This document provides an overview of septic shock, including its pathophysiology and management. It begins with historical context and then covers epidemiology, predisposing conditions, pathophysiological mechanisms mediated by cytokines like TNF-α, and the core principles of resuscitation and treatment, including early antibiotics, fluid resuscitation, and vasopressors if needed. Poor prognostic factors are advanced age, resistant organisms, impaired immunity, and continued vasopressor need beyond 24 hours. Morality remains high despite management advances.

1. Pathophysiology and
management of septic shock
Dr Adegoke K.T. Adeniyi
Registrar

2. Outline
• Introduction
• Historical background
• Epidemiology
• Pathophysiology
• Management
• Conclusion
• References

3. Introduction
It’s a clinical picture of failing cellular function
resulting from oxygen lack emanating from
poor tissue perfusion

4. Introduction
• The concept and the understanding of “sepsis” has
evolved over time as the medical knowledge of sepsis
pathophysiology, aetiological factors, and clinical
progression have increased and improved
• The first consensus definition of sepsis, Sepsis-1,
developed in 1991, was based on systemic
inflammatory response syndrome (SIRS) criteria in
response to infection and defined sepsis according to
severity, that is, sepsis, severe sepsis and septic shock .
Although the term “severe sepsis” was used to
describe sepsis complicated by organ dysfunction, the
Sepsis-1 definition did not state what constituted organ
dysfunction

5. Introduction
• The Sepsis-1 definition was subsequently revised in
2001 (Sepsis-2) and the term “severe sepsis” became
“sepsis complicated by organ dysfunction”.
• Furthermore, Sepsis-2 produced an expanded list of
symptoms, signs and laboratory values that could
indicate sepsis in the presence of infection and
suggested that scoring systems (for example, the
multiple organ dysfunction syndrome and the
Sequential Organ Failure Assessment [SOFA] score)
could be used to define organ dysfunction (

6. Introduction
• Nevertheless, there was little discernible difference
between the Sepsis-1 and -2 definitions as signs,
symptoms and/or laboratory values defined by the
Sepsis-2 definition were considered too ambiguous.
• The most recent definition of sepsis, Sepsis-3, was
developed in 2016 and defines sepsis as “life-
threatening organ dysfunction caused by a
dysregulated host response to infection”, where organ
dysfunction is identified as an acute increase in the
total SOFA score of two or more due to infection

7. Introduction
• SOFA score
• Used to define organ dysfunction

8. Introduction
• Septic shock: a subset of sepsis in which
particularly profound circulatory, cellular and
metabolic abnormalities are associated with a
greater risk of mortality than with sepsis
alone. Source: Singer M, et al. The Third
International Consensus Definitions for Sepsis
and Septic Shock (Sepsis-3). JAMA.
2016;315(8):801-10

9. Historical background
19th century Claude Bernard and Walter B
Cannon Maintenance of state of homeostasis;
Internal millieu
• Failure of physiologic systems to buffer the
organism against external forces result in
organ and cellular dysfunction

10. Epidemiology
• A recent global study reported 49 million cases
and 11 million sepsis-related deaths in 2017,
accounting for approximately 20% of all annual
deaths globally. [global burden of disease sepsis
study]
• Hospital mortality rate of sepsis was estimated to
be 27% from a systematic review of the literature
and mortality is estimated to be 42% in intensive
care patients treated for sepsis.

11. Epidemiology
• Among adult sepsis survivors, one in three
died within a year and one in six experienced
significant, long-term morbidity
• While sepsis can affect any individual
worldwide, significant regional disparities in
incidence and mortality exist with the highest
rates in lower-middle-income countries
(LMICs).

12. Epidemiology
• Sepsis and septic shock occur at all ages.
• However, a strong correlation exists between
advanced age and the incidence of septic shock,
with a sharp increase in the number of cases in
patients older than 50 years.
• Epidemiologic data have shown that the age-
adjusted incidence and mortality rate are
consistently greater in men;
• the percentage of affected male patients ranges
from 52% to 66%.

13. Epidemiology
• With regard to ethnicity, one large epidemiologic
study showed that the risk of septicemia in the
nonwhite population is almost twice that in the
white population, with the highest risk accruing
to black men.
• Potential reasons for this difference in surgical
patients include issues relating to decreased
access to health care, delayed presentation to
appropriate healthcare facility and increased
prevalence of underlying medical conditions.

14. Epidemiology
• Mortality figures for sepsis and septic shock have
commonly been quoted as ranging from 20% to
50%.
• Clinical trials from the past decade have found
the mortality associated with septic shock to
range from 24% to 41%.
• one report noted that crude hospital mortality
for severe sepsis was significantly lower in the
United States (28%) than in Europe (41%),

15. Epidemiology
• Factors consistently associated with increased
mortality in sepsis include advanced age,
comorbid conditions, and clinical evidence of
organ dysfunction

16. Predisposing conditions in shock
Gut Obstruction, Gangrene, Inflammation,
Per- foration, Operation
Peritoneum Peritonitis, Abscess
Biliary tract Cbolecystitis, cholangitis ,operation
Urinary tract Infection, Obstruction Instrumentation,
Operation
Female genital tract Abortal sepsis, peurperial sepsis , PID
Operation
Respiratory tract Pneumonia, Mediastinitis Tracheostomy
with IPPV
Vascular system Venous cuts, Indwelliig catheters
Others Hypovolaemia, Burns, Severe injuries Skin
or soft tissue infection, Acute pancreatitis,
Gangrene, Immunosuppressioo
Agranulocytosis, Leukemia

17. Pathophysiology
• The initial physiologic responses in shock are
driven by tissue hypoperfusion and the
developing cellular energy deficit.
• This imbalance between cellular supply and
demand leads to neuroendocrine and
inflammatory responses, the magnitude of
which is usually proportional to the degree
and duration of shock.

18. Pathophysiology
• Septic shock is mediated mainly by Tumour
Necrosis Factor (TNF)-a, a 17,000 MW
polypeptide cytokine,
• synthesized and secreted by activated
macrophages, monocytes and T-lymphocytes, but
also by activated Factor xii and Complement
Components.
• These mediators are also involved in
inflammation. The magnitude of TNF release
determines the occurrence, severity and duration
of shock.

19. Pathophysiology
• It binds to specific receptors found on most
tissues, especially the Reticuloendothelial cells
and endothelium of the renal, pulmonary and
hepatic organs.
• The stimulus to TNF production and activation of
Factor xii and complement is endotoxin
(lipopolysaccharide especially the lipid A moeity)
in the cell-wall which is released on the death of
gram-negative bacteria, or teehnoic acid and
peptidoglycan residues released from the cell-
wall of gram-positive bacteria.

20. Pathophysiology
• Direct TNF activity on various cells and also
through activation of the cyclo-oxygenase
andlipo-oxygenase pathways result in release of
secondary mediators.
• prostaglandins, especially PGI, (a potent
vasodilator), thromboxane A2, histamine, kinins,
serotonins, leukotrienes, platelet activator factor
(PAF),
• products of complement activation (C3a. C5a), IL-
l and IL-6

21. Pathophysiology
End point and entry point to shock includes
• Damage of vascular endothelium ;
extravasation of fluid
• Vasodilatation of microcirculation ; peripheral
pooling of blood
• Activation of Neutrophils; release of
inflamatory factors causing vicious cycle of
endothelial damage
• Diminished force of cardiac action

22. Management
• Recognizing septic shock begins with defining the patient at
risk. Which includes history taking and clinical examination
• The clinical manifestations of septic shock will usually
become evident and prompting the initiation of treatment
before bacteriologic confirmation of an organism or the
source of an organism is identified.
• In addition to fever, tachycardia, and tachypnea, signs of
hypoperfusion such as confusion, malaise, oliguria, or
hypotension may be present. These should prompt an
aggressive search for infection, including a thorough
physical examination, inspection of all wounds, evaluation
of intravascular catheters or other foreign bodies

23. History taking
• Biodata
• Presenting complaint
• History of presenting complaint
• Past medical and surgical history
• Drug history
• Family and social history

24. Physical examination
The physical examination should first involve
assessment of the patient’s general condition,
including :
assessment of airway, breathing, and circulation
(ie, the ABCs), as well as mental status.
An acutely ill, flushed, and toxic appearance is
observed universally in patients with serious
infections

25. Physical examination
The following physical signs help localize the source of an infection:
• Abdominal and GI infections – Abdominal distention, localized
tenderness, guarding or rebound tenderness, and rectal tenderness
or swelling
• Pelvic and GU infections – Costovertebral angle tenderness, pelvic
tenderness, pain on cervical motion, adnexal tenderness or masses,
and cervical discharge
• Bone and soft-tissue infections – Focal erythema, edema,
tenderness, crepitus in necrotizing infections, fluctuance, pain with
joint range of motion, and joint effusions and associated warmth or
erythema
• Skin infections – Petechiae, purpura, erythema, ulceration, bullous
formation, and fluctuance

26. Continued
• Central nervous system (CNS) infection – altered
consciousness and signs of meningismus (neck
stiffness)
• Head and neck infections – Inflamed or swollen
tympanic membranes, sinus tenderness, nasal
congestion or exudate, pharyngeal erythema and
exudates, inspiratory stridor
• Pulmonary infections – Dullness on percussion,
bronchial breath sounds, localized rales, or any
evidence of consolidation
• Cardiac infections – Any new murmur, especially in
patients with a history of injection or IV drug use

27. Investigations
Work up
• complete blood count
• Coagulation studies
• Blood chemistries
• Microbiological studies
• Radiological studies

28. Treatment
1. Resuscitation
2. Definitive treatment

29. Treatment
• Core principles in the management of patients in
septic shock include:
(a) septic shock is an emergency, and
treatment/resuscitation should begin as early as
possible;
(b) specific anatomic diagnosis of infection
requiring emergent source control be identified or
excluded as rapidly as possible and that any
required source control intervention be
implemented as soon as medically and logistically
practical;

30. Continued
• (c) initiation of broad spectrum antibiotics
within 1 hour of diagnosis;
• (d) in the resuscitation from sepsis-induced
hypoperfusion, at least 30 mL/kg of
intravenous crystalloid fluid be given within
the first 3 hours, and additional fluids be
guided by frequent reassessment of
hemodynamic status;

31. Continued
• (e) vasopressors (norepinephrine) should be
added to achieve a mean arterial pressure of
65 mmHg if fluid resuscitation is inadequate

32. Resuscitation
Septic shock is a life threatening condition requiring prompt
and aggressive resuscitation
Surviving Sepsis Campaign bundles of care to be initiated
within the first hour after presentation in the patient with
sepsis
• Measure serum lactate level. Obtain blood culture prior to
administration of antibiotics. Rapid administration of 30
mL/kg crystalloid for hypotension or lactate ≥4 mmol/L
• Administer broad spectrum antibiotics
• Use vasopressors if the patient is hypotensive during or
after fluid resuscitation to maintain a mean arterial
pressure ≥65 mmHg

33. Resuscitation
• After first-line therapy of the septic patient
with antibiotics, IV fluids, and intubation if
necessary, vasopressors may be necessary to
treat patients with septic shock.
• Catecholamines are the vasopressors used
most often, with norepinephrine being the
first-line agent followed by epinephrine

34. Resuscitation
• The majority of septic patients normal cardiac
output and low systemic vascular resistance.
• On occasion, septic patients may have low
cardiac output despite volume resuscitation
and even vasopressor support.
• Dobutamine therapy is recommended for
patients with cardiac dysfunction

35. Definitive treatment
• Source control; surgery as soon as possible
and when required for control of source of
infection If a septic focus, e.g.. gangrenous
bowel, is responsible for the shock, then it
must be dealt with as soon as practicable
especially if response to shock therapy is poor.

36. Differentials
• Acute kidney injury
• Diabetic ketoacidosis
• Disseminated intravascular coagulation
• Other forms of shock
• Heat stroke
• Pulmonary embolism
• Blood transfusion reaction

37. Recent advances in treatment
• Monoclonal antibodies to TNF, &l, L6:
• Clinical trials are awaited before this form of
treatment is introduced.
• Theoretically, it will be useful in septic shock of
gram negative and gram-positive organisms.
• Recombinant interleukin- l receptor antagonist
has been shown experimentally to reduce the
mortality significantly when infused soon after
the induction of septicaemia

38. Prognosis
• Mortality in this group is high.
• Despite the increasing incidence of septic shock
over the past several decades, the overall
mortality rates have changed little.
• Studies of interventions, including
immunotherapy, resuscitation to pulmonary
artery endpoints with hemodynamic optimization
(cardiac output and O2 delivery, even to
supranormal values), and optimization of mixed
venous O2 measurements up to 72 hours after
admission to the ICU, have not changed mortality

39. Prognosis
• Poor prognostic factors included the following:
• Advanced age
• Infection with a resistant organism
• Impaired host immune status
• Poor prior functional status
• Continued need for vasopressors past 24 hours
• Development of sequential organ failure, despite
adequate supportive measures and antimicrobial
therapy

40. Causes of death in shock
Causes of death in shock
1. Pulmonary insufficiency
2. Cardiac failure/arrest
3. Cerebral failure
4. Re-renal failure/ATN
5. Metabolic acidosis

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