What is the recommended initial management for an adult patient presenting with septic shock of unknown source?

Initial Management of Septic Shock in Adults

Begin immediate resuscitation with at least 30 mL/kg of IV crystalloid within the first 3 hours, obtain blood cultures, and administer broad-spectrum antibiotics within the first hour of recognizing septic shock. 1

Immediate Actions (First Hour)

Fluid Resuscitation

• Administer a minimum of 30 mL/kg of crystalloid fluid within the first 3 hours of recognizing sepsis-induced hypoperfusion (hypotension after initial fluid challenge or lactate ≥4 mmol/L). 1
• Use either balanced crystalloids or normal saline as your initial fluid of choice. 1
• Continue fluid challenges as long as hemodynamic parameters (MAP, heart rate, urine output, mental status, capillary refill) continue to improve. 1
• Consider adding albumin when patients require substantial amounts of crystalloids to maintain adequate MAP. 1
• Never use hydroxyethyl starch solutions—they increase acute kidney injury and mortality. 1

Antimicrobial Therapy

• Administer broad-spectrum IV antibiotics within 1 hour of recognizing septic shock. 1
• Obtain at least 2 sets of blood cultures (aerobic and anaerobic) before antibiotics, but do not delay antibiotics more than 45 minutes to obtain cultures. 1
• Draw one set percutaneously and one through each vascular access device (unless inserted <48 hours ago). 1
• Choose empiric antibiotics with activity against all likely pathogens (bacterial, fungal, or viral) that penetrate adequately into the presumed source tissues. 1

Source Control

• Identify the anatomic source of infection as rapidly as possible using imaging studies performed promptly. 1
• Implement source control intervention (drainage, debridement, device removal) as soon as medically and logistically practical after diagnosis, ideally within 12 hours. 1
• Remove intravascular access devices that are possible infection sources after establishing alternative vascular access. 1

Hemodynamic Targets and Monitoring

Initial Resuscitation Goals

• Target MAP ≥65 mmHg as your initial blood pressure goal. 1
• Aim for urine output ≥0.5 mL/kg/hour. 1
• Guide resuscitation to normalize lactate in patients with elevated lactate levels as a marker of tissue hypoperfusion. 1
• Monitor mental status, capillary refill time, and peripheral perfusion as additional markers of adequate resuscitation. 2

Fluid Responsiveness Assessment

• Use dynamic variables (pulse pressure variation, stroke volume variation) over static variables (CVP, heart rate) when available to predict fluid responsiveness. 1
• Reassess hemodynamic status frequently with thorough clinical examination and available physiologic variables. 1
• Stop fluid administration when hemodynamic parameters no longer improve with additional fluid challenges. 1

Vasopressor Therapy

First-Line Agent

• Start norepinephrine as the first-choice vasopressor to target MAP ≥65 mmHg. 1, 3
• Initiate vasopressors early—do not wait until fluid resuscitation is completed if hypotension persists. 3, 4
• Place an arterial catheter as soon as practical for continuous blood pressure monitoring in all patients requiring vasopressors. 1

Second-Line Agents

• Add vasopressin 0.03 units/min to norepinephrine when additional MAP support is needed or to decrease norepinephrine dosage. 1, 3
• Never exceed vasopressin 0.03-0.04 units/min—higher doses are reserved only for salvage therapy and risk ischemic complications. 1, 3
• Add epinephrine as a third agent if hypotension persists despite norepinephrine plus vasopressin. 1, 3

Agents to Avoid

• Do not use dopamine except in highly selected patients (absolute or relative bradycardia, low tachyarrhythmia risk)—it increases arrhythmias and mortality by 11% compared to norepinephrine. 1, 3
• Never use low-dose dopamine for renal protection (Grade 1A recommendation against). 1, 3
• Avoid phenylephrine except in specific scenarios: norepinephrine-induced serious arrhythmias, known high cardiac output with persistent low BP, or salvage therapy. 1

Inotropic Support

• Administer dobutamine 2.5-20 mcg/kg/min when myocardial dysfunction is present (elevated cardiac filling pressures with low cardiac output) or when signs of hypoperfusion persist despite adequate intravascular volume and MAP ≥65 mmHg. 1, 3, 5
• Do not use strategies to increase cardiac index to predetermined supranormal levels. 1

Corticosteroids

• Avoid IV hydrocortisone if adequate fluid resuscitation and vasopressor therapy restore hemodynamic stability. 1
• If hemodynamic stability cannot be achieved, consider hydrocortisone 200 mg/day IV only after ≥4 hours of high-dose vasopressor therapy. 1, 3
• Do not use ACTH stimulation testing to identify patients who should receive hydrocortisone. 1

Critical Pitfalls to Avoid

• Do not assume all tachycardia is pathologic—ensure adequate volume resuscitation, pain control, and sepsis treatment before aggressively targeting heart rate reduction. 3
• Do not delay antibiotics to obtain cultures—if obtaining cultures will delay antibiotics beyond 45 minutes, start antibiotics first. 1
• Do not rely solely on CVP to guide fluid therapy—it is a poor marker of intravascular volume status and fluid responsiveness. 1, 6
• Do not continue aggressive fluid administration when hemodynamic parameters stop improving—this causes fluid overload, delays organ recovery, and increases mortality. 6, 7
• Do not use amiodarone aggressively before hemodynamic optimization in patients with atrial fibrillation—it may worsen hypotension. 3

Ongoing Management

• Reassess antimicrobial regimen daily for potential de-escalation once culture results and susceptibility profiles are available. 1
• Typical antibiotic duration is 7-10 days; longer courses may be needed for slow clinical response, undrainable foci, S. aureus bacteremia, or immunodeficiency. 1
• Address goals of care and prognosis with patients and families as early as feasible, but within 72 hours of ICU admission. 1