Fever in the ICU

1. Fever in the ICU Simranjit Singh Galhotra, MD, MBA George Washington University Fellow, Pulmonary and Critical Care Medicine January 1998

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

6. 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

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

8. 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. 9 Diagnostic Approach Fever is a non-specific sign seen in inflammatory processes that may be infectious noninfectious, including neoplastic The �102� Rule�

10. 10 Temp < 102� Acute cholecystitis Acute MI Dressler�s Syndrome Thrombophlebitis GI bleed Acute pancreatitis Pulmonary embolism or infarct Viral hepatitis Uncomplicated wound infection Helps avoid needless antibiotic therapyHelps avoid needless antibiotic therapy

11. 11 Temp � 102� Cholangitis Suppurative phlebitis Pericarditis Septic pulmonary embolism Pancreatic abscess Non-viral liver disease: drug fever, leptospirosis� Complicated wound infection Bowel infarction Helps avoid needless antibiotic therapyHelps avoid needless antibiotic therapy

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

13. 13 Systemic Inflammatory Response Syndrome Definition of SIRS T > 38�C or < 36�C HR > 90 RR > 20 or pCO2 < 32 WBC > 12 or < 4 Circulating inflammatory cytokines have been found that initiate a SIRS in CPBCirculating inflammatory cytokines have been found that initiate a SIRS in CPB

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

15. 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%

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

17. 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 Randomized controlled trial at UVA from 10/88 to 1/90 all patients admitted to the ICU who needed triple-lumen central venous catheters or pulm-artery catheters inserted via SC or IJ for more than 3 days. Four groups: 1 replaced every 3 days with a new stick 2 replaced every 3 days over a guidewire 3 replaced only if clinically indicated (fever, mechanical complications) with new stick 4 replaced only if clinically indicated (fever, mechanical complications) over a guidewire Total 160 pts andRandomized controlled trial at UVA from 10/88 to 1/90 all patients admitted to the ICU who needed triple-lumen central venous catheters or pulm-artery catheters inserted via SC or IJ for more than 3 days. Four groups: 1 replaced every 3 days with a new stick 2 replaced every 3 days over a guidewire 3 replaced only if clinically indicated (fever, mechanical complications) with new stick 4 replaced only if clinically indicated (fever, mechanical complications) over a guidewire Total 160 pts and

18. 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. 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. 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. 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. 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. 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. 24 Nosocomial Sinusitis Fever and leukocytosis often present Purulent nasal discharge often lacking Common in trauma and neurosurgical units

25. 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. 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. 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. 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. 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. 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. 31 Drug Fever On physical patient looks �inappropriately well� for degree of fever fever usually 102� to 104� relative bradycardia 5-10% have rash

32. 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. 33 Common Causes of Drug Fever Antibiotics Sleep medications Antiepileptics Stool Softeners Diuretics Antihypertensives Antidepressants Antiarrhythmics NSAIDs

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

35. 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

36. 36 Postoperative Fever Garibaldi* found that 72% of fevers within the 48� after surgery were non-infectious Wound, urinary tract, and respiratory infections occur later than 48�

37. 37 Postoperative Fever Empiric antibiotics should be withheld in patients with fever within 48� 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. 38 Fever in Neurosurgical Patient Most important causes are Wound infection Meningitis, an infrequent post-op complication, especially after open-head trauma Wound infection and meningitis are the most important causes. Post-op bacterial meningitis is an infrequent complication, especially after open-head trauma The commonest clinical entity confused with post-neurosurgical meningitis is posterior fossa syndrome--stiff neck, low CSF glucose, protein elevated, and mostly PMNs. Can occur after any intracranial procedure; sx due to blood in CSF. Cx are (-) and decrease in meningeal sx as the RBCs decrease over time. Central fever may be caused by any intracranial space-occupying lesion or trauma, esp. if it affects the base of the brain or hypothalamus. Are usually very high.Wound infection and meningitis are the most important causes. Post-op bacterial meningitis is an infrequent complication, especially after open-head trauma The commonest clinical entity confused with post-neurosurgical meningitis is posterior fossa syndrome--stiff neck, low CSF glucose, protein elevated, and mostly PMNs. Can occur after any intracranial procedure; sx due to blood in CSF. Cx are (-) and decrease in meningeal sx as the RBCs decrease over time. Central fever may be caused by any intracranial space-occupying lesion or trauma, esp. if it affects the base of the brain or hypothalamus. Are usually very high.

39. 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. 40 Causes of High Fever (� 106�) 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 102� to 106�)

41. 41 Causes of High Fever (� 106�) 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. 42 Causes of High Fever (� 106�) 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. 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