Pharmacologic Vasopressin Levels May Protect Renal Function in a Porcine (Sus Scrofa) Model of Vasodilatory Septic Shock

Abstract

Acute renal failure commonly occurs with severe sepsis and is associated with high mortality. Pharmacologic administration of vasopressin (VP) increases urine output in septic shock. To elucidate the mechanism by which pharmacologic VP induces diuresis, VP was administered at a low dose of 10 and a high dose of 100 ng/kg/min to piglets with endotoxin‐induced septic shock. VP‐100 produced a 4‐fold increase in urine flow (0.05 ± 0.02 vs. 0.23 ± 0.04 ml/kg/min), creatinine clearance, and filtration fraction compared to VP‐10 while the mean arterial pressure (MAP), delta MAP, and renal blood flow were similar between the groups. High dose VP demonstrated increased osmolar clearance (0.07 ± 0.05 vs. 0.21 ± 0.13 ml/kg/min), Na excretion, and fractional excretion (FE) of sodium (2.04 ± 0.83 vs. 4.51 ± 0.57) despite an increase in aldosterone and no change in renin levels. There was no change in the FE of urea or potassium between groups. The production of dilute urine was evidenced by increased free water clearance (−0.02 ± 0.01 to 0.03 ± 0.02 ml/kg/min), decreased urine osmolality (415 ± 21 vs. 282 ± 22 mOsm/kg H2O), and decreased urine protein (5.3 ± 0.87 vs. 1.9 ± 0.54 mg/ml) observed in the high but not low dose of VP. Thus at high dose VP, the increase in the filtration fraction and the FENa which lead to an increased excretion of dilute urine suggest a tubular osmotic mechanism that may be renal protective in septic shock.