Randomized, Placebo Controlled, Pilot Trial of Statin Use in Burn Patients

Infection and sepsis are the major causes of morbidity and mortality in burn patients. Several observational studies have shown that HMG-CoA reductase inhibitors, known as statins, before or after illness or injury results in decreased mortality and incidence of sepsis.

We performed a pilot retrospective chart review of 223 patients admitted to the Vanderbilt University Burn Service from 2006-2008 who were ≥55 years of age. Patients were identified as using statin drugs prior to burn, and compared to those who were not. There was a significant decrease in mortality of 83% (P=.004) in the statin group and a 50% reduction in septic shock (p=.155) that was not significant likely due to the low numbers of patients with septic shock (n=30). These effects were unchanged after controlling for cardiovascular comorbidities.

Animal studies have also shown decreased mortality and sepsis with pre-injury statin administration. Mechanisms of statin effect on mortality and septic shock are attributed to the so-called pleiotropic effects.

If the use of statins is potentially expected to reduce mortality, it is even more relevant to understand the long-term cognitive and functional outcomes of the survivors. In the last years researchers highlighted how survivors from acute respiratory distress syndrome (ARDS) largely experience cognitive and functional decline after their acute illness. More recently Jackson et al. advocated a relationship between delirium in intensive care unit (ICU) patients and cognitive impairment; more specifically 1 of 3 survivors of critically illness with delirium developed cognitive impairment. Though every year several patients are admitted to burn units in the United States, to date only one small report has been published addressing the long-term cognitive outcomes of burn ICU patients. In these preliminary data, Varney et al. found that of the eight patients all were found to have significant problems as evidenced in neuropsychological tests, activities of daily living, and from relatives' reports.

The causes of development of a de-novo cognitive impairment in this population are probably multifactorial and could be linked to the development of and duration of delirium or to the exposure to large amount of sedatives-analgesics used to assure the comfort of the patients on the ventilator and to control pain secondary to the burn. ICU delirium is a common acute brain dysfunction with a prevalence as high as 80% in critically ill surgical and medical ICU patients depending on the severity of illness and the instrument used to diagnose delirium. Different risk factors have been called to cause delirium including exposure to drugs. In particular, previous studies have shown how exposure to benzodiazepines (i.e. lorazepam and midazolam) and opiates have been associated to transition to delirium in medical and surgical ICU patients. If sedatives and analgesics are widely used in the medical and surgical ICUs, this is even more striking for the burn units where large amounts of drugs are infused for patient comfort and pain control. Therefore a large exposure to these drugs in burn patients has the potential to influence the prevalence of delirium even more.