SEPSIS
PRESENTER: DR.B.N.SIREESHA
MODERATOR: DR.SHAILAJA
ASSISTANT PROFESSOR
DEPARTMENT OF ANAESTHESIOLOGY,
ASRAM MEDICAL COLLEGE

DEFINITIONS
INFECTION- When a pathogen is detected in blood
or tissue.
Bacteremia-presence of viable bacteria in the blood.
SIRS-Defined as the generalized inflammatory
response of the body to a variety of clinical
conditions including infection but not limited to
infection

Response manifested by 2 or more of following:
1. Temperature >38˚c or <36˚c.
2. Heart rate >90bpm
3. Respiratory rate >20 beats/min or paco2<32mmhg.
4. WBC >12,000 cells/mm3,<4000mm3 or >10%
immature (band) forms.

Definitions
 Sepsis-A life threatening condition caused by a dysregulated host
response to infection, resulting in organ dysfunction.
 Severe sepsis- progression of sepsis to organ dysfuntion ,tissue
hypoperfusion or hypotension.
 Septic shock-circulatory, cellular and metabolic abnormalities in
septic patients, presenting as fluid refractory hypotension requiring
vasopressor therapy with associated tissue
hypoperfusion(lactate>2mmol/L).

Definitions
 MULTIPLE ORGAN DYSFUNCTION SYNDROME(MODS)-
presence of altered organ function lasting for more than 24
hours in an acutely ill patients such that homeostasis cannot
be maintained without intervention.
 It is progressive dysfunction of 2 or more organs in acutely ill
patients in whom homeostasis cannot be maintained without
intervention

Risk factors
 elderly populations
 Increasing invasive devices and procedures
 In immunocompromised patients
 Use of cytotoxic drugs and immunosuppressant agents
 Malnutrition
 Alcoholism
 Malignancy
 DM

Risk factors
 Transplant recipients and transplantation procedures
 Community acquired and nosocomial infections
 Antibiotic resistance
 Burns ,wounds and multiple trauma

Source of infection
 Lung- strep pneumoniae, H influenzae,legionella sp,
chlamedia pneumoniae
 Abdomen-E coli, bacteriodes fragilis
 Skin & soft tissue- strep pyogenes, staphy aureus,clostridum
specis,
 UTI- E coli, klebsiella sp, enterobater sp .
 CNS- strep pneumoniae, N meningitidis,L monocytogenes, E
coli,H influenzae

Pathophysiology of sepsis
 Innate immunity and inflammatory mediators:
 The first step in the initiation of the host response to the
pathogen is the activation of innate immune cells,
constituted primarily by macrophages, monocytes,
neutrophils, and natural killer cells.
This occurs via the binding of pathogen-associated
molecular patterns (PAMPs), such as bacterial endotoxins
and fungal β-glucans to specific pattern recognition
receptors, on these cells.

pathophysiology
 These bind to specific receptors on monocytes and
macrophages such as toll-like receptors (TLRs),
C-type leptin receptors,
NOD-like receptors (nucleotide-binding oligomerization
domain) and
RIG-1 like receptors (retinoic acid inducible gene 1).
 This results in release of pro inflammatory cytokines like TNF
α, IL1 and IL 6.

PATHOPHYSIOLOGY
 Proinflammatory cytokines cause activation and proliferation
of leukocytes,
activation of the complement system,
upregulation of endothelial adhesion molecules
and chemokine expression,
tissue factor production,and
induction of hepatic acute phase reactants.

PATHOPHYSIOLOGY
Dysregulation of haemostasis:
 activation of both the inflammatory and the coagulation
cascades
 The hypercoagulability of sepsis is thought to be driven by the
release of tissue factor from disrupted endothelial cells (other
sources include monocytes and polymorphonuclear cells).
 Tissue factor then causes the systemic activation of the
coagulation cascade resulting in the production of thrombin,
activation of platelets, and formation of platelet–fibrin clots.

pathophysiology
 These microthrombi can cause local perfusion defects
resulting in tissue hypoxia and organ dysfunction.
 depression of the anticoagulant effects of protein C and
antithrombin.
 In patients with sepsis, there are decreased plasma levels of
protein C, downregulation of thrombomodulin, and low levels
of protein S
 There is reduction in fibrinolysis and fibrin removal resulting in
formation of microvascular thrombosis.

pathophysiology
Immunosupression:
 immune system in a septic individual is unable to stage an
effective immune response to secondary bacterial, viral, or
fungal infections.
Cellular, tissue and organ dysfunction:
 Organ dysfunction mainly due to hypoperfusion due to
cardiovascular dysfunction.
 TNFα and IL-1β , can cause depression of cardiac myocytes
and an interference with their mitochondrial function.

pathophysiology
 Second, the low left ventricular ejection fraction is
accompanied by normal or low left ventricular filling pressures
(unlike in cardiogenic shock) with increased left ventricular
compliance.
 arterial and venous dilation (induced by inflammatory
mediators) and consequent reduced venous return, a state of
hypotension and distributive shock is produced by sepsis.
 Along with there is microvascular thrombosis resulting in
hypoperfusion to tissues and organs.
 Increase in anaerobic glycolysis resulting in lactate
production.

pathophysiology
 The reactive oxygen species(ROS) causes dysregulation of
mitochondria and drop in ATP levels.
 There are significant alterations to the endothelium with
disruption of its barrier function, vasodilation, increased
leukocyte adhesion, and the creation of a procoagulant state.
This results in accumulation of edema fluid in the interstitial
spaces, body cavities, and subcutaneous tissue.

Clinical features

Severe sepsis
 Pathogenesis of sever sepsis depends upon infecting microbe
 Ability of host innate defense mechanisms to sense it
 Site of primary infection
 Presence or absence of immune defects
 Prior physiological status of host
 Genetic factors

Organ dysfunction
 Brains and kidneys are normally protected from swings in
blood pressure by autoregulation
 Late sepsis-vasoperesis occurs
 Autoregulation fails.

Septic shock and specific organ response
 Regional circulation
Altered blood flow
 Microcirculation
 Development of microthrombi
Decreased functional capillaries
Abnormal O2 utilization
Increased microvascular permeability

Specific organ response
 Lung:
V/Q mismatch
Hypoxemia
Increased microvascular permeability
Interstitial/alveolar edema
ARDS
 Gastrointestinal:
Impaired GI motility
Bacterial translocation >> MODS
Stress-ulcer GI bleeding
Hepatic dysfunction

Specific organ response
 Kidney:
 Altered renal function
 ATN/ acute renal failure
Increases mortality rate
 Neurologic:
 Encephalopathy
 Peripheral polyneuropathy
 Hematologic:
 Leukocytosis/leukopenia
 Thrombocytopenia
 Coagulopathy- DIC
 diffuse endothelial injury
 microvascular thrombi

Metabolic alterations in sepsis

Signs and symptoms
 Temperature ↑ or ↓
 WBC ↑ or↓
 Rigors
 Sweating
 Nausea and vomiting
 Tachycardia
 Hypotension
 Tachyapnea(ALI)
 Bounding pulse
 Confusion
 Oliguria and jaundice.

 Increase glucose
 Increase lactate
 Increasingly negative base excess
 Decreased albumin
 Increased INR, APTT,
 ↓ platelets.

Identifying high risk

Identifying high risk
q sofa:
 Respiratory rate at least 22 breaths/minute
 Systolic blood pressure 100 mm Hg or lower
 Altered mental status (Glasgow Coma Scale score < 15).
 A qSOFA score of 2 or more with a suspected or confirmed
infection was proposed as a trigger for aggressive treatment,
including frequent monitoring and ICU admission.
 qSOFA has the advantage of its elements being easy to
obtain in clinical practice.

Investigations
Basic
WBC
Platelets
Coagulation factors
Renal function
Glucose
Albumin
LFT
ABG
Specific ?Source
Urine
CxR
Blood Cultures x 2
LP
Aspirate
Biopsy

Diagnosis
 Before the initiation of antimicrobial therapy, at least two
blood cultures should be obtained
 Other cultures such as urine, cerebrospinal fluid, wounds,
respiratory secretions or other body fluids should be obtained
as the clinical situation dictates
 Other diagnostic studies such as imaging and sampling
should be performed promptly to determine the source and
causative organism of the infection

Biomarkers
 C-Reactive protein and erythrocyte sedimentation rate.
 Procalcitonin: has emerged as a method to help detect
bacterial infections early and to guide de-escalation or
discontinuation of antibiotics.
 Procalcitonin-guided de-escalation of antibiotics reduces
duration of antibiotic exposure.
 Galactomannan and beta-D-glucan can be used to detect
infections with fungi, specially Aspergillus. Beta-d-glucan is
more sensitive for invasive Aspergillus, while galactomannan
is more specific.

Biomarkers
 Cytokines such as interleukins (eg, IL-6, IL-8, IL-10), tumor
necrosis factor alpha,acute-phase proteins.
 The decision to initiate, escalate, and de-escalate therapy
should be based on clinical assessment, with procalcitonin or
other biomarkers used as an adjunct to other clinical factors.

Surviving Sepsis Campaign
 Guidelines for the management of severe sepsis and septic
shock.
 This include sepsis resuscitation bundle(3hour bundle) and
sepsis management bundle(6hour bundle).
 Therapeutic goals to be completed in 3 hours and 6 hours.
 In 2018 3 & 6 hour bundles are combined as Single 1 hour
bundle.

Lactate level as a resuscitation guide
 Lactate-guided resuscitation can significantly lessen the high
mortality rate associated with elevated lactate levels (> 4
mmol/L).
 A rise in lactate during sepsis can be due to tissue hypoxia,
accelerated glycolysis from a hyperadrenergic state,or liver
failure.
 Measuring the lactate level is an objective way to assess
response to resuscitation, better than other clinical markers,

Management
Antibiotic therapy:
 Start intravenous antibiotic therapy within the first hour of
recognition of severe sepsis after obtaining appropriate cultures
 Empirical choice of antimicrobials should include one or more
drugs with activity against likely pathogens, both bacterial or fungal
 Penetrate presumed source of infection
 Guided by susceptibility patterns in the community and
hospital
 Continue broad spectrum therapy until the causative
organism and its susceptibilities are defined

Management
 Reassess after 48-72 hours to narrow the spectrum of antibiotic
therapy
 Duration of therapy should typically be 7-10 days and guided by
clinical response .
ANTIFUNGAL:
 Antifungals should be considered for patients at risk, such as those
who have had total parenteral nutrition, recent broad-spectrum
antibiotic exposure, perforated abdominal viscus, or
immunocompromised status, or when clinical suspicion of fungal
infection is high

Source control
 Evaluate patients for focus of infection amenable to source
control measures
 Drainage of an abscess or local focus of infection
 Debridement of infected necrotic tissue
 Removal of a potentially infected device
 Definitive control of a source of ongoing microbial
contamination

Fluid resuscitation
 The goals of resuscitation in sepsis and septic shock are to restore
intravascular volume, increase oxygen delivery to tissues, and reverse
organ dysfunction.
 A crystalloid bolus of 30 mL/kg is recommended within 3 hours of
detecting severe sepsis or septic shock.
 Excess fluid administration can result in pulmonaryedema, hypoxemic
respiratory failure, organ edema, intra-abdominal hypertension,
prolonged ICU stay and time on mechanical ventilation, and even
increased risk of death.

Fluid resuscitation
 fluid resuscitation should be managed as follows during consecutive
phases:
 Rescue: During the initial minutes to hours, fluid boluses (a 1- to 2-L fluid
bolus of crystalloid solution) are required to reverse hypoperfusion and
shock
 Optimization: During the second phase, the benefits of giving additional
fluid to improve cardiac output and tissue perfusion should be weighed
against potential harms.
 Stabilization: During the third phase, usually 24 to 48 hours after the
onset of septic shock, an attempt should be made to achieve a net-neutral
or a slightly negative fluid balance
 De-escalation: The fourth phase, marked by shock resolution and organ
recovery, should trigger aggressive fluid removal

vasopressors
 Nor epinephrine: is the 1st line vasopressor.
 norepinephrine remains the preferred vasopressor for
achieving the target mean arterial pressure and is strongly
recommended by the Surviving Sepsis Campaign guidelines.
 A second vasopressor is routinely added when
norepinephrine doses exceed 40 or 50 μg/min.
 Vasopressin. Septic shock involves relative vasopressin
deficiency. Adding vasopressin as a replacement hormone
has been shown to have a sparing effect on norepinephrine,
resulting in a lower dose needed.

vasopressors
 Epinephrine is recommended by the Surviving Sepsis
Campaign guidelines as a second-line vasopressor. It has
potent alpha and beta-adrenergic activity, which increases
mean arterial pressure by increasing cardiac output and
vasomotor tone.
 Use of epinephrine is limited by significant risk of
tachycardia, arrhythmia, and transient lactic acidosis.
 Dopamine: particularly useful in patients with compromised
systolic function but causes more tachycardia and may be
more arrhythmogenic.
 Phenylephrine: used as adjunct for refractory vasodilatory
shock.

Inotropes
 Inotropic agents may be required for patients with inadequate
CO after fluid resuscitation due to sepsis induced
cardiomyopathy or combined shock
 Epinephrine and dobutamine are most commonly used.
 Response to use of inotropes should be monitored by
measuring change in CO and central venous oxygen
saturation.

corticosteroids
 Not recommended in sepsis or severe sepsis if fluid
resuscitation and vasopressors are sufficient to restore
hemodynamic stability
 If corticosteroids are used in septic shock,current guidelines
recommend hydrocortisone
 200 mg per day intravenously as a continuous drip or 50 mg
bolus in 4 divided doses. for at least 3 days,
 a longer course of low-dose steroids is associated with a
lower mortality rate

 Blood glucose correction: target 80 to 150mg/dl.
 Red cells, FFP and platelet: keep hemoglobin between 7 to 9
g/dl.
 FFP only to cover invasive procedures and surgery.
 Platelet transfusion to keep counts >50,000mm3 for invasive
procedure and surgery.
 Mechanical ventilation: limit tidal volume 6 to 8 ml/kg lean
mass and plateau pressure<30cm h20.
 Hemodialysis: Support for acute renal failure by continuous
veno venous hemo filteration.

Deep vein thrombosis prophylaxis
 DVT prophylaxis with either low-dose unfractionated heparin
or low molecular weight heparin should be used in severe
sepsis patients
 Use a mechanical prophylactic device or intermittent
compression in patients with contraindications to heparin
 Use a combination of pharmacological and mechanical
therapy in very high risk patients (eg, severe sepsis and
history of DVT).

Strees ulcer prophylaxis
 Stress ulcer prophylaxis should be given to all patients with
severe sepsis
 H2 receptor blockers are more efficacious than sucralfate and
are the preferred agents

Thank you