Can you prepare detailed, point‑wise notes on sepsis using the latest guidelines and articles, with subheadings highlighting all key points for maximum exam marks?

Sepsis: Comprehensive Exam-Focused Notes

Definition and Pathophysiology

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection 1, 2.

• Key pathophysiologic mechanisms include:

  • Concurrent hyperinflammation and immune suppression occurring simultaneously 3, 4
  • Severe macro- and microcirculatory dysfunction leading to global hypoperfusion 2
  • Activation of proinflammatory and anti-inflammatory cytokines 5
  • Coagulation cascade activation with resultant coagulopathy 5
  • Cellular apoptosis and mitochondrial dysfunction 5
  • Failure of immune response to return to homeostasis 3

• Sepsis differs from simple bloodstream infection by the presence of organ dysfunction from dysregulated host response 5

Recognition and Screening

NEWS2 Score (Preferred Initial Screening Tool)

Use NEWS2 for initial risk stratification in adults with suspected sepsis in acute hospital, mental health, and ambulance settings 1, 6.

• NEWS2 has superior sensitivity (84-86%) compared to qSOFA (28-42%) 6

• Six physiological parameters assessed 1:

  • Respiration rate (per minute)
  • Oxygen saturation (SpO₂) with two scales available
  • Supplemental oxygen requirement (air vs oxygen)
  • Systolic blood pressure (mm Hg)
  • Pulse rate (per minute)
  • Level of consciousness (Alert vs CVPU)
  • Temperature (°C)

• Risk stratification based on aggregate score 1:

  • Score 0: Very low risk
  • Score 1-4: Low risk
  • Score 5-6: Moderate risk
  • Score ≥7: High risk requiring evaluation every 30 minutes 6

qSOFA Score (For Prognostication, Not Initial Screening)

Do not use qSOFA as a single screening tool due to insufficient sensitivity, but utilize it for risk stratification and prognostication 6.

• qSOFA criteria (1 point each) 1, 7:

  • Systolic blood pressure ≤100 mm Hg
  • Respiratory rate ≥22/min
  • Altered mental status

• qSOFA ≥2 indicates 7, 6:

  • 10% mortality risk

  • Higher likelihood of ICU admission ≥3 days
  • Need for immediate full SOFA assessment
  • Patients who may benefit most from aggressive interventions

SIRS Criteria (Historical Context)

• Two or more of the following 8:
  • Temperature >38°C or <36°C
  • Heart rate >90 bpm
  • Respiratory rate ≥20/min or PaCO₂ <32 mm Hg
  • White blood cell count >12,000/μL or <4,000/μL, or >10% immature forms

Diagnostic Criteria and Evaluation

Clinical Manifestations Indicating Sepsis

Look for signs of infection plus organ dysfunction or tissue hypoperfusion 1, 8.

• General variables 1:

  • Fever (>38.3°C) or hypothermia (<36°C)
  • Tachycardia (>90 bpm or >2 SD above normal)
  • Tachypnea or altered mental status
  • Significant edema or positive fluid balance (>20 mL/kg over 24 hours)
  • Hyperglycemia (>140 mg/dL) without diabetes

• Inflammatory markers 1:

  • Leukocytosis (>12,000/μL) or leukopenia (<4,000/μL)
  • Normal WBC with >10% immature forms
  • Elevated C-reactive protein or procalcitonin (>2 SD above normal)

• Hemodynamic variables 1:

  • Arterial hypotension (SBP <90 mm Hg, MAP <70 mm Hg, or SBP decrease >40 mm Hg)

• Organ dysfunction indicators 1:

  • Arterial hypoxemia (PaO₂/FiO₂ <300)
  • Acute oliguria (<0.5 mL/kg/hr for ≥2 hours despite adequate fluids)
  • Creatinine increase >0.5 mg/dL
  • Coagulation abnormalities (INR >1.5 or elevated aPTT)
  • Thrombocytopenia (<100,000/μL)
  • Hyperbilirubinemia (>4 mg/dL)
  • Ileus (absent bowel sounds)

• Tissue hypoperfusion markers 1, 8:

  • Hyperlactatemia (>1 mmol/L) 8
  • Lactate 2.0 mmol/L = intermediate risk; >4 mmol/L = high risk of septic shock 8
  • Decreased capillary refill or mottling

Severe Sepsis Definition

Severe sepsis = sepsis plus sepsis-induced tissue hypoperfusion or organ dysfunction 1.

• Sepsis-induced hypotension
• Lactate above upper laboratory normal limits
• Urine output <0.5 mL/kg/hr for >2 hours despite adequate fluids
• Acute lung injury with PaO₂/FiO₂ <250 (or <200 if pneumonia is source)

Septic Shock Definition

Septic shock = sepsis-induced tissue hypoperfusion with hypotension persisting after initial fluid challenge or blood lactate >4 mmol/L 1.

• Monitor for persistent hypotension despite adequate fluid resuscitation requiring vasopressor support 8

Diagnostic Workup

Microbiologic Cultures

Obtain appropriate cultures before antimicrobial therapy if this causes no substantial delay (<45 minutes) 1.

• At least 2 sets of blood cultures (aerobic and anaerobic bottles) 1:

  • At least 1 drawn percutaneously
  • At least 1 drawn through each vascular access device (unless device inserted <48 hours prior)

• Additional testing when indicated 1:

  • 1,3-β-D-glucan assay if invasive candidiasis in differential
  • Mannan and anti-mannan antibody assays if invasive candidiasis suspected

Imaging Studies

Perform imaging promptly to confirm potential source of infection 1.

Biomarkers

• Lactate measurement is essential for risk stratification and monitoring response to therapy 8
• Procalcitonin can assist in discontinuing empiric antibiotics in patients with no subsequent evidence of infection 1

Initial Resuscitation

Fluid Resuscitation

Administer at least 30 mL/kg IV crystalloid fluid within the first 3 hours for sepsis-induced hypoperfusion 1.

• Crystalloids are preferred over colloids for initial resuscitation 1
• Following initial fluid resuscitation, guide additional fluids by frequent reassessment of hemodynamic status 1
• Use dynamic variables over static variables to predict fluid responsiveness 1

Resuscitation Goals (First 6 Hours)

Target the following parameters during initial resuscitation 1:

• Mean arterial pressure (MAP) ≥65 mm Hg 1
• Central venous pressure 8-12 mm Hg 1
• Urine output ≥0.5 mL/kg/hr 1
• Central venous oxygen saturation ≥70% or mixed venous ≥65% 1
• Normalize lactate as rapidly as possible in patients with elevated levels 1

Hemodynamic Assessment

Perform thorough clinical examination and frequent reassessment 1:

• Evaluate heart rate, blood pressure, oxygen saturation, respiratory rate, temperature, urine output
• Conduct further hemodynamic assessment (such as cardiac function evaluation) if clinical examination does not lead to clear diagnosis 1
• Serial lactate monitoring to assess response to resuscitation 8

Antimicrobial Therapy

Timing of Antibiotics

Administer effective IV antimicrobials within the first hour of recognition 1, 8:

• Within 1 hour for septic shock 1
• Within 1 hour for severe sepsis without shock 1
• Timing guided by NEWS2 risk level per updated NICE 2024 guidance 1

Empiric Antimicrobial Selection

Initial empiric therapy must include one or more drugs active against all likely pathogens (bacterial, fungal, or viral) that penetrate adequately into presumed source tissues 1.

• Combination empirical therapy recommended for 1:
  • Neutropenic patients with severe sepsis
  • Difficult-to-treat multidrug-resistant pathogens (Acinetobacter, Pseudomonas)
  • Severe infections with respiratory failure and septic shock
  • P. aeruginosa bacteremia (extended-spectrum β-lactam plus aminoglycoside or fluoroquinolone)
  • Septic shock from bacteremic Streptococcus pneumoniae (β-lactam plus macrolide)

De-escalation and Duration

Reassess antimicrobial regimen daily for potential de-escalation 1.

• Empiric combination therapy should not exceed 3-5 days 1
• De-escalate to most appropriate single therapy once susceptibility profile known 1
• Typical duration: 7-10 days 1
• Longer courses appropriate for 1:
  • Slow clinical response
  • Undrainable foci of infection
  • S. aureus bacteremia
  • Fungal and viral infections
  • Immunologic deficiencies including neutropenia

Antiviral Therapy

Initiate antiviral therapy as early as possible for sepsis of viral origin 1.

Important Caveat

Do not use antimicrobial agents in severe inflammatory states determined to be of noninfectious cause 1.

Source Control

Seek and diagnose anatomical source of infection requiring emergent source control as rapidly as possible 1.

• Undertake intervention for source control within first 12 hours after diagnosis if feasible 1
• Remove or exchange infected devices (e.g., tunneled catheters with purulent drainage) 8

Performance Improvement and Screening

Hospitals must have a performance improvement program for sepsis 1.

• Implement routine screening of potentially infected seriously ill patients for sepsis 1
• Screen acutely ill, high-risk patients to allow earlier implementation of therapy 1

Organ Dysfunction Assessment

Sequential Organ Failure Assessment (SOFA) Score

Use SOFA score to assess severity and guide treatment 2.

• Organ systems commonly affected 2:

  • Kidneys (most frequent)
  • Liver
  • Lungs
  • Heart
  • Central nervous system
  • Hematologic system

• Multiple organ failure is the hallmark of sepsis and determines patient course from infection to recovery or death 2

Key Clinical Pitfalls to Avoid

• Do not rely on qSOFA alone for initial screening—use NEWS2 6
• Do not delay antibiotics beyond 1 hour while awaiting cultures 1
• Do not continue combination therapy beyond 3-5 days without reassessment 1
• Do not use static variables alone to guide fluid responsiveness 1
• Do not overlook source control—intervene within 12 hours 1
• Do not forget serial lactate monitoring to assess resuscitation adequacy 8
• Do not miss elevated lactate >1 mmol/L as indicator for aggressive intervention 8