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558 PART 5: Infectious Disorders

or an oral temperature >38.0°C for at least 1 hour. Using this defini- TABLE 63-1 Common Causes of Fever in Critically Ill Patients
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tion, up to 70% of critically ill adults have fever at some time during
their ICU stay. 10 Noninfectious Infectious
Although the presence of fever may be an adverse prognostic indica- Heat stroke Urinary tract infection
tor, animal data support a teleological role for fever during infection; Serotonin syndrome Pneumonia
that is, modest elevations in body temperature improve host defenses Neuroleptic malignant syndrome Catheter-associated infection
against infection. 11,12 The mechanisms by which fever can favorably Malignant hyperthermia Sinusitis
affect immunity are diverse. For example, fever can induce the produc- Drug fever Surgical wound infection
tion of heat shock proteins and it can have counter regulatory effects on Acute myocardial infarction Acalculous cholecystitis
proinflammatory cytokines. 13-15 Venous thromboembolism C difficile colitis
Along this same theme, the inability to mount a febrile response to Pancreatitis Spontaneous bacterial peritonitis
infection can be an ominous prognostic sign. Septic patients who expe- Intracranial hemorrhage Endocarditis
rience natural hypothermia (<35.5°C) have a significantly increased risk Transfusion reactions
of death (62% vs 26%) and have higher Sequential Organ Failure Scores Surgical trauma
(SOFA) when compared to febrile patients. 16,17 Burn injury
In spite of the purported beneficial effects of fever, most intensivists Ischemic colitis
correctly associate fever with adverse outcomes. Febrile ICU patients tend Cancer
to experience more agitation, undergo more laboratory testing, have a Thyrotoxicosis
longer ICU length of stay, have increased hospital costs, and have higher Adrenal insufficiency
mortality than patients without fever. 10,17-23 In a retrospective cohort Connective tissue disease
of 24,204 ICU admissions, the cumulative incidence of fever was 44%.
Fever was more common among patients with trauma or neurological
illness, and more common among males and younger patients. Seventeen
percent of patients who had fever had positive cultures and those with
high fever had an increased risk of death. In a second study, up to 1/3 related to devices, for example, urinary catheters, endotracheal tubes,
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of patients with traumatic brain injury had prolonged fever, which was nasogastric tubes, or central venous catheters. The early removal of
associated with tachycardia, hypertension, tachypnea, excessive diapho- devices when they are no longer needed is a very cost-effective strategy
resis, extensor posturing, or severe dystonia. In a third observational for reducing ICU infections and many ICUs now utilize the daily goals
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study, febrile elderly patients in a medical-surgical ICU had almost twice checklists on interdisciplinary rounds to document the necessity for
the risk of agitation than normothermic control patients. And those with each device.
higher temperature had a greater risk of severe agitation. Blood cultures should be obtained from all ICU patients with a new
The health care costs of responding to fever are also significant. fever when the clinical picture does not strongly suggest a noninfec-
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Nursing time is increased among febrile patients, which can have tious cause. In order to maximize the sensitivity of blood cultures for
adverse effects on the allocation of nursing personnel. One estimate true bacteremia, guidelines from the American College of Critical Care
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suggests that fever might add approximately $17,000 in additional costs Medicine and the Infectious Diseases Society of America emphasize
to the care of critically ill neurological patients and that 3/4 of these that the blood cultures should be obtained prior to antibiotic initia-
costs occur in the ICU. 22 tion and that an adequate volume of blood should be instilled into the
collection bottles (usually 20-30 mL per culture). Spacing out sets
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of blood cultures over time does not increase the yield. In order to
DIFFERENTIAL DIAGNOSIS OF FEVER IN THE ICU avoid contamination, the blood cultures should be drawn only after
proper hand washing and after sterilization of the intended site with an
The recognition of fever in a critically ill patient often leads to the approved individually prepackaged chlorhexidine, alcohol, or iodine-
reflex ordering of blood, sputum, and urine cultures and the initia- based applicator.
tion of empiric, intravenous, broad-spectrum antibiotics. This shotgun
approach can add unnecessary costs and risks to patient care. In 2008, a ■
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panel composed of members of the Society of Critical Care Medicine and CATHETER-ASSOCIATED BLOOD STREAM INFECTIONS
the Infectious Diseases Society of America published a consensus guide- There has been an explosion in the use of central venous catheters
line on the recommended management of new onset fever in the ICU in the ICU and with it an increase in risk of central line–associated
population. The panel stressed that fever has many noninfectious causes bloodstream infection (CLABSI). Use of full barrier precautions,
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in addition to the usual infectious ones, and, therefore, a careful clinical shorter duration of catheter use, use of antibiotic impregnated cath-
evaluation should precede laboratory testing, x-rays, and empiric treat- eters, avoidance of femoral venous access, and care by a central-line
ment. Consideration of the unique factors of each patient was empha- team are factors associated with a lower risk of CLABSI. Measurement
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sized over the initiation of routine order sets. This approach should then of the “differential time to positivity,” that is, the difference in time for
lead to an individualized differential diagnosis of the potential causes blood cultures to become positive when they are drawn simultane-
of fever and thereby more focused and cost-effective diagnostic testing. ously through a central venous catheter and a peripheral vein, has
Common causes of fever in ICU patients are listed in Table 63-1. The been shown to have high sensitivity and specificity for catheter-related
prevalence of each of these diagnoses will largely depend on the patient infection. When line sepsis is suspected, the line should be removed
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population being studied. For example, benign postoperative fever (sur- aseptically and 5 cm of the line tip submitted for semiquantitative
gical trauma) would be overrepresented in a surgical ICU while fever due culture. Isolation of ≥15 colony-forming units (CFUs) on semiquan-
to stroke would be more commonly seen in a neurointensive care unit. titative culture of the catheter tip correlates with true line-associated
infection. Isolation of <15 CFUs usually represents contamination
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SELECTED INFECTIOUS CAUSES OF FEVER during removal. However, it is not recommended to routinely culture
line tips upon removal from asymptomatic patients. In one epide-
The evaluation of fever in the ICU usually begins with a search for miologic study of intensive care unit-acquired bloodstream infections,
signs of infection, since approximately only half of febrile events in multiple antibiotic-resistant organisms were uncommon suggesting
the ICU are due to infection and the majority of these infections are it may be safer to use a more narrowed spectrum of antibiotics. 31

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