Fever in the ICU

1. Fever in the ICU Bahram Hadjikarim MD / MPH Zanjan University of Medical Science Assistant Professor of Infectious and Tropical Dis. January 2010

2. Fever, A Little History • Hippocrates recognized fever as a beneficial sign during infection • Thomas Sydenham (1624-1689), English physician: “Fever is Nature’s engine which she brings into the field to remove her enemy.” • Fever therapy used in many societies world-wide

3. Fever, Late 1800s • Liebermeister, German physician • Fever is the regulation of body temperature at a higher level • Fever dangerous if too high or prolonged • Antipyretic drugs should be used only for high fevers or of long duration

4. Fever, Late 1800s • Antipyretic drugs widely available: aspirin, other salicylates • Many physicians advocated reducing fever • Fever considered harmful by-product of infection, not host-defense response • Why? Perhaps because salicylates are analgesic and antipyretic

5. Evolutionary Biology • Fever is energetically costly • In mammals increasing temperature 2-3ºC increases energy consumption 20% • Since such a response is preserved across invertebrates and vertebrates, fever must have an adaptive function

6. Mechanism of Protective Effect • Enhanced neutrophil migration • Increased production of antibacterial substances by neutrophils • Increased production of interferon • Increased antiviral and antitumor activity of interferon • Increased T-cell proliferation • *Kluger MJ. Inf Dis Clin of NA 10:1-20, 1996

7. Nosocomial Fevers • Hospital-acquired fevers occur in one-third of all medical inpatients • Nosocomial fevers even more common in the ICU

8. Fever in the ICU • ICU patients have several underlying medical/surgical conditions • ICU patients undergo many invasive diagnostic and therapeutic procedures • Therefore, fever in ICU patients must be thoroughly and promptly evaluated to discriminate infectious from non-infectious etiologies

9. Diagnostic Approach • Fever is a non-specific sign seen in inflammatory processes that may be • infectious • noninfectious, including neoplastic • The “102º Rule”

10. Acute cholecystitis Acute MI Dressler’s Syndrome Thrombophlebitis GI bleed Acute pancreatitis Pulmonary embolism or infarct Viral hepatitis Uncomplicated wound infection Temp < 102º

11. Cholangitis Suppurative phlebitis Pericarditis Septic pulmonary embolism Pancreatic abscess Non-viral liver disease: drug fever, leptospirosis… Complicated wound infection Bowel infarction Temp ³ 102º

12. SIRS Intravenous-line infections Nosocomial pneumonia Nosocomial sinusitis Intraabdominal infections Urinary catheter-associated bacteriuria Drug fever Post-operative fever Neurosurgical causes Causes of Fever in the ICU

13. Systemic Inflammatory Response Syndrome • Definition of SIRS • T > 38ºC or < 36ºC • HR > 90 • RR > 20 or pCO2 < 32 • WBC > 12 or < 4

14. SIRS • Often noninfectious etiology found: • Pulmonary embolism • Myocardial infarction • Gastrointestinal bleed • Acute pancreatitis • Cardiopulmonary bypass

15. Intravenous-line Infections • Prevalence: 5% in ICU patients in a University of VA study of triple-lumen and pulmonary artery catheters* • Bloodstream infection is a serious catheter-related complication: case fatality rate ~10-20% *Cobb DK. NEJM 327:1062-8, 1992

16. Intravenous-line Infections • Look for local signs of infection: present in < 50% • Remove line if no other source and T > 102º

17. Scheduled Replacement? • UVA study* • Inclusion criteria: All patients admitted to the ICU who needed triple-lumen central venous catheters or pulmonary artery catheters inserted via SC or IJ for > 3 days *Cobb DK. NEJM 327:1062-8, 1992

18. Scheduled Replacement? • Four groups • 1 replaced q 3 days with a new stick • 2 replaced every 3 days over guidewire • 3 replaced only if clinically indicated (fever, mechanical complications) with new stick • 4 replaced only if clinically indicated over guidewire

19. Scheduled Replacement? • Total of 160 patients enrolled; 523 catheters. • No statistically significant difference in catheter-related bloodstream infections among groups • Statistically significant increase in mechanical complications with new sticks vs. guidewire exchange

20. Scheduled Replacement? • No support for changing lines every 3-5 days; change only if unexplained fever or catheter malfunction occurs • Concurs with CDC’s Guideline for Prevention of Intravascular Device-Related Infections. Am J Infect Control 1996;24:262-293

21. Nosocomial Pneumonia • Almost all cases occur in mechanically ventilated patients • Signs are • fever • leukocytosis • purulent tracheal secretions • new or worsening infiltrates on CXR

22. Nosocomial Pneumonia • However, none of these are predictive of pneumonia; nosocomial pneumonia remains a clinical diagnosis • Can be confused with fibroproliferative phase of ARDS, usually accompanied by low-grade fever • Semi-quantitative BAL and protected-brush specimen may be helpful, but not widely available

23. Nosocomial Sinusitis • Bacteriology differs markedly from community-acquired disease • Gram-negative bacilli cause most cases in intubated patients • Polymicrobial infection in upto 50% of cases, reflecting ICU flora • Paranasal sinusitis accounts for about 5% of nosocomial ICU infections

24. Nosocomial Sinusitis • Fever and leukocytosis often present • Purulent nasal discharge often lacking • Common in trauma and neurosurgical units

25. Nosocomial Sinusitis • Risk factors • nasotracheal tubes • nasogastric tubes • nasal packing • facial fractures • steroid therapy • Diagnosis made easier with sinus CT, which is more sensitive than plain films • Avoid prolonged nasotracheal intubation

26. Intra-abdominal Infections • Suspect intra-abdominal abscess in patients with prolonged post-operative fever after abdominal surgery • Acalculous cholecystitis and subsequent biliary sepsis may complicate post-operative period

27. Intra-abdominal Infections • Suspect antibiotic-associated colitis due to Clostridium difficile in patients on broad-spectrum antibiotics • Fever and leukocytosis may be present prior to diarrhea or abdominal symptoms • Splenic or hepatic abscesses may complicate other intra-abdominal infections (cholecystitis, appendicitis) causing prolonged fevers

28. Catheter-Associated Bacteriuria • Foley catheters • Result in acquisition of bacteriuria • Nearly always represents colonization, not infection • Pyuria often accompanies CAB, mimicking a UTI

29. Catheter-Associated Bacteriuria • Foley + high fever + bacteriuria • does not necessarily mean urosepsis • unless their is partial or total obstruction or pre-existing renal disease • Asymptomatic CAB • in normal hosts need not be treated • in compromised hosts and chronically immunosuppressed must be treated promptly

30. Drug Fever • Some 3-7% of fevers on an inpatient medical service are drug reactions • History of atopy is a risk factor • Patient may have been on the “sensitizing medication” for days to years

31. Drug Fever • On physical patient looks “inappropriately well” for degree of fever • fever usually 102º to 104º • relative bradycardia • 5-10% have rash

32. Drug Fever • Lab tests show • leukocytosis with left shift • eosinophils on peripheral smear (common) • eosinophilia (low-grade) • elevated ESR • mildly elevated AP, AST, ALT

33. Antibiotics Sleep medications Antiepileptics Stool Softeners Diuretics Antihypertensives Antidepressants Antiarrhythmics NSAIDs Common Causes of Drug Fever

34. Digoxin Steroids Diphenhydramine Aspirin Vitamins Aminoglycosides Tetracyclines Erythromycins Chloramphenicol Vancomycin Imipenim Quinolones Rare Causes of Drug Fever

35. Postoperative Fever • Fever common post-operatively • Most episodes noninfectious • Probably due to intraoperative tissue trauma with subsequent release of endogenous pyrogens into the bloodstream *Garibaldi RA. Infect Control 6:273, 1985

36. Postoperative Fever • Garibaldi* found that 72% of fevers within the 48º after surgery were non-infectious • Wound, urinary tract, and respiratory infections occur later than 48º *Garibaldi RA. Infect Control 6:273, 1985

37. Postoperative Fever • Empiric antibiotics should be withheld in patients with fever within 48º of surgery if they lack a specific diagnosis after thorough evaluation • Continuing perioperative prophylactic antibiotics does not prevent infection, only selects for resistant organisms

38. Fever in Neurosurgical Patient • Most important causes are • Wound infection • Meningitis, an infrequent post-op complication, especially after open-head trauma

39. Fever in Neurosurgical Patient • Commonest clinical entity is posterior fossa syndrome • stiff neck, low CSF glucose, elevated protein, mostly neutrophils • Can occur after any intracranial procedure • Symptoms due to blood in CSF • Culture negative, and symptoms subside as RBCs decrease over time in CSF

40. Causes of High Fever (³ 106º) • Central fevers • intracranial hemorrhage, head trauma, infection, malignancy • especially if the base of the brain or hypothalamus affected • Infusion-related sepsis (contaminated infusate) • Rarely, bacterial infection • Drug fever (usually 102º to 106º)

41. Causes of High Fever (³ 106º) • Malignant hyperthermia • Rare genetic disorder, probably autosomal dominant • Incidence 1:15,000 in kids; less in adults • Hypercatabolic reaction to anesthetic drugs • Sustained muscle contraction -> excess heat • Tachycardia occurs in >90% of pts within 30 minutes • Treated with dantrolene; mortality ~7%

42. Causes of High Fever (³ 106º) • Malignant neuroleptic syndromes • Confusion, hyperthermia, muscle stiffness, autonomic instability • Drugs implicated: phenothiazines, thioxanthines, butyrphenones--antipsychotics, tranquilizers, and antiemetics • Dantrolene or bromocriptine, a dopamine agonist, effective in uncontrolled studies

43. Summary • Fever in the ICU can have many infectious and noninfectious etiologies • Crucial to identify the precise cause as some of the conditions in each groups are life-threatening, while others require no treatment • “Routine fever work-up” not cost-effective • If initial evaluation shows no infection, antibiotics should be withheld • Empiric antibiotics may be started in the unstable patient, but stopped if infection is not evident later