20. Fever in Critically Ill Patients

Overview

A temperature > 38.3°C in an ICU patient raises the possibility of a new infection – and warrants at least a clinical assessment, if not laboratory and radiologic studies. Remember that immunocompromised patients or patients on a circuit (e.g. on CRRT or ECMO) may not mount a fever while infected.

Etiologies

The most common etiologies:

  • Catheter-related blood stream infection (CRBSI): common pathogens causing CRBSI include coag-negative Staph, S. aureus, GNRs, Candida, Enterococcus.
  • Ventilator-associated pneumonia (VAP): 
    • Pneumonia that develops > 48hr after intubation.
    • A clinical diagnosis can be made based on a new or progressive CXR infiltrate which is associated with 2 or more of the following (70% sensitive, 75% specific for diagnosis of VAP):
      • Fever > 38ºC.
      • Leukocytosis or leukopenia.
      • Purulent secretions.
      • Increasing oxygen requirement.

**Note, the following organisms are rarely pathologic when isolated from tracheal aspirates: Enterococcus, viridans group Streptococci, coagulase-negative Staphylococci, Candida species.

  • Clostridioides difficile colitis: consider in all patients with:
    • Liquid stools (3 or more stools in a 24 hour period).
    • New fever or leukocytosis.
    • Exposure to antibiotics within the previous 60 days.
  • Catheter-associated urinary tract infection (CA-UTI): typically develop > 48 hours after catheter placement.
    • Note, most of the time, bacteriuria and candiduria in the setting of a foley represent colonization (e.g. asymptomatic bacteriuria) and not true infection.
    • Most patients with an indwelling foley for > 48 hours will have pyuria so this is not a reliable marker of true infection. However, the absence of pyuria (in non-neutropenic patients) suggests an alternative diagnosis.
    • CA-UTI can be diagnosed when signs or symptoms are present (these may just be fever, sepsis, altered mental status, etc.) without an alternative diagnosis.
    • Asymptomatic bacteriuria should not be treated except for the following: kidney transplant within last 1 month, neutropenia, pregnancy and urologic procedures expected to induce mucosal bleeding.
  • Other infectious etiologies: including sinusitis (increased risk with nasogastric/nasotracheal tubes, although a rare cause of fever in the ICU), surgical site infections, and CNS infection (rare).
  • Non-infectious fever: consider drug-related fever (especially antibiotics), NMS, pulmonary emboli, adrenal insufficiency, transfusion reaction, gout or CPPD, venous thrombosis, phlebitis, acalculous cholecystitis, and tumor.

Evaluation

  • CRBSI: at least 2 blood cultures from distinct peripheral sites. If central venous catheter (CVC) is present, one peripheral and one from CVC can be drawn at the same time and sent for differential time to positivity (if the line culture grows > 2 hours before the peripheral culture, this suggests the line is the source). Check line and PIV sites looking for septic thrombophlebitis.
  • Pneumonia: chest x-ray, tracheal aspirate for gram stain/culture.
  • Diarrhea: stool for C. difficile.
  • CA-UTI: urine specimen for UA and culture (aspirated from catheter port, NOT from catheter bag). If you are sending a urine culture, ALWAYS send a UA.
  • Sinusitis: can consider sinus CT but this is a very rare cause of fever in the ICU.
  • Surgical site infection: evaluate wounds, remove bandages and examine wounds.
  • Non-infectious fever: look for rash +/- eosinophilia suggesting drug fever (always get a diff on the CBC).
  • Acalculous cholecystitis: check LFTs as a possible clue. Consider RUQ US if suspicion is high.
  • Undiagnosed fever: if etiology remains unclear, can consider cross sectional imaging (e.g. CT C/A/P).

Management

  • Empiric broad-spectrum antibiotics should be given in patients who are critically ill or deteriorating after cultures are obtained. 
  • Antimicrobial coverage should be active against MRSA and resistant GNRs. 
  • Common regimens include vancomycin plus cefepime (or piperacillin-tazobactam). Consider the empiric use of a carbapenem (imipenem, meropenem) with or without a second agent (an aminoglycoside or fluoroquinolone) in critically ill patients with significant prior broad-spectrum antibiotic exposure. Many ICUs recommend double coverage for Pseudomonas because of high resistance rates. Consult your own institutions guidelines and antibiogram.

Key Points

  • Be sure to complete infectious evaluation (including cultures) prior to the initiation of antibiotics.
  • Removal of central line is not warranted unless there is clinically documented blood stream infection.
  • Threshold for fever may change in immunocompromised patients.

O'Grady NP, Barie PS, Bartlett JG, et al.; Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America. Crit Care Med 2008;36: 1330-49.

Laupland KB, Shahpori R, Kirkpatrick AW, Ross T, Gregson DB, Stelfox HT. Occurrence and outcome of fever in critically ill adults. Crit Care Med. 2008;36(5):1531‐1535. doi:10.1097/CCM.0b013e318170efd3

Circiumaru B, Baldock G, Cohen J. A prospective study of fever in the intensive care unit. Intensive Care Med. 1999;25(7):668‐673. doi:10.1007/s001340050928

Key Words: Fever, ventilator-associated pneumonia, Clostridioides difficile, UTI, urinary tract infection, catheter-related infection