Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Critically Ill Neonatal Foals
Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis occurs frequently in critically ill humans, particularly patients with sepsis and septic shock, and has been shown to have a significant impact on survival in human critical care. However, the prevalence and significance of HPA axis dysfunction in critically ill neonatal foals are not well characterized. The purpose of this study was to assess HPA axis function in foals < 7 days of age at the time of admission to tertiary referral centers and to determine correlations between HPA axis dysfunction and indicators of disease severity and outcome. Basal plasma endogenous ACTH and total serum cortisol concentrations were measured with chemiluminescent assays in 71 foals, and a synthetic ACTH stimulation test (measurement of serum total cortisol concentration before and 90 minutes after intravenous administration of 100 µg synthetic ACTH) was performed in 59/71 foals. HPA axis dysfunction was defined as: 1) an inappropriately low basal serum cortisol concentration, and 2) an inadequate increase in serum cortisol concentration (delta cortisol) after administration of synthetic ACTH. Specifically, an inappropriately low basal cortisol concentration was defined as a basal cortisol concentration less than the lowest cortisol concentration (mean-1 standard deviation) achieved after administration of a physiologic dose (10 µg) of synthetic ACTH to healthy age-matched foals. An inadequate delta cortisol was defined as a delta cortisol less than the mean delta cortisol achieved in healthy age-matched foals using the same synthetic ACTH stimulation protocol. Data were analyzed using chi-square and Student's t-tests with significance set at P<0.05.
Using these two criteria independently, HPA axis dysfunction was diagnosed in 49% (35/71) and 51% (30/59) of foals, respectively. Seventy-six percent of foals (54/71) met criteria for sepsis (sepsis score > 11 and/or positive blood culture); HPA axis dysfunction was diagnosed in 37% (20/54) and 41% (22/54) of septic foals, respectively, with the above criteria. In septic foals, low delta cortisol was correlated with non-survival (death or euthanasia for prognostic reasons during hospitalization; P=0.04). In addition, 90% of the septic foals with an increased basal serum cortisol concentration and a low delta cortisol did not survive, as compared to a non-survival rate of only 9% in foals with a high basal cortisol concentration and an appropriate delta cortisol (P=0.02). Finally, septic foals with a low delta cortisol were more likely to have multiple organ failure (P=0.03) and shock (P=0.04) than were septic foals with an appropriate delta cortisol. These findings suggest that HPA axis dysfunction occurs with significant prevalence in critically ill foals and that septic foals with concurrent HPA axis dysfunction are more likely to have shock and multiple organ failure, and are less likely to survive.