To determine the effectiveness of early, routine antioxidant supplementation using ␣-tocopherol and ascorbic acid in reducing the rate of pulmonary morbidity and organ dysfunction in critically ill surgical patients. Summary Background Data Oxidative stress has been associated with the development of the acute respiratory distress syndrome (ARDS) and organ failure through direct tissue injury and activation of genes integral to the inflammatory response. In addition, depletion of endogenous antioxidants has been associated with an increased risk of nosocomial infections. The authors postulated that antioxidant supplementation in critically ill surgical patients may reduce the incidence of ARDS, pneumonia, and organ dysfunction.

Understanding and appreciating the science of pharmacoeconomics have become even more important for health care providers and insurers during the recent economic downturn. Evaluating the true costs of any disease is complex; both direct costs, such as costs of drug therapy and the provision of care, and indirect costs, such as lost earnings and reduced quality of life, must be taken into account. With chronic liver disease, the most recent data indicate that direct costs were more than $2 billion whereas indirect costs were more than $450 million. Hepatic encephalopathy, a common complication of chronic liver disease, contributes to this economic burden. Although patients' length of stay during hospitalization for hepatic encephalopathy decreased from almost 9 days to 6 days (and has remained stable over the past few years) from 1993 to 2007, hospitalization costs rose from $13,000 to $30,000/hospital stay. In addition, 22% of patients were discharged directly to nursing homes or rehabilitation centers, which increases total costs. When assessing therapy for hepatic encephalopathy, it is important to consider the total costs of the disease, not just treatment costs. Although more expensive on a daily basis than lactulose, rifaximin has been shown to reduce hospitalization rates, has a better adverse-effect profile, and increases patient compliance. One study found that rifaximin produced a cost savings/patient/year of more than $3000 over lactulose therapy.

Noncompliance with treatment protocols produces an increased burden on the health care system. Reports show that 23% of annual admissions to nursing homes in the United States (380,000 patients) are due to noncompliance, resulting in overall costs of over $31 billion. More than 10% of all patients (3.5 million) are hospitalized each year due to complications related to noncompliance, with over $15 billion spent. In addition, nearly half of the 2 billion prescriptions filled each year are not taken correctly. Patients with cirrhosis and hepatic encephalopathy who are prescribed lactulose experience a greater frequency of adverse effects, require more hospitalizations, and suffer more disease recurrence than those prescribed rifaximin.