Skip to Main Content

++

KEY POINTS

++

KEY POINTS

  1. Early candidate gene studies and more recent genomewide association studies suggest that susceptibility to adverse perioperative events including cardiac (myocardial infarction, ventricular dysfunction, atrial fibrillation), neurologic, and renal, among other events, is genetically determined. A particular focus is now placed on determining whether a specific genetic variant warrants clinical action.

  2. Potential applications of biomarkers in perioperative medicine and critical care include prognosis, diagnosis, and monitoring of adverse outcomes, as well as informing and refining therapeutic decisions. Very few so far have been rigorously evaluated to demonstrate additive performance to existing risk stratification models (clinical validity) or change therapy (clinical utility). Most promising among those are natriuretic peptides and C-reactive protein for cardiovascular risk prediction, postoperative troponin surveillance to diagnose myocardial injury, and procalcitonin to assess infection in the critically ill.

  3. Ongoing systematic evaluation of existing genomic evidence to make clinical decisions in the perioperative continuum, update practice guidelines, and reimburse the generation and use of genomic information is required to facilitate its translation to medical practice.

++

SCIENTIFIC FOUNDATIONS OF PRECISION MEDICINE

++

The perioperative period represents a unique and extreme example of gene-environment interaction. As we appreciate in our daily practice in both operating rooms and intensive care units, one hallmark of perioperative physiology is the striking variability in patient responses to the acute, robust, and systemic stressors induced by surgical injury, hemodynamic challenges, vascular cannulation, extracorporeal circulation, intraaortic balloon counterpulsation, mechanical ventilation, partial/total organ resection, transient limb/organ ischemia, transfusions, anesthetic agents, and the pharmacopoeia used in the perioperative period. This translates into substantial inter-individual variability in the incidence or severity of immediate perioperative adverse events and critical illness, as well as long-term outcomes (Table 84-1). For decades we have attributed this variability to many complexities such as age, frailty, nutritional state, cardiopulmonary fitness, and comorbidities – what we colloquially term “protoplasm.” Now we are beginning to appreciate that genomic variation is also in part responsible for this observed variability in outcomes. Overall, one’s susceptibility to adverse perioperative events stems not only from genomic contributions to the development of comorbid risk factors (like CAD or reduced preoperative cardiopulmonary reserve) during one’s lifetime but also from genomic variability in specific biological pathways participating in the host response to surgery (Figure 84-1). With increasing evidence suggesting that genomic regulation can significantly modulate risk of adverse perioperative events,1-4 the emerging field of perioperative genomics aims to apply innovative functional genomic approaches and technologies to discover underlying biological mechanisms that explain why similar patients have such dramatically different outcomes after surgery, and is justified by a unique combination of environmental insults and postoperative phenotypes that characterize surgical and critically ill patient populations.

++
FIGURE 84-1.

Perioperative adverse events are complex traits, characteristically involving an interaction between robust operative environmental perturbations (surgical trauma, hemodynamic challenges, exposure to extracorporeal circulation, drug administration) and multiple susceptibility genes. The observed variability in perioperative outcomes can ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.