Plasma adrenomedullin concentrations in critically ill neonatal foals

Abstract

Background: Bacterial sepsis remains a leading cause of morbidity and mortality in neonatal foals, but accurate diagnostic and prognostic markers are lacking. Adrenomedullin (AM) is a polypeptide with diverse biologic effects on the cardiovascular system that increases in septic humans and laboratory animals.

Hypotheses: Plasma AM concentration (p[AM]) is increased in septic neonatal foals compared to sick nonseptic and healthy control foals, and p[AM] is predictive of survival in septic neonatal foals.

Animals: Ninety critically ill (42 septic, 48 sick nonseptic) and 61 healthy foals <1 week of age.

Methods: A prospective observational clinical study was performed. Venous blood was collected from critically ill foals at admission and from healthy foals at 24 hours of age. Critically ill foals were categorized as septic or sick nonseptic based on blood culture results and sepsis score. Plasma [AM] was measured by using a commercially available ELISA for horses. Data were analyzed by using the Mann-Whitney U-test and P < .05 was considered significant.

Results: Plasma [AM] was not significantly different between septic and sick nonseptic foals (P = .71), but critically ill foals had significantly increased p[AM] compared to healthy controls (P < .0001). In critically ill foals, p[AM] was not predictive of survival (P = .051). A p[AM] cutoff concentration of 0.041 ng/mL provided a test sensitivity of 91% and specificity of 54% to predict illness.

Conclusions and clinical relevance: Plasma [AM] shows promise as a marker of health in neonatal foals, but p[AM] increases nonspecifically during perinatal illnesses and is not necessarily associated with sepsis.

Keywords: Foal; Sepsis; Survival.

Figure 1

Scatterplot of relationship between plasma adrenomedullin concentration in critically ill neonatal foals (n = 90) and sepsis score on admission. The thick horizontal line is the median plasma adrenomedullin concentration in healthy neonatal foals, and the dashed horizontal lines are the 95% confidence interval for the plasma adrenomedullin concentration in healthy neonatal foals. Filled circles represent foals that did not survive and open circles represent foals that survived to discharge from the hospital.

Figure 2

Receiver operating characteristic curve plotting test sensitivity against (1 – test specificity) at the optimal cutoff value for plasma adrenomedullin concentration (0.041 ng/mL) in differentiating healthy from critically ill nenonatal foals. The dashed diagonal line is the chance line (sensitivity [Se] = specificity [Sp] = 0.50; equivalent to tossing a coin, area under the curve = 0.50). The filled circle is the test Se (0.91) and Sp (0.54) at the optimal cutoff value for plasma adrenomedullin concentration. The area under the curve is 0.75.