PATHOPHYSIOLOGY AND

MANAGEMENT OF SEPTIC
SHOCK

PRESENTER: Dr SANI KABIRU

MODERATOR: Dr D CHITUMU

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 OUTLINE
• INTRODUCTION
• DEFINITION OF TERMS
• EPIDEMIOLOGY
• PATHOPHYSIOLOGY
• MANAGEMENT
• FUTURE TRENDS
• CONCLUSION

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 Learning objectives

• To discus the current definition of sepsis and septic shock

• To describe the epidemiology of sepsis
• To describe the current understanding of the mechanisms underlying the
pathogenesis of sepsis
• To discus the clinical approach in the diagnosis of sepsis and recognition of organ
dysfunction
• To discus the current guidelines and principles in the management of sepsis

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 Introduction

• Sepsis exists on a continuum of severity that ranges from infection and bacteraemia

to sepsis and septic shock, which can lead to multiple organ dysfunction syndrome

(MODS) and death

• The definitions of sepsis and septic shock have rapidly evolved since the early 1990s

with the Society of Critical Care Medicine (SCCM) and the European Society of

Intensive Care Medicine (ESICM) coming up with a consensus definitions in 2016

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 Introduction

• People in low- to middle-income (LMICS) regions of the world, particularly sub-

Saharan Africa - suffer disproportionately high morbidity and mortality compared to

those from high-income countries

• In Africa sepsis remain under recognized,underdiagnosed and under reported

• High index of suspicion and early treatment is key

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 DEFINITION OF TERMS- Sepsis 1&2
• Systemic Inflammatory Response Syndrome (SIRS): 2 or more of;

• Temperature >38°C or <36°C;

• Heart rate >90 beats per minute;
• Respiratory rate >20 breaths per minute or PaCO2 <32 mmHg; and
• White blood cell count >12,000/cu mm, <4,000/cu mm, or >10% immature
(band) forms
• Sepsis
• Infection plus SIRS
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 DEFINITION OF TERMS- Sepsis 1&2

• Severe sepsis
• Sepsis + organ dysfunction, hypoperfusion, or hypotension.
• Septic shock
• sepsis-induced hypotension despite adequate fluid resuscitation
• MODS
• Presence of ≥ 2 organ dysfunction such that homeostasis cannot be maintained
without intervention

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 DEFINITION OF TERMS- sepsis 3

• Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to

proven or suspected infection

• Organ dysfunction is total SOFA score ≥2 points

• A qSOFA identifies those at risk of death from sepsis

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 DEFINITION OF TERMS: SOFA
SOFA score

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 DEFINITION OF TERMS: qSOFA

• Screening for Sepsis

– Quick Sequential Organ Failure Assessment (qSOFA) scoring system

1. Altered mental status (GCS score <15)

2. Systolic blood pressure <100 mmHg

3. Respiratory rate >22/min

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 DEFINITION OF TERMS- septic shock
• Septic shock occurs in a subset of patients with sepsis and comprises of an
underlying circulatory and cellular/metabolic abnormality that is associated with
increased mortality
• It is defined by persistent hypotension

• Requiring vasopressors to maintain MAP of 65 mm Hg or higher

• A serum lactate level greater than 2mmol/L (18 mg/dL) despite adequate volume
resuscitation

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 DEFINITION OF TERMS

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EPIDEMIOLOGY

• Severe sepsis/septic shock is the most common cause of death in critically ill patients

• Septic shock is associated with the high mortality- approaching 50%

• It affects all ages

• Strong correlation exists between advanced age and the incidence of septic

shock

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 EPIDEMIOLOGY- Global burden

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 EPIDEMIOLOGY- Burden in Africa

• Total of 17 million cases (35% of global cases)

• Total of 3.5 million deaths (32% of global deaths) in 2017

• Every minute 30 people develop sepsis and 6 people die as a result of sepsis in Africa

• Affects younger people in Africa

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EPIDEMIOLOGY: Risk factors
• Sepsis is seen most frequently in elderly persons and in those with
comorbid conditions:
• Diabetes
• HIV infection
• Genetic susceptibility
• Other predisposing factors include:
• Malignancies
• Chronic liver disease
• Chronic kidney disease
• Major surgeries, Trauma, extensive Burns
• Recent hospital admission
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 ETIOLOGY

• Before the advent of antibiotics, Gram-positive bacteria were the principal organisms

that caused sepsis

• Gram-negative bacteria are now the key pathogens causing sepsis and septic shock

• Rarely, viruses and highly virulent fungi have also been implicated

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 ETIOLOGY
GENITAL TRACT INFECTIONS 1-5%
RESPIRATORY INFECTIONS 35-50% • Neisseria gonorrhoeae
• Gram-negative bacteria
• Streptococcus
• Streptococci
pneumoniae
• Klebsiella pneumoniae
• Escherichia coli SOFT TISSUE INFECTIONS 5-10%
• S aureus
ABDOMINAL INFECTIONS 20-40% • Staphylococcus
epidermidis
• E coli • Streptococci
• Enterococcus species
• Bacteroides fragilis
URINARY TRACT 10-20% INDWELLING CATHETERS

• Central lines
• E Coli
• Urethral catheter
• Klebsiella
• implants
• Proteus Spp
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 PATHOPHYSIOLOGY
• Sepsis is the result of a complex and dysregulated homeostatic response to infection
• Untreated, sepsis progresses to;
• hypoperfusion, hypoxia, and dysfunction at the level of cells, tissues, and
organ systems
• leading to death in at least 30% of case

• The clinical syndrome of sepsis is a manifestation of pro/anti-inflammatory

intermediates

•The severity of the response depends on both host and pathogen characteristics
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 Management

• The principles of management of septic shock entails:

• Early recognition
• Early resuscitation and continued support
• Early adequate antibiotics therapy
• Source control
• Supportive therapy

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 RECOGNITION: History
• Symptoms related to sepsis
• Fever
• Confusion
• Anxiety
• Difficulty in breathing
• Fatigue and malaise
• Nausea and vomiting

• Symptoms related to circulatory failure

• Restlessness
• Apprehension
• Confusion

• Organ Specific Symptoms

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 RECOGNITION; Examination
• General
• Febrile
• Altered sensorium
• Cold clammy extremities
• Petechiae or urpura

• Systemic
• Hypotension
• Tachycardia
• Tachypnoea
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 RECOGNITION; Investigations
• Full blood count
• Serum Electrolytes, Urea and Creatinine
• Culture
• Blood
• Urine
• Effluents
• Serum lactate
• Radiological imaging

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 RECOGNITION; Admission

• Patients in septic shock require admission to ICU

• Continuous monitoring and continued goal-directed therapy

• Central venous access is secured

• Arterial catheter inserted

• Urethral Catheter inserted

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 Goal directed therapy

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EARLY HAEMODYNAMIC RESUSCITATION
AND CONTINUED SUPPORT

• IV Crystalloids given @ 30ml/kg over 30-60min

• Followed by assessment of the response

•With additional fluid challenges as dictated by perfusion parameters

•Crystalloid solution is titrated to a goal of adequate tissue perfusion

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EARLY HAEMODYNAMIC RESUSCITATION AND
CONTINUED SUPPORT: VASO-PRESSORS

• Vasopressor administration is required for persistent hypotension

• The goal of vasopressor therapy is to reverse the pathologic vasodilation

• First-line agent for septic shock is norepinephrine

• The dosage range for Norepinephrine is 5-20 µg/min

• Second-line agent is Dopamine 5-10 µg/kg/min IV

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 EARLY HAEMODYNAMIC RESUSCITATION
AND
CONTINUED SUPPORT:VASOPRESSORS

• Third-line vasopressors include

• Epinephrine,
• Phenylephrine
• Synthetic human angiotensin II,
• Vasopressin

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 EARLY AND ADEQUATE ANTIBIOTIC
THERAPY

• Administered as soon as clinical diagnosis is made

• Broad spectrum initially

• Tailored to cover the responsible organism once culture data is available

• Choice based on site of infection and resident organism

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 SOURCE CONTROL

• Entails getting rid of the focus of infection particularly if amenable to surgical

treatment

• Should be done as soon as patient is haemodynamically fit

• Includes I&D, Percutaneous drainage, debridement of devitalised tissues

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 SUPPORTIVE THERAPY
• Oxygen therapy
• Mechanical ventilation
• Correction of anaemia
• Glycaemic control
• Nutritional support
• Temperature control
• Corticosteroid therapy
• DVT prophylaxis and management of DIC

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 SURVIVING SEPSIS CAMPAIN BUNDLE

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 MONITORING IN SEPTIC SHOCK: End
Points of Resuscitation
• CLINICAL
• Level of consciousness
• Normalisation of pulse rate
• Normalisation of blood pressure
• Adequate urine output
• Laboratory
• Lactate
• Base deficit
• Mixed venous Oxygen Saturation
• Haemodynamic
• Cardiac output
• Pulmonary artery wedge pressure
• Oxygen delivery and consumption

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 Summary - Recent change to sepsis
management
• The new guidelines (Since 2016):

• Removed Early Goal Directed Therapy

• Focus on frequent reevaluation (monitoring)

• Focus on patient-specific tailoring of hemodynamic therapy

• Deemphasized protocolization of care and invasive monitoring

• Also emphasizes hospitals to develop formal sepsis performance/quality

improvement programs, given a suggestion of mortality benefit

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 FUTURE TRENDS
• Use of Immunomodulation strategies
• Anti-endotoxin antibodies
• Anti-cytokine antibodies
• Cytokine receptor antagonists
• Immune enhancers
• Non–isoform-specific nitric oxide synthase inhibitor,
• O2 radical scavengers
• Extracorporeal Blood Purification

• Use of Artificial Intelligence in Sepsis, Gene Expression

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 CONCLUSION

• Septic shock is a life threatening condition associated with high mortality with multi-

systemic manifestations that requires early recognition, prompt commencement of

appropriate treatment and careful monitoring.

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 REFERENCES
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4. Andre K. Septic Shock, In Medscape. Updated 4th March, 2021
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https://doi.org/10.3389/fmed.2021.628302
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sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet (London,
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 THANK YOU FOR LISTENING

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