Sepsis Protocols: The Latest Updates and the APP's Role in Early Recognition

Sepsis remains one of the leading causes of death in hospitalized patients—and early recognition is the single biggest factor in survival. As an ICU APP, you're often the first provider to identify deterioration. Here's what you need to know.

Current Definitions: Sepsis-3

Since 2016, we've used the Sepsis-3 definitions:

Sepsis

Life-threatening organ dysfunction caused by a dysregulated host response to infection.

• Operationalized as: Suspected infection + SOFA score increase ≥2 points

Septic Shock

Sepsis with:

• Persistent hypotension requiring vasopressors to maintain MAP ≥65 mmHg
• AND lactate >2 mmol/L despite adequate fluid resuscitation

qSOFA (Quick SOFA)

Bedside screening for patients outside the ICU:

• Respiratory rate ≥22
• Altered mentation
• Systolic BP ≤100 mmHg

Note: qSOFA is a screening tool, not diagnostic criteria. Two or more points should trigger evaluation for sepsis.

The Hour-1 Bundle: What Matters Most

The Surviving Sepsis Campaign emphasizes early, aggressive treatment. The current recommendation is to begin resuscitation immediately upon recognition:

Within 1 Hour of Sepsis Recognition:

1. Measure lactate (remeasure if initial >2 mmol/L)
2. Obtain blood cultures before antibiotics (but don't delay antibiotics)
3. Administer broad-spectrum antibiotics
4. Begin rapid fluid resuscitation (30 mL/kg crystalloid) for hypotension or lactate ≥4 mmol/L
5. Start vasopressors if hypotensive during or after fluid resuscitation to maintain MAP ≥65 mmHg

Key Point: Don't Wait

Each hour of antibiotic delay increases mortality by ~7%. Get cultures, but don't wait for results to start empiric therapy.

Antibiotic Selection Principles

Empiric Coverage Should Include:

• Gram-positive organisms (including MRSA if risk factors)
• Gram-negative organisms (including Pseudomonas if risk factors)
• Consider fungal coverage in high-risk patients

Common Empiric Regimens:

Community-acquired, no MDR risk:

• Ceftriaxone + azithromycin, or
• Fluoroquinolone monotherapy

Healthcare-associated or MDR risk:

• Piperacillin-tazobactam or cefepime or meropenem
• PLUS vancomycin if MRSA concern
• Consider antifungal if prolonged hospitalization, TPN, immunocompromised

De-escalation

Once cultures return and source is identified, narrow antibiotics. De-escalation doesn't increase mortality and reduces resistance, costs, and adverse effects.

Fluid Resuscitation: Current Evidence

The 30 mL/kg Recommendation

This remains the starting point, but it's not a rigid requirement for all patients.

Evidence suggests:

• Initial fluid bolus improves outcomes in hypotension/hypoperfusion
• 30 mL/kg is a reasonable starting target
• But individualize based on response

When to Be Cautious with Fluids

• Known heart failure (start with smaller boluses, reassess)
• ESRD on dialysis
• Severe ARDS (fluid restriction may be beneficial after initial resuscitation)

Assessing Fluid Responsiveness

Rather than giving empiric liters, assess whether more fluid will help:

• Passive leg raise test: Raise legs 45°, if CO increases >10%, patient is fluid responsive
• Pulse pressure variation: If >13% with mechanical ventilation, likely fluid responsive
• IVC ultrasound: Collapsibility suggests volume responsiveness (limited by mechanical ventilation)

Vasopressor Selection

First-Line: Norepinephrine

• Potent alpha-1 agonist (vasoconstriction)
• Mild beta-1 effect (modest inotrope)
• Start at 0.05-0.1 mcg/kg/min, titrate to MAP ≥65

Second-Line: Vasopressin

• Add when norepinephrine is 0.25-0.5 mcg/kg/min
• Fixed dose: 0.03-0.04 units/min
• Catecholamine-sparing effect
• Does not titrate to MAP (set it and leave it)

Third-Line Options

• Epinephrine: If cardiac dysfunction suspected
• Phenylephrine: Pure alpha-agonist, use when tachyarrhythmias limit norepinephrine
• Angiotensin II: Newer agent for refractory vasoplegia

The APP's Role in Early Sepsis Recognition

Be the Early Warning System

• Review vitals proactively, not just when called
• Know which patients are high-risk (immunocompromised, recent surgery, indwelling devices)
• Trust nursing concerns—they see subtle changes first

Standardize Your Approach

When called for "patient doesn't look right":

1. Go to the bedside immediately
2. Assess ABCs
3. Check vitals, mental status
4. Look for infection source
5. Order lactate if any concern

Empower and Educate

• Teach nurses qSOFA and when to call
• Create clear escalation pathways
• Debrief after sepsis cases to improve recognition

Lactate: More Than Just a Number

Interpretation

• Lactate >2 mmol/L suggests tissue hypoperfusion
• Lactate >4 mmol/L indicates significant shock
• Lactate clearance correlates with survival

Causes of Elevated Lactate

• Type A (hypoxic): Shock, hypoxemia, CO poisoning
• Type B (non-hypoxic): Medications (metformin, albuterol), liver failure, malignancy, thiamine deficiency

Lactate-Guided Resuscitation

Target lactate normalization (or at least 10-20% decrease per 2 hours) as a resuscitation endpoint.

Source Control: Don't Forget the Basics

Antibiotics alone don't cure sepsis if the source remains:

• Drain abscesses
• Remove infected lines
• Debride necrotic tissue
• Relieve obstructions (biliary, urinary)

The most powerful antibiotic is the scalpel (or IR-guided drain).

Corticosteroids in Septic Shock

Current Guidance

Consider hydrocortisone (200 mg/day IV in divided doses or continuous infusion) if:

• Septic shock requiring escalating vasopressors
• Not responding adequately to fluids and initial vasopressors

Evidence Summary

• Small mortality benefit in most refractory cases
• Faster shock reversal
• Unclear optimal duration (typically 5-7 days, taper)

Monitoring and Reassessment

Hourly During Active Resuscitation

• Blood pressure and MAP
• Urine output (target >0.5 mL/kg/hr)
• Mental status
• Lactate trends

Every 6-12 Hours

• Repeat lactate until normalizing
• Reassess volume status
• Evaluate antibiotic adequacy
• Source control status

The Bottom Line

Sepsis outcomes depend on rapid recognition and aggressive early treatment. As an APP, you're positioned to:

1. Recognize sepsis before it becomes septic shock
2. Initiate the hour-1 bundle immediately
3. Select appropriate empiric antibiotics
4. Resuscitate thoughtfully and reassess continuously
5. Champion source control

Every hour counts. Be proactive, be aggressive, and save lives.