What are the recommended steps for early sepsis management, including fluid resuscitation, antibiotic timing, vasopressor use, source control, and monitoring?

Sepsis Management Guidelines

Sepsis and septic shock are medical emergencies requiring immediate, simultaneous action within the first hour: administer at least 30 mL/kg IV crystalloid, start broad-spectrum antibiotics, and initiate norepinephrine if hypotension persists despite fluids. 1, 2, 3

Immediate Recognition and Initial Actions (First Hour)

Recognize sepsis as a time-critical emergency where every hour of delayed treatment reduces survival by approximately 7.6%. 2, 4, 5 The following interventions must begin simultaneously, not sequentially:

Fluid Resuscitation (0–3 Hours)

• Administer at least 30 mL/kg of IV crystalloid within the first 3 hours (for a 70-kg adult, this equals approximately 2 liters). 1, 2
• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) as the preferred initial fluid rather than normal saline to reduce acid-base abnormalities. 3
• Deliver fluid in rapid boluses of 500–1000 mL over 15–30 minutes, reassessing hemodynamic response after each bolus. 3
• Stop fluid boluses immediately if signs of overload develop: pulmonary edema, new hepatomegaly, elevated jugular venous pressure, rising respiratory rate, or worsening oxygenation. 2, 3

Antimicrobial Therapy (Within 1 Hour)

• Administer broad-spectrum IV antibiotics within 60 minutes of recognizing sepsis or septic shock—this is the single most time-critical intervention. 1, 2, 4
• Obtain at least two sets of blood cultures (aerobic and anaerobic) before antibiotics, but never delay antibiotics more than 45 minutes to obtain cultures. 1, 2
• Choose empiric therapy covering gram-positive organisms (including MRSA when risk factors exist), gram-negative bacteria (including Pseudomonas in healthcare-associated infections), and anaerobes for intra-abdominal or aspiration sources. 2
• Add empiric antifungal coverage (e.g., echinocandin) in patients with immunosuppression, prolonged ICU stay, total parenteral nutrition, or recent broad-spectrum antibiotic exposure. 2

Hemodynamic Targets (First 6 Hours)

• Target mean arterial pressure (MAP) ≥ 65 mmHg in most adults; for patients with chronic hypertension, target 70–85 mmHg because their autoregulatory curve is shifted rightward. 1, 2, 3
• Maintain urine output ≥ 0.5 mL/kg/hour as a bedside marker of adequate renal perfusion. 1, 2
• Target central venous pressure (CVP) 8–12 mmHg (or 12–15 mmHg if mechanically ventilated) to assess fluid responsiveness. 1, 2
• Achieve central venous oxygen saturation (ScvO₂) ≥ 70% (or mixed venous O₂ saturation ≥ 65%) to confirm adequate 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 sepsis recognition as a baseline metabolic marker. 2, 3
• Repeat lactate within 2–6 hours if initially elevated (≥ 2 mmol/L); use lactate normalization as a resuscitation endpoint indicating resolution of tissue hypoperfusion. 1, 2, 3

Vasopressor Management

Initiation Criteria

• Start norepinephrine as the first-line vasopressor when MAP remains < 65 mmHg after the initial 30 mL/kg fluid bolus. 1, 2, 3, 6, 4
• Do not delay vasopressor initiation while attempting additional fluid resuscitation once the 30 mL/kg crystalloid challenge is complete and persistent hypotension indicates fluid-refractory shock. 6
• Peripheral administration of norepinephrine through a 20-gauge or larger IV line is safe and effective to avoid delays while obtaining central access. 2, 4

Dosing and Titration

• Begin norepinephrine at 0.05–0.1 µg/kg/min (approximately 5–10 µg/min for a 70-kg adult), titrating to maintain MAP ≥ 65 mmHg. 2, 6
• 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, 2, 4, 7
• Introduce epinephrine as a third-line agent if MAP targets remain unmet despite norepinephrine plus vasopressin. 1, 2, 4
• Avoid dopamine except in highly selected patients (e.g., low risk of tachyarrhythmias, bradycardia) because it is associated with more arrhythmias and worse outcomes compared with norepinephrine. 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, such as 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

Antimicrobial Stewardship and De-escalation

• Reassess antimicrobial therapy daily once pathogen identification and susceptibility results are available, typically within 48–72 hours. 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
• Plan a total antibiotic course of 7–10 days for most serious infections associated with septic shock. 1, 2
• Extend antibiotic duration for slow clinical response, undrained infection foci, Staphylococcus aureus bacteremia, fungal/viral infections, or immunodeficiency (e.g., neutropenia). 2

Adjunctive Therapies

Corticosteroids

• Do not use routine IV hydrocortisone in septic shock patients who achieve hemodynamic stability with adequate fluid resuscitation and vasopressor therapy. 2, 3
• Consider hydrocortisone 200 mg/day (e.g., 50 mg IV every 6 hours) if hemodynamic stability cannot be attained despite adequate resuscitation, especially when absolute adrenal insufficiency is suspected. 2, 3
• Do not use ACTH stimulation testing to decide whether a septic-shock patient receives hydrocortisone. 3

Blood Product Management

• Target hemoglobin 7–9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage. 2, 3
• Platelet transfusion thresholds: < 10,000/mm³ (no bleeding), < 20,000/mm³ (significant bleeding risk), ≥ 50,000/mm³ (active bleeding or invasive procedures). 2, 3

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)

• Use a tidal volume of 6 mL/kg predicted body weight and keep plateau pressures ≤ 30 cm H₂O to minimize ventilator-induced lung injury. 2, 3
• Apply positive end-expiratory pressure (PEEP) to prevent alveolar collapse; employ higher PEEP strategies in moderate-to-severe ARDS. 2, 3
• Maintain head-of-bed elevation of 30–45° to reduce ventilator-associated pneumonia risk. 2, 3
• Use prone positioning in patients with PaO₂/FiO₂ ratio < 150 mmHg to improve oxygenation. 2, 3

Ongoing Monitoring and Reassessment

• Reassess hemodynamic status after each 500–1000 mL fluid bolus, evaluating for improved perfusion markers: improved mental status, decreased heart rate, increased urine output, warming of extremities, and improved capillary refill. 2, 3
• Use dynamic indices (pulse-pressure variation, stroke-volume variation) over static variables to predict fluid responsiveness when available. 1, 2
• Establish continuous monitoring of heart rate, blood pressure, oxygen saturation, respiratory rate, mental status, and urine output. 2, 3

Common Pitfalls to Avoid

• Do not continue administering fluid boluses indefinitely in the absence of hemodynamic improvement; this represents fluid-refractory shock requiring vasopressor support. 6
• Do not rely solely on MAP; normal MAP can coexist with severe tissue hypoperfusion ("cold shock"). 2
• Do not delay vasopressor initiation to obtain central venous access; peripheral norepinephrine is safe and effective. 2, 4
• Avoid excessive fluid in patients with generalized peritonitis or at risk for abdominal compartment syndrome; fluid overload can worsen gut edema, raise intra-abdominal pressure, and precipitate respiratory compromise. 2

Goals of Care Discussion

• Address goals of care as early as feasible, but no later than within 72 hours of ICU admission, incorporating palliative care principles where appropriate. 1, 2