What is the appropriate treatment for a patient with sepsis?

Sepsis Treatment

Administer intravenous broad-spectrum antimicrobials within one hour of recognizing sepsis or septic shock, initiate aggressive fluid resuscitation with 30 mL/kg crystalloid bolus, and start vasopressors targeting mean arterial pressure ≥65 mmHg if hypotension persists despite adequate fluid loading. 1, 2

Immediate Actions (Within First Hour)

Antimicrobial Therapy

• Start IV broad-spectrum antibiotics within 1 hour of sepsis recognition - each hour of delay decreases survival by approximately 7.6% 2, 3
• Obtain at least two sets of blood cultures (one percutaneous, one through each vascular access device if present >48 hours) before antibiotics, but never delay antimicrobials beyond 45 minutes for culture collection 1, 2
• Select empiric coverage based on: suspected infection source, patient location (community vs hospital-acquired), local resistance patterns, recent antimicrobial exposure within 3 months, immunosuppression status, and indwelling devices 1
• Cover gram-negative bacteria, gram-positive organisms, and consider fungal/viral pathogens based on clinical context 1
• If vascular access is difficult, use intraosseous access or intramuscular β-lactams (imipenem/cilastatin, cefepime, ceftriaxone, ertapenem) rather than delaying treatment 1

Fluid Resuscitation

• Administer 30 mL/kg crystalloid bolus rapidly (over 5-10 minutes) for hypotension or lactate ≥4 mmol/L 2, 3
• Use crystalloids (normal saline or balanced solutions) as first-line resuscitation fluid 2
• Continue fluid loading if patient shows preload dependence with positive response: >10% increase in systolic/mean arterial pressure, >10% reduction in heart rate, or improvement in mental status, peripheral perfusion, or urine output 1
• Stop fluid resuscitation when no improvement occurs or signs of fluid overload develop (pulmonary crackles) 1
• Children may require up to 110 mL/kg during early resuscitation, but use caution with fluid boluses in profound anemia (particularly malaria) - consider blood transfusion instead 1

Hemodynamic Monitoring

• Measure serum lactate immediately and remeasure within 2-4 hours if initially elevated 2, 3
• Target mean arterial pressure (MAP) ≥65 mmHg 1, 2, 4
• Monitor urine output (target ≥0.5 mL/kg/hour), capillary refill time, skin mottling, peripheral pulses, and mental status 1, 2, 3

Vasopressor Therapy

First-Line Agent

• Use norepinephrine as first-choice vasopressor if MAP <65 mmHg persists despite adequate fluid resuscitation 1, 2
• Start vasopressors early to reduce organ failure incidence 1

Additional Vasopressor Support

• Add epinephrine when additional agent needed to maintain adequate blood pressure 2
• Use vasopressin (0.01-0.04 units/min) or terlipressin (boluses of 1-2 mg) as rescue therapy in refractory shock 1, 2

Inotropic Support

• Do not routinely use inotropes 1
• Indicate inotropes only when low cardiac output accompanies central/superior vena cava oxygen saturation (ScvO2/SvcO2) <70% despite optimal fluid resuscitation, anemia correction, and vasopressor use 1
• Use dobutamine plus norepinephrine as first-line inotropic combination, titrating to ScvO2/SvcO2 improvement, enhanced myocardial function, and lactate reduction 1

Pediatric differences: Norepinephrine remains first-line; consider phosphodiesterase III inhibitors for low cardiac output with normal arterial pressure 1

Source Control

• Identify and control infection source within 12 hours of diagnosis 1, 2
• Use least physiologically invasive effective intervention (percutaneous drainage preferred over surgical when feasible) 1
• Remove intravascular access devices promptly if suspected source, after establishing alternative access 1
• Delay definitive intervention for infected peripancreatic necrosis until adequate demarcation of viable/nonviable tissue occurs 1

Antimicrobial De-escalation and Duration

• Reassess antimicrobial regimen daily for potential de-escalation once pathogen identification and sensitivities established 1, 2
• Narrow to most appropriate single therapy as soon as susceptibility profile known 1
• Typical duration: 7-10 days; longer courses for slow clinical response, undrainable foci, S. aureus bacteremia, fungal/viral infections, or immunodeficiencies including neutropenia 1
• Consider procalcitonin or similar biomarkers to assist discontinuation in patients initially appearing septic but lacking subsequent infection evidence 1

Combination Antimicrobial Therapy

Use combination empiric therapy for:

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

Limit combination therapy to 3-5 days maximum, then de-escalate to single appropriate agent 1

Corticosteroid Therapy

• Use hydrocortisone 200-300 mg/day for at least 5 days (followed by taper) in septic shock patients not responding to vasopressors 1
• Pediatric dose: hydrocortisone 1 mg/kg every 6 hours 1

Respiratory Support

• Administer oxygen to achieve saturation ≥90% (target ≥95% per minimum monitoring) 1, 2, 3
• Position patients semi-recumbent (head of bed elevated 30-45°) or laterally if unconscious 2, 3
• Use low tidal volume ventilation (6 mL/kg predicted body weight) with plateau pressures ≤30 cmH2O for sepsis-induced ARDS 2, 3

Metabolic Management

• Check blood glucose in every septic patient; maintain >70 mg/dL by providing glucose calorie source 3
• Correct electrolyte imbalances, particularly sodium abnormalities 3

Critical Pitfalls to Avoid

• Never delay antimicrobials beyond one hour - mortality increases substantially with each hour of delay 2, 3
• Do not use hydroxyethyl starches for fluid resuscitation - contraindicated in sepsis 3
• Never leave septic patients unattended - ensure continuous observation and clinical examinations several times daily 1, 2
• Do not overlook inadequate source control - reassess for missed or insufficient source control if fever and organ dysfunction persist beyond 48-72 hours 3
• Avoid excessive fluid administration without frequent reassessment - can cause fluid overload and respiratory compromise 1, 2
• Balance adequate pulmonary gas exchange against optimum intravascular filling when mechanical ventilation unavailable, though this dilemma is infrequent within first 6 hours 1

Monitoring Strategy

Minimum parameters: 1

• SpO2 ≥95%
• MAP ≥65 mmHg (age-adjusted in children)
• Fluid loading: 500 mL/30 min
• Urine output ≥0.5 mL/kg/hour

Treatment goals: 1

• No clinical signs of hypoperfusion
• Continue fluid loading if preload dependence persists
• Titrate dobutamine (or epinephrine) based on monitoring parameters