Understanding the Transition to Acute Illness: The Promise of Perioperative Genomics

Abstract

Over the last decades, tremendous advances have been made in understanding the genomic basis of a large number of chronic human diseases. Such advances were made possible by studying large numbers of patients over relatively long periods of time. It is increasingly recognized that acute robust stress stimulates pathways activated in chronic disease, facilitating mechanistic studies in much shorter time frames. A new field of molecular medicine, called perioperative genomics, uses robust surgical stress as a perturbation designed to explore such mechanisms. This new field is described briefly below. KeywordsPerioperative Care; Genomics; Risk Assessment; Postoperative Complications; Acute Disease Importance of the Perioperative PeriodMore than 40 million patients undergo surgery in the United States each year, and that number is expected to rise by 25% by 2020 [1]. In terms of monetary costs, the numbers are staggering with current estimates of $450 billion spent annually in the perioperative period [2]. Adverse events such as perioperative myocardial injury, renal failure, cognitive dysfunction, and stroke are devastating. Cardiovascular complications can occur after procedures even in patients without known heart disease. This problem is increasing as the population ages and cardiac risk factors, such as hypertension and diabetes mellitus, become more prevalent.Outside of its overall economic impact, the perioperative period provides an ideal model of acute illness. Although a dynamic and complicated environment, the operating room offers unique advantages for studying patients. In this environment, physiologic changes from baseline with robust stress can be prospectively quantified (e.g., hemo-dynamic parameters or plasma biomarkers). Even perturbations such as drug administration and organ ischemic time can be studied. Exposure to extremes of physiology offers the advantage of revealing (uncovering) phenotypes which might otherwise be dormant or take years to be expressed. Indeed, for patients at risk for proinflammatory activation, the operating room may transition an otherwise healthy individual into one who is acutely ill and at risk for postoperative complications and organ dysfunction.Coronary thrombosis is one example of how perioperative genomics can aid our understanding of illness beyond the operating room. There are more than one million spontaneous myocardial infarctions annually in the United States, but despite this incidence, molecular events triggering

Genomics relevant to the neuroanaesthesiologist

“…[4] In the field of neurosurgery, reports of personalised therapy decisions based on genetic, epigenetic and molecular biomarkers have recently emerged -use of candidate molecular markers to complement diagnoses, aid prognosis and allow individualised treatment to patients with glioblastoma multiforme, thereby avoiding unnecessary therapy, reducing toxicity and associated costs. [5] While the decision to operate or not is being aided by genetics, the perioperative period is itself a model of stress and inflammation superimposed on complex disease and is associated with pain and haemodynamic/ metabolic shifts [6] -all these elements have a genetic basis for individual response variability. As can be imagined, surgical trauma triggers an integrated neuroendocrine reaction, and the body mounts a counter-regulatory response.…”