Advances in medical care have increased the proportion of elderly Americans and enabled them
to remain more physically active. This has resulted in an unprecedented increase in the
number of geriatric patients admitted to trauma centers. The elderly constitute 23% of trauma
center admissions, but 36% of all trauma deaths. This disproportionately high mortality is
attributable to a higher prevalence of pre-existing conditions, particularly, cardiac
disease. Multi-system injuries result in critical cardiac stress. Although beta-blockade has
been shown to decrease morbidity and mortality in patients at risk for myocardial infarction
after elective surgery, their use in trauma patients with potential underlying cardiac
disease has not been previously studied. We hypothesize that routine administration of
beta-blockers after resuscitation will reduce morbidity and mortality in elderly trauma
patients with, or at risk for, underlying cardiac disease.
This study is a randomized, prospective clinical trial. One cohort will receive routine
trauma intensive care, and the other, the same care plus beta-blockade after completion of
resuscitation. The primary outcome will be mortality. Secondary outcomes include MI, length
of stay, organ dysfunction, cardiac, and other complications.
Changes in outcome may not be due to reduction in myocardial oxygen demand and heart rate.
Laboratory studies demonstrate that circulating inflammatory cytokines contribute to cardiac
risk in trauma patients, and their production is influenced by adrenergic stimulation. We
will measure circulating IL-6, TNF alpha, IL-1beta, and measure NF-kB and p38 MAP kinase
activation in peripheral blood leukocytes, and determine the effect of beta-blockade on the
production of these inflammatory markers.
Finally, the wide variation in patient response to beta-blockers is attributed to genetic
variability in the adrenergic receptor. Therefore, we will identify single nucleotide
polymorphisms (SNPS) within the beta-adrenergic receptor, and determine their effects on
mortality and response to beta-blockade. This study will provide the first randomized,
prospective trial designed to reduce morbidity and mortality in elderly trauma patients at
risk for cardiac disease. The laboratory and genetic component will provide additional
insights that may explain treatment effects, lead to new therapeutic strategies, and have the
potential to lead to additional areas of investigation.