Elevated plasma norepinephrine concentrations in decompensated cirrhosis. Association with increased secretion rates, normal clearance rates, and suppressibility by central blood volume expansion

Abstract

Plasma norepinephrine concentrations are elevated in patients with decompensated cirrhosis, and correlate inversely with urinary sodium and water excretion. Increased plasma norepinephrine concentrations may result from a decreased metabolic clearance rate or an increased secretion rate, possibly in response to a decreased "effective arterial blood volume." If the latter hypothesis is correct, plasma norepinephrine might be expected to be suppressed when central blood volume is expanded by head-out water immersion. In the present study, plasma norepinephrine secretion and clearance rates were determined by infusion of tritiated norepinephrine. Norepinephrine secretion rates were elevated in eight cirrhotic patients as compared to control subjects (1.50 +/- 0.25 vs. 0.26 +/- 0.08 micrograms/m2 per min, P less than 0.001), whereas clearance rates were similar (3.13 +/- 0.48 vs. 2.60 +/- 0.28 liters/min, NS). Baseline plasma norepinephrine concentrations were markedly elevated in the cirrhotic patients (830 +/- 136 vs. 185 +/- 12 pg/ml, P less than 0.001). Head-out water immersion significantly suppressed plasma concentrations of both norepinephrine (704 +/- 72 to 475 +/- 70 pg/ml, P less than 0.005) and epinephrine (121 +/- 33 to 57 +/- 10 pg/ml, P less than 0.05) in all seven patients studied. We conclude that the high circulating catecholamine concentrations in cirrhosis are secondary to increased secretion, rather than to decreased metabolic clearance, and are suppressible by central blood volume expansion.