measure central venous pressure (CVP)*
b. Measure central venous oxygen saturation
3 Remeasure lactate if initial lactate was elevated
• The most important change in the revision of the SSC
bundles is that the 3-h and 6-h bundles have been
combined into a single “hour-1 bundle” with the explicit
intention of beginning resuscitation and management
immediately.
• More than 1 hour may be required for resuscitation to be
completed, but initiation of resuscitation and treatment,
such as obtaining blood for measuring lactate and blood
cultures, administration of fluids and antibiotics, and in the
case of life-threatening hypotension, initiation of
vasopressor therapy, are all begun immediately
In 2018 BUNDLE 3-h and 6- h bundles have been combined into a
single “hour-1 bundle
Initial Resuscitation Goals within first 6
hours
• • CVP 8-12 mm Hg
• • MAP ≥65 mm Hg
• • Urine Output ≥ 0.5 ml/kg/hr
• • Central Venous (SVC) or Mixed Venous
Oxygen Saturation 70% or 65% respectively
• In patients with elevated lactate, target to
decrease lactate
 Antibiotics
• Administration of effective intravenous antimicrobials
within the first hour of recognition of septic shock
• Antimicrobial regimen should be reassessed daily for
potential de-escalation
• Severe infections associated with respiratory failure and
septic shock (Pseudomonas) combination therapy :
extended beta lactam and
aminoglycosides/fluoroquinolones
• Empiric combination therapy should not be
administered for more than 3–5 days.
• Duration of therapy typically 7–10 days
• Antiviral therapy initiated as early as possible in patients
with severe sepsis or septic shock of viral origin
 Source control

• When source control in a severely septic

patient is required, the effective intervention
associated with the least physiologic insult
should be used (eg. percutaneous rather than
surgical drainage of an abscess)
• 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
 Fluid Therapy
• Crystalloid (RL, NS) as fluid @ 30 ml/kg
• Goal is to reach target MAP (≥ 65 mm Hg)
• Albumin: Used in fluid refractory septic shock and if >0.2
mcg/kg/min of Nor-adrenaline is required
• Dose: 100-200ml of 20% Human Albumin within 30-60
minutes.
• Fluid challenge technique be applied wherein fluid
administration is continued as long as there is
hemodynamic improvement either based on dynamic (eg,
change in pulse pressure, stroke volume variation) or static
(eg, arterial pressure, heart rate) variables
 Inotropes and vasopressors
• Target MAP ≥ 65 mm Hg .
• Noradrenaline 1 st Choice .
• Adrenaline: when additional agent is needed .
• Vasopressin 0.03 units-0.04 units/min: added to NE with
intent of either raising MAP or decrease Nor-adrenaline
dose (Salvage Therapy) .
• Low dose vasopressin not recommended .
• Dopamine: alternative to Nor-adrenaline only in selected
patients
• Patients with low risk of tachycardia or absolute relative
bradycardia.
• Phenylephrine: Not recommended except:
Norepinephrine is associated with serious arrythmias
• Cardiac output is known to be high as BP persistently low
• Dobutamine: Up to 20 mcg/kg/min in presence of:
Myocardial dysfunction as suggested by elevated cardiac
filling pressures and low cardiac output
• Ongoing signs of hypoperfusion, despite achieving
adequate intravascular volume and adequate MAP.
 Other Supportive Therapy

• 1. Infection Prevention:
• Limited patient contact
• Hand washing
• Prevent Ventilator associated pneumonia
• •Propped Up position
• Chlorhexidine mouth wash
• 2. Blood Products
• Once tissue hypoperfusion has resolved
• RBC transfusion only if Hb <7 g/dl
• NOT to use erythropoietin, antithrombin
• FFP not to be used to correct lab clotting abnormalities in
absence of bleeding or planned invasive procedure.
• Administer platelets prophylactically if:
• Platelets < 10,000/uL in absence of apparent bleeding
• Platelets < 20,000/uL if risk of bleeding
• Platelets < 50,000/uL if active bleeding, surgery
• No use of Selenium or Immunoglobulins
• Glucose Control
• If 2 consecutive blood glucose levels are >180 mg/dl, commence
insulin dosing
• Target: ≤ 180 mg/dl
• Glucose monitoring every 1-2 hours until glucose values and
insulin rates are stable and then every 4 hours thereafter.
• Bicarbonate:
• NOT to be used if pH ≥ 7.15
• Used after calculating deficit
• Shouldn't be corrected rapidly
• DVT Prophylaxis:
• Daily LMWH (Inj. Enoxaparin 40 mg SC OD)
• • If CrCl < 30 ml/min, use Dalteparin or another form of
LMWH that has low degree of renal metabolism.
• Graduated compression stockings or intermittent
compression devices
• 7. Stress Ulcer Prophylaxis:
• • H2 Histamine blocker
• • Proton Pump Inhibitors
• Nutrition:
• Oral or enteral feeding as tolerated within the
first 48 hours of diagnosis
• Low dose feeding(upto 500 calories/day) in
1st week, advancing only as tolerated.
• Use IV glucose and enteral nutrition rather
than TPN alone in first 7 days
 Sedation, Analgesia, and
Neuromuscular Blockade in Sepsis
• Continuous or intermittent sedation be minimized in
mechanically ventilated sepsis patients, targeting specific
titration endpoints .
• Neuromuscular blocking agents (NMBAs) be avoided if
possible in the septic patient without ARDS due to the risk
of prolonged neuromuscular blockade following
discontinuation.
• If NMBAs must be maintained, either intermittent bolus as
required or continuous infusion with train-of-four
monitoring of the depth of blockade should be used (grade
1C). °
• A short course of NMBA of not greater than 48 hours for
patients with early sepsis-induced ARDS and a Pao2/Fio2 <
150 mm Hg
THANKS