2007 Papers - Sung


Vasopressin increases cortisol levels independent of ACTH or catecholamine stimulation in a porcine model of septic shock

Chen Li Sung, Glenn Hashiro, Claudia Hernandez,
John Claybaugh, Catherine Uyehara
The Departments of Surgery and Clinical Investigation, Tripler Army Medical Center


Introduction: : In septic shock, hypoperfusion of end organs can result in decreased organ function. Adrenal insufficiency is of particular concern in the management of septic shock because cortisol levels can remain depressed, and an insufficient glucocorticoid stress response can prolong hypotension and derangement of glucose metabolism. Recently, vasopressin has demonstrated clinical utility in catecholamine-resistant septic shock by increasing blood pressure and redirecting blood flow to vital organs; we hypothesize that vasopressin may also be beneficial by stimulating adrenal function.

Objective: To demonstrate that vasopressin infusion increases cortisol levels in our porcine model of endotoxin-induced septic shock.

Methods: Sus scrofa piglets between 5-14 days of age were anesthetized, intubated, and hemodynamics were monitored using pulmonary artery and central venous catheters as well as urinary output. Following a post-procedure equilibration phase baseline blood samples were drawn. Purified E. coli endotoxin was then infused to produce a septic shock state, defined as a 20% drop in mean arterial pressure. Control animals were then given normal saline while experimental animals were given vasopressin infusion (100 ng/kg/min). Blood samples were taken and levels of vasopressin, cortisol, ACTH, epinephrine, norepinephrine, aldosterone, and dopamine were evaluated.

Results: Endotoxin caused an ACTH-induced increase in cortisol from baseline (5.6 ± 0.6 µg/dl vs. 17.8 ± 1.6 µg/dl, n=15, p<0.01). The cortisol increase remained constant in untreated pigs, while vasopressin further increased cortisol levels (27.3 ± 1.9 µg/dl; p<0.01). Vasopressin-induced cortisol increase was independent of any associated increase in ACTH and was glucocorticoid-specific, as aldosterone, epinephrine, norepinephrine, and dopamine levels were not elevated by vasopressin.

Conclusion: Vasopressin-mediated direct stimulation of cortisol could have important clinical implications in the treatment of adrenal insufficiency in septic shock.