What is the recommended initial management of septic shock, including antibiotics, fluid resuscitation, vasopressor selection, source control, and adjunctive therapies?

Septic Shock Management

Septic shock is a medical emergency requiring immediate, simultaneous interventions within the first hour: administer at least 30 mL/kg IV crystalloid within 3 hours, give broad-spectrum IV antibiotics within 1 hour of recognition, obtain blood cultures before antibiotics (but never delay antibiotics beyond 45 minutes), initiate norepinephrine if MAP remains <65 mmHg after initial fluids, measure lactate immediately and repeat within 6 hours if elevated, and identify/control the infection source within 12 hours. 1, 2

Immediate Recognition and Initial Actions (Hour One Bundle)

Fluid Resuscitation (First 3 Hours)

• Deliver at least 30 mL/kg of IV crystalloid (normal saline or balanced solution) within the first 3 hours of septic shock recognition—for a 70-kg adult this equals approximately 2 liters given as rapid 500–1000 mL boluses over 5–10 minutes. 1, 2
• Continue additional 250–500 mL crystalloid boluses while monitoring MAP, heart rate, mental status, urine output, and peripheral perfusion; stop when no further hemodynamic improvement is observed or signs of fluid overload appear (elevated jugular venous pressure, rising respiratory rate, decreasing oxygen saturation, pulmonary crackles). 1, 2, 3
• Avoid hydroxyethyl starch solutions entirely—they increase acute kidney injury and mortality. 3

Antimicrobial Therapy (Within 1 Hour)

• Administer IV broad-spectrum antibiotics within 1 hour of septic shock recognition—each hour of delay increases mortality by approximately 7.6%. 1, 2, 4
• Select empiric therapy covering gram-positive organisms (including MRSA when risk factors exist), gram-negative bacteria (including Pseudomonas aeruginosa in healthcare-associated infections), and anaerobes for intra-abdominal or aspiration sources. 1, 2, 4
• Add empiric antifungal coverage (e.g., an echinocandin) when immunosuppression, prolonged ICU stay, total parenteral nutrition, or recent broad-spectrum antibiotic exposure is present. 2
• Obtain at least two sets of blood cultures (aerobic and anaerobic) before antibiotics, but never postpone antimicrobial administration beyond 45 minutes to obtain cultures. 1, 2

Hemodynamic Targets (First 6 Hours)

• Target MAP ≥65 mmHg in most adults; consider higher targets (70–85 mmHg) for patients with chronic hypertension because their autoregulatory curve is shifted rightward. 1, 2
• Maintain urine output ≥0.5 mL/kg/hour as a bedside marker of adequate renal perfusion. 1, 2
• Achieve central venous pressure (CVP) 8–12 mmHg (or 12–15 mmHg if mechanically ventilated) to assess fluid responsiveness. 1, 2
• Ensure central venous oxygen saturation (ScvO₂) ≥70% (or mixed venous O₂ saturation ≥65%) to confirm sufficient tissue oxygen delivery. 1, 2
• Monitor clinical perfusion markers: capillary refill <2 seconds, warm extremities, normal mental status, and palpable peripheral pulses. 2

Lactate Monitoring

• Measure serum lactate immediately at septic shock recognition. 1, 2, 5
• Repeat lactate within 6 hours if the initial value is ≥2 mmol/L; use lactate trend toward normalization (≥10% reduction every 2 hours) to guide ongoing resuscitation. 1, 2, 5
• Lactate ≥4 mmol/L defines severe tissue hypoperfusion with 46.1% mortality and mandates immediate protocolized resuscitation. 2, 5

Vasopressor Management

First-Line Vasopressor

• Initiate norepinephrine when MAP remains <65 mmHg after the initial 30 mL/kg fluid bolus, starting at 0.05–0.1 µg/kg/min (approximately 5–10 µg/min for a 70-kg adult). 1, 2
• Norepinephrine is more effective than dopamine for reversing hypotension and causes fewer arrhythmias. 2
• Peripheral administration of norepinephrine is acceptable initially to avoid delays while central venous access is obtained. 2

Second-Line and Adjunctive Vasopressors

• Add vasopressin 0.03 U/min to norepinephrine when additional MAP support is required or to permit a lower norepinephrine dose; vasopressin should never be used as the sole initial vasopressor. 1, 2
• Introduce epinephrine as a third-line agent if MAP targets remain unmet despite norepinephrine plus vasopressin. 1, 2
• Avoid dopamine except in highly selected situations (e.g., bradycardia without tachyarrhythmia risk). 2

Inotropic Support

• Add dobutamine (2.5–5 µg/kg/min) when myocardial dysfunction or persistent tissue hypoperfusion ("cold shock") is evident despite adequate MAP and volume status—indicated by low cardiac output, cold extremities, or confusion. 2

Source Control (Within 12 Hours)

• Identify or exclude a specific anatomic infection source requiring emergent intervention (e.g., abscess, infected device, bowel perforation) within 12 hours of shock onset. 1, 2
• Perform definitive source-control procedures (drainage, debridement, removal of infected devices) as soon as medically and logistically feasible; inadequate source control is independently associated with increased mortality. 1, 2
• Choose the least physiologically invasive effective method—percutaneous drainage rather than open surgery when appropriate. 2
• Remove intravascular access devices that may be the infection source promptly after alternative access is secured. 2
• Exception: infected peripancreatic necrosis—delay definitive intervention until viable and non-viable tissue can be clearly demarcated. 2

Antimicrobial Stewardship and De-escalation

• Reassess antimicrobial therapy daily once pathogen identification and susceptibility results are available, typically within 48–72 hours. 1, 2
• De-escalate to the most appropriate single agent within 3–5 days based on culture data and clinical improvement; de-escalation is a protective factor for mortality. 2, 6, 7
• Plan a total antibiotic course of 7–10 days for most serious infections associated with septic shock. 1, 2, 7, 8
• Extend antibiotic duration for slow clinical response, undrained infection foci, Staphylococcus aureus bacteremia, fungal/viral infections, or immunodeficiency (e.g., neutropenia). 2, 7, 8

Adjunctive Therapies

Corticosteroids

• Do not use routine IV hydrocortisone in adult septic shock patients who achieve hemodynamic stability with fluids and vasopressors. 2
• Consider hydrocortisone 200 mg/day (e.g., 50 mg IV every 6 hours) only when hemodynamic stability cannot be attained despite adequate resuscitation. 2
• Taper hydrocortisone once vasopressor support is no longer required. 2

Blood Product Management

• Target hemoglobin 7–9 g/dL unless there is tissue hypoperfusion, ischemic coronary disease, or acute hemorrhage. 2
• Platelet transfusion thresholds: <10,000/mm³ (no bleeding), <20,000/mm³ (significant bleeding risk), ≥50,000/mm³ (active bleeding or invasive procedures). 2

Prophylaxis

• Provide pharmacologic deep-vein thrombosis prophylaxis unless contraindicated. 2
• Use stress-ulcer prophylaxis (H₂-blocker or proton-pump inhibitor) in patients with bleeding risk factors. 2

Mechanical Ventilation (When Required)

• For sepsis-induced ARDS, set tidal volume of 6 mL/kg predicted body weight. 2
• Keep plateau pressures ≤30 cm H₂O in passively inflated lungs. 2
• Apply positive end-expiratory pressure (PEEP) to prevent alveolar collapse; employ higher PEEP strategies in moderate-to-severe ARDS. 2
• Maintain head-of-bed elevation of 30–45° to reduce ventilator-associated pneumonia risk. 2
• Use prone positioning in patients with PaO₂/FiO₂ ratio <150 mmHg. 2

Common Pitfalls to Avoid

• Do not delay crystalloid resuscitation to give albumin first—crystalloids should always precede albumin; consider adding albumin only when large volumes of crystalloid fail to maintain MAP. 3
• Do not rely solely on MAP—normal MAP can coexist with severe tissue hypoperfusion ("cryptic shock"); always assess lactate, urine output, mental status, and capillary refill. 2, 5
• Do not assume a universal MAP target of 65 mmHg—adjust upward for chronic hypertension or intra-abdominal hypertension. 2
• Do not use dopamine as first-line therapy—it causes more arrhythmias and worse outcomes compared with norepinephrine. 2
• Do not give sodium bicarbonate when arterial pH is ≥7.15—it provides no hemodynamic benefit and may cause harm. 2, 5
• Do not treat uncorrected total calcium values in hypoalbuminemic patients—obtain ionized calcium measurement when symptomatic hypocalcemia is suspected. 3

Goals of Care Discussion

• Address goals of care early, ideally within the first 72 hours of ICU admission, incorporating palliative care principles where appropriate. 1, 2