The Natural History of Procalcitonin in Hemorrhagic Stroke

Withdrawn

Phase N/A Results N/A

Trial Description

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.

Detailed Description

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.

Trial Stopped: Anticipated grant was withdrawn and additional funding was unable to be obtained

Conditions

Interventions

  • Procalcitonin level Other
    Other Names: Procalcitonin level
    Intervention Desc: PCT level upon admission and on days 1, 3, and 5 following baseline level
    ARM 1: Kind: Experimental
    Label: Hemmorhagic Stroke
    Description: 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

Trial Design

  • Observation: Cohort
  • Perspective: Prospective
  • Sampling: Non-Probability Sample

Trial Population

Patients admitted to the Neurosurgical ICU with a diagnosis of intraventricular or intracerebral hemorrhage

Outcomes

Type Measure Time Frame Safety Issue
Primary Natural progression of PCT following hemorrhagic stroke Change in serum PCT level on day 0 (baseline) from serum PCT level day 1, 3, and 5. No
Secondary Markers of infection (if obtained by treating medical team) using SIRS criteria well as cultures. From date of enrollment to 28 days or until death or discharge, whichever comes first. No

Biospecimen Retention:Samples Without DNA - 3 mL of blood will be obtained for each PCT sample and will be sent to the Virology lab at CAMC Memorial hospital where the serum will be frozen until all samples are collected. After all samples from each of the 30 patients are obtained, the specimens will be analyzed for the PCT value and then discarded.

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