Fever in the ICU

Simranjit Singh Galhotra, MD, MBA

George Washington University Fellow, Pulmonary and Critical Care Medicine January 1998

Fever, A Little History

Hippocrates

recognized fever as a beneficial sign during infection Thomas Sydenham (1624-1689), English physician: Fever is Natures engine which she brings into the field to remove her enemy. Fever therapy used in many societies worldwide
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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
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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
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Evolutionary Biology
Fever

is energetically costly In mammals increasing temperature 2-3C increases energy consumption 20% Since such a response is preserved across invertebrates and vertebrates, fever must have an adaptive function
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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
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Nosocomial Fevers
Hospital-acquired

fevers occur in one-third of all medical inpatients Nosocomial fevers even more common in the ICU

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
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Diagnostic Approach
Fever

is a non-specific sign seen in inflammatory processes that may be

infectious noninfectious, including neoplastic

The

102 Rule

Temp < 102

Acute cholecystitis Acute MI Dresslers Syndrome Thrombophlebitis GI bleed

Acute pancreatitis Pulmonary embolism or infarct Viral hepatitis Uncomplicated wound infection

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Temp 102
Cholangitis Suppurative phlebitis Pericarditis Septic pulmonary embolism Pancreatic abscess

Non-viral liver disease: drug fever, leptospirosis Complicated wound infection Bowel infarction

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Causes of Fever in the ICU

SIRS Intravenous-line infections Nosocomial pneumonia Nosocomial sinusitis Intraabdominal infections

Urinary catheterassociated bacteriuria Drug fever Post-operative fever Neurosurgical causes

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Systemic Inflammatory Response Syndrome

Definition

of SIRS

T > 38C or < 36C HR > 90 RR > 20 or pCO2 < 32 WBC > 12 or < 4

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SIRS
Often

noninfectious etiology found:

Pulmonary embolism Myocardial infarction Gastrointestinal bleed Acute pancreatitis Cardiopulmonary bypass

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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
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Intravenous-line Infections
Look

for local signs of infection: present in < 50% Remove line if no other source and T > 102

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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

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Scheduled Replacement?
Four

groups
replaced q 3 days with a new stick replaced every 3 days over guidewire replaced only if clinically indicated (fever, mechanical complications) with new stick replaced only if clinically indicated over guidewire
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1 2 3

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
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Scheduled Replacement?
No

support for changing lines every 3-5 days; change only if unexplained fever or catheter malfunction occurs Concurs with CDCs Guideline for Prevention of Intravascular DeviceRelated Infections. Am J Infect Control 1996;24:262-293
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Nosocomial Pneumonia
Almost

all cases occur in mechanically ventilated patients Signs are

fever leukocytosis purulent tracheal secretions new or worsening infiltrates on CXR

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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

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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

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Nosocomial Sinusitis
Fever

and leukocytosis often present Purulent nasal discharge often lacking Common in trauma and neurosurgical units
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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
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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 postoperative period

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Intra-abdominal Infections
Suspect antibiotic-associated colitis due to Clostridium difficile in patients on broadspectrum 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

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Catheter-Associated Bacteriuria
Foley

catheters

Result in acquisition of bacteriuria Nearly always represents colonization, not infection Pyuria often accompanies CAB, mimicking a UTI

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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
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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

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Drug Fever
On

physical patient looks inappropriately well for degree of fever

fever usually 102 to 104 relative bradycardia 5-10% have rash

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Drug Fever
Lab

tests show

leukocytosis with left shift eosinophils on peripheral smear (common) eosinophilia (low-grade) elevated ESR mildly elevated AP, AST, ALT

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Common Causes of Drug Fever

Antibiotics Sleep Antihypertensives Antidepressants Antiarrhythmics NSAIDs

medications Antiepileptics Stool Softeners Diuretics

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Rare Causes of Drug Fever

Digoxin Steroids Diphenhydramine Aspirin Vitamins Aminoglycosides Tetracyclines

Erythromycins Chloramphenicol Vancomycin Imipenim Quinolones

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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
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Postoperative Fever
Garibaldi*

found that 72% of fevers within the 48 after surgery were noninfectious Wound, urinary tract, and respiratory infections occur later than 48

*Garibaldi RA. Infect Control 6:273, 1985

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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

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Fever in Neurosurgical Patient

Most

important causes are

Wound infection Meningitis, an infrequent post-op complication, especially after openhead trauma

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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
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Causes of High Fever ()

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)

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Causes of High Fever ()

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%
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Causes of High Fever ()

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
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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
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