APPROACH TO SEPSIS

AND SEPTIC SHOCK

MANAGEMENT

• Prepared and Presented By Dr.Ermias

Getachew (GP).
 OUTLINE

 Introduction.
 Investigation
 Sepsis screening tool.
 Treatment
 Predisposing Factor
 Complication
 Etiology.
 Prognosis.
 Pathogenesis
 Prevention.
 Clinical Manifestation
 References.
 Diagnosis

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 INTRODUCTION

Sepsis is life-threatening organ dysfunction caused

by a dysregulated host response to infection
Septic shock is a type of vasodilatory or distributive
shock and defined as sepsis that has circulatory,
cellular, and metabolic abnormalities that are
associated with a greater risk of mortality than
sepsis alone.

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 Con’t…

 Sepsis in children is operationalized as a Phoenix

Sepsis Score of at least 2 points from a composite
four-organ system model that includes criteria for
respiratory, neurologic, coagulation, and
cardiovascular dysfunction,
 septic shock is sepsis with at least 1 point in the
cardiovascular sub score.

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 ORGAN DYSFUNCTION

 Organ dysfunction is defined as SOFA score ≥ 2

 SOFA score is an organ dysfunction score.
 The SOFA score is widely studied in the ICU among
patients with infection, sepsis, and shock.
 With ≥2 new SOFA points, the infected patient is
considered septic and may be at ≥10% risk of in-hospital
death

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Mar 12, 2025 8
 SCREENING AND EARLY
TREATMENT

 Sepsis screening tools are designed to promote early

identification of sepsis and consist of manual methods.
 systemic inflammatory response syndrome (SIRS) criteria,
 quick Sequential Organ Failure Score (qSOFA)
 National Early Warning Score (NEWS),
 Modified Early Warning Score (MEWS)

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 Con’t…

Mar 12, 2025 10

 Drawback of SIRS
 SIRS lacks sensitivity to
define sepsis.
 SIRS is not specific to
sepsis because had non
infections causes.
 SIRS does not reflect the
severity of disease
process.
 Only one third of patient
with >2 SIRS score have
underlying infection.
Mar 12, 2025 11
 Con’t….
 To aid in early identification of infected patients, the quick
SOFA (qSOFA) and the National Early Warning Score
(NEWS) scores are proposed as clinical prompts to identify
patients at high risk of sepsis outside the ICU.
 The qSOFA score ranges from 0 to 3 points, with 1 point
each for systolic hypotension (≤100 mmHg), tachypnea
(≥22 breaths/min), or altered mentation.
 A qSOFA score of ≥2 points has a predictive value for
sepsis similar to that of more complicated measures of
organ dysfunction.

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 Con’t….
 The National Early
Warning Score (NEWS)
is an aggregate scoring
system derived from
six physiologic
parameters, including
respiratory rate,
oxygen saturation,
systolic blood pressure,
heart rate, altered
mentation, and
temperature.
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 RISK FACTORS
Age<1 year or >65 years  Pregnancy
Immunosuppression:-  Postpartum women
DM and Obesity  Post abortion or
Community acquired miscarriage
infection  Bacteremia,
Previous hospitalization  people with indwelling
ICU admission lines or catheters

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 ETIOLOGY

 Sepsis can arise from both community-acquired and

hospital-acquired 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.

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 Con’t…

 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 isolate.

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 PATHOPHYSIOL
OGY

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 TRANSITION TO SEPSIS

 Sepsis occurs when the release of

proinflammatory mediators in response to an
infection exceeds the boundaries of the local
environment, leading to a more generalized
response.

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 SYSTEMIC EFFECTS OF SEPSIS

 Tissue ischemia
 Cytopathic injury…Mitochondrial dysfunction.
 Altered Cell death pathways
 Mitochondrial dysfunction in sepsis-induced multiple organ
failure
 Immunosuppression
 Activation of coagulation system and vascular endothelium

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 PATHOGENESIS

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 CLINICAL PRESENTATION

Patients with suspected or documented sepsis

typically present with hypotension, tachycardia,
fever, and leukocytosis.
As severity worsens, signs of shock (e.g., cool skin
and cyanosis) and organ dysfunction may develop.
Importantly, the presentation is nonspecific such
that many other conditions may present similarly

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 Con’t…

 The symptoms and signs of sepsis are nonspecific but may

include the following:
 Symptoms and signs specific to an infectious source.
 Temperature >38.3 0r <36
 Tachycardia.
 Tachypnea.
 Hypotension.
 Sign of organ dysfunction.
Mar 12, 2025 23
 Con’t….
 Signs of end-organ perfusion.
 Warm, flushed skin may be present in the early phases of sepsis.
 As sepsis progresses to shock, the skin may become cool due to
redirection of blood flow to core organs.
 Decreased capillary refill, cyanosis, or mottling may indicate
shock.
 Additional signs of hypoperfusion include altered mental status,
obtundation or restlessness, and oliguria or anuria.
 Ileus or absent bowel sounds are often an end-stage sign of
hypoperfusion.
Mar 12, 2025 24
 Con’t….

 These findings may be modified by preexisting disease or

medications. As examples, older patients, diabetic patients,
and patients who take beta-blockers may not exhibit an
appropriate tachycardia as blood pressure falls.
 In contrast, younger patients frequently develop a severe
and prolonged tachycardia and fail to become hypotensive
until acute decompensation later occurs, often suddenly.
 Patients with chronic hypertension may develop critical
hypoperfusion at a higher blood pressure than healthy
patients (ie, relative hypotension).
Mar 12, 2025 25
 DIAGNOSIS

a constellation of clinical, laboratory, radiologic,

physiologic, and microbiologic data is typically
required for the diagnosis of sepsis and septic
shock.
laboratory features are nonspecific and may be
associated with abnormalities due to the
underlying cause of sepsis or to tissue
hypoperfusion or organ dysfunction from sepsis.

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Mar 12, 2025 28
 LABORATORY FINDING.

 Leukocytosis or leukopenia.
 Normal WBC count with greater than 10 percent immature forms.
 Hyperglycemia .
 PaO2/ FiO2 <300.
 Acute oliguria or Creatinine increase >0.5 mg/dL above baseline.
 Coagulation abnormalities ( INR >1.5 or aPTT >60 seconds).
 Thrombocytopenia platelet <100,000.
 Hyperbilirubinemia (plasma total bilirubin >4 mg/dl.

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 MANAGEMENT

 ABC of life.
 Secure bilateral IV line.
 Administer rapid IV boluses
 If hemodynamic response to IV fluids is inadequate or
constrained by fluid overload (e.g., heart failure) administer
vasopressor.
 Antimicrobial medication.
 Transfuse if Hg <7 mg/dl.
 Additional Managements and therapy .

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 BUNDLE OF CARE
 The treatment elements listed above form the basis for a 1-h
bundle of care, replacing the previous guidelines
recommending treatment initiation within 3−6 h.
 This management bundle includes five components:
 measurement of serum lactate levels,
 collection of blood for culture before antibiotic administration,
 administration of appropriate broad-spectrum antibiotics,
 initiation of a 30 mL/kg crystalloid bolus in adult or 20ml/kg in
pediatrics for hypotension or lactate ≥4 mmol/L, and
 treatment with vasopressors for persistent hypotension or
shock.

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Mar 12, 2025 32
 IV FLUID THERAPY
 Rapid infusions of IVF (30 mL/kg) are indicated as initial
therapy for septic shock unless there is convincing
evidence of significant pulmonary edema.
 The clinical and hemodynamic response and the
presence or absence of pulmonary edema should be
assessed before and after each bolus.
 Fluid resuscitation should stop if pulmonary edema
ensues or if further fluid administration fails to
augment perfusion.
 In children’s 20ml/kg as fast as possible (up to
60ml/kg/hr).
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 CHOICE OF FLUID

 Balanced crystalloid rather than normal saline is

preferred if there is a perceived need to avoid or
treat the hyperchloremia that occurs when large
volumes of nonbuffered crystalloid (e.g., normal
saline) are administered.
 Albumin in patients who received large volume of
crystalloids.

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Mar 12, 2025 35
 PEDIATRIC
SEPTIC
SHOCK
ALGORITHM

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 THE GOAL OF INITIAL
RESUSCITATION.

CVP:- 8 to 12 mmHg or 12-15 mmHg in intubated

patient.
MAP :->=65 mmHg.
Urine Output >=0.5 ml/kg/hr. or above 1ml/kg/hr. in
children.
Central venous oxyhemoglobin saturation >=70%.
Hematocrit >=30%.

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 Clinical signs of successful
resuscitation

 Decrease in HR and respiratory rate,

 Increase in BP or MAP
 Improved urine output to >0.5 mL/ kg/hr.
 Normalization of mental status,
 Decreased capillary refill time,
 warmth of distal extremities, and improved peripheral
pulses.
 Rise in Svo2 to >70% and sao2>94% in adult with
heathy lungs.
 Decreasing in blood lactate levels
Mar 12, 2025 38
 EMPIRICAL ANTIMICROBIAL
THERAPY.
 The choice of antimicrobials depends on the following
factors:-
 The patient's history (e.g., recent antibiotics received,
previous organisms),
 comorbidities (e.g., diabetes, organ failures),
 immune defects (e.g., human immune deficiency virus),
 clinical context (e.g., community- or hospital-acquired),
 suspected site of infection,
 presence of invasive devices,
 Gram stain data, and local prevalence and resistance
Mar 12, 2025 patterns. 39
 Con't…
 For most patients, it’s recommended that empirical broad
spectrums therapy with one or more antimicrobials activity
should started to cover all likely pathogens.
 Broad spectrum is defined as therapeutic agent(s) with
sufficient activity to cover a range of gram-negative and
gram-positive organisms.
 Among organisms isolated from patients with sepsis, the most
common include Escherichia coli, Staphylococcus aureus,
Klebsiella pneumoniae, and Streptococcus pneumoniae, such
that coverage of these organisms should be kept in mind
when choosing an agent.
Mar 12, 2025 40
 RISK FACTOR FOR P-
AERUGINOSA

 Bronchiectasis or structural lung diseases.

 Profound neutropenia
 SAM patient
 Hx of hospitalization in last 90 days.
 Patient on chronic hemodialysis.
 Immunosuppressive patients.
 Long term therapy with corticosteroid.
 Hx of prior isolation
Mar 12, 2025 41
 If Pseudomonas is If Pseudomonas is a
unlikely pathogen, likely pathogen
 Combine vancomycin Combine vancomycin with one
with one of the of the following:-
following:- Antipseudomonal
 Ceftriaxone or cephalosporin (e.g., ceftazidime,
cefepime.
cefotaxime or Cefepime.
Antipseudomonal carbapenem
 Beta-lactamase inhibitor. (e.g., imipenem, meropenem.
 A carbapenem (eg, Ciprofloxacin
imipenem or Monobactam (e.g., aztreonam).
meropenem).

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 Con’t…

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Mar 12, 2025 44
 Con’t…

Antibiotic delay may be deadly. For every 1-h delay

among septic patients, a 3−7% increase in the
odds of in-hospital death is reported.
Antibiotics that has anti anaerobic coverage
includes :-
Metronidazole,
B-lactam (Carbapenems).
Azithromycin, Clindamycin, Cefoxitin,
Chloramphenicol,
Mar 12, 2025 45

 Con’t…
 The routine administration of empirical antifungal
therapy is not generally warranted in
nonneutropenic critically ill patients.

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 Risk Factor For Fungal
Infection.
 Neutropenia.  Sever thermal injury
 High dose steroid use.  GI perforation and
 Chemotherapy anastomotic leak.
 ARF and hemodialysis  CV catheterization for
long
 Prior colonization
 Longer ICU stay
 RVI patients
 IV drug user
 Broad-spectrum antibiotics
 Solid organ
transplantation.
 DM patient.
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 VASOACTIVE
DRUG
THERAPY

Mar 12, 2025 48

 ADRENERGIC RECEPTORS

 Alpha Adrenergic Receptor..

 Activation of alpha-1 adrenergic receptors, located in vascular walls, induces
significant vasoconstriction.
 Alpha-1 adrenergic receptors are also present in the heart and can increase the
duration of contraction without increased chronotropy
 Beta Adrenergic Receptor .
 Beta-1 adrenergic receptors are most common in the heart and it mediate
increases in inotropy and chronotropy with minimal vasoconstriction.
 Stimulation of beta-2 adrenergic receptors in blood vessels induces vasodilation.

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Mar 12, 2025 51
 VASOACTIVE DRUG THERAPY
 Consensus guidelines recommend norepinephrine as
the first-choice vasopressor in septic shock.
 Levels of the endogenous hormone vasopressin may
be low in septic shock, and the administration of
vasopressin can reduce the norepinephrine dose.
 Consensus guidelines suggest adding vasopressin (up
to 0.03 U/min) in patients without a contraindication
to norepinephrine, with the intent of raising mean
arterial pressure or decreasing the norepinephrine
dose.

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 Con’t…
 Initial choice of vasopressor in patients with sepsis is often
individualized and determined by additional factors.
 This factors include the presence of coexistent conditions
contributing to shock (eg, heart failure), arrhythmias, organ
ischemia, or agent availability.
 For example, in patients with significant tachycardia (eg,
fast atrial fibrillation, sinus tachycardia >160/minute),
agents that completely lack beta adrenergic effects (eg,
vasopressin) may be preferred.
 Similarly, dopamine (DA) may be acceptable in those with
significant bradycardia; but low dose DA should not be used
Mar 12, 2025
for the purposes of "kidney protection." 53
 Con’t…
 The addition of a second or third agent to norepinephrine
may be required.
 The addition of vasopressin to catecholamine vasopressors
(e.g., epinephrine, norepinephrine) resulted in a lower rate
of atrial fibrillation.
 For patients with refractory septic shock associated with a
low cardiac output, addition of an inotropic agent may be
useful.
 Inotropic support with dobutamine was associated with a
survival advantage.
Mar 12, 2025 54
 VASOACTIVE THERAPY IN
CHILDREN

Epinephrine or norepinephrine is recommended as

a first-line vasoactive agent for fluid-refractory
pediatric septic shock over dopamine.
Epinephrine is preferred if there is evidence of
myocardial dysfunction.
Vasoactive drug therapy should be initiated after
40 to 60 mL/kg of fluid resuscitation if the patient
continues to have evidence of abnormal perfusion.

Mar 12, 2025 55

 Con’t…
 In resource-limited settings, epinephrine is typically the
most available drug and is appropriate for treatment of
septic, cardiogenic, and anaphylactic shock.
 It can be safely administered through a peripheral IV access
site or intraosseous
 For peripheral administration of epinephrine, the
concentration should be no greater than 0.1 mg/mL .
 The starting dose is 0.02 to 0.05 mcg/kg per minute ,Start
with 0.02 mcg/kg per minute and infusion is then titrated,
as needed, up to 1 mcg/kg per minute.
Mar 12, 2025 56
 Con’t…

 Addition of second vasopressor is indicated if patients

have not responded to an epinephrine dose of 1.5
mcg/kg/minute
 For children with fluid-refractory, normotensive septic
shock, it’s suggested to add vasoactive therapy with low-
dose epinephrine infusion rather than norepinephrine or
dopamine.
 If patients do not respond to fluid resuscitation
augmented by low-dose epinephrine infusion, then
vasodilatory agents (e.g., dobutamine or milrinone) are
Mar 12, 2025
typically employed. 57
 Con’t…

 If abnormal perfusion, poor myocardial contractility, or

hypotension persist despite escalating doses of
epinephrine, options include:
 If SVR is normal or low – Addition of norepinephrine is
suggested to provide additional vasoconstriction.
 If SVR is high– If there is evidence of high SVR then
dobutamine or milrinone is suggested because of their
inotropic properties and afterload reduction.

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VASOPRESS
ER
THERAPY

Mar 12, 2025 59

 ADDITIONAL THERAPY.

Blood transfusion
Glucocorticoid therapy
Glycemic control
Avoid hypocalcemia
Nutritional support
Treat DIC
Stress ulcer prophylaxis for those at risk for GI
Mar 12, 2025
bleeding. 60
 BLOOD TRANSFUSION
In hemodynamically
unstable patients
For hemodynamically
with septic shock,
stable patients who
blood transfusion is
are not bleeding, the
suggested to
minimum safe
maintain a
threshold is 7 g/dL.
hemoglobin threshold
of 9-10 g/dL.

Mar 12, 2025 61

 Glucocorticoid Therapy.

 corticosteroid therapy may be appropriate in patients with

septic shock that is refractory to adequate fluid
resuscitation and vasopressor administration.
 Recommendation focuses on adults with septic shock and
ongoing requirement for vasopressor therapy.
 Ongoing requirement is defined as a dose of norepinephrine
or epinephrine ≥ 0.25 mcg/kg/min for at least 4 hours after
initiation to maintain the target MAP.

Mar 12, 2025 62

  Patients at risk for adrenal
insufficiency.
 Recent acute corticosteroid exposure
 Chronic corticosteroid exposure
 A hypothalamic-pituitary-adrenal axis disorder
 Congenital adrenal hyperplasia or other
corticosteroid-related endocrinopathy
 Recent treatment with ketoconazole or
etomidate.

Mar 12, 2025 63

 Con’t…

 For patient with fluid refractory, catecholamine-resistant septic

shock, administer stress-dose glucocorticoids (e.g., hydrocortisone)
 Appropriate regimens consist of hydrocortisone 50 to 100 mg/m or 1
to 2 mg/kg (maximum 100 mg/day in children and 200 mg/day in
adult) as an initial dose followed by the same dose QID.
 Glucocorticoid therapy should be discontinued when the patient
becomes hemodynamically stable and no longer requires vasoactive
medication administration and need to be tapered before
discontinued.

Mar 12, 2025 64

 Manage Glucose Abnormalities.

Hypoglycemia remains a concern during the initial

management phase of septic shock. Children have
limited glycogen stores and may develop profound
hypoglycemia during periods of stress
Hyperglycemia is commonly present in children
with septic shock. Insulin therapy is reasonable to
maintain a glucose concentration between 140 and
180 mg/dL .

Mar 12, 2025 65

 Avoid Hypocalcemia .

For patients with persistent shock and an ionized

calcium < 1.1 mmol/L or 4.8 mg/dl or those with
symptomatic hypocalcemia (eg, positive Chvostek
or Trousseau signs, seizures, prolonged QT interval
on electrocardiogram, or cardiac arrhythmias) in
association with low ionized calcium , treat with
calcium gluconate 10 percent solution in a dose of
50 mg/kg or 0.5-1 ml/kg IV slowly over 5-10 min.

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 COMPLICATION.
 ARDS
 Acute renal failure
 DIC
 Encephalopathy
 Myocardial dysfunction and MI
 Liver failure
 Multiorgan failure
 Complication following intubation and mechanical
ventilations.
Mar 12, 
2025 DVT and PE 67
 PROGNOSTIC FACTORS

Host related
Site of infection
Types of infection
Timing and types Antimicrobial Therapy
Restoration of perfusion

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 HOST RELATED
 Hypothermia comorbidities such as AIDS
 Development of leukopenia, , Liver disease ,Cancer :-
 Thrombocytopenia, Alcohol dependence ,
 Hyperchloremia, Immune suppression ,
 New-onset atrial fibrillation, Pulmonary arterial
 Age >40 years hypertension
 Hyperglycemia Right or left ventricular
 Hypocoagulability dysfunction

Mar 12, 2025 69

 SITE OF INFECTION

 Mortality from sepsis was 50 to 55 percent when the source

of infection was unknown, gastrointestinal, or pulmonary,
compared with only 30 percent when the source of infection
was the urinary tract .
 The highest mortality in those with sepsis from ischemic
bowel (78 %) and the lowest rates in those with obstructive
uropathy-associated urinary tract infection .
 When bloodstream infections become severe (eg, septic
shock), the outcome is similar regardless of whether the
pathogens are Gram-negative or Gram-positive bacteria
Mar 12, 2025 70
 TYPES OF INFECTION

Sepsis due to nosocomial pathogens has a higher

mortality than sepsis due to community-acquired
pathogens .
Increased mortality is associated with bloodstream
infections due to methicillin-resistant staphylococcus
aureus , non-candidal fungus, candida , methicillin
sensitive staphylococcus aureus and pseudomonas ,
as well as polymicrobial infection

Mar 12, 2025 71

 ANTI MICROBIAL THERAPY

Early institution of adequate antibiotic therapy was

associated with a 50 % reduction in the mortality
rate,
In contrast, prior antibiotic therapy (within the past
90 days) may be associated with increased
mortality[resistance related]

Mar 12, 2025 72

 RESTORATION OF PERFUSION

Failure to aggressively try to restore perfusion early

(i.e., failure to initiate early goal-directed therapy)
may also be associated with mortality.
A severely elevated lactate (>4 mmol/L) is
associated with a poor prognosis in patients with
sepsis with one study reporting a mortality of 78 %.

Mar 12, 2025 73

 RECOMMENDATION

 For adults with sepsis or septic shock, we recommend using

low molecular weight heparin (LMWH) over unfractionated
heparin (UFH) for VTE prophylaxis. Strong recommend.
 For adults with sepsis or septic shock, we recommend initiating
insulin therapy at a glucose level of ≥ 180mg/dL (10 mmol/L).
target glucose range of 140−180 mg/dL.
 For adult patients with sepsis or septic shock who can be fed
enterally, we suggest early (within 72 hours) initiation of
enteral nutrition

Mar 12, 2025 74

THANK YOU
FOR YOUR
ATTENTION
REFERENCE
Nelson 22nd edition
Harrison 21st edition
UpToDate 2024 .
NICE Sepsis guideline 2024.
Surviving Sepsis Campaign International Guidelines.
National Integrated Emergency Medicine 2020.
STG 4th edition