What are the guideline-recommended steps for the initial management of a patient with suspected sepsis?

Initial Management of Suspected Sepsis

Use the NEWS2 score immediately to stratify risk and determine the urgency of antibiotic administration: give antibiotics within 1 hour for high-risk patients (NEWS2 ≥7), within 3 hours for moderate-risk (NEWS2 5-6), and within 6 hours for low-risk patients (NEWS2 1-4). 1

Immediate Risk Stratification

Calculate the NEWS2 score using six physiological parameters: respiratory rate, oxygen saturation, supplemental oxygen requirement, systolic blood pressure, heart rate, level of consciousness, and temperature. 1

Interpret NEWS2 scores in clinical context:

• NEWS2 ≥7 = High risk requiring immediate intervention and monitoring every 30 minutes 1
• NEWS2 5-6 = Moderate risk requiring hourly monitoring 1
• NEWS2 1-4 = Low risk requiring monitoring every 4-6 hours 1

Automatically escalate risk assessment if any of these danger signs are present, regardless of NEWS2 score: 1

• Mottled or ashen skin appearance
• Non-blanching petechial or purpuric rash
• Cyanosis of skin, lips, or tongue

Re-evaluate risk higher than the NEWS2 suggests if the patient's condition is deteriorating or not improving despite interventions. 1

The Hour-1 Bundle: Five Critical Actions

1. Measure Lactate Immediately

Obtain a lactate level within the first hour and remeasure within 2-4 hours if elevated (≥2 mmol/L), targeting lactate normalization as a marker of adequate tissue perfusion. 2, 3 Elevated lactate ≥4 mmol/L indicates severe tissue hypoperfusion requiring aggressive resuscitation. 2, 3

2. Obtain Blood Cultures Before Antibiotics

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

3. Administer Broad-Spectrum Antibiotics

Antibiotic timing is risk-stratified based on NEWS2: 1

• High risk (NEWS2 ≥7): within 1 hour 1, 2
• Moderate risk (NEWS2 5-6): within 3 hours 1
• Low risk (NEWS2 1-4): within 6 hours 1

Select empiric antibiotics that cover all likely pathogens with adequate tissue penetration to the presumed infection source. 2, 3 For patients without known allergies or recent culture data, start an extended-spectrum β-lactam such as piperacillin-tazobactam, cefepime, or a carbapenem. 2

Add combination therapy (aminoglycoside or fluoroquinolone) for: 2

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

If IV access is unavailable, use intraosseous or intramuscular administration rather than delaying therapy. 2

4. Rapid Fluid Resuscitation

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

Continue fluid administration as long as hemodynamic parameters improve, monitoring: 2, 3

• Systolic/mean arterial pressure increase >10%
• Heart rate reduction >10%
• Improved mental status
• Improved peripheral perfusion (capillary refill, skin temperature)
• Urine output ≥0.5 mL/kg/hour

Never use hydroxyethyl starches—they are contraindicated in sepsis. 2 Consider albumin when patients require substantial amounts of crystalloids to maintain adequate mean arterial pressure. 1, 2

5. Initiate Vasopressors for Persistent Hypotension

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

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

Source Control

Identify and control the infection source within 12 hours when feasible—do not delay surgical intervention or drainage procedures. 2, 3 Use the least physiologically invasive effective intervention (percutaneous drainage rather than surgical drainage of an abscess when possible). 2

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

Ongoing Monitoring and Reassessment

Re-calculate NEWS2 score at these intervals: 1

• Every 30 minutes for high-risk patients (NEWS2 ≥7)
• Every hour for moderate-risk patients (NEWS2 5-6)
• Every 4-6 hours for low-risk patients (NEWS2 1-4)

Monitor vital signs, capillary refill, skin mottling, mental status, and urine output continuously. 2, 3 Remeasure lactate within 2-4 hours if initially elevated, targeting normalization. 2, 3

Daily Antimicrobial Reassessment

Reassess antimicrobial therapy daily for potential de-escalation once culture results and clinical response are available. 2, 3 Narrow to the most appropriate single agent as soon as susceptibility profiles are known. 2 Discontinue combination therapy within 3-5 days if the patient shows clinical improvement. 2

Use procalcitonin levels to support shortening antimicrobial duration or discontinuing empiric antibiotics in patients with limited clinical evidence of infection. 2, 3

Additional Supportive Care

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. 2

Target hemoglobin between 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage. 1, 2

Provide pharmacological or mechanical deep vein thrombosis prophylaxis. 1, 2

Consider hydrocortisone 200 mg/day for patients with refractory septic shock not responding to vasopressor therapy after at least 4 hours of norepinephrine or epinephrine at ≥0.25 µg/kg/min. 2, 3

Common Pitfalls to Avoid

Do not rely solely on qSOFA for sepsis screening—it has poor sensitivity (31-50%) and should not delay treatment initiation. 2 qSOFA is a bedside screening tool, not a diagnostic criterion.

Do not wait for lactate results or culture acquisition to delay antibiotics beyond the risk-stratified time windows. 2, 3

Avoid inadequate initial fluid resuscitation, but also monitor for fluid overload and pulmonary edema with serial reassessment. 3

Do not interpret persistent tachycardia as antibiotic failure alone—it may indicate inadequate resuscitation or uncontrolled infection source requiring further investigation. 4