Implantable infusion pump in the therapy of canine adrenal insufficiency

To test the feasibility of a commercially available infusion pump in the treatment of human adrenal insufficiency, we employed the pumps initially in dogs. Two dogs underwent total adrenalectomy and placement of an Infusaid Model 400 infusion pump. These pumps have a drug reservoir of 45 ml and are refilled by percutaneous injection approximately every 2 weeks. Hydrocortisone phosphate was used as replacement glucocorticoid. Serum cortisol values correlated with the amount of drug delivered, and daily administration of 10 to 50 mg/day maintained the plasma cortisol level within the normal range (1 to 6 micrograms/dl). Mineralocorticoid replacement initially consisted of fludrocortisone by mouth and subsequently aldosterone via infusion pump. Serum electrolytes fluctuated with the amount of drug delivered, and doses of approximately 100 to 400 micrograms administered orally per day and 70 to 100 micrograms/day per pump maintained serum electrolytes within the normal range. Dependence upon and effectiveness of pump administration of steroids for long-term survival was demonstrated by: (1) ACTH-stimulation tests after operation and approximately 1 year later, (2) autopsy studies demonstrating total adrenalectomy, (3) repeatedly undetectable plasma cortisol levels during periods of no glucocorticoid supplementation, and (4) repeated hyperkalemia and hyponatremia during periods of no mineralocorticoid supplementation. This study demonstrates that glucocorticoid and mineralocorticoid preparations can remain bioactive for 2 to 3 weeks at 37 degrees C and can be delivered in amounts adequate to sustain a totally adrenalectomized dog via a commercially available infusion pump. In the adrenalectomized dog hydrocortisone sufficient to maintain plasma cortisol values in the normal range does not provide adequate mineralocorticoid replacement.