What is the appropriate approach to assess and manage a patient with suspected sepsis?

Approach to Suspected Sepsis

Immediately initiate the Hour-1 Bundle when sepsis is suspected: measure lactate, obtain blood cultures, administer broad-spectrum IV antibiotics within 1 hour, give 30 mL/kg crystalloid bolus for hypotension or lactate ≥4 mmol/L, and start vasopressors if hypotension persists despite fluids. 1, 2

Initial Recognition and Risk Stratification

Use the NEWS2 scoring system to rapidly assess severity and guide management intensity. 3, 2, 4 The NEWS2 assigns points based on seven physiological parameters: respiratory rate, oxygen saturation, supplemental oxygen use, systolic blood pressure, heart rate, level of consciousness, and temperature. 4

Risk categories are:

• High risk: NEWS2 ≥7 - requires immediate intervention 3, 2, 4
• Moderate risk: NEWS2 5-6 3, 2, 4
• Low risk: NEWS2 1-4 3, 2, 4
• Very low risk: NEWS2 0 3, 2, 4

Additional red flags regardless of NEWS2 score include mottled or ashen skin, non-blanching petechial/purpuric rash, or cyanosis of skin/lips/tongue. 2

The Hour-1 Bundle: Five Critical Actions

1. Measure Lactate Immediately

Draw lactate level immediately upon sepsis recognition and target normalization (<2 mmol/L) as a marker of adequate tissue perfusion. 1, 2 Remeasure within 2-4 hours if initially elevated (≥2 mmol/L) to guide ongoing resuscitation. 1

2. Obtain Blood Cultures Before Antibiotics

Draw at least two sets of blood cultures (aerobic and anaerobic bottles) before starting antibiotics—one set percutaneously and one through any vascular access device in place >48 hours. 3, 1, 2 However, never delay antibiotics beyond 45 minutes waiting for cultures. 1, 2

3. Administer Broad-Spectrum Antibiotics

Antibiotic timing is risk-stratified by NEWS2 score: 3, 4

• High risk (NEWS2 ≥7): within 1 hour 3, 1, 4
• Moderate risk (NEWS2 5-6): within 3 hours 3, 4
• Low risk (NEWS2 1-4): within 6 hours 3, 4

Select empiric therapy covering all likely pathogens with adequate tissue penetration to the presumed infection source. 3, 1, 2 Start an extended-spectrum β-lactam (piperacillin-tazobactam, cefepime, or carbapenem) in patients without known allergies or recent culture data. 1

Add combination therapy (aminoglycoside or fluoroquinolone to the β-lactam) for: 1

• Neutropenic patients
• Suspected multidrug-resistant organisms (Acinetobacter, Pseudomonas)
• Septic shock with respiratory failure where Pseudomonas is suspected

If IV access is unavailable, use intra-osseous or intramuscular administration rather than delaying therapy. 1

4. Aggressive Fluid Resuscitation

Administer 30 mL/kg IV crystalloid bolus rapidly (over 5-10 minutes) for hypotension or lactate ≥4 mmol/L. 3, 1, 2 Use either balanced crystalloids or normal saline as the initial fluid of choice. 1, 2

Continue fluid administration as long as hemodynamic factors improve based on dynamic or static variables: 1

• Dynamic: pulse pressure variation, stroke volume variation
• Static: arterial pressure, heart rate, capillary refill, skin mottling, mental status, urine output (target >0.5 mL/kg/hour)

The average patient receives approximately 30 mL/kg pre-randomization in major sepsis trials, but many require substantially more. 3 Following initial resuscitation, guide additional fluids by frequent reassessment of hemodynamic status rather than static measurements like CVP alone. 3, 2

5. Initiate Vasopressors for Persistent Hypotension

Start norepinephrine as the first-line vasopressor if hypotension persists despite adequate fluid resuscitation, targeting MAP ≥65 mmHg. 3, 1, 2 Do not delay vasopressor initiation while obtaining additional vascular access. 1

Consider hydrocortisone (up to 300 mg/day) or prednisolone (up to 75 mg/day) for patients with refractory septic shock not responding to vasopressor therapy. 3, 1

Source Control

Identify and control the infection source within 12 hours when feasible—do not delay surgical intervention or drainage procedures. 1, 2 Use the least physiologically invasive effective intervention (percutaneous drainage rather than open surgery when possible). 1, 2

Drain or debride infection sources including: 3, 2

• Abscesses (except pulmonary)
• Necrotizing soft tissue infections
• Gastrointestinal perforation
• Cholangitis
• Obstructive urinary tract infection
• Deep space infections (pleural empyema, septic arthritis)

Remove intravascular access devices promptly after establishing alternative access if they are a possible infection source. 1, 2

Ongoing Monitoring and Reassessment

Monitoring frequency based on NEWS2 risk category: 3, 4

• High risk: every 30 minutes 3, 4
• Moderate risk: every hour 3, 4
• Low risk: every 4-6 hours 3, 4

Reassess for: 3

• Heart rate, blood pressure, arterial oxygen saturation, respiratory rate, temperature
• Urine output, mental status
• Capillary refill time, skin mottling, peripheral pulse quality
• Lactate clearance

Antimicrobial De-escalation

Reassess antimicrobial therapy daily for potential de-escalation once culture results and clinical response are available. 3, 1, 2 Narrow to the most appropriate single agent as soon as susceptibility profiles are known. 1

Discontinue combination therapy within 3-5 days if the patient shows clinical improvement. 1 Use procalcitonin levels to support stopping empiric antibiotics in patients with no subsequent evidence of infection. 3, 1, 2

Respiratory Support

Administer oxygen to achieve saturation ≥90%. 3, 1 Position patients semi-recumbent (head of bed raised 30-45°) or laterally if unconscious. 3, 1

Use non-invasive ventilation for increased work of breathing or hypoxemia despite oxygen therapy. 3, 1 For mechanically ventilated patients with sepsis-induced ARDS, use lower tidal volumes (6 mL/kg ideal body weight) and limit plateau pressures to ≤30 cmH₂O. 1

Common Pitfalls to Avoid

• Delaying antimicrobial therapy beyond one hour in high-risk patients—each hour of delay decreases survival by approximately 7.6%. 1, 2
• Failing to obtain appropriate cultures before starting antibiotics (but never delaying antibiotics >45 minutes). 1, 2
• Inadequate initial fluid resuscitation—the fixed 30 mL/kg bolus enables clinicians to initiate resuscitation while obtaining more specific hemodynamic information. 3, 2
• Using CVP alone to guide fluid resuscitation—CVP cannot predict fluid responsiveness when within normal range (8-12 mmHg). 3
• Not reassessing for potential de-escalation of antimicrobial therapy once cultures and clinical response are available. 1, 2
• Missing occult sources of infection requiring source control—perform detailed examination and use imaging (CT chest with IV contrast for respiratory symptoms) to identify septic foci. 2, 4