Critical Care Medicine

Jean Mantz
2010 Anesthesiology  
Genetic variation and loss of physiologic complexity are associated with mortality in 644 trauma patients. Ann Surg 2009; 250:524 -30 Personalized medicine merges genetics, physiology, and outcome with patient care. In the intensive care unit (ICU), identification of patients for whom standard of care is suboptimal may be difficult because of the variation in morbidity and mortality in this patient population. Decreased heart rate (HR) variability has been associated with increased mortality
more » ... morbidity in trauma and other critically ill populations and has been used as a biomarker for autonomic nervous system dysfunction. Genetic variations in ␣-1A and ␤-2 adrenergic receptors (ADRA1A, ADRB2) have been associated with changes in smooth muscle tone in various tissues and implicated in bronchial hyperresponsiveness, metabolic syndrome, and other disorders. In this retrospective study, complexity data and genetic samples were collected from a cohort of 644 ICU admissions to a level 1 trauma center. Two autonomic nervous system receptor polymorphisms (rs1048101, alpha ADRA1A and rs1042714, beta ADRB2) were genotyped, and HR multiscale entropy was measured over 6-h intervals (21,600 HR data points/interval/patient). Further analyses examined the relationship of genotypes, complexity, and probability of survival, an acuity score incorporating age, injury mechanism/ severity, and admission vitals, to risk of death. Ninety-three patients (15%) died before hospital discharge. Nonsurvivors were older and more severely injured with significantly lower HR variability at early, middle, and late portions of ICU stay (median multiscale entropy at least 25% less in nonsurvivors, P Ͻ 0.001). Nonsurvivors also had a significantly lower incidence of the GG ADRB2 genotype (8 vs. 18%, P Ͻ 0.001) and higher proportion of the CC ADRB2 genotype (P ϭ 0.028). The GG ADRB2 genotype carried approximately a threefold decrease in mortality odds (odds ratio, 0.33) independent of significant effects in HR multiscale entropy (odds ratio, 0.93; P Ͻ 0.001) and probability of survival (odds ratio, 0.22; P Ͻ 0.001). Interpretation Trauma patients with decreased HR variability and lower incidence of the GG ADRB2 genotype of the adrenoreceptor had increased mortality odds. These data suggest that adrenoreceptor genotype might impact mortality risk in these patients after trauma. Additional studies assessing the effects of different polymorphisms will be required to validate this association.
doi:10.1097/aln.0b013e3181cbff41 fatcat:b2wdz7dklrapjpopy35q5jckgi