What is sepsis and how is it treated?

Sepsis: Definition, Recognition, and Management

What is Sepsis?

Sepsis is a life-threatening emergency where the body's dysregulated response to an infection causes organ dysfunction, requiring immediate medical attention to prevent death or permanent disability. 1

It's not the infection itself that causes the damage—it's the body's overreaction to that infection that harms organs. 1 Think of it as your immune system going into overdrive and causing collateral damage to your own organs while fighting the infection. 1

Current Clinical Definition

• Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, operationally identified by an increase in the Sequential Organ Failure Assessment (SOFA) score of ≥2 points, which is associated with >10% in-hospital mortality. 2
• The old concepts of SIRS (Systemic Inflammatory Response Syndrome) and "severe sepsis" are no longer used in current clinical practice. 2
• More than 90% of sepsis cases are caused by bacteria (Gram-negative and Gram-positive occurring with equal frequency), with fungi like Candida responsible for a significant minority. 2

Recognizing Sepsis: Warning Signs

For rapid bedside identification outside the ICU, use the quick SOFA (qSOFA) criteria—presence of at least 2 of these 3 findings suggests high risk:

• Respiratory rate ≥22 breaths/minute 2
• Altered mental status (Glasgow Coma Scale score ≤13) 2
• Systolic blood pressure ≤100 mmHg 2

Additional Critical Warning Signs

• Temperature abnormalities: Fever >38°C (100.4°F) or hypothermia <36°C with shivering 1
• Neurological changes: Confusion, slurred speech, unusual drowsiness, or any altered mental state 1
• Cardiovascular signs: Fast heart rate (racing or pounding), dizziness when standing, low blood pressure 1
• Respiratory distress: Shortness of breath or rapid breathing 1
• Metabolic indicators: Extreme weakness, severe muscle pain 1
• Renal dysfunction: Decreased urination (not urinating for a whole day) 1
• Skin changes: Mottled, discolored, clammy or sweaty skin, or new rash that doesn't blanch when pressed 1

Special Population Considerations

• Elderly patients may not show typical fever and may have only subtle symptoms—any change in mental status with suspected infection warrants immediate evaluation. 1
• Immunocompromised patients (cancer, HIV, diabetes, chronic steroids) are at much higher risk and should have a lower threshold for seeking emergency care. 1
• Very young children and infants require immediate evaluation for any suspected serious infection. 1

Septic Shock: The Most Severe Form

Septic shock is a subset of sepsis with profound circulatory, cellular, and metabolic abnormalities associated with >40% hospital mortality. 3

Diagnostic Criteria for Septic Shock

• Requirement for vasopressor therapy to maintain mean arterial pressure (MAP) ≥65 mmHg 3
• Serum lactate level >2 mmol/L (>18 mg/dL) 3
• Both criteria must persist despite adequate fluid resuscitation 3

Treatment Approach: Time is Critical

Treatment must start within hours, not days—delays in antimicrobial administration are associated with increased mortality. 1, 4

Initial Resuscitation (First Hour)

Fluid Resuscitation:

• Administer 30 mL/kg crystalloid IV for hypotension or lactate ≥4 mmol/L 3
• Use balanced crystalloids rather than normal saline when possible 3
• Critical pitfall: Avoid excessive fluid administration and fluid overload, which may worsen outcomes 3

Antimicrobial Therapy:

• Administer broad-spectrum antibiotics within one hour of recognition 3, 4
• Obtain blood cultures before antibiotics when possible, but do not delay antibiotics for cultures 3
• De-escalate based on culture results and clinical response 3

Vasopressor Management

Norepinephrine is the first-line vasopressor for septic shock: 3, 4

• Target MAP of 65-70 mmHg 3
• Initiate early rather than delaying with excessive fluid administration 3
• Safe administration: Peripheral vasopressor use through a 20-gauge or larger IV line is safe and effective 4
• Second-line agents: If hypotension persists, add vasopressin, followed by epinephrine 4

Critical pitfall: Do not delay vasopressor initiation while continuing excessive fluid administration—patients receiving vasopressors may still have perfusion abnormalities despite normal blood pressure. 3

Additional Supportive Measures

• Oxygen support: May be needed if lungs are affected 1
• Steroids: Consider hydrocortisone and fludrocortisone in refractory septic shock 4
• Glucose control: Target <180 mg/dL 3
• Organ support: Lung-protective ventilation for ARDS, renal replacement therapy for acute kidney injury when indicated 3

Monitoring Parameters

• Mean arterial pressure (target ≥65 mmHg) 3
• Lactate levels 3
• Mental status 4
• Capillary refill time 4
• Urine output 4

Long-Term Implications and Recovery

• Recovery can take weeks to months, and some organ damage may be permanent depending on severity. 1
• Even after surviving sepsis, patients may experience long-term effects on their immune system and increased susceptibility to future infections. 1
• Follow-up care: Patients must complete all prescribed antibiotics and attend follow-up appointments. 1
• Goals-of-care discussions and shared decision-making should occur early, with attention to long-term outcomes across the continuum of care. 5

Key Management Principles: Evolution of Care

Modern sepsis management has transitioned to a less aggressive approach over the last two decades: 6

• Early fluid resuscitation and antibiotic therapy remain cornerstones 6
• Avoid routine mixed venous oxygen saturation and central venous pressure monitoring 6
• Avoid excessive fluid resuscitation, routine inotrope use, and excessive red blood cell transfusions 6
• Peripheral vasopressor use is safe and rising in practice 6
• Use balanced crystalloids and a restrictive fluid strategy 6