The Natural History of Procalcitonin in Hemorrhagic Stroke

Stroke is the second leading killer worldwide and the third leading cause of death in the
United States. The two major mechanisms causing brain damage in stroke are, ischemia and
hemorrhage. Several complications can arise from these cerebral insults ranging from minor
neurologic dysfunction, complete immobility, or death. In the intensive care setting,
clinicians combat the pathophysiologic processes that lead to the aforementioned sequelae of
stroke and contest other acute issues which may or may not be secondary to the stroke
itself, with one such issue being hyperthermia. Hyperthermia is defined by the Society of
Critical Care Medicine as a temperature greater than 38.3°C. In one prospective study,
hyperthermia was reported to occur in 43% of patients during the first week of
hospitalization following an ischemic or hemorrhagic (excluding subarachnoid hemorrhage)
stroke. Hyperthermia in the stroke patient can be detrimental leading to increased infarct
size and worsened neurological outcomes. The etiology of the hyperthermia may not be clear
upon initial evaluation but cessation of fever is essential to prevent further damage.

One possible cause of hyperthermia in the stroke patient is bacterial infection. Infection
complicating cerebral insult can lead to poor functional outcome and increased mortality.
Kilpatrick and colleagues found that fever occurred in 47% of patients who were admitted
with either a traumatic or ischemic brain injury and 70% of these patients received at least
one antibiotic within 24 hours of their febrile episode, however the antibiotics had no
effect on controlling the fevers. With bacterial resistance ever increasing, it is vital
that clinicians reserve antibiotics for patients in whom the source of fever is believed to
be secondary to an infectious process. It has been estimated that the United States health
care system spends more than $20 billion annually on antibiotic-resistant infections and
these infections result in more than eight million additional hospital days. Antibiotic use
across health care disciplines has been estimated to be administered either inappropriately
or unnecessarily 50% of the time. Considering clinical symptoms of infection can mirror
other disease processes, reliable diagnostic biomarkers would be useful in helping determine
the appropriate diagnosis.

PCT is a 116 amino acid peptide with a sequence identical to calcitonin but lacking hormonal
activity. PCT was first utilized by Assicot et al in the setting of sepsis to help
determine whether the inflammatory response from the patient was secondary to bacterial
infection. Since this finding, PCT has been shown in several studies to have a high
sensitivity and specificity for indicating systemic bacterial infections. During infection
PCT is secreted into the bloodstream without increasing calcitonin. PCT has been shown
prospectively to only be elevated in patients with bacterial infections while remaining
consistently low in patients infected with viruses or other inflammatory processes. Often
when insulted, the body utilizes proteins and metabolic products, and the changes noted in
these substances are often used as markers of inflammation. Unlike erythryocyte
sedimentation rate (ESR) and C-reactive protein (CRP), PCT remains low during these
inflammatory states. Furthermore, it has been shown that PCT levels increase earlier after
stimulation (3-6hrs) compared to C-reactive protein (12-24hrs), indicating PCT can be
utilized to rapidly detect bacterial infections. Normal PCT levels in adults are less than
0.1 ng/mL while PCT values greater than 0.5ng/mL have been determined to be predictive of
bacterial infection. PCT has been evaluated in several clinical scenarios to help
determine a bacterial versus a non-bacterial source of infection, however, to our knowledge,
the effects of hemorrhagic stroke on PCT are not yet known. Determining the natural history
of PCT in a hemorrhagic stroke patient would provide beneficial information as to whether
PCT can be used as a biomarker in this population to help differentiate a bacterial from a
non-bacterial cause of hyperthermia.

Inclusion Criteria:

- Hospitalization for an admitting diagnosis of hemorrhagic stroke admitted to the
neurosurgical intensive care unit

- Age greater than 18 years

- No evidence of ischemic cerebrovascular injury

Exclusion Criteria:

- Concomitant traumatic brain injury

- Antibiotics on admission to the NICU

- Immunocompromised by chemotherapy or HIV positive or patient with neutropenia (ANC
<1000)

- Women who are pregnant and/or of childbearing age where a pregnancy test has not
already occurred