What is the initial management for a patient with sepsis?

Initial Management of Sepsis

Administer IV broad-spectrum antimicrobials within one hour of recognizing sepsis or septic shock, immediately after obtaining blood cultures, while simultaneously initiating aggressive fluid resuscitation with 30 mL/kg crystalloid. 1

Immediate Actions (Within First Hour)

Obtain Cultures Before Antibiotics

• Draw at least two sets of blood cultures (both aerobic and anaerobic bottles) before starting antimicrobials, but do not delay antibiotics beyond 45 minutes to obtain them 1
• One set should be drawn percutaneously and one through each vascular access device (unless inserted within 48 hours) 1
• Sample any suspected infection source (fluid, tissue) when feasible 2
• Consider 1,3-β-D-glucan assay, mannan, and anti-mannan antibody assays if invasive candidiasis is in the differential 1

Initiate Antimicrobial Therapy

• Start IV antimicrobials within one hour for both sepsis and septic shock—this is a strong recommendation with moderate quality evidence 1
• Use empiric broad-spectrum therapy covering all likely pathogens (bacterial, and potentially fungal or viral) 1
• Select agents with good penetration into the presumed infection source 3
• For septic shock specifically, use combination therapy with at least two antibiotics from different antimicrobial classes targeting the most likely bacterial pathogens 1, 4
• Account for healthcare-associated infection risk factors (hospitalization >1 week, previous antimicrobial therapy, healthcare setting acquisition) when selecting agents 5

Fluid Resuscitation

• Administer at least 30 mL/kg of IV crystalloid within the first 3 hours for sepsis-induced hypoperfusion 1, 4
• Some patients may require more rapid administration and greater fluid volumes 1
• Continue fluid challenges as long as hemodynamic improvement occurs based on dynamic or static variables 1
• After initial resuscitation, guide further fluids by frequent reassessment of hemodynamic status 2

Measure Lactate

• Obtain serum lactate levels as a marker of tissue hypoperfusion 4
• Guide resuscitation to normalize lactate in patients with elevated levels 1

Hemodynamic Support (If Hypotension Persists)

Vasopressor Therapy

• Target mean arterial pressure (MAP) ≥65 mmHg in patients requiring vasopressors 1, 4
• Norepinephrine is the first-choice vasopressor 1, 4
• Add epinephrine when an additional agent is needed to maintain adequate blood pressure 1
• Vasopressin (0.03 U/min) can be added to norepinephrine to raise MAP or decrease norepinephrine dose, but should not be used as the initial vasopressor 1
• Dopamine is not recommended except in highly selected circumstances 1

Inotropic Support

• Administer dobutamine infusion in the presence of myocardial dysfunction (elevated cardiac filling pressures and low cardiac output) or ongoing signs of hypoperfusion despite adequate intravascular volume and MAP 1

Source Control

• Identify and implement source control interventions as soon as possible after diagnosis, ideally within 12 hours when feasible 2
• Remove intravascular access devices confirmed as the infection source after establishing alternative vascular access 4
• Drain or debride infection sources when possible 2

Antimicrobial Stewardship (Daily Reassessment)

De-escalation Strategy

• Reassess antimicrobial regimen daily for potential de-escalation 1
• Narrow therapy once pathogen identification and sensitivities are established and/or adequate clinical improvement is noted 1
• If combination therapy is used for septic shock, discontinue it within the first few days in response to clinical improvement or evidence of infection resolution 1

Duration of Therapy

• Antimicrobial treatment duration of 7-10 days is adequate for most serious infections associated with sepsis 1, 3
• Longer courses are appropriate for slow clinical response, undrainable foci of infection, Staphylococcus aureus bacteremia, some fungal/viral infections, or immunologic deficiencies including neutropenia 1
• Shorter courses are appropriate for rapid clinical resolution following effective source control of intra-abdominal or urinary sepsis, and anatomically uncomplicated pyelonephritis 1

Common Pitfalls to Avoid

• Do not delay antimicrobials beyond one hour while waiting for cultures or imaging—the risk of progression from severe sepsis to septic shock increases 8% for each hour before antibiotics are started 6
• Do not use sustained systemic antimicrobial prophylaxis in patients with severe inflammatory states of noninfectious origin (e.g., severe pancreatitis, burn injury) 1
• Do not routinely use combination therapy for ongoing treatment of most serious infections without shock, including bacteremia and sepsis without shock 1
• Do not use combination therapy for routine treatment of neutropenic sepsis/bacteremia 1
• Avoid hetastarch formulations for fluid resuscitation 1
• Do not use IV hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy restore hemodynamic stability 1

Optimizing Antimicrobial Dosing

• Optimize dosing strategies based on accepted pharmacokinetic/pharmacodynamic principles and specific drug properties 1
• Consider loading doses for all patients, then individualize further doses according to PK/PD and presence of renal/liver dysfunction 7
• Extended or continuous infusion of beta-lactams and therapeutic drug monitoring can help achieve therapeutic levels 7