How should I immediately manage a patient with septic shock, including airway and breathing support, early broad‑spectrum antibiotics, fluid resuscitation, vasopressor therapy, source control, and adjunctive measures?

Immediate Management of Septic Shock

Begin resuscitation immediately with at least 30 mL/kg IV crystalloid within the first 3 hours, administer broad-spectrum antibiotics within 1 hour, and start norepinephrine if MAP remains <65 mmHg after initial fluid bolus. 1

Initial Resuscitation (First Hour)

Airway and Breathing Support

• Provide high-flow oxygen via face mask or high-flow nasal cannula to maintain SpO₂ >90%, escalating to non-invasive ventilation if respiratory distress persists despite oxygen therapy. 2, 1
• Prepare for endotracheal intubation if the patient develops worsening mental status, cannot protect the airway, or has refractory hypoxemia; perform cardiovascular resuscitation with fluids and vasopressors before intubation to minimize hemodynamic collapse during the procedure. 2
• If mechanical ventilation is required, use lung-protective strategies with tidal volumes of 6 mL/kg predicted body weight, plateau pressures ≤30 cm H₂O, and elevate the head of the bed to 30–45°. 2, 1

Fluid Resuscitation (First 3 Hours)

• Administer a minimum of 30 mL/kg IV crystalloid (normal saline or balanced solution) within the first 3 hours—this translates to approximately 2 liters for a 70-kg adult given as rapid 500–1000 mL boluses over 5–10 minutes. 2, 1
• Continue additional fluid boluses only while hemodynamic improvement is observed: rising blood pressure, improved mental status, increasing urine output, warming of extremities, and capillary refill <2 seconds. 1
• Stop fluid administration immediately if signs of fluid overload develop: new pulmonary rales, worsening respiratory distress, or hepatomegaly—these indicate the need for vasopressor/inotropic support rather than more fluid. 2, 1

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, 3
• Obtain at least two sets of blood cultures (aerobic and anaerobic) before starting antibiotics, but never delay antimicrobial administration beyond 45 minutes to obtain cultures. 1
• Choose empiric therapy that covers gram-positive organisms (including MRSA if risk factors present), gram-negative bacteria (including Pseudomonas aeruginosa in healthcare-associated infections), and anaerobes for intra-abdominal or aspiration sources. 1
• Add empiric antifungal coverage (e.g., an echinocandin) in patients with immunosuppression, prolonged ICU stay, total parenteral nutrition, or recent broad-spectrum antibiotic exposure. 1

Hemodynamic Targets (First 6 Hours)

Primary Resuscitation Endpoints

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

Lactate Monitoring

• Measure serum lactate immediately at septic shock recognition. 1
• Repeat lactate measurement within 6 hours if the initial value is elevated (≥2 mmol/L); use lactate normalization as a dynamic resuscitation endpoint indicating resolution of tissue hypoperfusion. 1, 3

Vasopressor Therapy (When MAP <65 mmHg After Fluids)

First-Line Vasopressor

• Initiate norepinephrine as the first-choice vasopressor 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, 3
• Norepinephrine can be safely administered through a peripheral 20-gauge or larger IV line while obtaining central venous access—do not delay vasopressor initiation waiting for a central line. 1, 3
• Norepinephrine is superior to dopamine, providing more reliable MAP elevation with fewer arrhythmic complications and better survival outcomes. 1

Second-Line and Adjunctive Vasopressors

• Add vasopressin at a fixed dose of 0.03 U/min to norepinephrine when additional MAP support is required or to reduce norepinephrine dose; vasopressin should never be used as the sole initial vasopressor. 1, 3
• Introduce epinephrine as a third-line agent if MAP targets remain unmet despite norepinephrine plus vasopressin. 1, 3
• Avoid dopamine as first-line therapy except in highly selected patients with low risk of tachyarrhythmias; it is associated with more arrhythmias and worse outcomes than norepinephrine. 1

Inotropic Support

• Add dobutamine (starting at 2.5–5 µg/kg/min) when myocardial dysfunction or ongoing tissue hypoperfusion persists despite adequate MAP and volume status—this "cold shock" physiology (cold extremities, confusion despite normal MAP) indicates low cardiac output requiring inotropic augmentation. 2, 1

Source Control (Within 12 Hours)

• Identify or exclude a specific anatomic infection source requiring emergent intervention (abscess, infected device, bowel perforation, necrotizing soft tissue infection) within 12 hours of shock onset. 1
• 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
• Choose the least physiologically invasive effective method, such as percutaneous drainage rather than open surgery when appropriate. 1
• Remove intravascular access devices that may be the infection source promptly after alternative access is secured. 1

Adjunctive Measures

Corticosteroids

• Do not use routine IV hydrocortisone in adult septic shock patients who achieve hemodynamic stability with fluids and vasopressors. 1
• Consider hydrocortisone 200 mg/day (or 50 mg IV every 6 hours) if hemodynamic stability cannot be attained despite adequate fluid resuscitation and vasopressor therapy, particularly in patients with suspected or proven absolute adrenal insufficiency. 2, 1

Blood Product Management

• Target hemoglobin 7–9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage; during active resuscitation with ScvO₂ <70%, a higher target of 10 g/dL may be considered. 2, 1
• Platelet transfusion thresholds: <10,000/mm³ without bleeding, <20,000/mm³ with significant bleeding risk, ≥50,000/mm³ for active bleeding or invasive procedures. 1

Prophylaxis

• Provide pharmacologic deep-vein thrombosis prophylaxis (low-molecular-weight heparin or unfractionated heparin) unless contraindicated. 1
• Use stress-ulcer prophylaxis (H₂-blocker or proton-pump inhibitor) in patients with bleeding risk factors. 1

Antimicrobial Stewardship (48–72 Hours)

• Reassess antimicrobial therapy daily once pathogen identification and susceptibility results are available, typically within 48–72 hours. 1, 4
• 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. 1, 4
• Plan a total antibiotic course of 7–10 days for most serious infections associated with septic shock. 1
• Extend antibiotic duration for slow clinical response, undrained infection foci, Staphylococcus aureus bacteremia, fungal/viral infections, or immunodeficiency (e.g., neutropenia). 1

Common Pitfalls to Avoid

• Do not continue fluid boluses indefinitely without hemodynamic improvement—recognize fluid-refractory shock (persistent hypotension after 30 mL/kg) and start vasopressors promptly rather than administering excessive fluid that risks pulmonary edema and abdominal compartment syndrome. 1
• Do not delay antibiotics while awaiting cultures or imaging—administer within 1 hour as this is the most time-critical intervention. 1, 3
• Do not rely solely on MAP to assess perfusion—normal MAP can coexist with severe tissue hypoperfusion ("cold shock"), so concurrently monitor mental status, urine output, skin perfusion, and lactate clearance. 1
• Do not wait for central venous access to start norepinephrine—peripheral administration through a 20-gauge or larger IV is safe and effective initially. 1, 3
• Do not assume a universal MAP target of 65 mmHg—adjust upward to 70–85 mmHg for patients with chronic hypertension to ensure adequate organ perfusion. 1