What is the recommended initial management for an adult patient with sepsis but without septic shock, including antimicrobial therapy, fluid resuscitation, lactate measurement, source control, hemodynamic targets, and monitoring?

Management of Sepsis Without Shock

For adult patients with sepsis but without septic shock, administer broad-spectrum intravenous antimicrobials within one hour of recognition, give at least 30 mL/kg crystalloid fluid within the first 3 hours, measure lactate immediately and repeat within 6 hours if elevated, obtain blood cultures before antibiotics (without delaying beyond 45 minutes), identify and control the infection source as rapidly as possible, and target a mean arterial pressure ≥65 mmHg with ongoing monitoring of tissue perfusion markers. 1, 2

Immediate Recognition and Initial Actions (First Hour)

Antimicrobial Therapy

• Administer IV broad-spectrum antibiotics within one hour of sepsis recognition—this is the single most time-critical intervention, as each hour of delay increases mortality risk. 1, 2, 3
• Choose empiric agents with activity against all likely pathogens (gram-positive, gram-negative, and anaerobic organisms when appropriate) that achieve adequate tissue penetration at the presumed infection source. 1, 2
• Obtain at least two sets of blood cultures (aerobic and anaerobic) before starting antibiotics, but never delay antimicrobials more than 45 minutes to obtain cultures. 1, 2, 4
• Draw one culture set percutaneously and one through each vascular access device unless the device was placed less than 48 hours ago. 1, 2

Lactate Measurement

• Measure serum lactate immediately at sepsis recognition as a marker of tissue hypoperfusion. 1, 2
• Repeat lactate measurement within 6 hours if the initial value is elevated (≥2 mmol/L), using lactate normalization to guide resuscitation. 1, 2, 5
• Target lactate clearance of at least 10% every 2 hours during the first 8 hours of resuscitation. 5

Fluid Resuscitation (First 3 Hours)

Initial Fluid Bolus

• Give at least 30 mL/kg of intravenous crystalloid (normal saline or balanced solution) within the first 3 hours for patients with sepsis-induced hypoperfusion (defined by hypotension or lactate ≥4 mmol/L). 1, 2, 4
• For a 70-kg adult, this equals approximately 2 liters administered as rapid 500–1000 mL boluses over 5–10 minutes. 2

Ongoing Fluid Administration

• Continue fluid challenges using dynamic indices (pulse-pressure variation, stroke-volume variation) or static variables (blood pressure, heart rate, urine output) to guide therapy, administering additional fluid only while hemodynamic improvement is observed. 1, 2
• Stop fluid administration when hemodynamic parameters no longer improve to avoid fluid overload, which can worsen outcomes. 2, 4

Common Pitfall: Do not rely on central venous pressure (CVP) alone to guide fluid therapy—the 2017 Surviving Sepsis Campaign explicitly states CVP can no longer justify fluid management decisions. 5 Dynamic measures of fluid responsiveness are preferred. 5

Hemodynamic Targets and Monitoring

Blood Pressure Goals

• Target a mean arterial pressure (MAP) ≥65 mmHg in most adults to ensure adequate organ perfusion. 1, 2, 4
• For patients with chronic hypertension, consider a higher MAP target of 70–85 mmHg because their autoregulatory curve is shifted rightward. 2

Tissue Perfusion Markers

• Monitor urine output with a target of ≥0.5 mL/kg/hour as a bedside indicator of renal perfusion. 1, 2, 5
• Assess mental status, capillary refill time (<2 seconds), skin temperature, and peripheral pulses as additional perfusion endpoints. 2
• Use lactate normalization (<2 mmol/L) as a resuscitation endpoint to indicate resolution of tissue hypoperfusion. 1, 2, 5

Important Note: MAP alone does not guarantee adequate tissue perfusion—normal MAP can coexist with severe tissue hypoperfusion ("cold shock"). 2 Always supplement MAP with additional bedside markers. 2

Source Control

Rapid Identification

• Identify or exclude a specific anatomic infection source requiring emergent control as rapidly as possible, ideally within 12 hours of sepsis onset. 1, 2, 4
• Obtain prompt imaging studies to confirm the potential source of infection. 1, 2

Intervention Timing

• Perform required source-control interventions (drainage, debridement, device removal) as soon as medically and logistically feasible. 1, 2, 4
• Remove intravascular devices that may be infection sources after establishing alternative vascular access. 2, 4

Vasopressor Therapy (If Needed)

Indications for Vasopressors

• Initiate vasopressor therapy if MAP remains <65 mmHg after adequate fluid resuscitation (after the initial 30 mL/kg bolus). 2, 4
• In severe shock with critically low diastolic pressure, start vasopressors emergently even before fluids are complete. 2

Vasopressor Selection

• Norepinephrine is the first-line vasopressor, starting at 0.05–0.1 µg/kg/min and titrating to maintain MAP ≥65 mmHg. 1, 2, 4
• Peripheral administration of norepinephrine is acceptable initially to avoid delays while central venous access is obtained. 2
• Add vasopressin 0.03 U/min to norepinephrine when additional MAP support is needed or to permit a lower norepinephrine dose; vasopressin should never be used as the sole initial agent. 1, 2, 4
• Epinephrine may be added as a second-line agent if norepinephrine alone is insufficient. 1, 2, 4

Common Pitfall: Avoid dopamine as first-line therapy—it is associated with more arrhythmias and worse outcomes compared with norepinephrine. 2, 4

Antimicrobial Stewardship

Daily Reassessment

• 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. 1, 2

Duration of Therapy

• Plan a total antibiotic course of 7–10 days for most serious infections associated with sepsis. 1, 2
• Extend duration for slow clinical response, undrainable infection foci, Staphylococcus aureus bacteremia, fungal/viral infections, or immunodeficiency (e.g., neutropenia). 1, 2

Ongoing Monitoring and Reassessment

Frequent Clinical Evaluation

• Reassess the patient frequently using clinical examination (heart rate, blood pressure, respiratory rate, temperature, urine output, mental status) to evaluate response to treatment. 2
• Monitor for signs of adequate tissue perfusion including capillary refill time, skin mottling, temperature of extremities, and peripheral pulses. 2

Serial Lactate Monitoring

• Measure lactate every 2–6 hours during acute resuscitation to objectively evaluate response to therapy. 5, 6
• Lactate normalization within 24 hours is associated with 100% survival, decreasing to 77.8% if normalized within 48 hours, and only 13.6% if elevated beyond 48 hours. 5

Key Differences from Septic Shock Management

In sepsis without shock, vasopressors are typically not required initially—the focus is on early antimicrobials, adequate fluid resuscitation, and source control. 1, 2 However, if hypotension persists despite 30 mL/kg crystalloid or if lactate remains elevated ≥4 mmol/L, the patient has progressed to septic shock and requires vasopressor support. 1, 2

Avoid routine use of corticosteroids in sepsis without shock—hydrocortisone is only considered in septic shock when hemodynamic stability cannot be achieved despite adequate fluids and vasopressors. 1, 4