Fluoropyrimidine-Induced Cardiotoxicity: Manifestations, Mechanisms, and Management.

Fluoropyrimidines-5-fluorouracil (5-FU) and capecitabine-have been implicated as cardiotoxic chemotherapy agents. This rare, albeit potentially serious toxicity has been described in nearly four decades of case reports, case series, and in vitro modeling; however, there is a paucity in clinical trials and prospective analyses focused on cardioprotective strategies and cardiotoxic surveillance of these agents. While much attention has focused on the well-known cardiac toxicity of anthracyclines and monoclonal antibody agents such as trastuzumab, fluoropyrimidines remain one of the most common causes of chemotherapy-associated cardiotoxicity. The introduction of capecitabine, an oral prodrug of 5-FU, has made the treatment of solid tumors more convenient along with a subsequent rise in documented cardiotoxic cases. This review discusses the symptomatology, clinical manifestations, and proposed molecular mechanisms that attempt to describe the heterogeneous spectrum of fluoropyrimidine-induced cardiotoxicity. Four case examples showcasing the varied manifestations of cardiotoxicity are presented. Finally, several proposed management strategies for cardiotoxicity and post-hospital course precautions are discussed.

Acute respiratory distress syndrome in nontrauma surgical patients: a 6-year study.

BACKGROUND: Acute respiratory distress syndrome (ARDS) has been shown to increase morbidity but not mortality in trauma patients; however, little is known about the effects of ARDS in nontrauma surgical patients. The purpose of this study is to evaluate the risk factors for and outcomes of ARDS in nontrauma surgical patients. STUDY: A prospective observational study was performed in the surgical intensive care unit (ICU) of an academic tertiary care center. From 2000 to 2005, all nontrauma surgical admissions to the surgical ICU were evaluated daily for ARDS based on predefined diagnostic criteria. Logistic regression analysis identified independent predictors for ARDS and ICU mortality. RESULTS: Of 2,046 patient identified, 125 (6.1%) met criteria for ARDS. The incidence of ARDS declined annually from 12.2% to 2.1% during the study period (p < 0.001). ARDS patients were significantly older (55.4 years vs. 51.8 years, p = 0.014) and more likely to be obese (32% vs. 22%, p = 0.007) than the non-ARDS population. Independent predictors of ARDS included use of pressors (relative risk, RR = 3.30), sepsis (RR = 1.72), and body mass index >or=30 kg/m (RR = 1.57). Independent predictors of ICU mortality included ARDS (RR = 6.88), pressors (RR = 2.85), positive fluid balance (RR = 2.27), Acute Physiology and Chronic Health Evaluation II (RR = 1.04), and age (RR = 1.02). CONCLUSIONS: Unlike trauma patients, ARDS was an independent predictor of ICU mortality in nontrauma surgical patients, independent of age and disease severity. Nontrauma surgical patients who developed ARDS were older, sicker, and had a longer ICU stay. Independent predictors of ARDS included use of pressors, sepsis, and obesity.