The management of sepsis and septic shock.

1. SEPSIS AND SEPTIC SHOCK
For mbbs 500 level

2. • In the United States, recent cohort studies
using administrative data suggest that
upwards of 2 million cases of sepsis occur
annually.
• The incidences of sepsis and septic shock are
also reported to be increasing (according to
ICD9-CM diagnosis and procedure codes),
with a rise of almost 50% in the past decade.

3. • Its impact on the populations of low- and
middle-income countries is probably even
more substantial because of the increased
incidence of infectious diseases and the high
prevalence of HIV in some parts of the
developing world.

4. Definition
Several definitions over time.
.1991/2003- documented /suspected infection +
presence of at least 2 of the SIRS criteria.
SEVERITY:
Severe sepsis
MODS
Septic shock

5. • Sepsis Definitions Task Force in 2016 :
• Sepsis is a dysregulated host response to
infection that leads to acute organ
dysfunction.
• A life-threatening organ dysfunction caused by
a dysregulated host response to infection

6. • Case–fatality rates in low- and middle-income
countries are also higher than those in high-
income countries, as exem-plified by two
observational cohorts in Brazil with mortality
rates >40%

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

8. Aetiology
• Sepsis can arise from both community-
acquired and hospital-acquired infections.
• Of these infections, pneumonia is the most
common source, accounting for about half of
cases; next most common are intraabdominal
and genitourinary infections.
• Blood cultures are typically positive in only
one-third of cases, while many cases are
culture negative at all sites.

9. • Staphylococcus aureus and Streptococcus
pneumoniae are the most common gram-
positive isolates, while Escherichia coli,
Klebsiella species, and Pseudomonas
aeruginosa are the most common gram-
negative isolates.

10. Risk factors
• Common risk factors for increased risk of
infection include chronic diseases (e.g., HIV
infection, chronic obstructive pulmonary
disease, cancers) and immunosuppression.
• Age, sex, and race/ethnicity all influence the
incidence of sepsis.

11. SEPSIS PATHOGENESIS
• For many years, the clinical features of sepsis
were considered the result of an excessive
inflammatory host response (SIRS).
• it has become apparent that infection triggers
a much more complex, variable, and
prolonged host response than was previously
thought.

12. • The specific response of each patient depends on
the pathogen (load and virulence) and the host
(genetic composition and comorbidity), with
different responses at local and systemic levels.
• Generally, proinflammatory reactions (directed at
eliminating pathogens) are responsible for
“collateral” tissue damage in sepsis, whereas anti-
inflammatory responses are implicated in the
enhanced susceptibility to secondary infections
that occurs later in the course.

13. • These mechanisms can be characterized as an
interplay between two “fitness costs”: direct
damage to organs by the pathogen and
damage to organs stemming from the host’s
immune response. The host’s ability to resist
as well as tolerate both direct and
immunopathologic damage will deter-mine
whether uncomplicated infection becomes
sepsis.

14. • Pathogens activate immune cells by an
interaction with pattern recognition receptors.
• Toll-like receptors (TLRs), RIG-I-like receptors, C-
type lectin receptors, and NOD-like receptors.
• The recognition of structures conserved across
microbial species—so-called pathogen-associated
molecular patterns (PAMPs)—by all these
receptors results in upreg-ulation of
inflammatory gene transcription and initiation of
innate immunity.

15. • A common PAMP is the lipid A moiety of
lipopolysaccha-ride (LPS or endotoxin) which
attaches to the LPS-binding protein on the
surface of monocytes, macrophages, and
neutrophils. LPS is trans-ferred to and signals
via TLR4 to produce and release cytokines
such as tumor necrosis factor that grow the
signal and alert other cells and tissues

16. • At the same time, these receptors also sense
endogenous molecules released from injured
cells—so-called damage-associated molecular
patterns (DAMPs). In addition to activating the
proinflammatory cytokines, the inflammatory
responses implicated in the pathogenesis of
sepsis also activate the complement system,
platelet-activating factor, arachidonic acid
metabolites, and nitric oxide

17. Organ dysfunction
• Sepsis is commonly associated with
coagulation disorders and frequently leads to
disseminated intravascular coagulation.
• Abnormalities in coagulation are thought to
isolate invading microorganisms and/or to
prevent the spread of infection and
inflammation to other tissues and organs.
Excess fibrin deposition is driven by
coagulation via tissue factor.

18. ORGAN DYSFUNCTION
• impaired tissue oxy-genation plays a key role.
Several factors contribute to reduced oxygen
delivery in sepsis and septic shock, including
hypotension, reduced red-cell deformability,
and microvascular thrombosis.
• Inflammation can cause dysfunction of the
vascular endothelium,

19. • An excessive and uncontrolled release of nitric
oxide causes vasomotor collapse, opening of
arteriovenous shunts, and pathologic shunting
of oxygenated blood from susceptible tissues.
With severe or prolonged insult, ATP levels fall
beneath a critical threshold, bioenergetic
failure ensues, toxic reactive oxygen species
are released, and apoptosis leads to
irreversible cell death and organ failure.

20. • Two of the most commonly affected organ
systems in sepsis are the respiratory and
cardiovascular systems.
• Respiratory compromise classically manifests
as acute respiratory distress syndrome (ARDS),
defined as hypoxemia and bilateral infiltrates
of non-cardiac origin that arise within 7 days
of the suspected infection.

21. • ARDS can be classified by Berlin criteria as
mild (PaO2/FiO2, 201–300 mmHg),
moderate (101–200 mmHg),
severe (≤100 mmHg).

22. • Cardiovascular compromise typically presents
as hypotension. The cause can be frank
hypovolemia, maldistribution of blood flow
and intravascular volume due to diffuse
capillary leakage, reduced systemic vascular
resistance, or depressed myocardial function.

23. • Kidney Injury
• Acute kidney injury (AKI) is documented in
>50% of septic patients, increasing the risk of
in-hospital death by six- to eightfold.
• AKI manifests as oliguria, azotemia, and rising
serum crea-tinine levels and frequently
requires dialysis.

24. • Neurologic Complications:
Typical central nervous system dys-function
presents as coma or delirium.
Critical-illness polyneuropathy and myopathy
are also common, especially in patients with a
prolonged course.

25. • Many other abnormalities occur in sepsis,
including ileus, elevated aminotransferase
levels, altered glycemic control,
thrombocytopenia and disseminated
intravascular coagulation, adrenal dysfunction,
and sick euthyroid syndrome.

26. DIAGNOSTIC CRITERIA
• NO SPECIFIC TEST FOR SEPSIS.
• INFECTION-documented or suspected.
Dysregulated response
• Organ dysfunction or failure/threat to life.

27. • Infection + SIRS
• SIRS is defined as two or more of the following
variables:
• Fever of more than 38°C (100.4°F) or less than 36°C
(96.8°F)
• Heart rate of more than 90 beats per minute
• Respiratory rate of more than 20 breaths per minute or
arterial carbon dioxide tension (PaCO 2) of less than 32
mm Hg
• Abnormal white blood cell count (>12,000/µL or <
4,000/µL or >10% immature [band] forms

28. Sequential organ failure assessment
(SOFA) Score
• Latest assessment for presence /severity of sepsis.
• Makes use of following parameters each of which
carries a score of 0-4 depending on degree of
dysfunction/failure.
• Systolic blood pressure
• Serum creatinine
• PaO2/FiO2ratio
• Platelets
• Glasgow coma scale
• Bilirubin

29. • Quick Sequential Organ Failure Assessment
q(SOFA) score
• qSOFA (Quick SOFA) Criteria Points
• Respiratory rate ≥ 22/min 1
• Change in mental status 1
• Systolic blood pressure ≤100 mmHg 1
• Score ≥ 2 predictive of sepsis.

30. Shock
• The presence of multisystem end-organ
hypoperfusion. The end result of multiorgan
hypoperfusion is tissue hypoxia,
• Clinical indicators include reduced mean
arterial pressure (MAP), tachycardia,
tachypnea, cool skin and extremities, acute
altered mental status, and oliguria.
Hypotension is usually, though not always,
present.

31. • Clinical evidence of diminished cardiac output
includes a narrow pulse pressure (systolic BP
minus diastolic BP)—a marker that correlates
with stroke volume—and cool extremities
with delayed capillary refill.

32. • Signs of increased cardiac output include a
widened pulse pressure (particularly with a
reduced diastolic pressure), warm extremities
with bounding pulses, and rapid capillary refill.
If a hypotensive patient has clinical signs of
increased cardiac output, it can be inferred
that the reduced blood pressure is from
decreased SVR

33. Types of shock
• Distributve- septic, anaphylactic
• Obstructive- cardiac tamponade, constrictive
pericarditis, pulmonary embolism.
• Cardiogenic- myocardia infarction.
• Hypovolemic- volume loss
• Mixed shock- combination.

34. Septic shock 2016 criteria
• Suspected (or documented) infection plus
vasopressor therapy needed to maintain mean
arterial pressure at ≥65 mmHg and serum
lactate >2.0 mmol/L despite adequate fluid
resuscitation.
Subset of sepsis.

35. • For clarity, criteria are proposed for septic
shock that include (1) sepsis plus (2) the need
for vasopressor therapy to elevate mean
arterial pressure to ≥65 mmHg, with (3) a
serum lactate concentration >2.0 mmol/L
after adequate fluid resuscitation.

36. treatment
• Diagnosis
Initial management:
• Laboratory samples-cultures,
• serum lactate
• Empirical antibiotics therapy within 1hr
• Control source of infection

37. • The management bundle includes
(1) an intravenous fluid bolus 30ml/kg within
first 3hrs,
(2) treatment with vasopressors for persistent
hypotension or shock- norepinephrine (first
choice), dobutamine.
(3) Re-measurement of serum lactate levels

38. others
• Oxygen therapy
• Mechanical ventilation
• Glucose mgt
• Blood transfusion
• Dvt prophylaxis
• Steroids ??
• Stress Ulcer prophylaxis
• Renal management
• Monitoring of response.

39. prognosis
• mortality rates for septic shock often exceeded 80% as
recently as 30 years ago
• with advances in training, surveillance, moni-toring,
and prompt initiation of supportive care for organ
dysfunction, the mortality rate from sepsis and septic
shock is now closer to 20% in many series
• Patients who survive to hospital discharge after sepsis
remain at increased risk of death in the following
months and years.

40. prevention
• The number of cases could be reduced by
avoiding unnecessary antibiotic use, limiting
use of indwelling devices and catheters,
minimizing immune suppression when it is not
needed, and increasing adherence to infection
control programs at hospitals and clinics.
earlier treatment,