What is the treatment for septic shock?

Treatment of Septic Shock

Septic shock requires immediate aggressive fluid resuscitation followed by early antimicrobial therapy within one hour of recognition, with norepinephrine as the first-line vasopressor if hypotension persists despite adequate fluid loading. 1

Immediate Resuscitation (First Hour)

Fluid Resuscitation

• Administer crystalloid fluid challenge of 30 mL/kg body weight as rapidly as possible 2
• Deliver 500 mL boluses over 30 minutes, targeting restoration of tissue perfusion 2
• Continue fluid loading if patient remains preload-dependent (responsive to volume) 2
• Stop fluid resuscitation immediately if hepatomegaly or pulmonary rales develop - this indicates fluid overload and necessitates inotropic support instead 2

Antimicrobial Therapy

• Obtain blood cultures (at least 2 sets: one percutaneous, one through vascular access) but do not delay antibiotics beyond 45 minutes 2, 1
• Administer broad-spectrum IV antimicrobials within 1 hour of septic shock recognition 2, 1
• Cover all likely pathogens including bacterial, and potentially fungal or viral organisms 2
• If IV access is unavailable, use intraosseous access or intramuscular administration of compatible antibiotics (ceftriaxone, cefepime, ertapenem, imipenem/cilastatin) 2

Hemodynamic Targets

• Mean arterial pressure (MAP) ≥ 65 mmHg 2
• SpO2 ≥ 95% 2
• Urine output ≥ 0.5 mL/kg/hour 2
• Central venous oxygen saturation (ScvO2) ≥ 70% 2

Vasopressor Therapy

First-Line Vasopressor

• If MAP < 65 mmHg persists after 30 mL/kg crystalloid challenge, initiate norepinephrine immediately 2
• Early vasopressor use reduces organ failure incidence 2
• Norepinephrine is the preferred first-line agent due to its potent vasoconstrictor properties 2

Inotropic Support

• Do not use inotropes routinely 2
• Add dobutamine only when low cardiac output is accompanied by ScvO2 < 70% despite adequate fluid resuscitation and vasopressor use 2
• Titrate to improvements in ScvO2, myocardial function indices, and lactate reduction 2
• The combination of dobutamine plus norepinephrine is recommended as first-line inotrope/vasopressor therapy 2
• Epinephrine is equally efficacious but reserved for refractory cases due to metabolic side effects 2

Refractory Shock

• For vasopressor-refractory shock, add vasopressin (0.01-0.04 units/min) or terlipressin (1-2 mg boluses) as rescue therapy 2
• Consider hydrocortisone 200-300 mg/day for at least 5 days (then taper) in patients not responding to vasopressors 2
• Do not use ACTH stimulation test to guide steroid therapy 2

Source Control

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

Antimicrobial Management

Combination Therapy

• Use empiric combination therapy (≥2 antibiotics from different classes) for initial management of septic shock 2
• Combination therapy specifically recommended for neutropenic patients and multidrug-resistant pathogens (Acinetobacter, Pseudomonas) 2
• For Pseudomonas bacteremia with respiratory failure/shock: extended-spectrum beta-lactam plus aminoglycoside or fluoroquinolone 2
• For bacteremic Streptococcus pneumoniae with shock: beta-lactam plus macrolide 2

De-escalation Strategy

• Narrow antimicrobial therapy once pathogen sensitivities are known or clinical improvement is evident 2, 1
• Discontinue combination therapy within first few days of clinical improvement 2
• Perform daily assessment for antimicrobial de-escalation 2, 1
• Procalcitonin levels can support shortening therapy duration or discontinuing empiric antibiotics in patients with limited infection evidence 2, 1

Duration

• 7-10 days is adequate for most serious infections causing septic shock 2, 1
• Longer courses warranted for: slow clinical response, undrainable infection foci, Staphylococcus aureus bacteremia, fungal/viral infections, or immunodeficiency including neutropenia 2, 1
• Shorter courses appropriate for rapid resolution after source control of intra-abdominal/urinary sepsis 2

Pediatric Considerations

• Children require 20 mL/kg crystalloid boluses over 5-10 minutes (not 30 mL/kg as in adults) 2
• Norepinephrine remains first-line vasopressor 2
• Phosphodiesterase III inhibitors may be considered for low cardiac output with normal blood pressure 2
• Hydrocortisone dosing: 1 mg/kg every 6 hours 2
• Hypotension develops later than in adults, making early recognition more challenging 2

Critical Pitfalls to Avoid

• Never delay antibiotics beyond 1 hour for any reason - mortality increases significantly with each hour of delay 2, 1
• Do not continue aggressive fluid resuscitation if signs of volume overload appear (rales, hepatomegaly) - switch to vasopressors/inotropes 2
• Do not use inotropes based solely on low cardiac output measurement - require concurrent ScvO2 < 70% 2
• Do not use antimicrobials in severe inflammatory states proven to be noninfectious 2, 1
• Avoid activated protein C solely for hemodynamic management 2