What is the initial workup for fever or sepsis?

Initial Workup of Fever/Sepsis

Obtain blood cultures (at least 2 sets—one peripheral, one from vascular access if present), initiate broad-spectrum IV antimicrobials within 1 hour, perform immediate imaging to identify infection source, measure serum lactate, and begin aggressive fluid resuscitation with 30 mL/kg crystalloid within 3 hours. 1, 2

Immediate Diagnostic Studies (Within First Hour)

Blood Cultures and Microbiologic Sampling

• Draw at least 2 sets of blood cultures (aerobic and anaerobic bottles) before antimicrobials, but do not delay antibiotics beyond 45 minutes 1
• One set must be drawn percutaneously via venipuncture 1
• One set drawn through each vascular access device (unless inserted <48 hours prior) 1
• If quantitative culture systems available, use them to diagnose catheter-related bloodstream infection 1
• Obtain cultures from all clinically appropriate sites (urine, respiratory secretions, wound sites, cerebrospinal fluid if indicated) before antimicrobials 1

Lactate Measurement

• Measure serum lactate immediately at sepsis recognition—lactate ≥4 mmol/L defines sepsis-induced tissue hypoperfusion requiring aggressive resuscitation 1, 2
• Repeat lactate within 6 hours after initial fluid resuscitation to guide ongoing therapy 2, 3
• Target lactate clearance of at least 10% every 2 hours during first 8 hours 3

Biomarkers for Infection Discrimination

• Serum procalcitonin levels can be used as adjunctive diagnostic tool to discriminate infection from other inflammatory causes of fever 1
  • Levels 0.5-2.0 ng/mL suggest systemic inflammatory response syndrome
  • Levels 2-10 ng/mL indicate severe sepsis
  • Levels >10 ng/mL suggest septic shock 1
• Endotoxin activity assay has 98.6% negative predictive value for Gram-negative infection 1
• Consider 1,3-β-D-glucan assay and mannan/anti-mannan antibody assays if invasive candidiasis is in differential diagnosis 1

Imaging Studies (Perform Promptly)

Chest Imaging

• CT chest with IV contrast is the preferred initial imaging modality for suspected thoracic source, with positive predictive value of 81.82% for identifying septic foci 1
• CT chest identifies infection source in 52.8% of cases and changes management in 45% of patients 1
• Pneumonia is most common source (38.6% of septic patients), and CT chest finds pathologic infectious source in 72% of patients with chest involvement 1
• Portable chest radiographs are adequate for initial fever evaluation in ICU patients, though unilateral air bronchograms have best predictive value for pneumonia 1
• Consider CT imaging for posterior-inferior lung bases, small nodular/cavitary lesions, or immunocompromised patients where standard radiographs may miss pathology 1

Advanced Imaging for Occult Sources

• FDG-PET/CT from skull base to mid-thigh identifies infection source in 56.4-78% of cases when initial workup unrevealing 1
• PET/CT leads to treatment modification in 14.7-33% of patients and has 100% negative predictive value in some studies 1
• Most useful when chest radiography unrevealing and source remains unknown after initial evaluation 1

Abdominal/Pelvic Imaging

• Perform CT abdomen/pelvis with IV contrast promptly if intra-abdominal source suspected 1
• Identify anatomic diagnosis requiring source control within first 12 hours 1

Physical Examination Focus

Critical Areas to Examine

• Search for silent sources of infection: otitis media, decubitus ulcers (sacrum, back, head), perineal/perianal abscesses, retained foreign bodies (tampons) 1
• Examine all vascular access sites for signs of catheter-related infection 1
• Assess for respiratory distress, altered mental status, and signs of organ dysfunction 4
• Evaluate skin and soft tissues thoroughly for cellulitis, abscess, or necrotizing infection 5

Common Infection Sites by Frequency

• Respiratory system (most common—pneumonia) 4
• Genitourinary system 4
• Gastrointestinal system 4
• Skin and soft tissue 4
• Intravascular catheters 1

Respiratory Secretion Sampling (If Pneumonia Suspected)

• For non-intubated patients: expectorated sputum, nasopharyngeal washing, or nasotracheal aspirate sufficient for initial evaluation 1
• For intubated patients: deep endotracheal suctioning without saline instillation preferred (saline dilutes specimen and may introduce pathogens) 1
• Consider bronchoscopic protected specimen brush or bronchoalveolar lavage if initial samples non-diagnostic 1

Hemodynamic Assessment

Initial Resuscitation Targets (First 6 Hours)

• Central venous pressure 8-12 mmHg 1, 2
• Mean arterial pressure ≥65 mmHg 1, 2
• Urine output ≥0.5 mL/kg/hour 1, 2
• Central venous oxygen saturation ≥70% (or mixed venous ≥65%) 1, 2

Fluid Resuscitation

• Administer at least 30 mL/kg IV crystalloid within first 3 hours 2
• Use crystalloids as fluid of choice; avoid hydroxyethyl starches 2
• Following initial resuscitation, guide additional fluids by frequent hemodynamic reassessment 2
• Use dynamic variables over static variables to predict fluid responsiveness when available 2

Special Populations

Neutropenic Patients

• Blood cultures remain gold standard despite only 30% positive yield 1
• Consider PCR-based methods for specific pathogens like CMV 1
• Combination empirical therapy recommended for neutropenic patients with severe sepsis 1
• Each hour delay in antimicrobial administration decreases survival by 7.6% 1

Immunocompromised Patients

• May have severe pneumonia without fever, cough, sputum, or leukocytosis 1
• CT imaging particularly valuable for detecting small nodular or cavitary lesions 1
• Consider viral pathogens and initiate antiviral therapy early if viral sepsis suspected 1

Critical Pitfalls to Avoid

• Never delay antimicrobials beyond 1 hour waiting for culture results—administration within first hour of septic shock recognition is associated with increased survival 1
• Do not stop at negative initial chest radiograph if clinical suspicion high—CT chest has much higher sensitivity 1
• Avoid empiric antimicrobial therapy in patients with inflammatory states determined to be non-infectious 1
• Do not use saline instillation routinely for endotracheal aspirates as it dilutes specimens 1
• Consider post-transfusion CMV syndrome in patients with spiking fevers unresponsive to antimicrobials with negative bacterial cultures—symptoms begin 1 month after transfusion 1
• Rule out malignant hyperthermia and neuroleptic malignant syndrome when fever especially high, as onset can be delayed up to 24 hours 1