Date of Graduation

Summer 8-8-2015

Degree Type

Capstone Project

Degree Name

Master of Science in Physician Assistant Studies

First Advisor

Mary Von, DHEd, MS, PA-C

Second Advisor

Annjanette Sommers, MS, PA-C

Abstract

Background:

Sepsis is the fourth most common admitting diagnosis to the ICU and the second leading cause of death. Despite aggressive management, sepsis continues to have a high mortality rate as high as 48.8% and costs an estimated $366 million annually. The need for an early prognostic marker to identify those at highest risk for mortality in order to optimize therapeutics is critical. Procalcitonin (PCT) and C-reactive protein (CRP) are the current standard markers in the ICU setting; however, each test carries significant limitations. Cholesterol may be a useful prognostic marker of sepsis given that lipid metabolism is significantly altered by systemic inflammation. These changes have been noted to occur within hours of an inflammatory state and are negatively correlated to clinical outcome. Few studies have evaluated the efficacy of serum cholesterol compared to PCT and CRP to identify those at high risk for mortality in the ICU. Can total cholesterol be a superior prognostic marker of mortality in patients admitted to the ICU for sepsis compared to the current gold standard of PCT or CRP?

Methods:

An exhaustive search was conducted using MEDLINE-Ovid, Web of Science, and CINAHL using the following keywords: cholesterol, procalcitonin or C-reactive protein, and sepsis. Relevant articles were assessed for quality using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). A search on the National Institute of Health (NIH) clinical trials inquiry site indicates that there are no current trials in any phase evaluating serum cholesterol as a prognostic marker in ICU septic patients.

Results:

Two studies met eligibility criteria and were included in this systematic review. A prospective observational trial with 106 participants demonstrated a statistically significant superiority of total cholesterol as a prognostic marker for septic ICU patients with infection only compared to PCT and CRP. A second prospective observational trial with 96 participants demonstrated no superior benefit of total cholesterol levels when compared to CRP but total cholesterol had statistically significant utility in predicting mortality separately.

Conclusion:

Total cholesterol may be a useful and superior prognostic marker of mortality for patients admitted to the ICU with sepsis secondary to infection compared to its CRP and PCT counterparts. Serum cholesterol could provide ICU clinicians a more sensitive screening tool for identifying those patients at highest risk for morbidity and mortality irrespective of other underlying comorbidities, whereas CRP may be more useful for monitoring response to therapy. Cholesterol pathophysiology may also yield insight on experimental therapy including the use of statin medications in septic patients in the ICU.

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