What are the management guidelines for a patient with sepsis and septic shock?

Sepsis and Septic Shock: Clinical Definition, History, Examination, and Management

Clinical Definition

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, while septic shock is sepsis with persistent hypotension requiring vasopressors to maintain MAP ≥65 mmHg and lactate >2 mmol/L despite adequate fluid resuscitation. 1, 2

• Sepsis represents a medical emergency requiring immediate recognition and treatment 3, 1
• The pathophysiology involves vasoplegic (distributive) shock, myocardial depression, altered microvascular flow, and diffuse endothelial injury 4

Clinical History - Key Elements to Identify

Focus on identifying infection source and risk factors for severe disease:

• Infection symptoms: fever, chills, new cough, dysuria, abdominal pain, wound drainage, or other localizing symptoms 5
• Timeline: duration and progression of symptoms, recent procedures or hospitalizations 5
• Immunocompromise: diabetes, malignancy, chemotherapy, chronic steroids, HIV, or organ transplantation 3
• Recent antibiotic exposure: increases risk of resistant organisms 3
• Indwelling devices: central lines, urinary catheters, or prosthetic materials that may serve as infection source 3

Clinical Examination - Specific Findings to Assess

Systematically evaluate for signs of organ dysfunction and tissue hypoperfusion:

• Hemodynamic status: hypotension (SBP <90 mmHg or MAP <65 mmHg), tachycardia, or relative bradycardia 1, 6
• Perfusion markers: altered mental status, delayed capillary refill (>3 seconds), mottled or cool extremities 1, 6
• Respiratory: tachypnea, hypoxemia, increased work of breathing suggesting acute lung injury 1
• Infection source: examine for pneumonia, abdominal tenderness/peritonitis, cellulitis, meningismus, or line site erythema 2
• Urine output: oliguria (<0.5 mL/kg/hr) indicates renal hypoperfusion 3

Management Guidelines - Algorithmic Approach

Step 1: Immediate Actions (Within First Hour)

Administer broad-spectrum IV antimicrobials within 1 hour of recognition - this is the single most critical mortality-reducing intervention. 3, 1, 6

• Obtain blood cultures (at least two sets) and other appropriate cultures BEFORE antibiotics, but do not delay antimicrobials beyond 1 hour 3, 2
• Choose empiric antibiotics covering all likely pathogens based on suspected source, local resistance patterns, and patient risk factors 3, 1
• For septic shock specifically, use combination therapy (two different antimicrobial classes) targeting the most likely pathogen 3
• Measure serum lactate immediately as a marker of tissue hypoperfusion 1, 2

Step 2: Fluid Resuscitation (First 3 Hours)

Administer at least 30 mL/kg of IV crystalloid fluid within the first 3 hours for sepsis-induced hypoperfusion. 3, 1, 7

• Use crystalloids (normal saline or balanced solutions like lactated Ringer's) as first-choice fluid - both are acceptable options 3, 7, 6
• Consider adding albumin only when patients require substantial amounts of crystalloids (>30 mL/kg) 3, 7
• Never use hydroxyethyl starches - they increase acute kidney injury and mortality 3, 2, 7
• Apply fluid challenge technique: continue giving fluid boluses as long as hemodynamic parameters improve (rising blood pressure, improving mental status, increasing urine output) 3, 7
• Use dynamic measures of fluid responsiveness (pulse pressure variation, stroke volume variation) over static measures (CVP) when available 3, 7

Step 3: Vasopressor Therapy (If Hypotension Persists)

Initiate vasopressors if MAP remains <65 mmHg despite adequate fluid resuscitation, targeting MAP ≥65 mmHg. 3, 2, 7

• Norepinephrine is the first-choice vasopressor - start this agent first 3, 1, 2, 6
• Add vasopressin (up to 0.03 units/min) as second agent if additional support needed 3, 1
• Add epinephrine as third agent if MAP target still not achieved 3, 2, 6
• Vasopressors can be safely administered through peripheral IV (20-gauge or larger) if central access not immediately available 6
• Place arterial catheter for continuous blood pressure monitoring once vasopressors initiated 3

Step 4: Source Control (Within 12 Hours)

Identify and control the anatomic source of infection as rapidly as possible, ideally within 12 hours. 1, 2

• Drain abscesses, debride infected tissue, or remove infected devices/foreign bodies 2
• Remove intravascular catheters that are possible infection sources after establishing alternative access 3, 2
• Use the source control intervention with least physiologic insult (e.g., percutaneous drainage over open surgery when feasible) 2

Step 5: Ongoing Reassessment and Monitoring

Perform frequent reassessment of hemodynamic status using clinical examination and physiologic variables. 3, 1, 7

• Monitor heart rate, blood pressure, oxygen saturation, respiratory rate, temperature, urine output, mental status, and peripheral perfusion 3, 7
• Remeasure lactate within 6 hours if initially elevated - guide resuscitation to normalize lactate levels 1, 2
• Reassess for fluid overload signs (pulmonary edema, increasing oxygen requirements) - avoid excessive fluid administration 2

Step 6: Antimicrobial De-escalation (Daily Review)

Reassess antimicrobial regimen daily for potential narrowing or discontinuation. 3, 2

• Narrow therapy once pathogen identified and sensitivities known 3, 1
• For septic shock, discontinue combination therapy within first few days once clinical improvement evident 3
• Typical treatment duration is 7-10 days for most serious infections 3, 1
• Consider procalcitonin levels to support shortening duration in patients with limited infection evidence 3, 2

Step 7: Adjunctive Therapies for Refractory Shock

Consider hydrocortisone (with or without fludrocortisone) for refractory septic shock not responding to fluids and vasopressors. 6

• This applies when hypotension persists despite norepinephrine and at least one additional vasopressor 6

Critical Pitfalls to Avoid

Antibiotic delays: Every hour delay in antimicrobial administration increases mortality - prioritize this over obtaining all cultures if vascular access difficult 3, 6, 8

Fluid overresuscitation: Excessive fluids prolong ICU stay, delay organ recovery, and increase mortality - stop fluid boluses once hemodynamic improvement plateaus 2, 9

Using CVP to guide fluids: Central venous pressure is a poor predictor of fluid responsiveness - use clinical assessment and dynamic measures instead 7

Inadequate source control: Failure to drain abscesses or remove infected devices leads to treatment failure regardless of antibiotics 2, 9

Wrong vasopressor choice: Dopamine increases arrhythmias compared to norepinephrine and should only be used in highly selected patients with bradycardia 3

Treating non-infectious inflammation: Do not use antimicrobials for severe inflammatory states of non-infectious origin (severe pancreatitis, burns) 3, 2

Special Considerations for Refractory Shock

When patients fail to improve after standard therapy (30 mL/kg fluids, two vasopressors including norepinephrine, antibiotics), systematically evaluate: 9

• Source control adequacy: Is there an undrained abscess or unremoved infected device? 9
• Antimicrobial coverage: Are resistant organisms or atypical pathogens possible? 9
• Fluid status: Is the patient truly volume depleted or now fluid overloaded? 9
• Complications: Consider abdominal compartment syndrome, respiratory failure, or adrenal insufficiency 9

Goals of Care Discussion

Discuss goals of care and prognosis with patients and families as early as feasible, but no later than 72 hours of ICU admission. 3, 1

• Incorporate goals into treatment and end-of-life care planning using palliative care principles when appropriate 3, 1