The Natural History of Procalcitonin in Hemorrhagic Stroke
The Natural History of Procalcitonin in Hemorrhagic Stroke
Approximately 12% of strokes in the United States are hemorrhagic.1 Hemorrhagic stroke can
 lead to multiple complications including fever that is not infectious. Identifying the cause
 of fever can help physicians choose the best care for the patient to try and prevent further
 damage to the already injured brain. Bacterial infection is one possible cause of fever in
 the stroke patient; however an incorrect diagnosis of infection can lead to unnecessary
 antibiotic use. Better screening tools for infection are being developed to help fight the
 problem of antibiotic resistance and unnecessary antibiotic use. Unnecessary use of
 antibiotics in patients increases the risk of adverse events and overall healthcare costs.
 Procalcitonin (PCT) is one such screening tool which has been used previously to help tell
 apart bacterial and nonbacterial causes of infection in other disease states; however, PCT
 has not been studied in hemorrhagic stroke patients. The purpose of this study is to
 understand the progress of PCT in hemorrhagic stroke patients in order to see whether PCT can
 be a useful marker for infection in these patients.
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