What is the treatment for sepsis?

Treatment of Sepsis

Sepsis treatment requires immediate action with three critical interventions within the first hour: broad-spectrum IV antimicrobials, aggressive crystalloid fluid resuscitation (30 mL/kg bolus), and vasopressor support (norepinephrine) if mean arterial pressure remains below 65 mmHg despite fluids. 1, 2

Immediate Recognition and Time-Critical Actions

Sepsis is a medical emergency requiring instant intervention—every hour of delay in treatment increases mortality. 1, 2, 3

First Hour Bundle (Time Zero = Recognition)

Antimicrobial Therapy:

• Administer broad-spectrum IV antimicrobials within 60 minutes of sepsis recognition 4, 1, 2, 5
• Obtain at least 2 sets of blood cultures (one percutaneous, one through vascular access) but never delay antibiotics beyond 45-60 minutes for culture results 1, 2
• Use combination therapy with ≥2 antibiotics from different classes covering all likely pathogens (gram-positive, gram-negative, anaerobes, and potentially fungal/viral) 1, 6, 2
• Each hour of antibiotic delay significantly increases mortality risk 1, 5

Fluid Resuscitation:

• Deliver 30 mL/kg IV crystalloid bolus as rapidly as possible for hypotension or lactate ≥4 mmol/L 1, 2, 5
• Administer 500 mL boluses over 30 minutes, targeting restoration of tissue perfusion 1
• Use either normal saline or balanced crystalloids as first choice 6, 2, 5
• Continue fluid loading only if patient remains preload-dependent (responsive to volume) 1, 6

Critical Pitfall: In children with profound anemia and severe sepsis (particularly malaria), administer fluid boluses cautiously and consider blood transfusion instead 4. Pediatric dosing is 20 mL/kg boluses over 5-10 minutes, not 30 mL/kg 1.

Hemodynamic Targets (Achieve Within 6 Hours)

Primary endpoints to guide resuscitation: 4, 1, 6, 2

• Mean arterial pressure (MAP) ≥65 mmHg
• Urine output ≥0.5 mL/kg/hour
• SpO₂ ≥90-95%
• Central venous oxygen saturation (ScvO₂) ≥70%
• Improvement in mental status and peripheral perfusion
• Lactate clearance

Monitor for positive response to fluid loading: ≥10% increase in systolic/mean arterial pressure, ≥10% reduction in heart rate, and/or improvement in mental state, peripheral perfusion, and urine output 4

Vasopressor Therapy

Initiate norepinephrine immediately if MAP <65 mmHg persists after the 30 mL/kg crystalloid challenge. 1, 2, 5

• Norepinephrine is the first-line vasopressor due to potent vasoconstrictor properties 1, 6, 5
• Start at 0.05-0.1 mcg/kg/min, titrate up to 2 mcg/kg/min 2
• Early vasopressor use reduces organ failure incidence 1, 6
• Peripheral administration through 20-gauge or larger IV line is safe and effective 5
• If hypotension persists, add vasopressin (0.01-0.04 units/min) or terlipressin (1-2 mg boluses) 6, 5
• Epinephrine is third-line if shock remains refractory 5

Critical Pitfall: Never continue aggressive fluid resuscitation if signs of volume overload appear (pulmonary rales/crepitations, hepatomegaly)—immediately switch to vasopressors/inotropes. 4, 1, 6

When to Stop Fluid Resuscitation

Immediately stop or interrupt fluid administration when: 4, 6

• No improvement in tissue perfusion occurs despite volume loading
• Development of pulmonary crepitations (indicates fluid overload or impaired cardiac function)
• Hepatomegaly develops
• Respiratory impairment occurs, especially if mechanical ventilation unavailable

Inotropic Support (Selective Use Only)

Do not use inotropes routinely. Only indicated when low cardiac output is accompanied by ScvO₂ <70% despite optimal fluid resuscitation, anemia correction, and vasopressor use. 6

• Combination of dobutamine and norepinephrine is first-line inotropic treatment 6
• Titrate to targeted response: improvements in ScvO₂, myocardial function, and lactate reduction 6

Critical Pitfall: Never use inotropes based solely on low cardiac output measurement—requires concurrent ScvO₂ <70%. 1, 6

Corticosteroid Therapy

Administer hydrocortisone only in vasopressor-dependent septic shock despite adequate fluid resuscitation. 6, 2, 5

• Hydrocortisone 200-300 mg/day (or up to 300 mg/day) for at least 5 days, then taper 4, 6
• Alternative: prednisolone up to 75 mg/day 4
• Consider adding fludrocortisone in refractory shock 5

Critical Pitfall: Do not use corticosteroids in sepsis without shock—no evidence of benefit and potential for harm. 6

Respiratory Support

Oxygen administration: 4, 2

• Apply oxygen to achieve SpO₂ ≥90-95%
• If no pulse oximeter available, administer oxygen empirically in severe sepsis/septic shock

Positioning and airway management: 4, 2

• Place patients semi-recumbent (head of bed 30-45 degrees) to prevent aspiration
• Unconscious patients should be placed in lateral position with clear airway

Mechanical ventilation (if required): 2

• Use low tidal volume ventilation (6 mL/kg ideal body weight)
• Limit plateau pressure ≤30 cmH₂O
• Consider non-invasive ventilation for dyspnea/persistent hypoxemia despite oxygen therapy if staff adequately trained 4

Source Control

Identify and control the infection source within 12 hours of diagnosis. 4, 1, 2

• Use the least invasive effective intervention (percutaneous drainage preferred over surgical when feasible) 4, 1
• Drain abscesses, debride necrotic tissue, remove infected foreign bodies/devices 4
• Common sources requiring intervention: necrotizing fasciitis, cholangitis, obstructive urinary tract infection, pleural empyema, septic arthritis 4
• Remove any artificial device (venous catheter, prosthesis) if device-related infection suspected 4

Post-Acute Management (Within 24 Hours)

Antimicrobial stewardship: 4, 2

• Reassess antimicrobial regimen daily for de-escalation once culture results available
• Narrow therapy to pathogen susceptibility to reduce resistance development
• Use procalcitonin levels to support shortening duration or discontinuing empiric antibiotics
• Administer antimicrobials for adequate but not prolonged duration (typically 7-10 days for most serious infections) 1

Supportive care: 4, 2

• Target hemoglobin 7-9 g/dL (transfuse if <7 g/dL unless active ischemia)
• Provide DVT prophylaxis with heparin and/or elastic bandages in post-pubertal children and adults
• Target blood glucose ≤180 mg/dL with insulin infusion if needed; maintain >70 mg/dL (>4 mmol/L) by providing glucose calorie source
• Resume oral feeding once patient is fully resuscitated and awake

Continuous Monitoring Requirements

Never leave the septic patient alone—ensure continuous observation. 4

• Perform clinical examinations several times per day 4
• Use continuous patient monitor with meaningful alarm limits when available 4
• Document vital signs at meaningful intervals 4
• If patient deteriorates or fails to improve, look for treatment failure causes: inadequate empirical therapy, missed/insufficient source control, new antimicrobial resistance, hospital-acquired infection, or alternative diagnosis 4

Common Pitfalls to Avoid

• Never delay antibiotics beyond 1 hour for any reason—mortality increases significantly with each hour of delay 1, 2
• Stop fluid resuscitation immediately if no improvement in tissue perfusion or signs of overload develop 4, 1, 6
• Do not use predetermined fluid protocols—titrate to individual clinical response 6
• Do not initiate steroids based on elevated inflammatory markers alone without vasopressor-dependent shock 6
• Ensure adequate antimicrobial dosing—pharmacokinetics/pharmacodynamics are significantly altered in septic shock, requiring individualized dosing with therapeutic drug monitoring 7