Fever in the ICU

Bahram Hadjikarim MD / MPHZanjan University of Medical Science

Assistant Professor of Infectious and Tropical Dis.

January 2010

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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

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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 2-3ºC

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

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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 “102º Rule”

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Temp < 102º

Acute cholecystitis Acute MI Dressler’s Syndrome Thrombophlebitis GI bleed

Acute pancreatitis Pulmonary embolism

or infarct Viral hepatitis Uncomplicated

wound infection

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Temp 102º

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 catheter-associated bacteriuria

Drug fever Post-operative fever Neurosurgical causes

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Systemic Inflammatory Response Syndrome

Definition of SIRS T > 38ºC or < 36ºC 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 > 102º

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Scheduled Replacement?

UVA study* Inclusion criteriaInclusion 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 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

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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 CDC’s Guideline for Prevention of Intravascular Device-Related 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 post-operative period

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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

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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 102º to 104º 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 medications Antiepileptics Stool Softeners Diuretics

Antihypertensives Antidepressants Antiarrhythmics NSAIDs

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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 48º after surgery were non-infectious

Wound, urinary tract, and respiratory infections occur later than 48º

*Garibaldi RA. Infect Control 6:273, 1985

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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

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Fever in Neurosurgical Patient

Most important causes are Wound infection Meningitis, an infrequent post-op

complication, especially after open-head trauma

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Fever in Neurosurgical Patient

Commonest clinical entity is posterior posterior fossa syndromefossa 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 (º)

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)

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Causes of High Fever (º)

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 (º)

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