Defining normal adrenal function testing in the intensive care unit setting: a canine study.

OBJECTIVE

To determine whether intensive care medicine therapies and testing influence hypothalamic-pituitary-adrenal test results. It is routine in intensive care medicine to measure hypothalamic-pituitary-adrenal function, commonly utilizing the adrenocorticotropic hormone stimulation test to diagnose absolute or relative adrenal insufficiency.

DESIGN

Prospective, 96-hr animal study.

SETTING

Research laboratory.

SUBJECTS

Twenty-four healthy canines.

INTERVENTIONS

Animals were randomized into two groups--awake and unrestrained or treated with intensive care medicine therapies, including sedation, intubation, and mechanical ventilation. Animals were further randomized to receive dexamethasone (or placebo) or undergo either a total of four or seven adrenocorticotropic hormone stimulation tests over 96 hrs.

MEASUREMENTS AND MAIN RESULTS

Sedation, intubation, and mechanical ventilation transiently increased both basal and postadrenocorticotropic hormone total and free cortisol concentrations >2-fold as compared with baseline for the first 24 hrs (p < or = .05 for both). Performance of seven stimulation tests increased both basal and postadrenocorticotropic hormone total and free cortisol concentrations from baseline by >1.5-fold for the duration of the 96-hr study (p < or = .05). Neither sedation, intubation, and mechanical ventilation nor the performance of more stimulation tests affected delta cortisol measurements (total or free cortisol, p = NS). In contrast, dexamethasone suppressed basal total cortisol concentrations by >2-fold (p < or = .005) at all time points and transiently increased delta total cortisol by approximately 35% during the first 24 hrs of the study (p < or = .05).

CONCLUSIONS

Total and free cortisol measurements--whether pre- or post- adrenocorticotropic hormone or as a calculated delta--were altered by intensive care therapies or frequent adrenocorticotropic hormone stimulation testing with one exception. Delta free cortisol was the only hypothalamic-pituitary-adrenal measurement unaffected by sedation, intubation, and mechanical ventilation, completion of more adrenocorticotropic hormone stimulation tests, or dexamethasone therapy. These findings support the need to determine normal ranges for hypothalamic-pituitary-adrenal testing in subjects receiving intensive care medicine before establishing laboratory criteria for the diagnosis of relative adrenal insufficiency.