Sepsis and Septic Shock

A 68 year old male presents with fever, productive cough, confusion, and progressive shortness of breath for 2 days. He has a history of diabetes mellitus and chronic kidney disease. On examination, temperature is 39°C, pulse is 122/min, respiratory rate is 30/min, blood pressure is 82/50 mmHg, and oxygen saturation is 88% on room air. He is confused and has cold extremities with delayed capillary refill. Laboratory investigations reveal leukocytosis, serum lactate of 4.5 mmol/L, elevated creatinine, and metabolic acidosis. Chest X-ray shows right lower lobe consolidation. Despite adequate IV fluid resuscitation, hypotension persists and vasopressor support is required. Diagnosis?

Diagnosis is septic shock secondary to pneumonia.

1. Definition

Sepsis

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

Operational definition:

• Suspected or confirmed infection with SOFA score ≥2

Septic Shock

Septic shock is a subset of sepsis characterized by:

1. Persistent hypotension requiring vasopressors to maintain MAP ≥65 mmHg
2. Serum lactate >2 mmol/L despite adequate fluid resuscitation

2. Pathophysiology

1. Infection triggers dysregulated immune activation
2. Cytokine release causes endothelial dysfunction and capillary leak
3. Vasodilation leads to relative intravascular hypovolemia
4. Microcirculatory dysfunction impairs tissue oxygen delivery
5. Mitochondrial dysfunction contributes to impaired oxygen utilization
6. Lactate elevation reflects hypoperfusion, metabolic stress, and impaired clearance
7. Progressive organ dysfunction may occur

Additional mechanisms include:

• Myocardial depression
• Dysregulated coagulation
• Microthrombosis

3. Etiology and Sources of Infection

1. Pneumonia (most common source)
2. Intra-abdominal infections
3. Genitourinary infections
4. Skin and soft tissue infections
5. Healthcare-associated infections
6. Catheter-related infections
7. Fungal or viral infections in high-risk patients

4. Risk Factors

1. Advanced age or infancy
2. Immunocompromised states
3. Diabetes mellitus
4. Chronic kidney disease
5. Malignancy
6. Indwelling devices
7. Recent hospitalization or surgery
8. Chronic liver disease

5. Clinical Features

5.1 Early Sepsis

1. Fever or hypothermia
2. Tachycardia
3. Tachypnea
4. Altered mental status
5. Leukocytosis or leukopenia

5.2 Septic Shock / Severe Disease

1. Hypotension
2. Vasopressor requirement
3. Elevated lactate
4. Oliguria
5. Altered mentation
6. Multiorgan dysfunction
7. Warm extremities early followed by cool extremities later

6. Diagnosis and Assessment

6.1 Diagnostic Criteria

1. Suspected or confirmed infection
2. SOFA score ≥2 indicating organ dysfunction

6.2 Laboratory Findings

1. Elevated serum lactate
2. Leukocytosis or leukopenia
3. Elevated inflammatory markers
4. Acute kidney injury
5. Metabolic acidosis
6. Coagulation abnormalities
7. Thrombocytopenia

6.3 Cultures and Investigations

1. Obtain blood cultures before antibiotics if feasible
2. Do not delay antibiotic administration
3. Identify source of infection with imaging or cultures

6.4 Screening Tools

1. NEWS or NEWS2
2. MEWS
3. SIRS criteria

qSOFA should not be used alone as a screening tool

7. Management

7.1 Core Principle

Sepsis and septic shock are time-critical medical emergencies requiring immediate treatment

7.2 Antimicrobial Therapy

1. Septic shock or definite sepsis: administer broad-spectrum antimicrobials immediately, ideally within 1 hour
2. Possible sepsis without shock: perform rapid evaluation and initiate antibiotics if infection remains likely
3. Obtain cultures before antibiotics when possible
4. Do not delay antibiotics for biomarkers or imaging
5. Reassess daily and de-escalate based on cultures and clinical response

7.3 Fluid Resuscitation

1. Initial rapid administration of approximately 30 mL/kg IV crystalloid is recommended in septic shock
2. Balanced crystalloids are preferred over normal saline
3. Use dynamic reassessment to guide further fluid therapy
4. Avoid both inadequate resuscitation and fluid overload

7.4 Dynamic Assessment Tools

1. Passive leg raise test
2. Stroke volume or cardiac output response
3. Capillary refill time
4. Bedside ultrasound

7.5 Hemodynamic Management

1. Target MAP ≥65 mmHg
2. First-line vasopressor: norepinephrine
3. Add vasopressin if needed
4. Add epinephrine in refractory shock
5. Add dobutamine if myocardial dysfunction with persistent hypoperfusion
6. Hydrocortisone 200 mg/day IV may be used in persistent vasopressor-dependent shock

7.6 Source Control

1. Early drainage, debridement, or device removal when indicated
2. Definitive source control is essential for recovery

7.7 Respiratory Support

1. Avoid unnecessary hyperoxia
2. Oxygen targets should be individualized
3. HFNC preferred over conventional oxygen in many patients
4. Mechanical ventilation may be required in respiratory failure

7.8 Mechanical Ventilation in ARDS

1. Low tidal volume ventilation: 6 mL/kg predicted body weight
2. Plateau pressure ≤30 cmH₂O
3. Appropriate PEEP strategies
4. Prone positioning for moderate to severe ARDS
5. Neuromuscular blockade may be considered in selected patients

7.9 Adjunctive Care

1. Restrictive transfusion strategy: transfuse if Hb <7 g/dL unless specific indications exist
2. LMWH preferred for VTE prophylaxis
3. Initiate insulin if glucose ≥180 mg/dL
4. Target glucose range: 144–180 mg/dL
5. Bicarbonate therapy only in selected severe metabolic acidosis with AKI
6. Early enteral nutrition within 24–72 hours

8. Monitoring and Targets

1. MAP ≥65 mmHg
2. Urine output ≥0.5 mL/kg/h
3. Lactate trend and clearance over time
4. Mental status and peripheral perfusion
5. Ongoing reassessment of fluid responsiveness and organ function

9. Complications

1. Acute respiratory distress syndrome (ARDS)
2. Acute kidney injury
3. Disseminated intravascular coagulation (DIC)
4. Multiorgan failure
5. Secondary infections
6. Death

10. Prognosis

1. Mortality increases with delayed recognition and treatment
2. Septic shock has significantly higher mortality than uncomplicated sepsis
3. Early antibiotics, hemodynamic resuscitation, and source control improve outcomes

11. Key Clinical Insight

Patient with suspected infection, hypotension, elevated lactate, altered mental status, and organ dysfunction strongly suggests septic shock

12. Key Exam Points

1. Sepsis = infection + organ dysfunction
2. Septic shock requires vasopressors and lactate >2 mmol/L despite fluids
3. Pneumonia is the most common source of sepsis
4. Early broad-spectrum antibiotics are essential
5. Balanced crystalloids are preferred for resuscitation
6. Norepinephrine is the first-line vasopressor
7. Lactate reflects illness severity and metabolic stress
8. qSOFA should not be used alone for screening
9. Source control is essential for definitive management
10. Early recognition and treatment significantly reduce mortality