What is the recommended sepsis bundle to initiate within the first hour for an adult patient with suspected sepsis or septic shock?

Sepsis Bundle: Hour-1 Bundle Components

For adult patients with suspected sepsis or septic shock, initiate the following five critical interventions within the first hour of recognition: measure lactate, obtain blood cultures before antibiotics, administer broad-spectrum IV antibiotics, give 30 mL/kg crystalloid bolus for hypotension or lactate ≥4 mmol/L, and start vasopressors if hypotension persists despite fluid resuscitation. 1

The Five Hour-1 Bundle Elements

1. Measure Lactate Level

• Obtain lactate immediately upon sepsis recognition and remeasure within 2-4 hours if initially elevated (≥2 mmol/L) 1
• Target lactate normalization (<2 mmol/L) as a marker of adequate tissue perfusion 2, 1
• Each 20-minute delay in obtaining lactate increases mortality risk 3

2. Obtain Blood Cultures Before Antibiotics

• Draw at least two sets of blood cultures (aerobic and anaerobic bottles) before starting antibiotics 2, 1
• Obtain one set percutaneously and one through any vascular access device present >48 hours 1
• Never delay antibiotics beyond 45 minutes waiting for cultures 1, 4
• Each 50-minute delay in obtaining blood cultures increases mortality 3

3. Administer Broad-Spectrum IV Antibiotics Within 1 Hour

• Give IV broad-spectrum antibiotics within 60 minutes of sepsis recognition—this is the single most time-critical intervention 1
• Each hour of antibiotic delay decreases survival by approximately 7.6% 1
• Delays beyond 125 minutes significantly increase mortality risk 3
• Empiric therapy must cover all likely pathogens (bacterial, fungal when appropriate) with adequate tissue penetration to the presumed infection source 1
• If IV access is unavailable, use intraosseous or intramuscular administration rather than delaying therapy 1

Recommended empiric regimens:

• Extended-spectrum β-lactam: piperacillin-tazobactam, cefepime, or carbapenem 1
• Add aminoglycoside or fluoroquinolone for neutropenic patients, suspected multidrug-resistant organisms, or septic shock with respiratory failure 1

4. Rapid Fluid Resuscitation

• Administer 30 mL/kg IV crystalloid bolus within the first 3 hours for hypotension or lactate ≥4 mmol/L 2, 1
• Infuse rapidly over 5-10 minutes, titrating to clinical response 1
• Use either balanced crystalloids or normal saline as initial fluid of choice 1
• Delays beyond 100 minutes in completing fluid bolus increase mortality 3
• Reassess hemodynamic status frequently after initial bolus: evaluate capillary refill, skin temperature, mental status, and urine output (target >0.5 mL/kg/hour) 2, 1

5. Initiate Vasopressors for Persistent Hypotension

• Start vasopressors if hypotension persists despite adequate fluid resuscitation 1
• Target mean arterial pressure (MAP) ≥65 mmHg 2, 1
• Norepinephrine is the first-line vasopressor agent 1
• Do not delay vasopressor initiation while obtaining additional vascular access 1

Critical Timing Evidence

The evidence strongly supports rapid bundle completion:

• Completing all bundle components within 3 hours is associated with significantly lower 28-day mortality (17.5% vs. 31.4%) and improved 90-day survival 5
• More rapid completion of the 3-hour bundle is associated with lower risk-adjusted in-hospital mortality (odds ratio 1.04 per hour delay) 6
• However, completion within 1 hour versus 1-3 hours shows no significant mortality advantage (21.5% vs. 15.9%, p=0.4), suggesting the 1-3 hour window is acceptable 5

Ongoing Management and De-escalation

Daily Antimicrobial Reassessment

• Reassess antibiotic therapy daily once culture and susceptibility results are available 1, 4
• Narrow to the most appropriate single agent as soon as susceptibility profiles are known 1
• Discontinue combination therapy within 3-5 days if clinical improvement occurs 1
• Use procalcitonin levels to support discontinuing empiric antibiotics in patients with no subsequent evidence of infection 1

Source Control

• Identify and control the infection source within 12 hours when feasible—do not delay surgical intervention or drainage procedures 1
• Use the least physiologically invasive effective intervention (percutaneous drainage rather than open surgery when possible) 1

Common Pitfalls to Avoid

• Do not wait for diagnostic certainty before initiating the bundle—sepsis is a medical emergency requiring immediate treatment 2, 1
• Do not delay antibiotics to obtain "perfect" cultures—sterilization of cultures occurs within minutes to hours after the first antibiotic dose 2
• Avoid inadequate initial fluid resuscitation, but monitor for fluid overload—use frequent reassessment rather than fixed volume targets beyond the initial 30 mL/kg 1
• Do not use hydroxyethyl starches—they are contraindicated in sepsis 1
• Failure to initiate appropriate empiric therapy increases mortality up to fivefold 4

Hemodynamic Targets During Resuscitation

Target the following endpoints 2:

• Capillary refill time <2 seconds
• Normal blood pressure for age (MAP >65 mmHg in adults)
• Warm extremities
• Urine output >0.5 mL/kg/hour
• Normal mental status
• Lactate <2 mmol/L