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Perioperative Genomics
Our goal is to use genetic variability to identify patients at risk for adverse events after surgery. Over 40 million patients undergo surgery annually in the U.S., resulting in costs of $450 billion per year; with ≈1.25 million having perioperative cardiovascular complications annually, this one clinical adverse outcome alone results in an additional $25 billion in health care expenditures. By the year 2020, it is projected that the number of surgeries in the U.S. will increase 25%, associated costs by 50%, and the likelihood of atherosclerotic-related cardiac, cerebral, and renal complications by 100%. Hence, the ability to identify patients at high risk for perioperative and peri-procedure complications is critical so that interventions can be identified to optimize outcome.
The Duke Perioperative Genomics Group is the first in the world to evaluate genomic variability as a tool to predict adverse outcome in a large cohort of patients (n=3500 by 2002, with collections continuing through the present 2006), particularly taking into account the contribution of multiple genetic variants in final clinical outcomes. The clinical endpoints we have examined thus far include bleeding, renal injury, stroke, neurocognitive deficits, myocardial injury, sepsis, and arrhythmias. 250 single-nucleotide polymorphisms (including 53 as controls for populations structure) represent 8 mechanistic pathways were evaluated in our patients. Clinical models, genetic models, and combined clinical/genetic models for adverse outcomes were determined. Plasma and RNA has also been collected for proteomic and microarray analyses. We use the operating room as a model of perturbation (robust stress) superimposed on complex disease. An interesting biologic and mechanistic theme emerging is that patients who have pro-inflammatory single-nucleotide polymorphisms are at higher risk for adverse events. While inflammation is an important component of wound healing, too robust of a pro-inflammatory response appears to be detrimental. In addition, most adverse events are related to combinations of pro-inflammatory single-nucleotide polymorphisms, not isolated single gene variants.
What is Perioperative Genomics
Perioperative Genomics seeks to apply functional genomic approaches to reveal the biological reasons why similar patients can have significantly different clinical outcomes after surgery. For the perioperative physician, these findings may soon translate into prospective risk assessment incorporating genomic profiling of markers important in inflammatory, thrombotic, vascular, and neurologic responses to perioperative stress, with implications ranging from individualized additional pre-operative testing and physiological optimization, to perioperative decision-making, options of monitoring approaches, and critical care resource utilization.
Overall Aim
As it aims to uncover the biological reasons behind the dramatically different postoperative outcomes, the emerging field of perioperative genomics attempts to link genetic/epigenetic variability to risk assessment, disease characterization and outcome prediction.
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